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Sample records for renal tubular dysfunction

  1. Prevalence of renal tubular dysfunction in beta thalassemia minor in shiraz

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    Ali Moradi Nakhodcheri

    2012-02-01

    Full Text Available  Background & objective: β-Thalassemia minor is an asymptomatic hereditary disease. The first study on the relation of renal tubular dysfunction and β-thalassemia minor was performed in 2002 but those studies seem inadequate.The main goal of this study is through evaluation of renal tubular function in 100 patients with thalassemia minor. Materials & Methods: 100 patients with β- thalassemia which confirmed by hemoglobin electrophoresis and CBC as well as RBC indices were studied.14 out of 100 cases exit because of Urinary Tract Infection, diabetes mellitus or hypertension.Complete chemistry profile was performed on serum and urine of all reminder 86 patients (46 female and 40 male. Patients classified into two groups: β-thalassemia minor with anemia and without anemia. Another control group include 50 healthy individuals also considered.Then data analyzed by proper statistical methods. Results: 20 out of 86 reminder cases e.g. 24% showed at least one index of renal tubular dysfunction.58% of patients was been anemic and 42% non anemic. The most prominent tubular dysfunction was seen in a 29 years old lady with glucosuria and without anemia. conclusion: β-Thalassemia minor is common in Iran specially in Fars province. This study revealed significant renal tubular dysfunction in patient with β-thalassemia minor. So it is necessary to check out thalassemic patients for renal function tests periodically. Key words: β-thalassemia, minor,renal tubular dysfunction

  2. Renal tubular dysfunction nephrocalcinosis in a patient with BetaThalassemia Minor

    International Nuclear Information System (INIS)

    Prabahar, M.R.; Jain, M.; Chandrasekaran, V.; Indumathi, E.; Soundrarajan, P.

    2008-01-01

    Thalassemia is a hereditary anemia resulting from defect in hemoglobinproduction. Beta thalassemia is due to impaired production. Beta thalassemiais due to impaired production of beta globin chains, leading to a relativeexcess of alpha globin chains. The term beta thalassemia minor is used todescribe heterozygotes, who carry one normal beta globin and one betathalassemic allele. The vast majority of these patients are asymptomatic.However, a variety of renal tubular abnormalities including hypercaliuria,hypomagnesemia with renal magnesium wasting, decreased tubular absorption ofphosphorous, hypouricemia with renal uric acid wasting, renal glycosuria andtubular proteinuria have been described even in patients with betathalassemia minor. We here in report a 24-year old patient who was found tohave thalassemia minor and nephrocalcinosis with evidence of renal tubulardysfunction. Investigations revealed normal renal function, hypercalciuria,reduced tubular reabsorption of phosphorous, hypomagnesemia and renalmagnesium wasting. Screening for aminoaciduria was found to be negative. Anacid loading test revealed normal urinary acidification. Ultrasonogram of theabdomen revealed nephrocalcinosis and splenomegaly. Detailed work up foranemia showed normal white cell and platelet count while peripheral smearshowed microcytic hypochromic anemia with few target cells. Hemoglobinelectrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% andhemoglobin F of 1.8% consistent with beta thalassemia minor. Her parentalscreening was normal. A diagnosis of beta thalassemia minor with renaltubular dysfunction was made and the patient was started on thiazidediuretics to reduce hypercalciuria and advised regular follow-up. (author)

  3. Renal tubular dysfunction in pediatric patients with beta-thalassemia major

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    Ali Ahmadzadeh

    2011-01-01

    Full Text Available To evaluate the prevalence of renal tubular dysfunction in children with β-thalassemia (β-T major, we studied the glomerular and tubular function in 140 children with β-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca, protein, uric acid (UA, creatinine (Cr, urine osmolality and urinary N-acetyl-β-D-glucosaminidase (UNAG activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN, fasting blood sugar, serum creatinine (SCr, electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16 years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR. The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L and 3.2 IU/L in the control group (P 0.21 (P = 0.006. Nine (6.4% thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2. Sixty-nine (49.3% out of the 140 patients and 45 (65.2% of the patients having UNAG had uricosuria also (UUA/UCr > 0.26. Ten (7% patients had microscopic hematuria and 10 (7% patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.

  4. Renal handling of technetium-99m DMSA in rats with proximal tubular dysfunction

    International Nuclear Information System (INIS)

    Provoost, A.P.; Van Aken, M.

    1985-01-01

    The renal handling of technetium-/sup 99m/ dimercaptosuccinic acid ([/sup 99m/Tc]DMSA) was studied in rats before and after treatment with Na-maleate (2 mmol/kg i.v.). In the control period, when measured 2 hr after the intravenous injection of [/sup 99m/Tc]DMSA, 39.9% of the injected dose was in the kidneys and 14.6% was in the bladder. After Na-maleate treatment, only 6.4% of the injected dose of [/sup 99m/Tc]DMSA was retained in the kidneys while 37.9% was found in the bladder. Subsequent studies revealed that Na-maleate produced a fall in the glomerular filtration rate, the effective renal plasma flow, and a generalized proximal tubular dysfunction. The latter was characterized by polyuria and an increased excretion of glucose, protein, albumin, calcium, and inorganic phosphate. It was concluded that proximal tubular dysfunction markedly alters the renal handling of [/sup 99m/Tc]DMSA. Whether this augmented urinary excretion is due to an inhibition of reabsorption or an enhanced cellular efflux of [/sup 99m/Tc]DMSA remains to be answered

  5. The association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium in China.

    Science.gov (United States)

    Chen, Xiao; Dai, Yan; Wang, Zhongqiu; Zhu, Guoying; Ding, Xiaoqiang; Jin, Taiyi

    2018-01-01

    Cadmium exposure can cause renal tubular dysfunction. Recent studies show that vitamin D can play multiple roles in the body. However, the association between serum vitamin D levels and renal tubular dysfunction in a general population exposed to cadmium has not been clarified. We performed study to assess the effects of cadmium on serum 25(OH) D levels and the association between serum 25(OH) D levels and renal tubular dysfunction in a population environmentally exposed to cadmium. A total of 133 subjects living in control area and two cadmium polluted areas were included in the present study. Cadmium in urine (UCd) and blood (BCd), urinary β2Microglobulin (UBMG), urinary retinol binding protein (URBP) and serum 25 (OH) D were determined. Logistic regression was used to estimate the association between 25 (OH) D and prevalence of renal tubular dysfunction. No significant differences were observed in serum 25(OH) D levels among the four quartile of UCd and BCd after adjusting with cofounders. After adjusted with the confounders, the odds ratio (OR) of subjects with 25(OH) D ≥ 40 ng/ml were 0.20 (95%CI: 0.1-0.8) if UBMG was chosen as indicators of renal dysfunction and 0.28 (95%CI: 0.1-1.1) if URBP was chosen as indicators of renal dysfunction, compared with those with 25(OH) D < 30 ng/ml, respectively. Similar results were observed in those subjects living in cadmium polluted areas or with high level of UCd or BCd. Our data indicated that cadmium exposure did not affect serum 25(OH) D level and high 25 (OH) D levels were associated with a decreased risk of renal tubular dysfunction induced by cadmium.

  6. Distal renal tubular acidosis

    Science.gov (United States)

    ... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...

  7. Reversal of Proximal Renal Tubular Dysfunction after Nucleotide Analogue Withdrawal in Chronic Hepatitis B

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    Abhasnee Sobhonslidsuk

    2017-01-01

    Full Text Available Aims. Proximal renal tubular dysfunction (PRTD is an infrequent complication after nucleotide analogue therapy. We evaluated the outcomes of PRTD and nephrotoxicity after nucleotide analogue withdrawal in chronic hepatitis B (CHB. Methods. A longitudinal follow-up study was performed in patients with PRTD after nucleotide analogue discontinuation. Serum and urine were collected at baseline and every 3 months for one year. The fractional excretion of phosphate (PO4, uric acid (UA, and potassium and tubular maximal reabsorption rate of PO4 to glomerular filtration rate (TmPO4/GFR were calculated. Renal losses were defined based on the criteria of substance losses. Subclinical PRTD and overt PRTD were diagnosed when 2 and ≥3 criteria were identified. Results. Eight subclinical and eight overt PRTD patients were enrolled. After nucleotide analogue withdrawal, there were overall improvements in GFR, serum PO4, and UA. Renal loss of PO4, UA, protein, and β2-microglobulin reduced over time. At one year, complete reversal of PRTD was seen in 13 patients (81.2%. Improvements in PRTD were seen in all but one patient. Conclusion. One year after nucleotide analogue withdrawal, PRTD was resolved in most patients. Changes in TmPO4/GFR, urinary protein, and β2-microglobulin indicate that urinary biomarkers may represent an early sign of PRTD recovery.

  8. Renal tubular dysfunction presenting as recurrent hypokalemic periodic quadriparesis in systemic lupus erythematosus

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    D Prasad

    2014-01-01

    Full Text Available We report recurrent hypokalemic periodic quadriparesis in a 30-year-old woman. Patient had also symptoms of multiple large and small joint pain, recurrent oral ulceration, photosensitivity and hair loss that were persisting since last 6 months and investigations revealed systemic lupus erythematosus (SLE with distal tubular acidosis. Our patient was successfully treated with oral potassium chloride, sodium bicarbonate, hydroxychloroquine and a short course of steroids. Thus, tubular dysfunction should be carefully assessed in patients with SLE.

  9. Urinary alpha 1-microglobulin as an indicator protein of renal tubular dysfunction caused by environmental cadmium exposure

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    Tohyama, C.; Kobayashi, E.; Saito, H.; Sugihara, N.; Nakano, A.; Mitane, Y.

    1986-06-01

    An epidemiologic investigation was carried out to clarify the significance of the urinary excretion of alpha 1-microglobulin (alpha 1-MG) in people aged 50 years and over living in a Cd-polluted area in Japan. Approximately 80% of the population participated in the health examination. The urinary and serum levels and the relative clearance of alpha 1-MG to creatinine clearance were compared with various parameters (age, urinary beta 2-microglobulin (beta 2-MG), total protein, Cd, Cu and Zn, serum beta 2-MG, creatinine and blood urea nitrogen and relative clearances of alpha 1-MG, beta 2-MG, inorganic phosphate and uric acid). It was found that the urinary excretion of alpha 1-MG is closely associated with the urinary Cd and Cu and with the indices of renal dysfunction listed above. These results suggest that the urinary alpha 1-MG level markedly reflects a degree of proximal tubular dysfunction and that it may be useful as one of the screening measures for proximal tubular dysfunction caused by environmental Cd exposure.

  10. Proximal tubular dysfunction as an indicator of chronic graft dysfunction

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    N.O.S. Câmara

    2009-03-01

    Full Text Available New strategies are being devised to limit the impact of renal sclerosis on graft function. Individualization of immunosuppression, specifically the interruption of calcineurin-inhibitors has been tried in order to promote better graft survival once chronic graft dysfunction has been established. However, the long-term impact of these approaches is still not totally clear. Nevertheless, patients at higher risk for tubular atrophy and interstitial fibrosis (TA/IF development should be carefully monitored for tubular function as well as glomerular performance. Since tubular-interstitial impairment is an early event in TA/IF pathogenesis and associated with graft function, it seems reasonable that strategies directed at assessing tubular structural integrity and function would yield important functional and prognostic data. The measurement of small proteins in urine such as α-1-microglobulin, N-acetyl-beta-D-glucosaminidase, alpha/pi S-glutathione transferases, β-2 microglobulin, and retinol binding protein is associated with proximal tubular cell dysfunction. Therefore, its straightforward assessment could provide a powerful tool in patient monitoring and ongoing clinical assessment of graft function, ultimately helping to facilitate longer patient and graft survival associated with good graft function.

  11. Renal Tubular Function in Systemic Lupus Erythematosus*

    African Journals Online (AJOL)

    immune' diseases such as. Sjogren's syndrome,'" systemic lupus erythematosus. (SLE),3 alveolitis' and chronic active hepatitis.' The reported abnormalities of renal tubular function include impairment of acid excretion and urinary concentration.

  12. A neglected case of Renal Tubular Acidosis

    International Nuclear Information System (INIS)

    Derakhshan, A.; Basiratnia, M.; Fallahzadeh, M.H.; Al-Hashemi, G.H.

    2007-01-01

    In this report, we present a case of a child with distal renal tubular acidosis, severe failure to thrive and profound rickets, who was only 7.8 Kg when presented at 6 years of age. His response to treatment and his follow up for four years is discussed. Although failure to thrive is a common finding in renal tubular acidosis but the physical and x-ray findings in our case were unique. (author)

  13. Distal renal tubular acidosis in recurrent renal stone formers

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    Renal acidification ability was examined in 90 recurrent renal stone formers, using fasting morning urinary pH levels followed by a short ammonium chloride loading test in subjects with pH levels above 6.0. Fifteen patients (16.6%) revealed a distal renal tubular acidification defect: one patient......, this has important therapeutic implications. The pathological sequence in renal stone formers with dRTA is discussed....

  14. Screening renal stone formers for distal renal tubular acidosis

    DEFF Research Database (Denmark)

    Osther, P J; Hansen, A B; Røhl, H F

    1989-01-01

    A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use...

  15. Cyclosporine A induces senescence in renal tubular epithelial cells

    NARCIS (Netherlands)

    Jennings, Paul; Koppelstaetter, Christian; Aydin, Sonia; Abberger, Thomas; Wolf, Anna Maria; Mayer, Gert; Pfaller, Walter

    The nephrotoxic potential of the widely used immunosuppressive agent cyclosporine A (CsA) is well recognized. However, the mechanism of renal tubular toxicity is not yet fully elucidated. Chronic CsA nephropathy and renal organ aging share some clinical features, such as renal fibrosis and tubular

  16. Environmental exposure to cadmium at a level insufficient to induce renal tubular dysfunction does not affect bone density among female Japanese farmers

    International Nuclear Information System (INIS)

    Horiguchi, Hyogo; Oguma, Etsuko; Sasaki, Satoshi; Miyamoto, Kayoko; Ikeda, Yoko; Machida, Munehito; Kayama, Fujio

    2005-01-01

    Some recent research suggests that environmental exposure to cadmium, even at low levels, may increase the risk of osteoporosis, and that the bone demineralization is not just a secondary effect of renal dysfunction induced by high doses of cadmium as previously reported. To investigate the effect of exposure to cadmium at a level insufficient to induce kidney damage on bone mineral density (BMD) and bone metabolism, we conducted health examinations on 1380 female farmers from five districts in Japan who consumed rice contaminated by low-to-moderate levels of cadmium. We collected peripheral blood and urine samples and medical and nutritional information, and measured forearm BMD. Analysis of the data for subjects grouped by urinary cadmium level and age-related menstrual status suggested that cadmium accelerates both the increase of urinary calcium excretion around the time of menopause and the subsequent decrease in bone density after menopause. However, multivariate analyses showed no significant contribution of cadmium to bone density or urinary calcium excretion, indicating that the results mentioned above were confounded by other factors. These results indicate that environmental exposure to cadmium at levels insufficient to induce renal dysfunction does not increase the risk of osteoporosis, strongly supporting the established explanation for bone injury induced by cadmium as a secondary effect

  17. Distal renal tubular acidosis and hepatic lipidosis in a cat.

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    Brown, S A; Spyridakis, L K; Crowell, W A

    1986-11-15

    Clinical and laboratory evidence of hepatic failure was found in a chronically anorectic cat. Simultaneous blood and urine pH determinations established a diagnosis of distal renal tubular acidosis. The cat did not respond to treatment. Necropsy revealed distal tubular nephrosis and hepatic lipidosis. The finding of distal renal tubular acidosis in a cat with hepatic lipidosis emphasizes the importance of complete evaluation of acid-base disorders in patients.

  18. Efficacy of ultrasonography-guided renal biopsy for the evaluation of renal dysfunction following renal transplantation

    International Nuclear Information System (INIS)

    Kim, Young Jae; Choi, Chul Soon; Min, Seon Jeong; Lee, Gyung Kyu; Lee, Eil Seong; Kang, Ik Won; Bae, Sang Hoon

    2003-01-01

    To evaluate the usefulness and complications of renal biopsy under ultrasonography-guidance in renal dysfunction after renal transplantation. Ultrasonography-guided renal biopsy was done in 47 patients with the transplanted kidney. The subjects consisted of 30 males and 17 females, age ranged from 16 to 66 years (average age=38 years). Biopsies were done once in 27 patients, twice in 17 patients, three times in 3 patients, a total of 70 biopsies. The success rate of renal biopsy for the accurate pathologic diagnosis and the incidence and types of complications following biopsy were evaluated. The success rate of renal biopsy for the accurate pathologic diagnosis was 96%(67/70). Pathologic diagnosis included 27 cases of acute rejection (39%), 8 cases of acute tubular necrosis (11%), 4 cases of acute rejection and acute tubular necrosis (6%), 4 cases of cyclosporin toxicity (6%), 4 cases of primary disease recurrence (6%), 4 cases of infection (6%) and others. Complications after renal biopsy included 15 cases of microscopic hematuria (21%), 1 case of gross hematuria with spontaneous cessation and 1 case of life threatening hemorrhage. Ultrasonography-guided renal biopsy is a safe and effective diagnostic method for the evaluation of renal dysfunction following renal transplantation.

  19. Hyperammonemia associated with distal renal tubular acidosis or urinary tract infection: a systematic review.

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    Clericetti, Caterina M; Milani, Gregorio P; Lava, Sebastiano A G; Bianchetti, Mario G; Simonetti, Giacomo D; Giannini, Olivier

    2018-03-01

    Hyperammonemia usually results from an inborn error of metabolism or from an advanced liver disease. Individual case reports suggest that both distal renal tubular acidosis and urinary tract infection may also result in hyperammonemia. A systematic review of the literature on hyperammonemia secondary to distal renal tubular acidosis and urinary tract infection was conducted. We identified 39 reports on distal renal tubular acidosis or urinary tract infections in association with hyperammonemia published between 1980 and 2017. Hyperammonemia was detected in 13 children with distal renal tubular acidosis and in one adult patient with distal renal tubular acidosis secondary to primary hyperparathyroidism. In these patients a negative relationship was observed between circulating ammonia and bicarbonate levels (P urinary tract infection was complicated by acute hyperammonemia and symptoms and signs of acute neuronal dysfunction, such as an altered level of consciousness, convulsions and asterixis, often associated with signs of brain edema, such as anorexia and vomiting. Urea-splitting bacteria were isolated in 28 of the 31 cases. The urinary tract was anatomically or functionally abnormal in 30 of these patients. This study reveals that both altered distal renal tubular acidification and urinary tract infection may be associated with relevant hyperammonemia in both children and adults.

  20. Inherited renal tubular defects with hypokalemia

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    Muthukrishnan J

    2009-01-01

    Full Text Available Bartter′s and Gitelman′s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter′s syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman′s syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.

  1. Intrarenal purinergic signaling in the control of renal tubular transport

    DEFF Research Database (Denmark)

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    Renal tubular epithelial cells receive hormonal input that regulates volume and electrolyte homeostasis. In addition, numerous intrarenal, local signaling agonists have appeared on the stage of renal physiology. One such system is that of intrarenal purinergic signaling. This system involves all......-reaching advances indicate that ATP is often used as a local transmitter for classical sensory transduction. This transmission apparently also applies to sensory functions in the kidney. Locally released ATP is involved in sensing of renal tubular flow or in detecting the distal tubular load of NaCl at the macula...

  2. Intrarenal purinergic signaling in the control of renal tubular transport

    DEFF Research Database (Denmark)

    Prætorius, Helle; Leipziger, Jens Georg

    2010-01-01

    -reaching advances indicate that ATP is often used as a local transmitter for classical sensory transduction. This transmission apparently also applies to sensory functions in the kidney. Locally released ATP is involved in sensing of renal tubular flow or in detecting the distal tubular load of NaCl at the macula...

  3. Genetics Home Reference: renal tubular acidosis with deafness

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    ... adults with renal tubular acidosis with deafness have short stature, and many develop kidney stones. The metabolic acidosis ... enlarged vestibular aqueduct, can be seen with medical imaging. The vestibular aqueduct is a bony canal that ...

  4. Acute renal dysfunction in liver diseases

    OpenAIRE

    Betrosian, Alex P; Agarwal, Banwari; Douzinas, Emmanuel E

    2007-01-01

    Renal dysfunction is common in liver diseases, either as part of multiorgan involvement in acute illness or secondary to advanced liver disease. The presence of renal impairment in both groups is a poor prognostic indicator. Renal failure is often multifactorial and can present as pre-renal or intrinsic renal dysfunction. Obstructive or post renal dysfunction only rarely complicates liver disease. Hepatorenal syndrome (HRS) is a unique form of renal failure associated with advanced liver dise...

  5. Luminal nucleotides are tonic inhibitors of renal tubular transport

    DEFF Research Database (Denmark)

    Leipziger, Jens Georg

    2011-01-01

    PURPOSE OF REVIEW: Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport. RECENT FINDINGS: Purinergic receptors are express...... discovered as an important signaling compartment in which local purinergic signaling determines an inhibitory tone for renal tubular transport. Blocking components of this system leads to tubular hyper-absorption, volume retention and elevated blood pressure.......PURPOSE OF REVIEW: Extracellular ATP is an essential local signaling molecule in all organ systems. In the kidney, purinergic signaling is involved in an array of functions and this review highlights those of relevance for renal tubular transport. RECENT FINDINGS: Purinergic receptors are expressed...... in all renal tubular segments and their stimulation generally leads to transport inhibition. Recent evidence has identified the tubular lumen as a restricted space for purinergic signaling. The concentrations of ATP in the luminal fluids are sufficiently high to inflict a tonic inhibition of renal...

  6. Diffuse Lymphomatous Infiltration of Kidney Presenting as Renal Tubular Acidosis and Hypokalemic Paralysis: Case Report

    Science.gov (United States)

    Jhamb, Rajat; Gupta, Naresh; Garg, Sandeep; Kumar, Sachin; Gulati, Sameer; Mishra, Deepak; Beniwal, Pankaj

    2007-01-01

    We report the case of a 22-year-old woman who presented with acute onset flaccid quadriparesis. Physical examination showed mild pallor with cervical and axillary lymphadenopathy, hepatomegaly, and bilateral smooth enlarged kidneys. Neurological examination revealed lower motor neuron muscle weakness in all the four limbs with hyporeflexia and normal sensory examination. Laboratory investigations showed anemia, severe hypokalemia, and metabolic acidosis. Urinalysis showed a specific gravity of 1.010, pH of 7.0, with a positive urine anion gap. Ultrasound revealed hepatosplenomegaly with bilateral enlarged smooth kidneys. Renal biopsy was consistent with the diagnosis of non-Hodgkin lymphoma (B cell type). Metabolic acidosis, alkaline urine, and severe hypokalemia due to excessive urinary loss in our patient were suggestive of distal renal tubular acidosis. Renal involvement in lymphoma is usually subclinical and clinically overt renal disease is rare. Diffuse lymphomatous infiltration of the kidneys may cause tubular dysfunction and present with hypokalemic paralysis. PMID:18074421

  7. Renal pathophysiologic role of cortical tubular inclusion bodies.

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    Radi, Zaher A; Stewart, Zachary S; Grzemski, Felicity A; Bobrowski, Walter F

    2013-01-01

    Renal tubular inclusion bodies are rarely associated with drug administration. The authors describe the finding of renal cortical tubular intranuclear and intracytoplasmic inclusion bodies associated with the oral administration of a norepinephrine/serotonin reuptake inhibitor (NSRI) test article in Sprague-Dawley (SD) rats. Rats were given an NSRI daily for 4 weeks, and kidney histopathologic, ultrastructural pathology, and immunohistochemical examinations were performed. Round eosinophilic intranuclear inclusion bodies were observed histologically in the tubular epithelial cells of the renal cortex in male and female SD rats given the NSRI compound. No evidence of degeneration or necrosis was noted in the inclusion-containing renal cells. By ultrastructural pathology, inclusion bodies consisted of finely granular, amorphous, and uniformly stained nonmembrane-bound material. By immunohistochemistry, inclusion bodies stained positive for d-amino acid oxidase (DAO) protein. In addition, similar inclusion bodies were noted in the cytoplasmic tubular epithelial compartment by ultrastructural and immunohistochemical examination.  This is the first description of these renal inclusion bodies after an NSRI test article administration in SD rats. Such drug-induced renal inclusion bodies are rat-specific, do not represent an expression of nephrotoxicity, represent altered metabolism of d-amino acids, and are not relevant to human safety risk assessment.

  8. Renal Impairment with Sublethal Tubular Cell Injury in a Chronic Liver Disease Mouse Model.

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    Tokiko Ishida

    Full Text Available The pathogenesis of renal impairment in chronic liver diseases (CLDs has been primarily studied in the advanced stages of hepatic injury. Meanwhile, the pathology of renal impairment in the early phase of CLDs is poorly understood, and animal models to elucidate its mechanisms are needed. Thus, we investigated whether an existing mouse model of CLD induced by 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC shows renal impairment in the early phase. Renal injury markers, renal histology (including immunohistochemistry for tubular injury markers and transmission electron microscopy, autophagy, and oxidative stress were studied longitudinally in DDC- and standard diet-fed BALB/c mice. Slight but significant renal dysfunction was evident in DDC-fed mice from the early phase. Meanwhile, histological examinations of the kidneys with routine light microscopy did not show definitive morphological findings, and electron microscopic analyses were required to detect limited injuries such as loss of brush border microvilli and mitochondrial deformities. Limited injuries have been recently designated as sublethal tubular cell injury. As humans with renal impairment, either with or without CLD, often show almost normal tubules, sublethal injury has been of particular interest. In this study, the injuries were associated with mitochondrial aberrations and oxidative stress, a possible mechanism for sublethal injury. Intriguingly, two defense mechanisms were associated with this injury that prevent it from progressing to apparent cell death: autophagy and single-cell extrusion with regeneration. Furthermore, the renal impairment of this model progressed to chronic kidney disease with interstitial fibrosis after long-term DDC feeding. These findings indicated that DDC induces renal impairment with sublethal tubular cell injury from the early phase, leading to chronic kidney disease. Importantly, this CLD mouse model could be useful for studying the

  9. 99mTc renal tubular function agents: Current status

    International Nuclear Information System (INIS)

    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr.

    1990-01-01

    Orthoiodohippuric (OIH) acid labeled with 131I is a widely used renal radiopharmaceutical agent and has been the standard radiopharmaceutical agent for the measurement of effective renal plasma flow (EPRF). Limitations to the routine clinical use of 131I OIH are related to the suboptimal imaging properties of the 131I radionuclide and its relatively high radiation dose. 123I has been substituted for 131I; however, its high cost and short shelf-life have limited its widespread use. Recent work has centered on the development of a new 99mTc renal tubular function agent, which would use the optimal radionuclidic properties and availability of 99mTc and combine the clinical information provided by OIH. The search for a suitable 99mTc renal tubular function agent has focused on the diamide dithiolate (N2S2), the paraaminohippuric iminodiacetic acid (PAHIDA), and the triamide mercaptide (N3S) donor ligand systems. To date, the most promising 99mTc tubular function agent is the N3S complex: 99mTc mercaptoacetyltriglycine (99mTc MAG3). Studies in animal models in diuresis, dehydration, acid or base imbalance, ischemia, and renal artery stenosis demonstrate that 99mTc MAG3 behaves similarly to 131I OIH. A simple kit formulation is available that yields the 99mTc MAG3 complex in high radiochemical purity. Studies in normal subjects and patients indicate that 99mTc MAG3 is an excellent 99mTc renal tubular agent, but its plasma clearance is only 50% to 60% that of OIH. In an effort to develop an improved 99mTc renal tubular function agent, changes have been made in the core N3S donor ligand system, but to date no agent has been synthesized that is clinically superior to 99mTc MAG3. 61 references

  10. Tubular overexpression of gremlin induces renal damage susceptibility in mice.

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    Alejandra Droguett

    Full Text Available A growing number of patients are recognized worldwide to have chronic kidney disease. Glomerular and interstitial fibrosis are hallmarks of renal progression. However, fibrosis of the kidney remains an unresolved challenge, and its molecular mechanisms are still not fully understood. Gremlin is an embryogenic gene that has been shown to play a key role in nephrogenesis, and its expression is generally low in the normal adult kidney. However, gremlin expression is elevated in many human renal diseases, including diabetic nephropathy, pauci-immune glomerulonephritis and chronic allograft nephropathy. Several studies have proposed that gremlin may be involved in renal damage by acting as a downstream mediator of TGF-β. To examine the in vivo role of gremlin in kidney pathophysiology, we generated seven viable transgenic mouse lines expressing human gremlin (GREM1 specifically in renal proximal tubular epithelial cells under the control of an androgen-regulated promoter. These lines demonstrated 1.2- to 200-fold increased GREM1 expression. GREM1 transgenic mice presented a normal phenotype and were without proteinuria and renal function involvement. In response to the acute renal damage cause by folic acid nephrotoxicity, tubule-specific GREM1 transgenic mice developed increased proteinuria after 7 and 14 days compared with wild-type treated mice. At 14 days tubular lesions, such as dilatation, epithelium flattening and hyaline casts, with interstitial cell infiltration and mild fibrosis were significantly more prominent in transgenic mice than wild-type mice. Tubular GREM1 overexpression was correlated with the renal upregulation of profibrotic factors, such as TGF-β and αSMA, and with increased numbers of monocytes/macrophages and lymphocytes compared to wild-type mice. Taken together, our results suggest that GREM1-overexpressing mice have an increased susceptibility to renal damage, supporting the involvement of gremlin in renal damage

  11. The rebirth of interest in renal tubular function.

    Science.gov (United States)

    Lowenstein, Jerome; Grantham, Jared J

    2016-06-01

    The measurement of glomerular filtration rate by the clearance of inulin or creatinine has evolved over the past 50 years into an estimated value based solely on plasma creatinine concentration. We have examined some of the misconceptions and misunderstandings of the classification of renal disease and its course, which have followed this evolution. Furthermore, renal plasma flow and tubular function, which in the past were estimated by the clearance of the exogenous aryl amine, para-aminohippurate, are no longer measured. Over the past decade, studies in experimental animals with reduced nephron mass and in patients with reduced renal function have identified small gut-derived, protein-bound uremic retention solutes ("uremic toxins") that are poorly filtered but are secreted into the lumen by organic anion transporters (OATs) in the proximal renal tubule. These are not effectively removed by conventional hemodialysis or peritoneal dialysis. Residual renal function, urine produced in patients with advanced renal failure or undergoing dialysis treatment, may represent, at least in part, secretion of fluid and uremic toxins, such as indoxyl sulfate, mediated by proximal tubule OATs and might serve as a useful survival function. In light of this new evidence of the physiological role of proximal tubule OATs, we suggest that measurement of renal tubular function and renal plasma flow may be of considerable value in understanding and managing chronic kidney disease. Data obtained in normal subjects indicate that renal plasma flow and renal tubular function might be measured by the clearance of the endogenous aryl amine, hippurate. Copyright © 2016 the American Physiological Society.

  12. Importance of early audiologic assessment in distal renal tubular acidosis

    Directory of Open Access Journals (Sweden)

    Elizabeth Norgett

    2010-12-01

    Full Text Available Anand P Swayamprakasam1, Elizabeth Stover1, Elizabeth Norgett1, Katherine G Blake-Palmer1, Michael J Cunningham2, Fiona E Karet11Department of Medical Genetics, Cambridge Institute for Medical Research, Cambridge, UK; 2Department of Otolaryngology, Massachusetts Eye and Ear Infirmary, Boston, MA, USAAbstract: Autosomal recessive distal renal tubular acidosis is usually a severe disease of childhood, often presenting as failure to thrive in infancy. It is often, but not always, accompanied by sensorineural hearing loss, the clinical severity and age of onset of which may be different from the other clinical features. Mutations in either ATP6V1B1 or ATP6V0A4 are the chief causes of primary distal renal tubular acidosis with or without hearing loss, although the loss is often milder in the latter. We describe a kindred with compound heterozygous alterations in ATP6V0A4, where hearing loss was formally diagnosed late in both siblings such that they missed early opportunities for hearing support. This kindred highlights the importance of routine audiologic assessments of all children with distal renal tubular acidosis, irrespective either of age at diagnosis or of which gene is mutated. In addition, when diagnostic genetic testing is undertaken, both genes should be screened irrespective of current hearing status. A strategy for this is outlined.Keywords: sensorineural hearing loss, renal tubular acidosis, recessive, genetics, mutation

  13. Electrolyte composition of renal tubular cells in gentamicin nephrotoxicity

    International Nuclear Information System (INIS)

    Matsuda, O.; Beck, F.X.; Doerge, A.T.; Thurau, K.

    1988-01-01

    The effect of long-term gentamicin administration on sodium, potassium, chloride and phosphorus concentrations was studied in individual rat renal tubular cells using electron microprobe analysis. Histological damage was apparent only in proximal tubular cells. The extent of damage was only mild after 7 days of gentamicin administration (60 mg/kg body wt/day) but much more pronounced after 10 days. GFR showed a progressive decline during gentamicin treatment. In non-necrotic proximal tubular cells, sodium was increased from 14.6 +/- 0.3 (mean +/- SEM) in controls to 20.6 +/- 0.4 after 7 and 22.0 +/- 0.8 mmol/kg wet wt after 10 days of gentamicin administration. Chloride concentration was higher only after 10 days (20.6 +/- 0.6 vs. 17.3 +/- 0.2 mmol/kg wet wt). Both cell potassium and phosphorus concentrations were diminished by 6 and 15, and by 8 and 25 mmol/kg wet wt after 7 and 10 days of treatment, respectively. In contrast, no major alterations in distal tubular cell electrolyte concentrations could be observed after either 7 or 10 days of gentamicin administration. As in proximal tubular cells, distal tubular cell phosphorus concentrations were, however, lowered by gentamicin treatment. These results clearly indicate that gentamicin exerts its main effect on proximal tubular cells. Decreased potassium and increased sodium and chloride concentrations were observed in proximal tubular cells exhibiting only mild histological damage prior to the onset of advanced tissue injury. Necrotic cells, on the other hand, showed widely variable intracellular electrolyte concentration patterns

  14. Recent advances in renal tubular calcium reabsorption.

    NARCIS (Netherlands)

    Mensenkamp, A.R.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2006-01-01

    PURPOSE OF REVIEW: Knowledge of renal Ca2+ reabsorption has evolved greatly in recent years. This review focuses on two recent discoveries concerning passive and active Ca2+ reabsorption. RECENT FINDINGS: The thiazide diuretics are known for their hypocalciuric effect. Recently, it has been

  15. Mathematical rationalization for the renal tubular transport: revised concepts.

    Science.gov (United States)

    Mioni, Roberto; Marega, Alessandra; Romano, Giulio; Montanaro, Domenico

    2017-09-01

    The current emphasis on kinetics and in situ control of molecular exchanges, across the tubular membrane, has not been paralleled by corresponding improvements in our understanding of tubular behaviour at the macroscopic level of classical physiology. In this paper, we propose a mathematical rationalization of macroscopic tubular transport by means of a principal transport equation, originating from the law of mass action between substrate and carrier. The other equations, derived from the main one, demonstrate the possibility of distinguishing between transporters with low affinity and high capacity and transporters with high affinity and low capacity. Moreover, our model formalizes both tubular reabsorption and tubular secretion. Regarding the renal calcium handling, our model confirms the two-compartment system proposed by Mioni in 1971, with some important variants, which are in agreement with the fractional reabsorptions of this cation along the tubule, as verified by micro-puncture technique. To obtain the frequency distribution of saturated tubules, we have utilized the infinitesimal analysis method, starting from the equations proposed by Smith in 1943, concluding that all titration curves result from the combined effect of enzymatic approach and anatomical heterogeneity of the nephrons. The theoretical equations included in our manuscript reflect substantial and palpable physiological mechanisms able to suggest diagnosis and therapy of some electrolyte and hormonal disorders. At the end of this paper, we highlight advantages and disadvantages detectable by comparing our mathematical approach with Marshall's and Bijvoet's methods, proposed, respectively, in 1976 and 1984.

  16. Renal tubular acidosis complicated with hyponatremia due to cortisol insufficiency

    OpenAIRE

    Izumi, Yuichiro; Nakayama, Yushi; Onoue, Tomoaki; Inoue, Hideki; Mukoyama, Masashi

    2015-01-01

    Adrenocortical insufficiency such as occurs in Addison's disease causes hyponatremia and renal tubular acidosis (RTA). Hyponatremia results from both aldosterone and cortisol insufficiency. RTA is due to aldosterone insufficiency. The involvement of cortisol in RTA is unclear. Here, we report a woman in her 70s who was admitted to our hospital with severe hyponatremia (106 mEq/l) and RTA. The patient exhibited low plasma cortisol levels with little response to rapid adrenocorticotropic hormon...

  17. CD47 regulates renal tubular epithelial cell self-renewal and proliferation following renal ischemia reperfusion.

    Science.gov (United States)

    Rogers, Natasha M; Zhang, Zheng J; Wang, Jiao-Jing; Thomson, Angus W; Isenberg, Jeffrey S

    2016-08-01

    Defects in renal tubular epithelial cell repair contribute to renal ischemia reperfusion injury, cause acute kidney damage, and promote chronic renal disease. The matricellular protein thrombospondin-1 and its receptor CD47 are involved in experimental renal ischemia reperfusion injury, although the role of this interaction in renal recovery is unknown. We found upregulation of self-renewal genes (transcription factors Oct4, Sox2, Klf4 and cMyc) in the kidney of CD47(-/-) mice after ischemia reperfusion injury. Wild-type animals had minimal self-renewal gene expression, both before and after injury. Suggestive of cell autonomy, CD47(-/-) renal tubular epithelial cells were found to increase expression of the self-renewal genes. This correlated with enhanced proliferative capacity compared with cells from wild-type mice. Exogenous thrombospondin-1 inhibited self-renewal gene expression in renal tubular epithelial cells from wild-type but not CD47(-/-) mice, and this was associated with decreased proliferation. Treatment of renal tubular epithelial cells with a CD47 blocking antibody or CD47-targeting small interfering RNA increased expression of some self-renewal transcription factors and promoted cell proliferation. In a syngeneic kidney transplant model, treatment with a CD47 blocking antibody increased self-renewal transcription factor expression, decreased tissue damage, and improved renal function compared with that in control mice. Thus, thrombospondin-1 via CD47 inhibits renal tubular epithelial cell recovery after ischemia reperfusion injury through inhibition of proliferation/self-renewal. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  18. Endo-lysosomal dysfunction in human proximal tubular epithelial cells deficient for lysosomal cystine transporter cystinosin.

    Directory of Open Access Journals (Sweden)

    Ekaterina A Ivanova

    Full Text Available Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include renal Fanconi syndrome, a generalized proximal tubular dysfunction. Current therapy of cystinosis is based on cystine-lowering drug cysteamine that postpones the disease progression but offers no cure for the Fanconi syndrome. We studied the mechanisms of impaired reabsorption in human proximal tubular epithelial cells (PTEC deficient for cystinosin and investigated the endo-lysosomal compartments of cystinosin-deficient PTEC by means of light and electron microscopy. We demonstrate that cystinosin-deficient cells had abnormal shape and distribution of the endo-lysosomal compartments and impaired endocytosis, with decreased surface expression of multiligand receptors and delayed lysosomal cargo processing. Treatment with cysteamine improved surface expression and lysosomal cargo processing but did not lead to a complete restoration and had no effect on the abnormal morphology of endo-lysosomal compartments. The obtained results improve our understanding of the mechanism of proximal tubular dysfunction in cystinosis and indicate that impaired protein reabsorption can, at least partially, be explained by abnormal trafficking of endosomal vesicles.

  19. Renal functional reserve and tubular function in patents with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Dilyara Makhmutrievna Khakimova

    2011-06-01

    Full Text Available Aim. To study renal functional reserve and partial functions in patents with type 2 diabetes mellitus in the absence of renal lesionsMaterials and methods. We examined 42 patients (17 men and 24 women aged 38-69 (mean 49.8?8.3 years with DM2 4.6?2.6 yr in duration.Control group comprised 32 practically healthy subjects. Intrarenal hemodynamics was estimated from RFR values. Ethanolamine, uric acid, Ca,and P levels were measured in sera and 24-hr urine; daily excretion of ammonia and aminonitrogen in the urine was determined. Results. The patients were divided into 2 groups based on the results of RFR measurement. FRF remained unaltered in 21 patients (mean 60.7?27.6%and decreased in the absence of filtration reserve in 20 (-25.8?23.4%. Correlation analysis revealed the relationship of lipid metabolism and abdominalobesity with the renal tubular function and intraglomerular hemodynamics. Conclusion. Examination of DM2 patients without clinical and laboratory signs of renal lesions revealed compromised function of all nephron compartments,viz. intraglomerular hypertension, impaired stability of renal cell membranes, and tubular dysfunction. The latter is related to hemodynamic disturbances.

  20. Renal transplantant blood flow in patients with acute tubular necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Huic, D; Crnkovic, S; Bubic-Filipi, L J; Grosev, D; Dodig, P; Porapat, M; Puretic, Z [Univ. Hospital Rebro, Zagreb (Croatia)

    1997-09-01

    The aim of this study was to investigate the quantity of renal transport blood flow in patients affected by acute tubular necrosis (ATN). During the four years period two hundred and thirty-three studies were performed using {sup 99m}Tc pertechnetate and {sup 131}I - OIH. Renal blood flow was calculated from the first-pass time activity curves generated over the kidney and aorta and expressed as a percentage of cardiac output (RBF/CO). Renal transplant blood flow is clearly diminished in ATN, similar as in acute rejection, and significantly related to the graft function, what means that RBF/CO value could potentially serve as a prognostic factor in the graft function recovery from ATN.

  1. Distal renal tubular acidosis and amelogenesis imperfecta: A rare association

    Directory of Open Access Journals (Sweden)

    P Ravi

    2013-01-01

    Full Text Available Renal tubular acidosis (RTA is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI.

  2. Amelogenesis Imperfecta with Distal Renal Tubular Acidosis: A Novel Syndrome?

    Science.gov (United States)

    Misgar, R A; Hassan, Z; Wani, A I; Bashir, M I

    2017-01-01

    Amelogenesis imperfecta (AI) is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA) have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

  3. Amelogenesis imperfecta with distal renal tubular acidosis: A novel syndrome?

    Directory of Open Access Journals (Sweden)

    R A Misgar

    2017-01-01

    Full Text Available Amelogenesis imperfecta (AI is a heterogeneous group of inherited dental enamel defects. It has rarely been reported in association with multiorgan syndromes and metabolic disorders. The metabolic disorders that have been reported in association with AI include hypocalciuria, impaired urinary concentrating ability, and Bartter-like syndrome. In literature, only three cases of AI and distal renal tubular acidosis (dRTA have been described: two cases in adults and a solitary case in the pediatric age group. Here, we report a child with AI presenting with dRTA; to the best of our knowledge, our reported case is the only second such case in pediatric age group. Our case highlights the importance of recognizing the possibility of renal abnormalities in patients with AI as it will affect the long-term prognosis.

  4. Factor H and Properdin Recognize Different Epitopes on Renal Tubular Epithelial Heparan Sulfate

    NARCIS (Netherlands)

    Zaferani, Azadeh; Vives, Romain R.; van der Pol, Pieter; Navis, Gerjan J.; Daha, Mohamed R.; van Kooten, Cees; Lortat-Jacob, Hugues; Seelen, Marc A.; van den Born, Jacob

    2012-01-01

    During proteinuria, renal tubular epithelial cells become exposed to ultrafiltrate-derived serum proteins, including complement factors. Recently, we showed that properdin binds to tubular heparan sulfates (HS). We now document that factor H also binds to tubular HS, although to a different epitope

  5. Hyperglycemia induced damage to mitochondrial respiration in renal mesangial and tubular cells: Implications for diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Anna Czajka

    2016-12-01

    Full Text Available Damage to renal tubular and mesangial cells is central to the development of diabetic nephropathy (DN, a complication of diabetes which can lead to renal failure. Mitochondria are the site of cellular respiration and produce energy in the form of ATP via oxidative phosphorylation, and mitochondrial dysfunction has been implicated in DN. Since the kidney is an organ with high bioenergetic needs, we postulated that hyperglycemia causes damage to renal mitochondria resulting in bioenergetic deficit. The bioenergetic profiles and the effect of hyperglycemia on cellular respiration of human primary mesangial (HMCs and proximal tubular cells (HK-2 were compared in normoglycemic and hyperglycemic conditions using the seahorse bio-analyzer. In normoglycemia, HK-2 had significantly lower basal, ATP-linked and maximal respiration rates, and lower reserve capacity compared to HMCs. Hyperglycemia caused a down-regulation of all respiratory parameters within 4 days in HK-2 but not in HMCs. After 8 days of hyperglycemia, down-regulation of respiratory parameters persisted in tubular cells with compensatory up-regulated glycolysis. HMCs had reduced maximal respiration and reserve capacity at 8 days, and by 12 days had compromised mitochondrial respiration despite which they did not enhance glycolysis. These data suggest that diabetes is likely to lead to a cellular deficit in ATP production in both cell types, although with different sensitivities, and this mechanism could significantly contribute to the cellular damage seen in the diabetic kidney. Prevention of diabetes induced damage to renal mitochondrial respiration may be a novel therapeutic approach for the prevention/treatment of DN.

  6. Renal dysfunction in African patients with acute heart failure

    NARCIS (Netherlands)

    Sani, Mahmoud U.; Davison, Beth A.; Cotter, Gad; Sliwa, Karen; Edwards, Christopher; Liu, Licette; Damasceno, Albertino; Mayosi, Bongani M.; Ogah, Okechukwu S.; Mondo, Charles; Dzudie, Anastase; Ojji, Dike B.; Voors, Adrian A.

    Aims In Western countries with typically elderly ischaemic acute heart failure patients, predictors and clinical outcome of renal dysfunction and worsening renal function are well described. However, the prevalence, predictors and clinical outcome of renal dysfunction in younger, mainly hypertensive

  7. Albumin Overload and PINK1/Parkin Signaling-Related Mitophagy in Renal Tubular Epithelial Cells.

    Science.gov (United States)

    Tan, Jin; Xie, Qi; Song, Shuling; Miao, Yuyang; Zhang, Qiang

    2018-03-01

    BACKGROUND Albumin, as a major urinary protein component, is a risk factor for chronic kidney disease progression. Mitochondrial dysfunction is one of the main causes of albumin-induced proximal tubule cells injury. Mitophagy is considered as a pivotal protective mechanism for the elimination of dysfunctional mitochondria. The objective of this research was to determine whether albumin overload-induced mitochondrial dysfunction can activate PINK1/Parkin-mediated mitophagy in renal tubular epithelial cells (TECs). MATERIAL AND METHODS Immunofluorescence assay and Western blot assay were used to detect the effects of albumin overload on autophagy marker protein LC3. Transmission electron microscopy and Western blot assay were used to investigate the role of albumin in mitochondrial injury. Western blot assay and co-localization of acidic lysosomes and mitochondria assay were employed to detect the activation of mitophagy induced by albumin. Finally, we explored the role of PINK1/Parkin signaling in albumin-induced mitophagy by inhibiting mitophagy by knockdown of PARK2 (Parkin) level. RESULTS Immunofluorescence and Western blot results showed that the expression level of LC3-II increased, and the maximum increase point was observed after 8 h of albumin treatment. Transmission electron microscopy results demonstrated that albumin overload-induced mitochondrial injury and quantity of autophagosomes increased. Additionally, expression of PINK1 and cytosolic cytochrome C increased and mitochondria cytochrome C decreased in the albumin group. The co-localization of acidic lysosomes and mitochondria demonstrated that the number of albumin overload-induced mitophagy-positive dots increased. The transient transfection of PARK2 siRNA result showed knockdown of the expression level of PARK2 can inhibit mitophagy induced by albumin. CONCLUSIONS In conclusion, our study suggests that mitochondrial dysfunction activates the PINK1/Parkin signaling and mitophagy in renal tubular

  8. Stem cell factor expression after renal ischemia promotes tubular epithelial survival.

    Directory of Open Access Journals (Sweden)

    Geurt Stokman

    Full Text Available BACKGROUND: Renal ischemia leads to apoptosis of tubular epithelial cells and results in decreased renal function. Tissue repair involves re-epithelialization of the tubular basement membrane. Survival of the tubular epithelium following ischemia is therefore important in the successful regeneration of renal tissue. The cytokine stem cell factor (SCF has been shown to protect the tubular epithelium against apoptosis. METHODOLOGY/PRINCIPAL FINDINGS: In a mouse model for renal ischemia/reperfusion injury, we studied how expression of c-KIT on tubular epithelium and its ligand SCF protect cells against apoptosis. Administration of SCF specific antisense oligonucleotides significantly decreased specific staining of SCF following ischemia. Reduced SCF expression resulted in impaired renal function, increased tubular damage and increased tubular epithelial apoptosis, independent of inflammation. In an in vitro hypoxia model, stimulation of tubular epithelial cells with SCF activated survival signaling and decreased apoptosis. CONCLUSIONS/SIGNIFICANCE: Our data indicate an important role for c-KIT and SCF in mediating tubular epithelial cell survival via an autocrine pathway.

  9. Effect of cisplatin on renal haemodynamics and tubular function in the dog kidney

    DEFF Research Database (Denmark)

    Daugaard, G; Abildgaard, U; Holstein-Rathlou, N H

    1987-01-01

    Administration of cisplatin (5 mg/kg) to dogs results in polyuric renal failure due initially to a proximal tubular functional impairment. 48-72 h after the cisplatin administration the depressed renal function can be attributed to impairment of proximal as well as distal tubular reabsorptive cap...... capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments....

  10. Osteomalacia complicating renal tubular acidosis in association with Sjogren's syndrome.

    Science.gov (United States)

    El Ati, Zohra; Fatma, Lilia Ben; Boulahya, Ghada; Rais, Lamia; Krid, Madiha; Smaoui, Wided; Maiz, Hedi Ben; Beji, Soumaya; Zouaghi, Karim; Moussa, Fatma Ben

    2014-09-01

    Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA), which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L), hypophosphatemia (0.4 mmol/L), hypocalcemia (2.14 mmol/L) and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L). The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7), glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer's test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®), calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  11. Hypokalaemia and Renal Tubular Acidosis due to Abuse of Nurofen Plus

    Directory of Open Access Journals (Sweden)

    M. J. Blackstock

    2012-01-01

    Full Text Available Nurofen Plus is a common analgesic containing ibuprofen and codeine. We present a case of a 38-year-old lady who developed renal tubular acidosis with severe hypokalaemia, after chronic abuse of Nurofen Plus tablets. She presented with confusion and profound biochemical abnormalities requiring critical care admission for electrolyte replacement. Ibuprofen causes renal tubular acidosis due to its effects on carbonic anhydrase activity.

  12. Autophagy Limits Endotoxemic Acute Kidney Injury and Alters Renal Tubular Epithelial Cell Cytokine Expression.

    Directory of Open Access Journals (Sweden)

    Jeremy S Leventhal

    Full Text Available Sepsis related acute kidney injury (AKI is a common in-hospital complication with a dismal prognosis. Our incomplete understanding of disease pathogenesis has prevented the identification of hypothesis-driven preventive or therapeutic interventions. Increasing evidence in ischemia-reperfusion and nephrotoxic mouse models of AKI support the theory that autophagy protects renal tubular epithelial cells (RTEC from injury. However, the role of RTEC autophagy in septic AKI remains unclear. We observed that lipopolysaccharide (LPS, a mediator of gram-negative bacterial sepsis, induces RTEC autophagy in vivo and in vitro through TLR4-initiated signaling. We modeled septic AKI through intraperitoneal LPS injection in mice in which autophagy-related protein 7 was specifically knocked out in the renal proximal tubules (ATG7KO. Compared to control littermates, ATG7KO mice developed more severe renal dysfunction (24hr BUN 100.1mg/dl +/- 14.8 vs 54.6mg/dl +/- 11.3 and parenchymal injury. After injection with LPS, analysis of kidney lysates identified higher IL-6 expression and increased STAT3 activation in kidney lysates from ATG7KO mice compared to controls. In vitro experiments confirmed an altered response to LPS in RTEC with genetic or pharmacological impairment of autophagy. In conclusion, RTEC autophagy protects against endotoxin induced injury and regulates downstream effects of RTEC TLR4 signaling.

  13. Distal renal tubular acidosis in two children with acquired hypothyroidism.

    Science.gov (United States)

    Guerra-Hernández, Norma E; Ordaz-López, Karen V; Vargas-Poussou, Rosa; Escobar-Pérez, Laura; García-Nieto, Víctor M

    2018-04-28

    Two cases of children diagnosed with renal tubular acidosis (RTA) associated with autoimmune hypothyroidism are presented. Case 1 developed an intestinal ileus at the age of five in the context of a respiratory problem. The tests performed confirmed metabolic acidosis, hyperchloraemia, hypokalaemia and nephrocalcinosis. Case 2 was diagnosed with hypothyroidism at the age of 11, and with RTA two years later. In both patients, the diagnosis of RTA was verified when decreased maximum urinary pCO 2 was found. In case 2, a proximal bicarbonate leak (type 3 RTA) was also confirmed. This was the first case to be published on the topic. The causes of RTA in patients with hypothyroidism are reviewed. The deleterious effect on the kidneys may be due to the absence of thyroid hormone and/or autoantibodies in the cases of autoimmune hypothyroidism. Copyright © 2018 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Quantitation of renal function with glomerular and tubular agents

    International Nuclear Information System (INIS)

    Dubovsky, E.V.; Russell, C.D.

    1982-01-01

    Quantitative methods to measure the glomerular and tubular function of the kidneys with radionuclides have been available for many years. They have not been widely used because the techniques and the calculations exceeded the scope of routine nuclear medicine practice. Validation of simplified methods and the introduction of computer technology have made measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) simple enough so that they can be performed reproducibly in most nuclear medicine departments. The estimation of ERPF with radioiodinated OIH and GFR with /sup 99m/TcDTPA can be achieved in many ways, all of which yield clinically useful results. How to get the best results using the simplest methods is still unclear. The required accuracy depends on the intended clinical use. Our preference at the present time is to use a single or double plasma sample to calculate global ERPF or GFR, and to use the 1-2 min OIH or 1-3 min Tc-DTPA uptake to calculate relative function of the two kidneys (split function ERPF or GFR). The choice of method will be influenced by local factors, such as the nature of the patient population, the case volume, and the resources available. A desirable goal for future studies is to document carefully the capabilities and limitations of each alternative method, so that the choice can be rational

  15. Transient acute tubular dysfunction in the newborn: CT findings

    International Nuclear Information System (INIS)

    McLaughlin, M.G.; Schwartz, J.R.; Swayne, L.C.; Columbia Univ., New York; Rubenstein, J.B.; University of Medicine and Dentistry of New Jersey, Newark, NJ; Block, D.C.

    1990-01-01

    We report the CT and sonographic findings of transient acute tubular disease in a newborn infant, who was dehydrated at birth. The initial CT scan demonstrated focal areas of increased attenuation within the central portions of both kidneys, and sonography showed echogenic medullary pyramids. After adequate hydration, a follow-up examination demonstrated complete spontaneous resolution. (orig.)

  16. Autoimmune Hepatitis with Distal Renal Tubular Acidosis and Small Bowel Partial Malrotation.

    Science.gov (United States)

    Kanaiyalal Modi, Tejas; Parikh, Hardik; Sadalge, Abhishek; Gupte, Amit; Bhatt, Pratin; Shukla, Akash

    2015-01-01

    Renal tubular acidosis (RTA) is not uncommon in patient with chronic autoimmune hepatitis (AIH), but usually remains latent. Here, we report a case of renal tubular acidosis RTA who presented with AIH. She was also diagnosed to have partial bowel malrotation. A 9-year-old girl, a case of distal RTA, presented with jaundice, abdominal distension and altered sensorium. She was diagnosed to be AIH, which was successfully treated with steroids and azathioprine. Coexistent midgut partial malrotation with volvulus was diagnosed during the treatment. She was treated successfully with anti-tuberculous treatment for cervical lymphadenitis. Autoimmune hepatitis should not be ruled out in each case of RTA presenting with jaundice. Modi TK, Parikh H, Sadalge A, Gupte A, Bhatt P, Shukla A. Autoimmune Hepatitis with Distal Renal Tubular Acidosis and Small Bowel Partial Malrotation. Euroasian J Hepato-Gastroenterol 2015;5(2):107-109.

  17. Tumor-promoting phorbol esters effect alkalinization of canine renal proximal tubular cells

    International Nuclear Information System (INIS)

    Mellas, J.; Hammerman, M.R.

    1986-01-01

    We have demonstrated the presence of specific receptors for tumor-promoting phorbol esters in the plasma membrane of the canine renal proximal tubular cell. These compounds affect proximal tubular metabolism in vitro. For example, we have shown that they inhibit gluconeogenesis in canine renal proximal tubular segments. Tumor-promoting phorbol esters have been shown to effect alkalinization of non-renal cells, by enhancing Na + -H + exchange across the plasma membrane. To determine whether the actions of tumor-promoting phorbol esters in proximal tubular segments might be mediated by a similar process, we incubated suspensions of segments from dog kidney with these compounds and measured changes in intracellular pH using [ 14 C]-5,5-dimethoxazoladine-2-4-dione (DMO) and flow dialysis. Incubation of segments with phorbol 12,13 dibutyrate, but not inactive phorbol ester, 4 γ phorbol, effected alkalinization of cells within the segments in a concentration-dependent manner. Alkalinization was dependent upon the presence of extracellular [Na + ] > intracellular [Na + ], was prevented by amiloride and was demonstrable in the presence of SITS. Our findings suggest that tumor-promoting esters stimulate the Na + -H + exchanger known to be present in the brush border membrane of the renal proximal tubular cell. It is possible that the stimulation reflects a mechanism by which phorbol esters affect metabolic processes in these cells

  18. Impact of Mannose-Binding Lectin Deficiency on Radiocontrast-Induced Renal Dysfunction

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    Michael Osthoff

    2013-01-01

    Full Text Available Contrast-induced nephropathy (CIN is the third leading cause of acute renal failure in hospitalized patients. Endothelial dysfunction, renal medullary ischemia, and tubular toxicity are regarded as the most important factors in the pathogenesis of CIN. Mannose-binding lectin (MBL, a pattern recognition protein of the lectin pathway of complement, has been found to aggravate and mediate tissue damage during experimental renal ischemia/reperfusion (I/R injury which was alleviated by inhibition with C1 inhibitor, a potent MBL, and lectin pathway inhibitor. In this paper, we highlight the potential role of MBL in the pathogenesis of human CIN. In experimental I/R models, MBL was previously found to induce tubular cell death independent of the complement system. In addition, after binding to vascular endothelial cells, MBL and its associated serine proteases were able to trigger a proinflammatory reaction and contribute to endothelial dysfunction. In humans, urinary MBL was increased after administration of contrast media and in individuals with CIN. Moreover, individuals with normal/high MBL levels were at increased risk to develop radiocontrast-induced renal dysfunction. Hence, MBL and the lectin pathway seem to be a promising target given that a licensed, powerful, human recombinant inhibitor exits to be added to the scarce armamentarium currently available for prophylaxis of CIN.

  19. Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction

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    Yan Qiang

    2012-01-01

    Full Text Available Abstract Objective To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Methods Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5 years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0 were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. Results The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. Conclusion There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. Virtual slides The virtual slide(s for this article can be found here: http

  20. Utility of Iron Staining in Identifying the Cause of Renal Allograft Dysfunction in Patients with Sickle Cell Disease

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    Yingchun Wang

    2015-01-01

    Full Text Available Sickle cell nephropathy (SCN is associated with iron/heme deposition in proximal renal tubules and related acute tubular injury (ATI. Here we report the utility of iron staining in differentiating causes of renal allograft dysfunction in patients with a history of sickle cell disease. Case 1: the patient developed acute allograft dysfunction two years after renal transplant. Her renal biopsy showed ATI, supported by patchy loss of brush border and positive staining of kidney injury molecule-1 in proximal tubular epithelial cells, where diffuse increase in iron staining (2+ was present. This indicated that ATI likely resulted from iron/heme toxicity to proximal tubules. Electron microscope confirmed aggregated sickle RBCs in glomeruli, indicating a recurrent SCN. Case 2: four years after renal transplant, the patient developed acute allograft dysfunction and became positive for serum donor-specific antibody. His renal biopsy revealed thrombotic microangiopathy (TMA and diffuse positive C4d stain in peritubular capillaries. Iron staining was negative in the renal tubules, implying that TMA was likely associated with acute antibody-mediated rejection (AAMR, type 2 rather than recurrent SCN. These case reports imply that iron staining is an inexpensive but effective method in distinguishing SCN-associated renal injury in allograft kidney from other etiologies.

  1. Pathophysiology of incomplete renal tubular acidosis in recurrent renal stone formers: evidence of disturbed calcium, bone and citrate metabolism

    DEFF Research Database (Denmark)

    Osther, P J; Bollerslev, Jens; Hansen, A B

    1993-01-01

    Urinary acidification, bone metabolism and urinary excretion of calcium and citrate were evaluated in 10 recurrent stone formers with incomplete renal tubular acidosis (iRTA), 10 recurrent stone formers with normal urinary acidification (NUA) and 10 normal controls (NC). Patients with iRTA had...

  2. Overall renal and tubular function during infusion of amino acids in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    sodium concentration] increased by 40% (P less than 0.001). Plasma renin concentration did not change significantly. 4. The results suggest that amino acids increase GFR by a primary effect on renal haemodynamics or, less likely, by reducing the signal to the tubuloglomerular feedback mechanism......1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during...... infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...

  3. Selective Cannabinoid 2 Receptor Stimulation Reduces Tubular Epithelial Cell Damage after Renal Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Pressly, Jeffrey D; Mustafa, Suni M; Adibi, Ammaar H; Alghamdi, Sahar; Pandey, Pankaj; Roy, Kuldeep K; Doerksen, Robert J; Moore, Bob M; Park, Frank

    2018-02-01

    Ischemia-reperfusion injury (IRI) is a common cause of acute kidney injury (AKI), which is an increasing problem in the clinic and has been associated with elevated rates of mortality. Therapies to treat AKI are currently not available, so identification of new targets that can be modulated to ameliorate renal damage upon diagnosis of AKI is essential. In this study, a novel cannabinoid receptor 2 (CB2) agonist, SMM-295 [3'-methyl-4-(2-(thiophen-2-yl)propan-2-yl)biphenyl-2,6-diol], was designed, synthesized, and tested in vitro and in silico. Molecular docking of SMM-295 into a CB2 active-state homology model showed that SMM-295 interacts well with key amino acids to stabilize the active state. In human embryonic kidney 293 cells, SMM-295 was capable of reducing cAMP production with 66-fold selectivity for CB2 versus cannabinoid receptor 1 and dose-dependently increased mitogen-activated protein kinase and Akt phosphorylation. In vivo testing of the CB2 agonist was performed using a mouse model of bilateral IRI, which is a common model to mimic human AKI, where SMM-295 was immediately administered upon reperfusion of the kidneys after the ischemia episode. Histologic damage assessment 48 hours after reperfusion demonstrated reduced tubular damage in the presence of SMM-295. This was consistent with reduced plasma markers of renal dysfunction (i.e., creatinine and neutrophil gelatinase-associated lipocalin) in SMM-295-treated mice. Mechanistically, kidneys treated with SMM-295 were shown to have elevated activation of Akt with reduced terminal deoxynucleotidyl transferase-mediated digoxigenin-deoxyuridine nick-end labeling (TUNEL)-positive cells compared with vehicle-treated kidneys after IRI. These data suggest that selective CB2 receptor activation could be a potential therapeutic target in the treatment of AKI. Copyright © 2018 by The American Society for Pharmacology and Experimental Therapeutics.

  4. Whole‐exome sequencing as a diagnostic tool for distal renal tubular acidosis

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    Paula Cristina Barros Pereira

    2015-11-01

    Conclusion: These results confirm the value of whole‐exome sequencing for the study of rare and complex genetic nephropathies, allowing the identification of novel and recurrent mutations. Furthermore, for the first time the application of this molecular method in renal tubular diseases has been clearly demonstrated.

  5. The proximal tubular cell, a key player in renal damage

    NARCIS (Netherlands)

    Timmeren, Mirjan Miranda van

    2008-01-01

    A decline in renal function is associated with the degree of proteinuria and with histological findings of glomerulosclerosis and interstitial fibrosis. Proteinuria is not only a marker of renal damage, but ultrafiltered proteins can be toxic to the kidney, thereby contributing to

  6. Abnormal distal renal tubular acidification in patients with low bone mass: prevalence and impact of alkali treatment.

    Science.gov (United States)

    Sromicki, Jerzy Jan; Hess, Bernhard

    2017-06-01

    Chronic acid retention is known to promote bone dissolution. In this study, 23 % of patients with osteopenia/osteoporosis were diagnosed with abnormal distal renal tubular acidification (dRTA), a kidney dysfunction leading to chronic acid retention. Treating those patients with alkali-therapy shows improvement in bone density. To evaluate the prevalence of abnormal distal renal tubular acidification in patients with low bone mass (LBM) and the impact of additional alkali treatment on bone density in patients with concomitant LBM and dRTA,183 patients referred for metabolic evaluation of densitometrically proven low bone mass were screened for abnormal distal renal tubular acidification between 2006 and 2013. In all LBM urine pH (U-pH) was measured in the 2nd morning urines after 12 h of fasting. If U-pH was ≥5.80, LBM underwent a 1-day ammonium chloride loading, and U-pH was remeasured the next morning. If U-pH after acid loading did not drop below 5.45, patients were diagnosed with abnormal distal renal tubular acidification. Normal values were obtained from 21 healthy controls. All LBM with dRTA were recommended alkali citrate in addition to conventional therapy of LBM, and follow-up DXAs were obtained until 2014. 85 LBM underwent NH 4 Cl loading. 42 LBM patients were diagnosed with incomplete dRTA (idRTA; prevalence 23.0 %). During follow-up (1.6-8 years) of idRTA-LBM patients, subjects adhering to alkali treatment tended to improve BMD at all sites measured, whereas BMD of non-adherent idRTA patients worsened/remained unchanged. (1) About one out of four patients with osteopenia/osteoporosis has idRTA. (2) Upon NH 4 Cl loading, idRTA patients do not lower urine pH normally, but show signs of increased acid-buffering by bone dissolution. (3) In idRTA patients with low bone mass on conventional therapy, additional long-term alkali treatment improves bone mass at lumbar spine and potentially at other bone sites. (4) All patients with low bone mass undergoing

  7. A Mathematical Model of Renal Blood Distribution Coupling TGF, MR and Tubular System

    Institute of Scientific and Technical Information of China (English)

    GAO Ci-xiu; YANG Lin; WANG Ke-qiang; XU Shi-xiong; DAI Pei-dong

    2009-01-01

    Objective:To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods:A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic response (MR), tubuloglomerular feedback (TGF) and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results:The results predict the dynamics of renal autoregulation on its blood pressure and flow,and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion:The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.

  8. The influence of angiotensin-converting enzyme inhibition on renal tubular function in progressive chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Holstein-Rathlou, N H; Leyssac, P P

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril...... on progression of renal failure. The pattern of proteinuria was followed over the first 9 months. At baseline, the glomerular filtration rate (GFR) was 5 to 68 mL/min. Absolute proximal tubular reabsorption rate of fluid (APR), estimated as the difference between GFR and C(Li), was 1 to 54 mL/min. Calculated...... in either treatment regimen was associated with a long-term slower progression of renal failure. Over 9 months, the 24-hour fractional clearance of albumin decreased in the ACE inhibitor group (P

  9. Clinical profile and outcome of renal tubular disorders in children: A single center experience

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    B Vijay Kiran

    2014-01-01

    Full Text Available Tubular disorders form a significant proportion of pediatric kidney diseases and are an important differential diagnosis of failure to thrive (FTT in children. Data regarding their outcome is scarce from India. We evaluated the clinical profile of these children and studied the outcome in terms of their growth and renal failure. This is a retrospective longitudinal study of all children with renal tubular disorders attending a tertiary care pediatric nephrology center from 2005 to 2010. Growth and renal outcomes were assessed by Z scores and estimated glomerular filtration rate at diagnosis and. The common disorders encountered were distal renal tubular acidosis (d-RTA (44%, Bartter-like (Bartter′s and Gitelman syndromes (22% followed by hereditary Fanconi syndrome (cystinosis and idiopathic Fanconi syndrome (13% and few cases of nephrogenic diabetes insipidus, hypophosphatemic rickets and idiopathic hypercalciuria. Male: female ratio was 1.22. The median age at diagnosis was 1.5 (range 0.13-11 years. Growth failure was the presenting feature in 86% of children followed by polyuria (60% and bone deformities (47%. In 60% of children with hereditary Fanconi syndrome, nephropathic cystinosis was diagnosed, all of whom progressed to stage III chronic kidney disease (CKD within 3.41 ± 1.42 years. With appropriate therapy, catch-up growth was noted in d-RTA and Bartter syndrome. Renal tubular disorders usually present with FTT. d-RTA is the most common etiology followed by Bartter-like syndrome. Renal function is preserved in all these disorders except for nephropathic cystinosis, who ultimately progressed to CKD. With appropriate and inexpensive therapy, these children do grow well.

  10. Distal renal tubular acidosis and hypokalemic paralysis in a patient with hypothyroidism

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    Parvaiz Ahmad Koul

    2011-01-01

    Full Text Available A 43- year- old woman on treatment for primary hypothyroidism presented with 1- day progressive weakness of all her limbs and history of similar episodes in the past. Clinical examination revealed grade 2 hyporeflexive weakness. Investigations revealed features of hypokalemia, metabolic acidosis, alkaline urine, and a fractional bicarbonate excretion of 3.5%, consistent with distal renal tubular acidosis. Antithyroid peroxidase and antithroglobulin antibodies were positive, suggesting an autoimmune basis for the pathogenesis of the functional tubular defect. Bicarbonate therapy resulted in a sustained clinical recovery.

  11. Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

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    Ding F

    2014-09-01

    Full Text Available Fengan Ding,1 Yiping Li,1 Jing Liu,1 Lei Liu,1 Wenmin Yu,1 Zhi Wang,1 Haifeng Ni,2 Bicheng Liu,2 Pingsheng Chen1,2 1School of Medicine, Southeast University, Nanjing, People’s Republic of China; 2Institute of Nephrology, The Affiliated Zhongda Hospital, Southeast University, Nanjing, People’s Republic of China Background: Gold nanoparticles (GNPs can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells.Results: Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM to human renal proximal tubular cells (HK-2 by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the

  12. Renal tubular acidosis secondary to jejunoileal bypass for morbid obesity

    DEFF Research Database (Denmark)

    Schaffalitzky de Muckadell, O B; Ladefoged, Jens; Thorup, Jørgen Mogens

    1985-01-01

    Renal handling of acid and base was studied in patients with persistent metabolic acidosis 3-9 years after jejunoileal bypass for morbid obesity. Excretion of acid was studied before and after intravenous infusion of NH4Cl and excretion of bicarbonate after infusion of NaHCO3. Bypass patients...

  13. Effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats.

    Science.gov (United States)

    Peng, Tao; Wang, Jie; Zhen, Junhui; Hu, Zhao; Yang, Xiangdong

    2014-07-01

    The aim of this study was to investigate the effect of benazepril on the transdifferentiation of renal tubular epithelial cells from diabetic rats. Thirty male Sprague-Dawley rats were included in the present study. Eight of the 30 rats were randomly selected and served as the normal control group (N group), while the remaining 22 rats, injected with streptozotocin (STZ), comprised the diabetic rat model. Rats with diabetes were randomly divided into the diabetic (DM group) and benazepril (B group) groups. The total course was conducted over 12 weeks. Blood glucose, body weight, kidney/body weight, 24-h urinary protein, serum creatinine and blood urea nitrogen were measured at the start and end of the study. We observed the tubulointerstitial pathological changes, and applied immunohistochemistry and western blotting to detect the expression of α-smooth muscle actin (α-SMA) in renal tissue. The levels of blood glucose, kidney/body weight, 24-h urinary protein, serum creatinine, blood urea nitrogen and tubulointerstitial damage index (TII) in the DM group were significantly higher than that in the N group (pbenazepril significantly reduced the expression of α-SMA in renal tubular epithelial cells obtained from diabetic rats, inhibited the transdifferentiation of renal tubular epithelial cells and played an important role in kidney protection.

  14. Interferon-γ Reduces the Proliferation of Primed Human Renal Tubular Cells

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    Omar García-Sánchez

    2014-01-01

    Full Text Available Background/Aims: Chronic kidney disease (CKD is a progressive deterioration of the kidney function, which may eventually lead to renal failure and the need for dialysis or kidney transplant. Whether initiated in the glomeruli or the tubuli, CKD is characterized by progressive nephron loss, for which the process of tubular deletion is of key importance. Tubular deletion results from tubular epithelial cell death and defective repair, leading to scarring of the renal parenchyma. Several cytokines and signaling pathways, including transforming growth factor-β (TGF-β and the Fas pathway, have been shown to participate in vivo in tubular cell death. However, there is some controversy about their mode of action, since a direct effect on normal tubular cells has not been demonstrated. We hypothesized that epithelial cells would require specific priming to become sensitive to TGF-β or Fas stimulation and that this priming would be brought about by specific mediators found in the pathological scenario. Methods: Herein we studied whether the combined effect of several stimuli known to take part in CKD progression, namely TGF-β, tumor necrosis factor-α, interferon-γ (IFN-γ, and Fas stimulation, on primed resistant human tubular cells caused cell death or reduced proliferation. Results: We demonstrate that these cytokines have no synergistic effect on the proliferation or viability of human kidney (HK2 cells. We also demonstrate that IFN-γ, but not the other stimuli, reduces the proliferation of cycloheximide-primed HK2 cells without affecting their viability. Conclusion: Our results point at a potentially important role of IFN-γ in defective repair, leading to nephron loss during CKD.

  15. Impact of renal transplantation on erectile dysfunction due to chronic renal failure in male patients

    International Nuclear Information System (INIS)

    Ahmad, M.; Rafiudding, Q.; Ahmad, A.

    2009-01-01

    Erectile dysfunction can be defined as the persistent inability of man to achieve penile erection and maintain it sufficient for satisfactory coitus. The objectives of this study were to find out the impact of successful renal transplantation on the degree and frequency of erectile dysfunction. Thirty patients of end stage renal disease that were on regular haemodialysis and candidates of renal transplantation of age range 20-55 years were included in the study after getting informed consent. Erectile functions were assessed by history, examination, investigations and international index of erectile function (IIEF) before and 3 and 6 months after renal transplantation, other information regarding disease and patient were collected in the performa. Out of thirty patients 14 (46.6%) patients had sever erectile dysfunction while 16 (53.3%) patients had moderate erectile dysfunction in the pre renal transplantation period. After three months of renal transplantation 15 (50%) had severe erectile dysfunction, 6 (20%) patients moderate erectile dysfunction and 9 (30%) patients mild erectile dysfunction. After six months 11 (36.6%), 10 (33.3%) and 8 (26.6%) patients had severe, moderate and mild erectile dysfunction respectively. There was improvement in 40%, no change in 53.3% and deterioration in 6.6% patients in the erectile functions after getting renal transplantation for end stage renal disease. (author)

  16. Furosemide/Fludrocortisone Test and Clinical Parameters to Diagnose Incomplete Distal Renal Tubular Acidosis in Kidney Stone Formers.

    Science.gov (United States)

    Dhayat, Nasser A; Gradwell, Michael W; Pathare, Ganesh; Anderegg, Manuel; Schneider, Lisa; Luethi, David; Mattmann, Cedric; Moe, Orson W; Vogt, Bruno; Fuster, Daniel G

    2017-09-07

    Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied. We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing. Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH 3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis. The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters. Copyright © 2017 by the American

  17. Insuficiencia renal aguda con necrosis tubular aguda secundaria a picadura masiva de abejas

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    Gustavo A. Aroca - Martínez

    2006-01-01

    Full Text Available Leñador de 46 años consulta al servicio de nefrología, de la Clínica Renal de la Costa en Barranquilla, con episodio de insuficiencia renal aguda 48 horas después de haber sufrido múltiples picaduras por abejas africanizadas. Durante su estancia hospitalaria presentó incremento de enzimas musculares (AST LDH, y de pruebas de función renal, motivo por el cual fue dializado en varias ocasiones. Con mejoría total, se decide egresar y manejar ambulatoriamente. Se concluye que el caso se trata de una insuficiencia renal por necrosis tubular aguda por rabdomiolisis debida a la picadura múltiple de abejas africanizadas.

  18. Roles of Akt and SGK1 in the Regulation of Renal Tubular Transport

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    Nobuhiko Satoh

    2015-01-01

    Full Text Available A serine/threonine kinase Akt is a key mediator in various signaling pathways including regulation of renal tubular transport. In proximal tubules, Akt mediates insulin signaling via insulin receptor substrate 2 (IRS2 and stimulates sodium-bicarbonate cotransporter (NBCe1, resulting in increased sodium reabsorption. In insulin resistance, the IRS2 in kidney cortex is exceptionally preserved and may mediate the stimulatory effect of insulin on NBCe1 to cause hypertension in diabetes via sodium retention. Likewise, in distal convoluted tubules and cortical collecting ducts, insulin-induced Akt phosphorylation mediates several hormonal signals to enhance sodium-chloride cotransporter (NCC and epithelial sodium channel (ENaC activities, resulting in increased sodium reabsorption. Serum- and glucocorticoid-inducible kinase 1 (SGK1 mediates aldosterone signaling. Insulin can stimulate SGK1 to exert various effects on renal transporters. In renal cortical collecting ducts, SGK1 regulates the expression level of ENaC through inhibition of its degradation. In addition, SGK1 and Akt cooperatively regulate potassium secretion by renal outer medullary potassium channel (ROMK. Moreover, sodium-proton exchanger 3 (NHE3 in proximal tubules is possibly activated by SGK1. This review focuses on recent advances in understanding of the roles of Akt and SGK1 in the regulation of renal tubular transport.

  19. Regulatory mechanism of ulinastatin on autophagy of macrophages and renal tubular epithelial cells

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    Wu Ming

    2018-04-01

    Full Text Available Kidney ischemia and hypoxia can cause renal cell apoptosis and activation of inflammatory cells, which lead to the release of inflammatory factors and ultimately result in the damage of kidney tissue and the whole body. Renal tubular cell and macrophage autophagy can reduce the production of reactive oxygen species (ROS, thereby reducing the activation of inflammatory cytoplasm and its key effector protein, caspase-1, which reduces the expression of IL-1β and IL-18 and other inflammatory factors. Ulinastatin (UTI, as a glycoprotein drug, inhibits the activity of multiple proteases and reduces myocardial damage caused by ischemia-reperfusion by upregulating autophagy. However, it can be raised by macrophage autophagy, reduce the production of ROS, and ultimately reduce the expression of inflammatory mediators, thereby reducing renal cell injury, promote renal function recovery is not clear. In this study, a series of cell experiments have shown that ulinastatin is reduced by regulating the autophagy of renal tubular epithelial cells and macrophages to reduce the production of reactive oxygen species and inflammatory factors (TNF-α, IL-1β and IL-1, and then, increase the activity of the cells under the sugar oxygen deprivation model. The simultaneous use of cellular autophagy agonists Rapamycin (RAPA and ulinastatin has a synergistic effect on the production of reactive oxygen species and the expression of inflammatory factors.

  20. Usefulness of zebrafish larvae to evaluate drug-induced functional and morphological renal tubular alterations.

    Science.gov (United States)

    Gorgulho, Rita; Jacinto, Raquel; Lopes, Susana S; Pereira, Sofia A; Tranfield, Erin M; Martins, Gabriel G; Gualda, Emilio J; Derks, Rico J E; Correia, Ana C; Steenvoorden, Evelyne; Pintado, Petra; Mayboroda, Oleg A; Monteiro, Emilia C; Morello, Judit

    2018-01-01

    Prediction and management of drug-induced renal injury (DIRI) rely on the knowledge of the mechanisms of drug insult and on the availability of appropriate animal models to explore it. Zebrafish (Danio rerio) offers unique advantages for assessing DIRI because the larval pronephric kidney has a high homology with its human counterpart and it is fully mature at 3.5 days post-fertilization. Herein, we aimed to evaluate the usefulness of zebrafish larvae as a model of renal tubular toxicity through a comprehensive analysis of the renal alterations induced by the lethal concentrations for 10% of the larvae for gentamicin, paracetamol and tenofovir. We evaluated drug metabolic profile by mass spectrometry, renal function with the inulin clearance assay, the 3D morphology of the proximal convoluted tubule by two-photon microscopy and the ultrastructure of proximal convoluted tubule mitochondria by transmission electron microscopy. Paracetamol was metabolized by conjugation and oxidation with further detoxification with glutathione. Renal clearance was reduced with gentamicin and paracetamol. Proximal tubules were enlarged with paracetamol and tenofovir. All drugs induced mitochondrial alterations including dysmorphic shapes ("donuts", "pancakes" and "rods"), mitochondrial swelling, cristae disruption and/or loss of matrix granules. These results are in agreement with the tubular effects of gentamicin, paracetamol and tenofovir in man and demonstrate that zebrafish larvae might be a good model to assess functional and structural damage associated with DIRI.

  1. Exosome production and its regulation of EGFR during wound healing in renal tubular cells.

    Science.gov (United States)

    Zhou, Xiangjun; Zhang, Wei; Yao, Qisheng; Zhang, Hao; Dong, Guie; Zhang, Ming; Liu, Yutao; Chen, Jian-Kang; Dong, Zheng

    2017-06-01

    Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing. Copyright © 2017 the American Physiological Society.

  2. High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Daisuke Ogawa

    2011-01-01

    Full Text Available Metallothionein (MT is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2 are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

  3. Tubular and endothelial chimerism in renal allografts using fluorescence and chromogenic in situ hybridization (FISH, CISH) technology.

    Science.gov (United States)

    Varga, Zsuzsanna; Gaspert, Ariana; Behnke, Silvia; von Teichman, Adriana; Fritzsche, Florian; Fehr, Thomas

    2012-04-01

    The role of endothelial and tubular chimerism in renal allograft adaptation and rejection varies in different studies. We addressed the correlation between different clinico-pathological settings and sex-chromosomal endothelial and/or tubular chimerism in renal allografts. We examined the presence or absence of the X and Y chromosomes by fluorescence and chromogenic in situ hybridization (FISH, CISH) methodology on paraffin embedded kidney biopsies in 16 gender mismatched renal transplants (1 to 12 years post-transplantation). Twelve patients were male, four female. Four groups were selected: (i) Vascular calcineurin inhibitor toxicity without rejection; (ii) T-cell mediated vascular rejection; (iii) antibody mediated rejection; and (iv) C4d-positivity in AB0-incompatible transplants with or without rejection. Twelve non-transplant kidney biopsies (8 female, 4 male) were used as controls. Tubular chimerism was detected more frequently (69%) than endothelial chimerism (12%) in renal transplants. One of 12 control patients had tubular and endothelial chimeric cells (8%). The Y chromosome occurred in 8/12 male recipients (67%) in tubular epithelial cells and in 5/12 male recipients (42%) in endothelial cells. Double X chromosomes were detected in 3/4 female recipients in tubular epithelium. Tubular chimerism occurred more often with endothelial chimerism and capillaritis without correlation with other parameters, such as rejection. Combined Y chromosomal tubular and lymphatic endothelial chimerism correlated with T-cell mediated vascular rejection in two out of three patients (66%). Combined Y chromosomal tubular and peritubular capillary chimerism correlated with antibody mediated C4d+ rejection in one out of two patients (50%). Tubular and/or endothelial chimerism occur frequently in gender mismatched renal allografts and, when combined, this is associated with T-cell mediated rejection. © 2012 The Authors. Pathology International © 2012 Japanese Society of

  4. [Case of distal renal tubular acidosis complicated with renal diabetes insipidus, showing aggravation of symptoms with occurrence of diabetes mellitus].

    Science.gov (United States)

    Liu, Hexing; Tomoda, Fumihiro; Koike, Tsutomu; Ohara, Maiko; Nakagawa, Taizo; Kagitani, Satoshi; Inoue, Hiroshi

    2011-01-01

    We report herein a 27-year-old male case of inherited distal renal tubular acidosis complicated with renal diabetes insipidus, the symptoms of which were aggravated by the occurrence of diabetes mellitus. At 2 months after birth, he was diagnosed as having inherited distal renal tubular acidosis and thereafter supplementation of both potassium and alkali was started to treat his hypokalemia and metabolic acidosis. At the age of 4 years, calcification of the bilateral renal medulla was detected by computed tomography. Subsequently his urinary volume gradually increased and polyuria of approximately 4 L/day persisted. At the age of 27 years, he became fond of sugar-sweetened drinks and also often forgot to take the medicine. He was admitted to our hospital due to polyuria of more than 10 L day, muscle weakness and gait disturbance. Laboratory tests disclosed worsening of both hypokalemia and metabolic acidosis in addition to severe hyperglycemia. It seemed likely that occurrence of diabetes mellitus and cessation of medications can induce osmotic diuresis and aggravate hypokalemia and metabolic acidosis. Consequently, severe dehydration, hypokalemia-induced damage of his urinary concentration ability and enhancement of the renin angiotensin system occurred and thereby possibly worsened his hypokalemia and metabolic acidosis. As normalization of hyperglycemia and metabolic acidosis might have exacerbated hypokalemia further, dehydration and hypokalemia were treated first. Following intensive treatment, these abnormalities were improved, but polyuria persisted. Elevated plasma antidiuretic hormone (12.0 pg/mL) and deficit of renal responses to antidiuretic hormone suggested that the polyuria was attributable to the preexisting renal diabetes insipidus possibly caused by bilateral renal medulla calcification. Thiazide diuretic or nonsteroidal anti-inflammatory drugs were not effective for the treatment of diabetes insipidus in the present case.

  5. Late renal dysfunction in adult survivors of bone marrow transplantation

    International Nuclear Information System (INIS)

    Lawton, C.A.; Cohen, E.P.; Barber-Derus, S.W.; Murray, K.J.; Ash, R.C.; Casper, J.T.; Moulder, J.E.

    1991-01-01

    Until recently long-term renal toxicity has not been considered a major late complication of bone marrow transplantation (BMT). Late renal dysfunction has been described in a pediatric population status post-BMT which was attributable to the radiation in the preparatory regimen. A thorough review of adults with this type of late renal dysfunction has not previously been described. Fourteen of 103 evaluable adult patients undergoing allogeneic (96) or autologous (7) bone marrow transplantation, predominantly for leukemia and lymphomas, at the Medical College of Wisconsin (Milwaukee, WI) have had a syndrome of renal insufficiency characterized by increased serum creatinine, decreased glomerular filtration rate, anemia, and hypertension. This syndrome developed at a median of 9 months (range, 4.5 to 26 months) posttransplantation in the absence of specific identifiable causes. The cumulative probability of having this renal dysfunction is 20% at 1 year. Renal biopsies performed on seven of these cases showed the endothelium widely separated from the basement membrane, extreme thickening of the glomerular basement membrane, and microthrombi. Previous chemotherapy, antibiotics, and antifungals as well as cyclosporin may add to and possibly potentiate a primary chemoradiation marrow transplant renal injury, but this clinical syndrome is most analogous to clinical and experimental models of radiation nephritis. This late marrow transplant-associated nephritis should be recognized as a potentially limiting factor in the use of some intensive chemoradiation conditioning regimens used for BMT. Some selective attenuation of the radiation to the kidneys may decrease the incidence of this renal dysfunction

  6. Urinary Beta-2Microglobulin: An Indicator of Renal Tubular Damage after Extracorporeal Shock Wave Lithotripsy.

    Science.gov (United States)

    Nasseh, Hamidreza; Abdi, Sepideh; Roshani, Ali; Kazemnezhad, Ehsan

    2016-12-08

    This study aims to determine extracorporeal shock wave lithotripsy (ESWL)-induced renal tubular damageand the affecting factors by measuring urinary beta2microglobulin (β2M) excretion. This is a cross-sectional study conducted on 91 patients with renal stones who underwentESWL during 2012. Urinary beta2microglobulin was measured immediately before and after the procedure foreach patient and analyzed based on different variables to evaluate factors affecting ESWL-induced renal tubularinjury. Mean ± SD urinary beta2-microglobulin values, before and after ESWL were 0.08 ± 0.07 and 0.22 ± 0.71mg/dL respectively, the average difference between which was equal to 0.14 ± 0.07 mg/dL. These figures exhibiteda 166.66% rise in the urinary β2M concentration after ESWL which was statistically significant (P ESWL (P = .02) were predictive factors ofhigher post-ESWL urinary beta2-microglobulin excretion. Urinary excretion of beta2-microglobulin increased significantly immediately after ESWL. Thesechanges could indicate that ESWL is a contributing factor to renal tubular damage. It also seems that in patientswith hypertension and a previous history of ESWL the likelihood of this injury is higher than others.

  7. Renal blood flow after transplantation: Effects of acute tubular necrosis, rejection, and cyclosporine toxicity

    International Nuclear Information System (INIS)

    Lear, J.L.; Raff, U.; Jain, R.; Horgan, J.G.

    1988-01-01

    The authors incorporated their recently developed radionuclide first pass-technique for the quantitative measurement of renal transplant perfusion into routine DTPA imaging. Using this technique they investigated the effects of acute tubular necrosis (ATN), rejection, and cyclosporing toxicity on renal blood flow in a series of 80 studies in 35 patients, with independent evaluation of renal function. Transplant flow values were as follows: normal functioning, 439 mL/min +-83; ATN 248 mL/min +-63; rejection, 128 mL/min +-58; cyclosporing toxicity, 284 mL/min +-97; (normal flow in nontransplanted kidneys, approximately 550 mL/min). Differences between normal functioning, ATN, and rejection were significant (P < .05). Interestingly, immediate postsurgical hyperemia frequently occurred, with flow values sometimes exceeding 700 mL/min

  8. Involvement of caspase-12-dependent apoptotic pathway in ionic radiocontrast urografin-induced renal tubular cell injury

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Cheng Tien [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Weng, Te I. [Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Chen, Li Ping [Department of Dentistry, Chang Gang Memorial Hospital, Chang Gang University, Taoyuan, Taiwan (China); Chiang, Chih Kang [Department of Integrated Diagnostics and Therapeutics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (China); Liu, Shing Hwa, E-mail: shinghwaliu@ntu.edu.tw [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Urology, National Taiwan University Hospital, Taipei, Taiwan (China)

    2013-01-01

    Contrast medium (CM) induces a direct toxic effect on renal tubular cells. This toxic effect subjects in the disorder of CM-induced nephropathy. Our previous work has demonstrated that CM shows to activate the endoplasmic reticulum (ER)-related adaptive unfolding protein response (UPR) activators. Glucose-regulated protein 78 (GRP78)/eukaryotic initiation factor 2α (eIF2α)-related pathways play a protective role during the urografin (an ionic CM)-induced renal tubular injury. However, the involvement of ER stress-related apoptotic signals in the urografin-induced renal tubular cell injury remains unclear. Here, we examined by the in vivo and in vitro experiments to explore whether ER stress-regulated pro-apoptotic activators participate in urografin-induced renal injury. Urografin induced renal tubular dilation, tubular cells detachment, and necrosis in the kidneys of rats. The tubular apoptosis, ER stress-related pro-apoptotic transcriptional factors, and kidney injury marker-1 (kim-1) were also conspicuously up-regulated in urografin-treated rats. Furthermore, treatment of normal rat kidney (NRK)-52E tubular cells with urografin augmented the expressions of activating transcription factor-6 (ATF-6), C/EBP homologous protein (CHOP), Bax, caspase-12, JNK, and inositol-requiring enzyme (IRE) 1 signals. Urografin-induced renal tubular cell apoptosis was not reversed by the inhibitors of ATF-6, JNK signals or CHOP siRNA transfection, but it could be partially reversed by the inhibitor of caspase-12. Taken together, the present results and our previous findings suggest that exposure of CM/urografin activates the ER stress-regulated survival- and apoptosis-related signaling pathways in renal tubular cells. Caspase-12-dependent apoptotic pathway may be partially involved in the urografin-induced nephropathy. -- Highlights: ► Ionic contrast medium-urografin induces renal tubular cell apoptosis. ► Urografin induces the ER stress-regulated survival and apoptosis

  9. Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

    Science.gov (United States)

    Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

    2013-07-13

    Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

  10. Proximal renal tubular injury in rats sub-chronically exposed to low fluoride concentrations

    Energy Technology Data Exchange (ETDEWEB)

    Cárdenas-González, Mariana C.; Del Razo, Luz M. [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); Barrera-Chimal, Jonatan [Unidad de Fisiología Molecular, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México and Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, México, D. F., México (Mexico); Jacobo-Estrada, Tania [Departmento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); López-Bayghen, Esther [Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), México, D. F., México (Mexico); and others

    2013-11-01

    Fluoride is usually found in groundwater at a very wide range of concentration between 0.5 and 25 ppm. At present, few studies have assessed the renal effects of fluoride at environmentally relevant concentrations. Furthermore, most of these studies have used insensitive and nonspecific biomarkers of kidney injury. The aim of this study was to use early and sensitive biomarkers to evaluate kidney injury after fluoride exposure to environmentally relevant concentrations. Recently weaned male Wistar rats were exposed to low (15 ppm) and high (50 ppm) fluoride concentrations in drinking water for a period of 40 days. At the end of the exposure period, kidney injury biomarkers were measured in urine and renal mRNA expression levels were assessed by real time RT-PCR. Our results showed that the urinary kidney injury molecule (Kim-1), clusterin (Clu), osteopontin (OPN) and heat shock protein 72 excretion rate significantly increased in the group exposed to the high fluoride concentration. Accordingly, fluoride exposure increased renal Kim-1, Clu and OPN mRNA expression levels. Moreover, there was a significant dose-dependent increase in urinary β-2-microglobulin and cystatin-C excretion rate. Additionally, a tendency towards a dose dependent increase of tubular damage in the histopathological light microscopy findings confirmed the preferential impact of fluoride on the tubular structure. All of these changes occurred at early stages in which, the renal function was not altered. In conclusion using early and sensitive biomarkers of kidney injury, we were able to found proximal tubular alterations in rats sub-chronically exposed to fluoride. - Highlights: • Exposure to low concentrations of fluoride induced proximal tubular injury • Increase in urinary Kim-1, Clu, OPN and Hsp72 in 50 ppm fluoride-exposed group • Increase in urinary B2M and CysC in 15 and 50 ppm fluoride-exposed groups • Fluoride exposure increased renal Kim, Clu and OPN mRNA expression levels.

  11. The urinary excretion of metformin, ceftizoxime and ofloxacin in high serum creatinine rats: Can creatinine predict renal tubular elimination?

    Science.gov (United States)

    Ma, Yan-Rong; Zhou, Yan; Huang, Jing; Qin, Hong-Yan; Wang, Pei; Wu, Xin-An

    2018-03-01

    The renal excretion of creatinine and most drugs are the net result of glomerular filtration and tubular secretion, and their tubular secretions are mediated by individual transporters. Thus, we hypothesized that the increase of serum creatinine (SCr) levels attributing to inhibiting tubular transporters but not glomerular filtration rate (GFR) could be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine. In this work, we firstly developed the creatinine excretion inhibition model with normal GFR by competitively inhibiting tubular transporters, and investigated the renal excretion of metformin, ceftizoxime and ofloxacin in vivo and in vitro. The results showed that the 24-hour urinary excretion of metformin and ceftizoxime in model rats were decreased by 25% and 17% compared to that in control rats, respectively. The uptake amount and urinary excretion of metformin and ceftizoxime could be inhibited by creatinine in renal cortical slices and isolated kidney perfusion. However, the urinary excretion of ofloxacin was not affected by high SCr. These results showed that the inhibition of tubular creatinine transporters by high SCr resulted to the decrease of urinary excretion of metformin and ceftizoxime, but not ofloxacin, which implied that the increase of SCr could also be used to evaluate the tubular excretion of drugs mediated by identical or partial overlap transporter with creatinine in normal GFR rats. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Pediatric Sjogren syndrome with distal renal tubular acidosis and autoimmune hypothyroidism: an uncommon association.

    Science.gov (United States)

    Agarwal, Amit; Kumar, Pradeep; Gupta, Nomeeta

    2015-11-01

    A 14-year-old female came with the history of sudden onset weakness; during work up, she was found to have hyperchloremic metabolic acidosis with normal anion gap and normal renal function suggesting the possibility of renal tubular acidosis (RTA). On further evaluation of RTA, she had positive antinuclear antibody, anti-Ro, and anti-La antibodies. On nuclear scan of salivary glands, her left parotid gland was nonfunctional. Her parotid biopsy revealed dilated interlobular ducts engulfed by lymphoid cells. She also had autoimmune hypothyroidism as suggested by raised TSH and positive anti-TPO antibodies. At admission, her serum potassium levels were low and she was treated with intravenous potassium chloride. After she recovered from acute hypokalemic paralysis, she was started on oral potassium citrate along with phosphate supplements, hydroxychloroquine, oral prednisolone and thyroxine supplements. Over the next 6 months, she has significant reduction in the dosage of potassium, bicarbonate and phosphate and gained 3 kg of weight and 3.5 cm of height. As primary Sjogren syndrome itself is rare in pediatric population and its association with renal tubular acidosis is even rarer, we suggest considering Sjogren syndrome as a differential diagnosis during the RTA work-up is worth trying.

  13. Effect of taurine on advanced glycation end products-induced hypertrophy in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Huang, J.-S.; Chuang, L.-Y.; Guh, J.-Y.; Yang, Y.-L.; Hsu, M.-S.

    2008-01-01

    Mounting evidence indicates that advanced glycation end products (AGE) play a major role in the development of diabetic nephropathy (DN). Taurine is a well documented antioxidant agent. To explore whether taurine was linked to altered AGE-mediated renal tubulointerstitial fibrosis in DN, we examined the molecular mechanisms of taurine responsible for inhibition of AGE-induced hypertrophy in renal tubular epithelial cells. We found that AGE (but not non-glycated BSA) caused inhibition of cellular mitogenesis rather than cell death by either necrosis or apoptosis. There were no changes in caspase 3 activity, bcl-2 protein expression, and mitochondrial cytochrome c release in BSA, AGE, or the antioxidant taurine treatments in these cells. AGE-induced the Raf-1/extracellular signal-regulated kinase (ERK) activation was markedly blocked by taurine. Furthermore, taurine, the Raf-1 kinase inhibitor GW5074, and the ERK kinase inhibitor PD98059 may have the ability to induce cellular proliferation and cell cycle progression from AGE-treated cells. The ability of taurine, GW5074, or PD98059 to inhibit AGE-induced hypertrophy was verified by the observation that it significantly decreased cell size, cellular hypertrophy index, and protein levels of RAGE, p27 Kip1 , collagen IV, and fibronectin. The results obtained in this study suggest that taurine may serve as the potential anti-fibrotic activity in DN through mechanism dependent of its Raf-1/ERK inactivation in AGE-induced hypertrophy in renal tubular epithelial cells

  14. Lipid myopathy associated with renal tubular acidosis and spastic diplegia in two brothers.

    Science.gov (United States)

    Tung, Y C; Tsau, Y K; Chu, L W; Young, C; Shen, Y Z

    2001-07-01

    Lipid myopathy is a group of disorders involving mitochondrial fatty acid oxidation. We describe two brothers, 3 years 8 months old and 2 years 9 months old, respectively, with progressive spastic diplegia, developmental delay, failure to thrive, and chronic metabolic acidosis who had lipid myopathy and renal tubular acidosis. Brain magnetic resonance imaging revealed demyelinating changes in the periventricular white matter, which was compatible with spastic diplegia. These symptoms may be related to errors in fatty acid metabolism. Cerebral palsy had been misdiagnosed in both of these patients at another hospital. Therefore, for patients with late-onset and progressive spastic diplegia, detailed investigations for underlying diseases are warranted.

  15. Evaluation of (o)-[77Br]bromohippuran as renal tubular function agent

    International Nuclear Information System (INIS)

    Aswegen, A. van; Roodt, J.P.; Pieters, H.; Herbst, C.P.; Otto, A.C.; Loetter, M.G.; Minnaar, P.C.; Haasbroek, F.J.

    1985-01-01

    (o)-[ 77 Br]bromohippuran (BHIP) was developed as renal tubular function agent due to its favourable chemical and physical properties and compared to (o)-[ 131 I]iodohippuran (IHIP). Renograms obtained from baboons were compared and absorbed radiation dose calculations performed. Although BHIP showed a delayed kidney uptake and washout pattern, good kidney clearance of the radionuclide was obtained after 30 min. Radiation dose values for BHIP were markedly lower than for IHIP indicating that larger activities of BHIP could be administered to increase counting statistics. BHIP imaging in normal volunteers did however not substantiate the favourable behaviour obtained in the primate. (author)

  16. Renal Tubular Acidosis an Adverse Effect of PD-1 Inhibitor Immunotherapy

    Directory of Open Access Journals (Sweden)

    Sandy El Bitar

    2018-01-01

    Full Text Available Immune checkpoint blockade therapy is gaining popularity among oncologists for treatment of solid and hematologic malignancies. The widespread use of these agents resulted in increasing incidence of renal immune-related adverse events. Reported renal toxicity described so far includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. We report the case of a 79-year-old female with metastatic non-small cell lung cancer on anti-PD-1 therapy nivolumab. After the 4th administration of nivolumab, the treatment course was complicated with normal anion gap metabolic acidosis. Urine and blood studies were in favor of distal renal tubular acidosis (RTA. Following a negative workup for an underlying etiology, immunotherapy-induced RTA was suspected. Withholding of the offending agent and initiation of steroid therapy resulted in adequate response. The present report provides the first presentation of RTA as a renal immune-related adverse event secondary to nivolumab. Nephrologists and oncologists should be familiar with potentially life-threatening renal side effects induced by immune checkpoint inhibitors.

  17. Methotrexate-induced Pancytopenia in Two Patients with Renal Dysfunction

    OpenAIRE

    Yusuf OĞUZ; Tayfun EYİLETEN; Murat KARAMAN; Seyid Ahmet AY; Mahmut İlker YILMAZ

    2011-01-01

    Methotrexate (MTX) is cleared primarily by renal excretion. The excretion of MTX is delayed in subjects with renal dysfunction and elevated plasma MTX concentrations develop which lead to bone marrow toxicities and possible pancytopenia. In this case report, we presented two advanced age patients with MTX-induced pancytopenia. The first patient on hemodialysis was diagnosed with seronegative arthritis while the second patient with congestive heart failure was diagnosed with rheumatoid arthrit...

  18. Distal renal tubular acidosis and quadriparaesis in Sjögren′s syndrome: A cunning congregate

    Directory of Open Access Journals (Sweden)

    Arundhati G Diwan

    2014-01-01

    Full Text Available Sjögren′s syndrome (SS is a chronic autoimmune disease, chiefly affecting the exocrine glandular function of salivary glands and lacrimal glands. Rarely, it involves the kidneys, central and peripheral nervous system, muscloskeletal apparatus and lungs. We report a rare constellation of SS with distal renal tubular acidosis and quadriparaesis in a young female. History of quadriparaesis was acute, with rapid progression. Supplementary treatment for severe hypokalemia was instituted at the earliest, lest the patient develop respiratory muscle weakness. Concomitantly, metabolic acidosis with alkaline urine was suspected and subsequently investigated. Eventually, this was attributed to impaired renal acidification of urine in the distal tubules. History of dryness of eyes and mouth since 6 months justified salivary gland biopsy. The results yielded a lymphocytic infiltrative pathology strongly favoring SS. The patient benefited from prompt potassium replacement therapy and had complete resolution over the next week. Supportive treatment for predictable manifestations was continued along with potassium supplements.

  19. Bilateral Proximal Femur Fractures in a Patient with Renal Tubular Acidosis: A Case Report

    Directory of Open Access Journals (Sweden)

    Charl SS

    2018-03-01

    Full Text Available The diagnosis of pathological fractures is on the rise. The morbidity involved does not only burden the patient and their families but it has a great toll on the healthcare system as well. Early identification of the patient at risk is an invaluable tool to cut cost and improve the patient’s quality of life. Multiple renal pathologies have been highlighted in relation to the risk of pathological fractures; however, complications in renal tubular acidosis have been rarely documented. Nevertheless, prompt action with adequate and relevant patient education ultimately can reduce the associated morbidity. We present a case of poor control of the disease and its debilitating pathological fracture complications.

  20. Effect of Diuretics on Renal Tubular Transport of Calcium and Magnesium

    DEFF Research Database (Denmark)

    Alexander, R Todd; Dimke, Henrik

    2017-01-01

    are important for both forming divalent cation permeable pores and channels, but also for generating the necessary driving forces for Ca2+ and Mg2+ transport. Alterations in these molecular constituents lead to profound effects on tubular Ca2+ and Mg2+ handling. Diuretics are used to treat a large range...... of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na+) transport, but also indirectly affect renal Ca2+ and Mg2+ handling, i.e. by establishing a prerequisite electrochemical gradient....... It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca2+ and Mg2+ handling are reviewed in the context of the current understanding of basal molecular mechanisms of Ca2+ and Mg2+ transport...

  1. Uric Acid Induces Renal Inflammation via Activating Tubular NF-κB Signaling Pathway

    Science.gov (United States)

    Zhou, Yang; Fang, Li; Jiang, Lei; Wen, Ping; Cao, Hongdi; He, Weichun; Dai, Chunsun; Yang, Junwei

    2012-01-01

    Inflammation is a pathologic feature of hyperuricemia in clinical settings. However, the underlying mechanism remains unknown. Here, infiltration of T cells and macrophages were significantly increased in hyperuricemia mice kidneys. This infiltration of inflammatory cells was accompanied by an up-regulation of TNF-α, MCP-1 and RANTES expression. Further, infiltration was largely located in tubular interstitial spaces, suggesting a role for tubular cells in hyperuricemia-induced inflammation. In cultured tubular epithelial cells (NRK-52E), uric acid, probably transported via urate transporter, induced TNF-α, MCP-1 and RANTES mRNA as well as RANTES protein expression. Culture media of NRK-52E cells incubated with uric acid showed a chemo-attractive ability to recruit macrophage. Moreover uric acid activated NF-κB signaling. The uric acid-induced up-regulation of RANTES was blocked by SN 50, a specific NF-κB inhibitor. Activation of NF-κB signaling was also observed in tubule of hyperuricemia mice. These results suggest that uric acid induces renal inflammation via activation of NF-κB signaling. PMID:22761883

  2. Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

    OpenAIRE

    Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

    2013-01-01

    Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of ...

  3. Sjögren syndrome presenting with hypopotassemic periodic paralysis due to renal tubular acidosis

    Science.gov (United States)

    Ataoglu, Esra Hayriye; Demir, Betul; Tuna, Mazhar; Çavus, Bilger; Cetin, Faik; Temiz, Levent Umit; Ozturk, Savas; Yenigun, Mustafa

    2012-01-01

    Summary Background: Sjögren syndrome (SS) is an autoimmune-lymphoproliferative disorder characterized by mononuclear cell infiltration of exocrine glands. Clinically, Sjögren syndrome (SS) has a wide spectrum, varying from autoimmune exocrinopathy to systemic involvement. There have been few cases reporting that primary SS developed with distal renal tubular acidosis clinically. Case Report: Here, we present a case with primary Sjögren syndrome accompanied by hypopotassemic paralysis due to renal tubular acidosis. Severe hypopotassemia, hyperchloremic metabolic acidosis, alkaline urine and disorder in urinary acidification test were observed in the biochemical examination of the 16-year-old female patient, who had applied to our clinic for extreme loss of muscle force. After the examinations it was determined that the patient had developed Type 1 RTA (distal RTA) due to primary Sjögren syndrome. Potassium and alkaline replacement was made and an immediate total recovery was achieved. Conclusions: Hypopotassemic paralysis due to primary Sjögren syndrome is a rare but severe disorder that could lead to death if not detected early and cured appropriately. Thus, effective treatment should be immediately initiated in cases where severe hypopotassemia is accompanied by metabolic acidosis, and the cases should also be examined for extraglandular involvement of SS. PMID:23569525

  4. Effects of aging on cadmium concentrations and renal dysfunction in inhabitants in cadmium-polluted regions in Japan.

    Science.gov (United States)

    Phuc, Hoang Duc; Kido, Teruhiko; Oanh, Nguyen Thi Phuong; Manh, Ho Dung; Anh, Le Thai; Oyama, Yuko; Okamoto, Rie; Ichimori, Akie; Nogawa, Kazuhiro; Suwazono, Yasushi; Nakagawa, Hideaki

    2017-09-01

    The absorption of cadmium (Cd) may lead to Cd-related diseases such as renal tubular dysfunction and bone disease, and it is known to take around 10-30 years to reduce Cd concentrations to half their original levels. Urinary β 2 -microglobulin (β 2 -MG), N-acetyl-β-D-glucosaminidase (NAG), protein, glucose and albumin were used as indicators of renal dysfunction caused by Cd exposure. Our previous study found that urinary Cd concentrations had increased recently and that age was more strongly associated with urinary β 2 -MG concentration than recent Cd body burden. Therefore, the purpose of the present study was to investigate the effect of aging on Cd concentrations and renal dysfunction. The Cd, β 2 -MG, NAG, protein, glucose and albumin concentrations in the urine of 40 Japanese subjects (20 females and 20 males) environmentally exposed to Cd were collected. They lived in the Kakehashi River basin and were divided into three age categories: 50-69, 70-79 and 80-99 years. Significant differences in urinary Cd and β 2 -MG concentrations were found among age groups, with urinary Cd levels tending to increase with age in both sexes. No significant correlations were found between urinary Cd and any indicators of renal dysfunction. The correlation between age, Cd and indicators of renal dysfunction was observed more clearly in females than in males. Age is more strongly correlated with indicators of renal dysfunction than Cd body burden. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Systemic lupus erythematosus associated with type 4 renal tubular acidosis: a case report and review of the literature

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    Young Larry

    2011-03-01

    Full Text Available Abstract Introduction Type 4 renal tubular acidosis is an uncommon clinical manifestation of systemic lupus erythematosus and has been reported to portend a poor prognosis. To the best of our knowledge, this is the first case report which highlights the successful management of a patient with systemic lupus erythematosus complicated by type 4 renal tubular acidosis who did not do poorly. Case presentation A 44-year-old Hispanic woman developed a non-anion gap hyperkalemic metabolic acidosis consistent with type 4 renal tubular acidosis while being treated in the hospital for recently diagnosed systemic lupus erythematosus with multi-organ involvement. She responded well to treatment with corticosteroids, hydroxychloroquine and mycophenolate mofetil. Normal renal function was achieved prior to discharge and remained normal at the patient's one-month follow-up examination. Conclusion This case increases awareness of an uncommon association between systemic lupus erythematosus and type 4 renal tubular acidosis and suggests a positive impact of early diagnosis and appropriate immunosuppressive treatment on the patient's outcome.

  6. Risk factors for renal dysfunction after total hip joint replacement

    DEFF Research Database (Denmark)

    Hassan, Basim Kamil; Sahlström, Arne; Dessau, Ram Benny Christian

    2015-01-01

    BACKGROUND AND PURPOSE OF THE STUDY: Renal injury and dysfunction are serious complications after major surgery, which may lead to increased morbidity and mortality. The objective of our study was to identify the possible risk factors for renal dysfunction after total hip joint replacement surger...... creatinine. Smoking, diabetes mellitus, high BMI, gender, and duration of surgery were not identified as significant risk factors........ METHODS: A retrospective study was conducted among 599 consecutive primary hip joint replacements performed between January 2011 and December 2013. According to the RIFLE criteria, increased postoperative serum creatinine was considered indicative of postoperative renal injury. The Welch two-sample test......, hypertension, general anesthesia, high ASA scores, low intra-operative systolic BP, and prophylactic dicloxacillin as significant risk factors. Low baseline systolic BP, low baseline diastolic blood pressure, and hip fracture diagnosis were independent risk factors for postoperative increase in serum...

  7. Is there a risk of permanent renal dysfunction after primary total hip and knee joint replacements?

    DEFF Research Database (Denmark)

    Hassan, Basim Kamil; Dessau, Ram Benny; Sahlström, Arne

    2016-01-01

    BACKGROUND: Permanent renal dysfunction is considered as being a serious complication which may occur after major surgery and which furthermore may lead to increased morbidity and mortality. The objective of this study was to analyze the incidence of long-term postoperative renal dysfunction after...... permanent renal dysfunction up to 1 year after the index surgery....

  8. The efficacy of antipsychotics for prolonged delirium with renal dysfunction

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    Asano S

    2017-11-01

    Full Text Available Satoko Asano, Yasuto Kunii, Hiroshi Hoshino, Yusuke Osakabe, Tetsuya Shiga, Shuntaro Itagaki, Itaru Miura, Hirooki Yabe Department of Neuropsychiatry, School of Medicine Fukushima Medical University, Fukushima, Japan Aim: Delirium is commonly encountered in daily clinical practice. To identify predictors influencing outcomes, we retrospectively examined the characteristics of inpatients with delirium who required psychiatric medication during hospitalization.Methods: We extracted all new inpatients (n=523 consulted for psychiatric symptoms at Fukushima Medical University Hospital between October 2011 and September 2013. We selected 203 inpatients with delirium diagnosed by psychiatrists. We analyzed data from 177 inpatients with delirium who received psychiatric medication. We defined an “early improvement group” in which delirium resolved in ≤3 days after starting psychiatric medication, and a “prolonged group” with delirium lasting for >3 days. Among the 83 inpatients with renal dysfunction (estimated glomerular filtration rate <60 mL/min/1.73 m2, we defined an “early improvement group with renal dysfunction” in which delirium resolved in ≤3 days after starting psychiatric medication and a “prolonged group with renal dysfunction” with delirium lasting for >3 days. We then examined differences between groups for different categorical variables.Results: Dose of antipsychotic medication at end point was significantly lower in the prolonged group with renal dysfunction than in the early improvement group with renal dysfunction.Conclusion: The results suggest that maintaining a sufficient dose of antipsychotics from an early stage may prevent prolongation of delirium even in inpatients with renal dysfunction. Keywords: antipsychotic, prolonged delirium, chronic kidney disease, pharmacokinetics 

  9. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... tubular flow. This suggests that on-going cimetidine treatment must be taken into account when graft function is evaluated by the CCr alone....

  10. Urinary excretion of beta 2-glycoprotein-1 (apolipoprotein H) and other markers of tubular malfunction in "non-tubular" renal disease.

    Science.gov (United States)

    Flynn, F V; Lapsley, M; Sansom, P A; Cohen, S L

    1992-07-01

    To determine whether urinary beta 2-glycoprotein-1 assays can provide improved discrimination between chronic renal diseases which are primarily of tubular or glomerular origin. Urinary beta 2-glycoprotein-1, retinol-binding protein, alpha 1-microglobulin, beta 2-microglobulin, N-acetyl-beta-D-glucosa-minidase and albumin were measured in 51 patients with primary glomerular disease, 23 with obstructive nephropathy, and 15 with polycystic kidney disease, and expressed per mmol of creatinine. Plasma beta 2-glycoprotein-1 was assayed in 52 patients and plasma creatinine in all 89. The findings were compared between the diagnostic groups and with previously published data relating to primary tubular disorders. All 31 patients with plasma creatinine greater than 200 mumol/l excreted increased amounts of beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin, and 29 had increased N-acetyl-beta-D-glucosaminidase; the quantities were generally similar to those found in comparable patients with primary tubular pathology. Among 58 with plasma creatinine concentrations under 200 mumol/l, increases in beta 2-glycoprotein-1, retinol-binding protein, and alpha 1-microglobulin excretion were less common and much smaller, especially in those with obstructive nephropathy and polycystic disease. The ratios of the excretion of albumin to the other proteins provided the clearest discrimination between the patients with glomerular or tubular malfunction, but an area of overlap was present which embraced those with obstructive nephropathy and polycystic disease. Increased excretion of beta 2-glycoprotein-1 due to a raised plasma concentration or diminution of tubular reabsorption, or both, is common in all the forms of renal disease investigated, and both plasma creatinine and urinary albumin must be taken into account when interpreting results. Ratios of urinary albumin: beta 2-glycoprotein-1 greater than 1000 are highly suggestive of primary glomerular disease and

  11. Influence of renal shielding on the incidence of late renal dysfunction associated with bone marrow transplantation

    International Nuclear Information System (INIS)

    Lawton, C.A.; Ash, R.C.; Murray, K.J.; Cohon, E.P.; Barher-Derus, S.W.; Moulder, J.E.

    1991-01-01

    This paper reports that late renal dysfunction following bone marrow transplantation has been described by a number of centers including the authors own. Total body irradiation seems to play a major causative role. In an effort to decrease the incidence of this renal toxicity, the authors have added customized partial transmission renal blocking to their total body irradiation regimen. The purpose of this study is to evaluate the effect of the renal blocking. The authors total body irradiation dose is 14 Gy. With the shielding used, the kidneys received approximately 12 Gy. Fifty-five adult patients have received total body irradiation with this renal shielding, compared with 73 adult patients who were treated without renal shielding. Eighteen percent (13 of 73) of patients who did not have renal shielding compared with only 7% (4 of 55) of patients with renal shielding have developed late renal dysfunction. Median follow-up in the non-blocked patients is 451 days after transplantation versus 282 days for the blocked patients

  12. Assessment of early renal allograft dysfunction with blood oxygenation level-dependent MRI and diffusion-weighted imaging

    Energy Technology Data Exchange (ETDEWEB)

    Park, Sung Yoon [Department of Radiology and Research Institute of Radiological Science, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Chan Kyo, E-mail: chankyokim@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, Byung Kwan [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Sung Ju; Lee, Sanghoon [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Huh, Wooseong [Department of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2014-12-15

    Highlights: • R2* and ADC in renal allografts are moderately correlated with eGFR. • R2* and ADC are lower in early allograft dysfunction than normal allograft function. • No significant difference between AR and ATN was found in both R2* and ADC. - Abstract: Purpose: To investigate blood oxygenation level-dependent (BOLD) MRI and diffusion-weighted imaging (DWI) at 3 T for assessment of early renal allograft dysfunction. Materials and methods: 34 patients with a renal allograft (early dysfunction, 24; normal, 10) were prospectively enrolled. BOLD MRI and DWI were performed at 3 T. R2* and apparent diffusion coefficient (ADC) values were measured in cortex and medulla of the allografts. Correlation between R2* or ADC values and estimated glomerular filtration rate (eGFR) was investigated. R2* or ADC values were compared among acute rejection (AR), acute tubular necrosis (ATN) and normal function. Results: In all renal allografts, cortical or medullary R2* and ADC values were moderately correlated with eGFR (P < 0.05). Early dysfunction group showed lower R2* and ADC values than normal function group (P < 0.05). AR or ATN had lower R2* values than normal allografts (P < 0.05), and ARs had lower cortical ADC values than normal allografts (P < 0.05). No significant difference of R2* or ADC values was found between AR and ATN (P > 0.05). Conclusion: BOLD MRI and DWI at 3 T may demonstrate early functional state of renal allografts, but may be limited in characterizing a cause of early renal allograft dysfunction. Further studies are needed.

  13. Role of mitochondrial permeability transition in human renal tubular epithelial cell death induced by aristolochic acid

    International Nuclear Information System (INIS)

    Qi Xinming; Cai Yan; Gong Likun; Liu Linlin; Chen Fangping; Xiao Ying; Wu Xiongfei; Li Yan; Xue Xiang; Ren Jin

    2007-01-01

    Aristolochic acid (AA), a natural nephrotoxin and carcinogen, can induce a progressive tubulointerstitial nephropathy. However, the mechanism by which AA causes renal injury remains largely unknown. Here we reported that the mitochondrial permeability transition (MPT) plays an important role in the renal injury induced by aristolochic acid I (AAI). We found that in the presence of Ca 2+ , AAI caused mitochondrial swelling, leakage of Ca 2+ , membrane depolarization, and release of cytochrome c in isolated kidney mitochondria. These alterations were suppressed by cyclosporin A (CsA), an agent known to inhibit MPT. Culture of HK-2 cell, a human renal tubular epithelial cell line for 24 h with AAI caused a decrease in cellular ATP, mitochondrial membrane depolarization, cytochrome c release, and increase of caspase 3 activity. These toxic effects of AAI were attenuated by CsA and bongkrekic acid (BA), another specific MPT inhibitor. Furthermore, AAI greatly inhibited the activity of mitochondrial adenine nucleotide translocator (ANT) in isolated mitochondria. We suggested that ANT may mediate, at least in part, the AAI-induced MPT. Taken together, these results suggested that MPT plays a critical role in the pathogenesis of HK-2 cell injury induced by AAI and implied that MPT might contribute to human nephrotoxicity of aristolochic acid

  14. BAG3 regulates ECM accumulation in renal proximal tubular cells induced by TGF-β1.

    Science.gov (United States)

    Du, Feng; Li, Si; Wang, Tian; Zhang, Hai-Yan; Li, De-Tian; Du, Zhen-Xian; Wang, Hua-Qin; Wang, Yan-Qiu

    2015-01-01

    Previously we have demonstrated that Bcl-2-associated athanogene 3 (BAG3) is increased in renal fibrosis using a rat unilateral ureteral obstruction model. The current study investigated the role of BAG3 in renal fibrosis using transforming growth factor (TGF)-β1-treated human proximal tubular epithelial (HK-2) cells. An upregulation of BAG3 in vitro models was observed, which correlated with the increased synthesis of extracellular matrix (ECM) proteins and expression of tissue-type plasminogen activator inhibitor (PAI)-1. Blockade of BAG3 induction by shorting hairpin RNA suppressed the expression of ECM proteins but had no effect on PAI-1 expression induced by TGF-β1. Forced overexpression of BAG3 selectively increased collagens. TGF-β1-induced BAG3 expression in HK-2 cells was attenuated by ERK1/2 and JNK MAPK inhibitors. In addition, forced BAG3 overexpression blocked attenuation of collagens expression by ERK1/2 and JNK inhibitors. These data suggest that ERK1/2 and JNK signaling events are involved in modulating the expression of BAG3, which would ultimately contribute to renal fibrosis by enhancing the synthesis and deposition of ECM proteins.

  15. Autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury induced by albumin overload.

    Science.gov (United States)

    Tan, Jin; Wang, Miaohong; Song, Shuling; Miao, Yuyang; Zhang, Qiang

    2018-01-10

    Proteinuria (albuminuria) is an important cause of aggravating tubulointerstitial injury. Previous studies have shown that autophagy activation can alleviate renal tubular epithelial cell injury caused by urinary protein, but the mechanism is not clear. Here, we investigated the role of clearance of damaged mitochondria in this protective effect. We found that albumin overload induces a significant increase in turnover of LC3-II and decrease in p62 protein level in renal proximal tubular (HK-2) cells in vitro. Albumin overload also induces an increase in mitochondrial damage. ALC, a mitochondrial torpent, alleviates mitochondrial damage induced by albumin overload and also decreases autophagy, while mitochondrial damage revulsant CCCP further increases autophagy. Furthermore, pretreatment of HK-2 cells with rapamycin reduced the amount of damaged mitochondria and the level of apoptosis induced by albumin overload. In contrast, blocking autophagy with chloroquine exerted an opposite effect. Taken together, our results indicated autophagy activation promotes removal of damaged mitochondria and protects against renal tubular injury caused by albumin overload. This further confirms previous research that autophagy activation is an adaptive response in renal tubular epithelial cells after urinary protein overload.

  16. Whole-exome sequencing as a diagnostic tool for distal renal tubular acidosis

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    Paula Cristina Barros Pereira

    2015-11-01

    Full Text Available Objective: Distal renal tubular acidosis (dRTA is characterized by metabolic acidosis due to impaired renal acid excretion. The aim of this study was to demonstrate the genetic diagnosis of four children with dRTA through use of whole-exome sequencing. Methods: Two unrelated families were selected; a total of four children with dRTA and their parents, in order to perform whole-exome sequencing. Hearing was preserved in both children from the first family, but not in the second, wherein a twin pair had severe deafness. Whole-exome sequencing was performed in two pooled samples and findings were confirmed with Sanger sequencing method. Results: Two mutations were identified in the ATP6V0A4 and ATP6V1B1 genes. In the first family, a novel mutation in the exon 13 of the ATP6V0A4 gene with a single nucleotide change GAC → TAC (c.1232G>T was found, which caused a substitution of aspartic acid to tyrosine in position 411. In the second family, a homozygous recurrent mutation with one base-pair insertion (c.1149_1155insC in exon 12 of the ATP6V1B1 gene was detected. Conclusion: These results confirm the value of whole-exome sequencing for the study of rare and complex genetic nephropathies, allowing the identification of novel and recurrent mutations. Furthermore, for the first time the application of this molecular method in renal tubular diseases has been clearly demonstrated. Resumo: Objetivo: A acidose tubular renal distal (ATRd é caracterizada por acidose metabólica devido a excreção renal de ácido prejudicada. O objetivo deste artigo é apresentar o diagnóstico genético de quatro crianças com ATRd utilizando o sequenciamento total do exoma. Métodos: Selecionamos duas famílias não relacionadas, totalizando quatro crianças com ATRd e seus pais, para realizar o sequenciamento total do exoma. A audição foi preservada em ambas as crianças da família um, porém em nenhuma criança da família dois, na qual um par de gêmeas teve

  17. INSUFICIENCIA RENAL AGUDA POR CISPLATINO: REPORTE DE UN CASO

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    Rodriguez Macías EL

    2016-01-01

    Full Text Available Cisplatin nephrotoxicity should always be considered as a potential cause of renal damage in acute renal failure installed in the context of its use. Among its mechanisms of renal functional impairment are: acute tubular necrosis, proximal tubular and loop of Henle dysfunctions, as well as the deterioration of various organelles, especially the mitochondria.

  18. Intracellular kinases mediate increased translation and secretion of netrin-1 from renal tubular epithelial cells.

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    Calpurnia Jayakumar

    Full Text Available BACKGROUND: Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS to determine the signaling pathways that regulate netrin-1 production in response to injury. METHODS AND PRINCIPAL FINDINGS: Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. CONCLUSION: Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells.

  19. Intracellular Kinases Mediate Increased Translation and Secretion of Netrin-1 from Renal Tubular Epithelial Cells

    Science.gov (United States)

    Jayakumar, Calpurnia; Mohamed, Riyaz; Ranganathan, Punithavathi Vilapakkam; Ramesh, Ganesan

    2011-01-01

    Background Netrin-1 is a laminin-related secreted protein, is highly induced after tissue injury, and may serve as a marker of injury. However, the regulation of netrin-1 production is not unknown. Current study was carried out in mouse and mouse kidney cell line (TKPTS) to determine the signaling pathways that regulate netrin-1 production in response to injury. Methods and Principal Findings Ischemia reperfusion injury of the kidney was induced in mice by clamping renal pedicle for 30 minutes. Cellular stress was induced in mouse proximal tubular epithelial cell line by treating with pervanadate, cisplatin, lipopolysaccharide, glucose or hypoxia followed by reoxygenation. Netrin-1 expression was quantified by real time RT-PCR and protein production was quantified using an ELISA kit. Cellular stress induced a large increase in netrin-1 production without increase in transcription of netrin-1 gene. Mitogen activated protein kinase, ERK mediates the drug induced netrin-1 mRNA translation increase without altering mRNA stability. Conclusion Our results suggest that netrin-1 expression is suppressed at the translational level and MAPK activation leads to rapid translation of netrin-1 mRNA in the kidney tubular epithelial cells. PMID:22046354

  20. Renal Tubular Acidosis after Jejunoileal Bypass for Morbid Obesity: role of secondary hyperparathyroidism

    DEFF Research Database (Denmark)

    Andersen, NN; Ladefoged, NN

    1991-01-01

    The effect of calcium infusion was studied in patients with renal tubular acidosis (RTA) and secondary hyperparathyroidism. Both developed after jejunoileal bypass operation (JIB) for morbid obesity. In three of four cases the acidification defect was abolished, probably due to a decrease of serum...... parathyroid hormone. As we found RTA in 9% (95% confidence limits 2-21%) of our patients, screening for acidosis is recommended in obesity patients after malabsorptive operations. RTA can be verified through an ammonium loading test. Before deciding on re-establishing bowel continuity due to RTA, we suggest...... and vitamin D supplementation. If RTA can be abolished through correction of calcium homeostasis, reoperation may be avoided. Before deciding on re-establishing bowel continuity in JIB patients with RTA, we therefore suggest that patients be evaluated for secondary hyperparathyroidism and any calcium...

  1. The need for genetic study to diagnose some cases of distal renal tubular acidosis.

    Science.gov (United States)

    Heras Benito, Manuel; Garcia-Gonzalez, Miguel A; Valdenebro Recio, María; Molina Ordás, Álvaro; Callejas Martínez, Ramiro; Rodríguez Gómez, María Astrid; Calle García, Leonardo; Sousa Silva, Lisbeth; Fernández-Reyes Luis, María José

    We describe the case of a young woman who was diagnosed with advanced kidney disease, with an incidental finding of nephrocalcinosis of unknown aetiology, having been found asymptomatic throughout her life. The genetic study by panels of known genes associated with tubulointerstitial disease allowed us to discover autosomal dominant distal renal tubular acidosis associated with a de novo mutation in exon 14 of the SLC4A1 gene, which would have been impossible to diagnose clinically due to the advanced nature of the kidney disease when it was discovered. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  2. Endogenous versus exogenous lithium clearance for evaluation of dopamine-induced changes in renal tubular function

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Fogh-Andersen, N; Strandgaard, S

    1996-01-01

    1. The present randomized, double-blind cross-over study compared endogenous and exogenous lithium clearance (CLi) for estimation of the effect of dopamine on tubular sodium reabsorption. Twelve normal, salt-repleted male subjects were investigated on three different occasions with either placebo...... or 450 mg or 600 mg of lithium given in random order at 22.00 hours. After an overnight fast, renal clearance studies were performed during a 1 h baseline period and subsequently during the second hour of an infusion of 3 micrograms min-1 kg-1 of dopamine. 2. Baseline values of endogenous CLi.......3-31.0)% (P lithium increased the baseline sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5-46.5) ml/min (endogenous lithium, P

  3. A paracrine mechanism involving renal tubular cells, adipocytes and macrophages promotes kidney stone formation in a simulated metabolic syndrome environment.

    Science.gov (United States)

    Zuo, Li; Tozawa, Keiichi; Okada, Atsushi; Yasui, Takahiro; Taguchi, Kazumi; Ito, Yasuhiko; Hirose, Yasuhiko; Fujii, Yasuhiro; Niimi, Kazuhiro; Hamamoto, Shuzo; Ando, Ryosuke; Itoh, Yasunori; Zou, Jiangang; Kohri, Kenjiro

    2014-06-01

    We developed an in vitro system composed of renal tubular cells, adipocytes and macrophages to simulate metabolic syndrome conditions. We investigated the molecular communication mechanism of these cells and their involvement in kidney stone formation. Mouse renal tubular cells (M-1) were cocultured with adipocytes (3T3-L1) and/or macrophages (RAW264.7). Calcium oxalate monohydrate crystals were exposed to M-1 cells after 48-hour coculture and the number of calcium oxalate monohydrate crystals adherent to the cells was quantified. The expression of cocultured medium and M-1 cell inflammatory factors was analyzed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction, respectively. The inflammatory markers MCP-1, OPN and TNF-α were markedly up-regulated in cocultured M-1 cells. OPN expression increased in M-1 cells cocultured with RAW264.7 cells while MCP-1 and TNF-α were over expressed in M-1 cells cocultured with 3T3-L1 cells. Coculturing M-1 cells simultaneously with 3T3-L1 and RAW264.7 cells resulted in a significant increase in calcium oxalate monohydrate crystal adherence to M-1 cells. Inflammatory cytokine changes were induced by coculturing renal tubular cells with adipocytes and/or macrophages without direct contact, indicating that crosstalk between adipocytes/macrophages and renal tubular cells was mediated by soluble factors. The susceptibility to urolithiasis of patients with metabolic syndrome might be due to aggravated inflammation of renal tubular cells triggered by a paracrine mechanism involving these 3 cell types. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  4. CD147/basigin reflects renal dysfunction in patients with acute kidney injury.

    Science.gov (United States)

    Nagaya, Hiroshi; Kosugi, Tomoki; Maeda-Hori, Mayuko; Maeda, Kayaho; Sato, Yuka; Kojima, Hiroshi; Hayashi, Hiroki; Kato, Noritoshi; Ishimoto, Takuji; Sato, Waichi; Yuzawa, Yukio; Matsuo, Seiichi; Kadomatsu, Kenji; Maruyama, Shoichi

    2014-10-01

    Acute tubular necrosis (ATN) describes a form of intrinsic acute kidney injury (AKI) that results from persistent hypoperfusion and subsequent activation of the immune system. A glycosylated transmembrane protein, CD147/basigin, is involved in the pathogenesis of renal ischemia and fibrosis. The present study investigated whether CD147 can reflect pathological features and renal dysfunction in patients with AKI. Plasma and spot urine samples were collected from 24 patients (12 controls and 12 with ATN) who underwent renal biopsy between 2008 and 2012. In another study, patients undergoing open surgery to treat abdominal aortic aneurysms (AAAs) were enrolled in 2004. We collected urine and plasma samples from seven patients with AKI and 33 patients without AKI, respectively. In these experiments, plasma and urinary CD147, and urinary L-fatty acid-binding protein (L-FABP) levels were measured, and the former expression in kidneys was examined by immunostaining. In biopsy tissues of ATN with severe histological features, CD147 induction was strikingly present in inflammatory cells such as macrophages and lymphocytes in the injured interstitium, but not in damaged tubules representing atrophy. Both plasma and urinary CD147 levels were strikingly increased in ATN patients; both values showed greater correlations with renal dysfunction compared to urinary L-FABP. In patients who had undergone open AAA surgery, urinary and plasma CD147 values in AKI patients were significantly higher than in non-AKI patients at post-operative day 1, similar to the profile of urinary L-FABP. CD147 was prominent in its ability to detect AKI and may allow the start of preemptive medication.

  5. Determination of Clara cell protein urinary elimination as a marker of tubular dysfunction.

    Science.gov (United States)

    Martín-Granado, Ascensión; Vázquez-Moncholí, Carmen; Luis-Yanes, María Isabel; López-Méndez, Marisela; García-Nieto, Víctor

    2009-04-01

    Clara cell 16-kDa protein (CC16) is a protein expressed primarily by the bronchial cells. It is rapidly eliminated by glomerular filtration, reabsorbed almost entirely, and catabolized in proximal tubule cells. To date, normal values for urinary CC16 in healthy children have not been determined. We have studied 63 pediatric patients (mean age 8.17 +/- 3.91 years) and 31 healthy children (control group; mean age 8.83 +/- 3.65 years). In the control group, the CC16/creatinine ratio was 1.22 +/- 1.52 microg/g. In 16 out of 31 control children, the value of the ratio was zero. Fourteen patients (22.2%) showed a high CC16/creatinine ratio; in contrast, among these same patients, the ratio N-acetyl-beta-D: -glucosaminidase (NAG)/creatinine was elevated in seven cases (11.1%) and the ratio beta2-microglobulin/creatinine was elevated in seven cases (11.1%). The three parameters were in agreement in 51 patients (80.9%). Among the patients, the CC16/creatinine ratio was correlated with both the beta2-microglobulin/creatinina ratio (r = 0.76, P < 0.001) and the NAG/creatinine ratio (r = 0.6, P < 0.001). Our findings indicate that CC16 is a good marker of proximal tubular function in childhood. The highest observed values were in children with proximal tubulopathies, in children with chronic renal failure, and in those treated with cyclosporine.

  6. Effect of diuretics on renal tubular transport of calcium and magnesium.

    Science.gov (United States)

    Alexander, R Todd; Dimke, Henrik

    2017-06-01

    Calcium (Ca 2+ ) and Magnesium (Mg 2+ ) reabsorption along the renal tubule is dependent on distinct trans- and paracellular pathways. Our understanding of the molecular machinery involved is increasing. Ca 2+ and Mg 2+ reclamation in kidney is dependent on a diverse array of proteins, which are important for both forming divalent cation-permeable pores and channels, but also for generating the necessary driving forces for Ca 2+ and Mg 2+ transport. Alterations in these molecular constituents can have profound effects on tubular Ca 2+ and Mg 2+ handling. Diuretics are used to treat a large range of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na + ) transport, but also indirectly affect renal Ca 2+ and Mg 2+ handling, i.e., by establishing a prerequisite electrochemical gradient. It is therefore not surprising that substantial alterations in divalent cation handling can be observed following diuretic treatment. The effects of diuretics on renal Ca 2+ and Mg 2+ handling are reviewed in the context of the present understanding of basal molecular mechanisms of Ca 2+ and Mg 2+ transport. Acetazolamide, osmotic diuretics, Na + /H + exchanger (NHE3) inhibitors, and antidiabetic Na + /glucose cotransporter type 2 (SGLT) blocking compounds, target the proximal tubule, where paracellular Ca 2+ transport predominates. Loop diuretics and renal outer medullary K + (ROMK) inhibitors block thick ascending limb transport, a segment with significant paracellular Ca 2+ and Mg 2+ transport. Thiazides target the distal convoluted tubule; however, their effect on divalent cation transport is not limited to that segment. Finally, potassium-sparing diuretics, which inhibit electrogenic Na + transport at distal sites, can also affect divalent cation transport. Copyright © 2017 the American Physiological Society.

  7. Complicated pregnancies in inherited distal renal tubular acidosis: importance of acid-base balance.

    Science.gov (United States)

    Seeger, Harald; Salfeld, Peter; Eisel, Rüdiger; Wagner, Carsten A; Mohebbi, Nilufar

    2017-06-01

    Inherited distal renal tubular acidosis (dRTA) is caused by impaired urinary acid excretion resulting in hyperchloremic metabolic acidosis. Although the glomerular filtration rate (GFR) is usually preserved, and hypertension and overt proteinuria are absent, it has to be considered that patients with dRTA also suffer from chronic kidney disease (CKD) with an increased risk for adverse pregnancy-related outcomes. Typical complications of dRTA include severe hypokalemia leading to cardiac arrhythmias and paralysis, nephrolithiasis and nephrocalcinosis. Several physiologic changes occur in normal pregnancy including alterations in acid-base and electrolyte homeostasis as well as in GFR. However, data on pregnancy in women with inherited dRTA are scarce. We report the course of pregnancy in three women with hereditary dRTA. Complications observed were severe metabolic acidosis, profound hypokalemia aggravated by hyperemesis gravidarum, recurrent urinary tract infection (UTI) and ureteric obstruction leading to renal failure. However, the outcome of all five pregnancies (1 pregnancy each for mothers n. 1 and 2; 3 pregnancies for mother n. 3) was excellent due to timely interventions. Our findings highlight the importance of close nephrologic monitoring of women with inherited dRTA during pregnancy. In addition to routine assessment of creatinine and proteinuria, caregivers should especially focus on acid-base status, plasma potassium and urinary tract infections. Patients should be screened for renal obstruction in the case of typical symptoms, UTI or renal failure. Furthermore, genetic identification of the underlying mutation may (a) support early nephrologic referral during pregnancy and a better management of the affected woman, and (b) help to avoid delayed diagnosis and reduce complications in affected newborns.

  8. Recombinant human erythropoietin in humans down-regulates proximal renal tubular reabsorption and causes a fall in glomerular filtration rate

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Aachmann-Andersen, Niels Jacob; Oturai, Peter

    2010-01-01

    HuEPO for 28 days in doses raising the hematocrit to 48.3 (4.1) %. Renal clearance studies with urine collections (N = 8) were done at baseline and at days 4, 11, 29, and 42. Glomerular filtration rate (GFR) was measured by (51)Cr-EDTA. Renal clearance of lithium (C(Li)) was used as an index of proximal...... tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in hematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), r...... and water (APR = GFR - C(Li), P

  9. Linezolid-induced thrombocytopenia in two patients with renal dysfunction

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    Engin Melek

    2016-12-01

    Full Text Available Linezolid is an oxazolidinone antibiotic, active against gram positive bacteria that are resistant to other antibiotics including glycopeptides. Thrombocytopenia is an adverse effect of linezolid. Although various risk factors have been suggested, the mechanisms behind this side effect are largely unknown. Here, we report two adolescents with the diagnosis of chronic kidney disease who developed thrombocytopenia following treatment with linezolid. Our purpose in highlighting these cases is to increase the clinical awareness concerning this side effect of linezolid. While it is well known that thrombocytopenia may develop during linezolid treatment, it is relatively unknown that patients with renal dysfunction have an increased risk for the development of thrombocytopenia compared to patients without renal dysfunction. [Cukurova Med J 2016; 41(4.000: 808-810

  10. Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

    Science.gov (United States)

    Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

    2016-02-01

    Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

  11. Epoetin Delta Reduces Oxidative Stress in Primary Human Renal Tubular Cells

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    Annelies De Beuf

    2010-01-01

    Full Text Available Erythropoietin (EPO exerts (renal tissue protective effects. Since it is unclear whether this is a direct effect of EPO on the kidney or not, we investigated whether EPO is able to protect human renal tubular epithelial cells (hTECs from oxidative stress and if so which pathways are involved. EPO (epoetin delta could protect hTECs against oxidative stress by a dose-dependent inhibition of reactive oxygen species formation. This protective effect is possibly related to the membranous expression of the EPO receptor (EPOR since our data point to the membranous EPOR expression as a prerequisite for this protective effect. Oxidative stress reduction went along with the upregulation of renoprotective genes. Whilst three of these, heme oxygenase-1 (HO-1, aquaporin-1 (AQP-1, and B-cell CLL/lymphoma 2 (Bcl-2 have already been associated with EPO-induced renoprotection, this study for the first time suggests carboxypeptidase M (CPM, dipeptidyl peptidase IV (DPPIV, and cytoglobin (Cygb to play a role in this process.

  12. Ultrastructural study of electron dense deposits in renal tubular basement membrane: prevalence and relationship to epithelial atrophy.

    Science.gov (United States)

    Yong, Jim L C; Killingsworth, Murray C

    2014-08-01

    This study reports the prevalence of immune deposits associated with the proximal and distal tubules in a series of routine renal biopsies received in our department during a single calendar year. From 87 cases, 65 (74%) were found to have glomerular immune deposits by immunofluorescence. Tubular immune deposits were found in 12 cases (18%), 3 of which had no glomerular deposits. By transmission electron microscopy (EM), 58 cases (66%) were found to have deposits of granular or vesicular material associated with the tubular basement membranes (TBM). Finely granular electron dense deposits appeared to correspond to the immune deposits seen by immunofluorescence microscopy (IF) and may be a sensitive marker of immune deposition.

  13. Renal dysfunction prevalence and clinical impact in heart failure

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    Palazzuoli A

    2011-09-01

    Full Text Available Alberto Palazzuoli, Susanna Benincasa, Stefanie Grothgar, Pasquale Di Sipio, Giovanni Paganini, Marco Pellegrini, Ranuccio NutiDepartment of Internal Medicine and Metabolic Diseases, Cardiology Section, Le Scotte Hospital, University of Siena, ItalyAbstract: Chronic kidney disease (CKD is associated with a significant increase in death and cardiovascular mortality. However the exact mechanism by which CKD impairs the cardiovascular outcome is not well established. Some reasons may lie in the association of CKD with several other cardiovascular and noncardiovascular disorders including accelerated systemic atherosclerosis, endothelial dysfunction, increased levels of inflammatory factors, anemic status, bone mineral dysfunction, electrolyte imbalance, and renin–angiotensin–aldosterone system (RAAS activation. Therefore several risk factors such as hypertension, diabetes, lipid disorders, and older age are common in both conditions. In patients affected with heart failure (HF a key role is represented by the neurohormonal activation. This condition causes fluid and sodium retention, peripheral vasoconstriction, as well as increased congestion and cardiac workload. Moreover, HF during the decompensated phases is often associated with a worsening renal function that leads to further RAAS activation, microvascular damage, and intrarenal flow redistribution. In order to clarify the interactions between these factors, several questions need to be answered: the universal definition of “worsening renal function,” the identification of the best laboratory parameters to investigate renal function in terms of sensitivity and specificity, and a better definition of the comorbidities’ role in the determination of the outcome, especially in patients with chronic HF. A clarification of these key points could lead to the individualization of new specific therapeutic targets and to a reduction in mortality and hospitalization in patients with HF and

  14. Osteomalacia complicating renal tubular acidosis in association with Sjogren′s syndrome

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    Zohra El Ati

    2014-01-01

    Full Text Available Renal involvement in Sjogren′s syndrome (SS is not uncommon and may precede other complaints. Tubulointerstitial nephritis is the most common renal disease in SS and may lead to renal tubular acidosis (RTA, which in turn may cause osteomalacia. Nevertheless, osteomalacia rarely occurs as the first manifestation of a renal tubule disorder due to SS. We herewith describe a 43-year-old woman who was admitted to our hospital for weakness, lumbago and inability to walk. X-ray of the long bones showed extensive demineralization of the bones. Laboratory investigations revealed chronic kidney disease with serum creatinine of 2.3 mg/dL and creatinine clearance of 40 mL/min, hypokalemia (3.2 mmol/L, hypophosphatemia (0.4 mmol/L, hypocalcemia (2.14 mmol/L and hyperchloremic metabolic acidosis (chlorine: 114 mmol/L; alkaline reserve: 14 mmol/L. The serum alkaline phosphatase levels were elevated. The serum levels of 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D were low and borderline low, respectively, and the parathyroid hormone level was 70 pg/L. Urinalysis showed inappropriate alkaline urine (urinary PH: 7, glycosuria with normal blood glucose, phosphaturia and uricosuria. These values indicated the presence of both distal and proximal RTA. Our patient reported dryness of the mouth and eyes and Schirmer′s test showed xerophthalmia. An accessory salivary gland biopsy showed changes corresponding to stage IV of Chisholm and Masson score. Kidney biopsy showed diffuse and severe tubulo-interstitial nephritis with dense lymphoplasmocyte infiltrates. Sicca syndrome and renal interstitial infiltrates indicated SS as the underlying cause of the RTA and osteomalacia. The patient received alkalinization, vitamin D (Sterogyl ®, calcium supplements and steroids in an initial dose of 1 mg/kg/day, tapered to 10 mg daily. The prognosis was favorable and the serum creatinine level was 1.7 mg/dL, calcium was 2.2 mmol/L and serum phosphate was 0.9 mmol/L.

  15. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    International Nuclear Information System (INIS)

    Liao, Xiao-hui; Zhang, Ling; Chen, Guo-tao; Yan, Ru-yu; Sun, Hang; Guo, Hui; Liu, Qi

    2014-01-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT

  16. Augmenter of liver regeneration inhibits TGF-β1-induced renal tubular epithelial-to-mesenchymal transition via suppressing TβR II expression in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Xiao-hui [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Zhang, Ling, E-mail: lindazhang8508@hotmail.com [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Chen, Guo-tao; Yan, Ru-yu [Department of Nephrology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Sun, Hang; Guo, Hui [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China); Liu, Qi, E-mail: txzzliuqi@163.com [Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010 (China)

    2014-10-01

    Tubular epithelial-to-mesenchymal transition (EMT) plays a crucial role in the progression of renal tubular interstitial fibrosis (TIF), which subsequently leads to chronic kidney disease (CKD) and eventually, end-stage renal disease (ESRD). We propose that augmenter of liver regeneration (ALR), a member of the newly discovered ALR/Erv1 protein family shown to ameliorate hepatic fibrosis, plays a similar protective role in renal tubular cells and has potential as a new treatment option for CKD. Here, we showed that recombinant human ALR (rhALR) inhibits EMT in renal tubular cells by antagonizing activation of the transforming growth factor-β1 (TGF-β1) signaling pathway. Further investigation revealed that rhALR suppresses the expression of TGF-β receptor type II (TβR II) and significantly alleviates TGF-β1-induced phosphorylation of Smad2 and nuclear factor-κB (NF-κB). No apparent adverse effects were observed upon the addition of rhALR alone to cells. These findings collectively suggest that ALR plays a role in inhibiting progression of renal tubular EMT, supporting its potential utility as an effective antifibrotic strategy to reverse TIF in CKD. - Highlights: • ALR is involved in the pathological progression of renal EMT in NRK-52E cells. • ALR suppresses the expression of TβRII and the phosphorylation of Smad2 and NF-κB. • ALR plays a role in inhibiting progression of renal tubular EMT.

  17. GSTA3 Attenuates Renal Interstitial Fibrosis by Inhibiting TGF-Beta-Induced Tubular Epithelial-Mesenchymal Transition and Fibronectin Expression.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Tubular epithelial-mesenchymal transition (EMT has been widely accepted as the underlying mechanisms of renal interstitial fibrosis (RIF. The production of reactive oxygen species (ROS plays a vital role in tubular EMT process. The purpose of this study was to investigate the involved molecular mechanisms in TGF-beta-induced EMT and identify the potential role of glutathione S-transferase alpha 3 (GSTA3 in this process. The iTRAQ screening was performed to identify protein alterations of the rats underwent unilateral-ureteral obstruction (UUO. Protein expression of GSTA3 in patients with obstructive nephropathy and UUO rats was detected by immunohistochemistry. Protein and mRNA expression of GSTA3 in UUO rats and NRK-52E cells were determined by Western blot and RT-PCR. siRNA and overexpression plasmid were transfected specifically to assess the role of GSTA3 in RIF. The generation of ROS was measured by dichlorofluorescein fluorescence analysis. GSTA3 protein and mRNA expression was significantly reduced in UUO rats. Immunohistochemical analysis revealed that GSTA3 expression was reduced in renal cortex in UUO rats and patients with obstructive nephropathy. Treating with TGF-β1 down-regulated GSTA3 expression in NRK-52E cells, which have been found to be correlated with the decreased expression in E-cadherin and megalin and increased expression in α-smooth muscle actin. Furthermore, knocking down GSTA3 in NRK-52 cells led to increased production of ROS and tubular EMT, whereas overexpressing GSTA3 ameliorated ROS production and prevented the occurrence of tubular EMT. GSTA3 plays a protective role against tubular EMT in renal fibrosis, suggesting GSTA3 is a potential therapeutic target for RIF.

  18. Impact of obesity on development of chronic renal allograft dysfunction

    International Nuclear Information System (INIS)

    Jahromi, Alireza Hamidian; Jalali, Ghanbar Ali Raiss; Roozbeh, Jamshid

    2009-01-01

    Obesity in nontransplant patients has been associated with hypertension, hyperlipidemia, diabetes, and proteinuria. To determine whether renal transplant recipients with an elevated BMI have worse long term graft survival, we prospectively studied 92 patients transplanted between April 1999 and July 2000. Weight (Wt) and height of the patients were recorded prior to transplantation and two weeks, one, two and three years post transplantation. Blood urea nitrogen (BUN), creatinine (Cr) and blood pressure were checked monthly, while triglyceride, cholesterol, high density lipoprotein (HDL), and low density lipoprotein (LDL) were obtained 3 monthly for 3 years post transplantation. Graft dysfunction was defined as serum Cr > 1.8 mg/dL. While BMI and Wt of the patients before transplantation did not show any significant correlation with chronic renal allograft dysfunction (CRAD), patients with higher Wt and BMI two weeks after transplantation showed an increased risk of developing CRAD during the three year post transplant independent of other risk factors (P< 0.05). Patients with greater Wt loss in the first two weeks post transplantation showed a decreased risk of developing CRAD in the following 3 years (P< 0.001). Our study suggests that high Wt and BMI are significantly associated with worse graft survival 3 years post renal transplantation. (author)

  19. Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells.

    Science.gov (United States)

    Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

    2017-01-22

    The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 -/- ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells

    International Nuclear Information System (INIS)

    Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

    2017-01-01

    The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 −/− ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.

  1. In vitro generation of renal tubular epithelial cells from fibroblasts: implications for precision and regenerative medicine in nephrology.

    Science.gov (United States)

    Wyatt, Christina M; Dubois, Nicole

    2017-02-01

    Prior efforts to generate renal epithelial cells in vitro have relied on pluripotent or bone marrow-derived mesenchymal stem cells. A recent publication in Nature Cell Biology describes the generation of induced tubular epithelial cells from fibroblasts, potentially offering a novel platform for personalized drug toxicity screening and in vitro disease modeling. This report serves as a promising proof of principle study and opens future research directions, including the optimization of the reprogramming process, efficient translation to adult human fibroblasts, and the generation of highly specific functional renal cell types. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  2. Cleistanthus collinus induces type I distal renal tubular acidosis and type II respiratory failure in rats.

    Science.gov (United States)

    Maneksh, Delinda; Sidharthan, Anita; Kettimuthu, Kavithapriya; Kanthakumar, Praghalathan; Lourthuraj, Amala A; Ramachandran, Anup; Subramani, Sathya

    2010-06-01

    A water decoction of the poisonous shrub Cleistanthus collinus is used for suicidal purposes. The mortality rate is 28%. The clinical profile includes distal renal tubular acidosis (DRTA) and respiratory failure. The mechanism of toxicity is unclear. To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram and respiratory movements were recorded. Either aqueous extract of C. collinus or control solution was administered intraperitoneally. Serial measurements of blood gases, electrolytes and urinary pH were made. Isolated brush border and basolateral membranes from rat kidney were incubated with C. collinus extract and reduction in ATPase activity was assessed. Venous blood samples from human volunteers and rats were incubated with an acetone extract of C. collinus and plasma potassium was estimated as an assay for sodium-potassium pump activity. The mortality was 100% in tests and 17% in controls. Terminal event in test animals was respiratory arrest. Controls had metabolic acidosis, respiratory compensation acidic urine and hyperkalemia. Test animals showed respiratory acidosis, alkaline urine and low blood potassium as compared to controls. C. collinus extract inhibited ATPase activity in rat kidney. Plasma K(+) did not increase in human blood incubated with C. collinus extract. Active principles of C. collinus inhibit proton pumps in the renal brush border, resulting in type I DRTA in rats. There is no inhibition of sodium-potassium pump activity. Test animals develop respiratory acidosis, and the immediate cause of death is respiratory arrest.

  3. A review of dietary supplement-induced renal dysfunction.

    Science.gov (United States)

    Gabardi, Steven; Munz, Kristin; Ulbricht, Catherine

    2007-07-01

    Complementary and alternative medicine (CAM) is a multibillion-dollar industry. Almost half of the American population uses some form of CAM, with many using them in addition to prescription medications. Most patients fail to inform their health care providers of their CAM use, and physicians rarely inquire. Annually, thousands of dietary supplement-induced adverse events are reported to Poison Control Centers nationwide. CAM manufacturers are not responsible for proving safety and efficacy, because the Food and Drug Administration does not regulate them. However, concern exists surrounding the safety of CAM. A literature search using MEDLINE and EMBASE was undertaken to explore the impact of CAM on renal function. English-language studies and case reports were selected for inclusion but were limited to those that consisted of human subjects, both adult and pediatric. This review provides details on dietary supplements that have been associated with renal dysfunction and focuses on 17 dietary supplements that have been associated with direct renal injury, CAM-induced immune-mediated nephrotoxicity, nephrolithiasis, rhabdomyolysis with acute renal injury, and hepatorenal syndrome. It is concluded that it is imperative that use of dietary supplements be monitored closely in all patients. Health care practitioners must take an active role in identifying patients who are using CAM and provide appropriate patient education.

  4. Amelioration of renal ischaemia-reperfusion injury by liposomal delivery of curcumin to renal tubular epithelial and antigen-presenting cells.

    Science.gov (United States)

    Rogers, N M; Stephenson, M D; Kitching, A R; Horowitz, J D; Coates, P T H

    2012-05-01

    Renal ischaemia-reperfusion (IR) injury is an inevitable consequence of renal transplantation, causing significant graft injury, increasing the risk of rejection and contributing to poor long-term graft outcome. Renal injury is mediated by cytokine and chemokine synthesis, inflammation and oxidative stress resulting from activation of the NF-κB pathway. We utilized liposomal incorporation of a potent inhibitor of the NF-κB pathway, curcumin, to target delivery to renal tubular epithelial and antigen-presenting cells. Liposomes containing curcumin were administered before bilateral renal ischaemia in C57/B6 mice, with subsequent reperfusion. Renal function was assessed from plasma levels of urea and creatinine, 4 and 24 h after reperfusion. Renal tissue was examined for NF-κB activity and oxidative stress (histology, immunostaining) and for apoptosis (TUNEL). Cytokines and chemokines were measured by RT-PCR and Western blotting. Liposomal curcumin significantly improved serum creatinine, reduced histological injury and cellular apoptosis and lowered Toll-like receptor-4, heat shock protein-70 and TNF-α mRNA expression. Liposomal curcumin also reduced neutrophil infiltration and diminished inflammatory chemokine expression. Curcumin liposomes reduced intracellular superoxide generation and increased superoxide dismutase levels, decreased inducible NOS mRNA expression and 3-nitrotyrosine staining consistent with limitations in nitrosative stress and inhibited renal tubular mRNA and protein expression of thioredoxin-interacting protein. These actions of curcumin were mediated by inhibition of NF-κB, MAPK and phospho-S6 ribosomal protein. Liposomal delivery of curcumin promoted effective, targeted delivery of this non-toxic compound that provided cytoprotection via anti-inflammatory and multiple antioxidant mechanisms following renal IR injury. © 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  5. Renal Tubular Acidosis Secondary to FK506 in Living Donor Liver Transplantation: A Case Report

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    Keiko Ogita

    2003-10-01

    Full Text Available FK506 is an immunosuppressant that is thought to be less nephrotoxic than cyclosporine A. However, complications due to renal tubular acidosis (RTA have recently been reported. We report a case of RTA secondary to FK506 administration in liver transplantation. A 6-month-old girl was treated with FK506 after undergoing living donor liver transplantation for fulminant hepatitis. On postoperative day 17, she demonstrated hyperkalaemia and metabolic acidosis; she was diagnosed to have hyperkalaemic distal RTA with aldosterone deficiency (type IV. Intravenous sodium bicarbonate and furosemide, and intrarectal calcium polystyrenesulfonate were administered to correct the acidosis and promote potassium secretion. Thereafter, the FK506 concentration in whole blood gradually decreased, and the hyperkalaemia and metabolic acidosis following RTA improved. RTA is one type of nephrotoxicity induced by FK506, and it is reversible in mild cases when appropriately treated. The mechanism of RTA induced by FK506 has not yet been clearly elucidated. Surgeons and physicians should therefore be aware of the potential for RTA to occur with FK506 after any organ transplantation. The treatment for acidosis and hyperkalaemia should be started as soon as RTA is diagnosed, and the dosage of FK506 should also be reduced if possible.

  6. Ceramide-Induced Apoptosis in Renal Tubular Cells: A Role of Mitochondria and Sphingosine-1-Phoshate

    Science.gov (United States)

    Ueda, Norishi

    2015-01-01

    Ceramide is synthesized upon stimuli, and induces apoptosis in renal tubular cells (RTCs). Sphingosine-1 phosphate (S1P) functions as a survival factor. Thus, the balance of ceramide/S1P determines ceramide-induced apoptosis. Mitochondria play a key role for ceramide-induced apoptosis by altered mitochondrial outer membrane permeability (MOMP). Ceramide enhances oligomerization of pro-apoptotic Bcl-2 family proteins, ceramide channel, and reduces anti-apoptotic Bcl-2 proteins in the MOM. This process alters MOMP, resulting in generation of reactive oxygen species (ROS), cytochrome C release into the cytosol, caspase activation, and apoptosis. Ceramide regulates apoptosis through mitogen-activated protein kinases (MAPKs)-dependent and -independent pathways. Conversely, MAPKs alter ceramide generation by regulating the enzymes involving ceramide metabolism, affecting ceramide-induced apoptosis. Crosstalk between Bcl-2 family proteins, ROS, and many signaling pathways regulates ceramide-induced apoptosis. Growth factors rescue ceramide-induced apoptosis by regulating the enzymes involving ceramide metabolism, S1P, and signaling pathways including MAPKs. This article reviews evidence supporting a role of ceramide for apoptosis and discusses a role of mitochondria, including MOMP, Bcl-2 family proteins, ROS, and signaling pathways, and crosstalk between these factors in the regulation of ceramide-induced apoptosis of RTCs. A balancing role between ceramide and S1P and the strategy for preventing ceramide-induced apoptosis by growth factors are also discussed. PMID:25751724

  7. Involvement of endoplasmic reticulum stress in albuminuria induced inflammasome activation in renal proximal tubular cells.

    Directory of Open Access Journals (Sweden)

    Li Fang

    Full Text Available Albuminuria contributes to the progression of tubulointerstitial fibrosis. Although it has been demonstrated that ongoing albuminuria leads to tubular injury manifested by the overexpression of numerous proinflammatory cytokines, the mechanism remains largely unknown. In this study, we found that the inflammasome activation which has been recognized as one of the cornerstones of intracellular surveillance system was associated with the severity of albuminuria in the renal biopsies specimens. In vitro, bovine serum albumin (BSA could also induce the activation of NLRP3 inflammasome in the cultured kidney epithelial cells (NRK-52E. Since there was a significant overlap of NLRP3 with the ER marker calreticulin, the ER stress provoked by BSA seemed to play a crucial role in the activation of inflammasome. Here, we demonstrated that the chemical chaperone taurine-conjugated ursodeoxycholic acid (TUDCA which was proved to be an enhancer for the adaptive capacity of ER could attenuate the inflammasome activation induced by albuminuria not only in vitro but also in diabetic nephropathy. Taken together, these data suggested that ER stress seemed to play an important role in albuminuria-induced inflammasome activation, elimination of ER stress via TUDCA might hold promise as a novel avenue for preventing inflammasome activation ameliorating kidney epithelial cells injury induced by albuminuria.

  8. Expression of Nestin, Vimentin, and NCAM by Renal Interstitial Cells after Ischemic Tubular Injury

    Directory of Open Access Journals (Sweden)

    David Vansthertem

    2010-01-01

    Full Text Available This work explores the distribution of various markers expressed by interstitial cells in rat kidneys after ischemic injury (35 minutes during regeneration of S3 tubules of outer stripe of outer medulla (OSOM. Groups of experimental animals (n=4 were sacrificed every two hours during the first 24 hours post-ischemia as well as 2, 3, 7, 14 days post-ischemia. The occurrence of lineage markers was analyzed on kidney sections by immunohistochemistry and morphometry during the process of tubular regeneration. In postischemic kidneys, interstitial cell proliferation, assessed by 5-bromo-2′-deoxyuridine (BrdU and Proliferating Cell Nuclear Antigen (PCNA labeling, was prominent in outer medulla and reach a maximum between 24 and 72 hours after reperfusion. This population was characterized by the coexpression of vimentin and nestin. The density of -Neural Cell Adhesion Molecule (NCAM positive interstitial cells increased transiently (18–72 hours in the vicinity of altered tubules. We have also localized a small population of α-Smooth Muscle Actin (SMA-positive cells confined to chronically altered areas and characterized by a small proliferative index. In conclusion, we observed in the postischemic kidney a marked proliferation of interstitial cells that underwent transient phenotypical modifications. These interstitial cells could be implicated in processes leading to renal fibrosis.

  9. Scleroderma Renal Crisis: A Reversible Cause of Left Ventricular Dysfunction.

    Science.gov (United States)

    Martínez-Milla, Juan; Gaebelt, Hans Paul; Sánchez-Pernaute, Olga; Kallmeyer, Andrea; Romero, José; Farré, Jerónimo

    2018-05-02

    We report a case of acute left ventricular dysfunction due to myocarditis, in the setting of a scleroderma renal crisis. The case is particularly intriguing for the favorable outcome of both symptoms and heart function following immunosuppressive therapy. We also highlight the changes observed over time with image techniques as well as in electrocardiograms. Copyright © 2018 Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. Lack of passive transfer of renal tubulointerstitial disease by serum or monoclonal antibody specific for renal tubular antigens in the mouse.

    Science.gov (United States)

    Evans, B D; Dilwith, R L; Balaban, S L; Rudofsky, U H

    1988-01-01

    Mice immunized with rabbit renal basement membranes form autoantibodies to their kidney glomerular and tubular basement membranes (GBM/TBM). Development of renal tubular disease (RTD) consists of deposition of autoantibodies along the GBM/TBM with the inter- and intratubular accumulation of lymphocytes and macrophages and destruction of the TBM. Transfer of this disease in mice with either serum or monoclonal antibodies, however, has been difficult to demonstrate and, therefore, attempts were made to confirm a report that RTD is passively transferred by anti-TBM autoantibodies. Using the revised protocol in this later report, we found that 12 weeks after transfer autoantibodies were deposited along the GBM and/or TBM of the recipients, yet RTD was not observed. Although qualitative and quantitative characteristics of the antibody may play a role in the pathogenesis in the murine model of RTD, we could not obtain evidence to support and confirm this study.

  11. Renal dysfunction induced by long-term exposure to depleted uranium in rats

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Guoying; Xiang, Xiqiao; Chen, Xiao; Wang, Lihua; Hu, Heping; Weng, Shifang [Fudan University, Institute of Radiation Medicine, Shanghai (China)

    2009-01-15

    Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in

  12. Renal dysfunction induced by long-term exposure to depleted uranium in rats

    International Nuclear Information System (INIS)

    Zhu, Guoying; Xiang, Xiqiao; Chen, Xiao; Wang, Lihua; Hu, Heping; Weng, Shifang

    2009-01-01

    Depleted uranium (DU) is a kind of radioactive heavy metal which can enter into the body via inhalation (aerosols), ingestion (drinking and eating) and wounds (embedded), and causes chemical and/or radiation-induced toxicities. In this study, male Sprague Dawley rats were surgically implanted in gastrocnemius muscle with DU fragments at three dose levels (low-dose, medium-dose and high-dose), with biologically inert tantalum (Ta) fragments served as controls. At 1 day, 7 days, and 3, 6, and 12 months after implantation, the rats were euthanized and tissue samples were collected, and uranium levels were measured in a variety of tissues by inductively coupled plasma-mass spectrometry (ICP-MS) to analyze the dynamic changes and distribution of uranium in rats. Thereafter, at 3, 6 and 12 months after implantation, the rats were euthanized after the collection of 24 h urine, blood and kidney samples were collected for analysis of DU-induced renal histopathologic changes and renal dysfunction. It was observed that DU concentrations in all the DU implanted groups were higher than that in Ta control group, and DU concentrations in the kidney increased with the implanted times, peaked at the 90 days after implantation, with a high correlation to the implanted DU doses, and then began to decrease gradually and slowly, and the DU concentrations in kidney still maintained at a relatively high level even at the 360 days after implantation. Otherwise, chronic DU contamination could induce the pathological changes of renal glomeruli, tubules and mesenchyme, such as interstitial fibrosis, enlarged interstice of renal tubular epithelial cells, tumefactions and necrosis of epithelial cells, shrinkage and disappearance of cavity of Bowman's capsule. By TEM, it was shown that the basement membrane of glomerulus was incrassated, mitochondrial of kidney proximal tubule had visible tumefaction and became bigger, and the mitochondrial cristae became shorter and disorderly in alignment

  13. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

    Science.gov (United States)

    Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

    2015-01-01

    ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

  14. Ex vivo hyperpolarized MR spectroscopy on isolated renal tubular cells: A novel technique for cell energy phenotyping.

    Science.gov (United States)

    Juul, Troels; Palm, Fredrik; Nielsen, Per Mose; Bertelsen, Lotte Bonde; Laustsen, Christoffer

    2017-08-01

    It has been demonstrated that hyperpolarized 13 C MR is a useful tool to study cultured cells. However, cells in culture can alter phenotype, which raises concerns regarding the in vivo significance of such findings. Here we investigate if metabolic phenotyping using hyperpolarized 13 C MR is suitable for cells isolated from kidney tissue, without prior cell culture. Isolation of tubular cells from freshly excised kidney tissue and treatment with either ouabain or antimycin A was investigated with hyperpolarized MR spectroscopy on a 9.4 Tesla preclinical imaging system. Isolation of tubular cells from less than 2 g of kidney tissue generally resulted in more than 10 million live tubular cells. This amount of cells was enough to yield robust signals from the conversion of 13 C-pyruvate to lactate, bicarbonate and alanine, demonstrating that metabolic flux by means of both anaerobic and aerobic pathways can be quantified using this technique. Ex vivo metabolic phenotyping using hyperpolarized 13 C MR in a preclinical system is a useful technique to study energy metabolism in freshly isolated renal tubular cells. This technique has the potential to advance our understanding of both normal cell physiology as well as pathological processes contributing to kidney disease. Magn Reson Med 78:457-461, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

  15. Sirt1 protects against oxidative stress-induced renal tubular cell apoptosis by the bidirectional regulation of catalase expression

    International Nuclear Information System (INIS)

    Hasegawa, Kazuhiro; Wakino, Shu; Yoshioka, Kyoko; Tatematsu, Satoru; Hara, Yoshikazu; Minakuchi, Hitoshi; Washida, Naoki; Tokuyama, Hirobumi; Hayashi, Koichi; Itoh, Hiroshi

    2008-01-01

    NAD + -dependent protein deacetylase Sirt1 regulates cellular apoptosis. We examined the role of Sirt1 in renal tubular cell apoptosis by using HK-2 cells, proximal tubular cell lines with or without reactive oxygen species (ROS), H 2 O 2 . Without any ROS, Sirt1 inhibitors enhanced apoptosis and the expression of ROS scavenger, catalase, and Sirt1 overexpression downregulated catalase. When apoptosis was induced with H 2 O 2 , Sirt1 was upregulated with the concomitant increase in catalase expression. Sirt1 overexpression rescued H 2 O 2 -induced apoptosis through the upregulation of catalase. H 2 O 2 induced the nuclear accumulation of forkhead transcription factor, FoxO3a and the gene silencing of FoxO3a enhanced H 2 O 2 -induced apoptosis. In conclusion, endogenous Sirt1 maintains cell survival by regulating catalase expression and by preventing the depletion of ROS required for cell survival. In contrast, excess ROS upregulates Sirt1, which activates FoxO3a and catalase leading to rescuing apoptosis. Thus, Sirt1 constitutes a determinant of renal tubular cell apoptosis by regulating cellular ROS levels

  16. THE FAILURE OF CHLOROFORM ADMINISTERED IN THE DRINKING WATER TO INDUCE RENAL TUBULAR CELL NEOPLASIA IN MALE F344/N RATS

    Science.gov (United States)

    The failure of chloroform administered in drinking water to induce renal tubular cell neoplasia in male F344/N rats Chloroform (TCM) has been demonstrated to be a renal carcinogen in the male Osborne-Mendel rat when administered either by corn oil gavage or in drin...

  17. The entire miR-200 seed family is strongly deregulated in clear cell renal cell cancer compared to the proximal tubular epithelial cells of the kidney

    NARCIS (Netherlands)

    Duns, Gerben; van den Berg, Anke; van Dijk, Marcory C. R. F.; van Duivenbode, Inge; Giezen, Cor; Kluiver, Joost; van Goor, Harry; Hofstra, Robert M. W.; van den Berg, Eva; Kok, Klaas

    Despite numerous studies reporting deregulated microRNA (miRNA) and gene expression patterns in clear cell renal cell carcinoma (ccRCC), no direct comparisons have been made to its presumed normal counterpart: the renal proximal tubular epithelial cells (PTECs). The aim of this study was to

  18. Renal tubular NHE3 is required in the maintenance of water and sodium chloride homeostasis.

    Science.gov (United States)

    Fenton, Robert A; Poulsen, Søren B; de la Mora Chavez, Samantha; Soleimani, Manoocher; Dominguez Rieg, Jessica A; Rieg, Timo

    2017-08-01

    The sodium/proton exchanger isoform 3 (NHE3) is expressed in the intestine and the kidney, where it facilitates sodium (re)absorption and proton secretion. The importance of NHE3 in the kidney for sodium chloride homeostasis, relative to the intestine, is unknown. Constitutive tubule-specific NHE3 knockout mice (NHE3 loxloxCre) did not show significant differences compared to control mice in body weight, blood pH or bicarbonate and plasma sodium, potassium, or aldosterone levels. Fluid intake, urinary flow rate, urinary sodium/creatinine, and pH were significantly elevated in NHE3 loxloxCre mice, while urine osmolality and GFR were significantly lower. Water deprivation revealed a small urinary concentrating defect in NHE3 loxloxCre mice on a control diet, exaggerated on low sodium chloride. Ten days of low or high sodium chloride diet did not affect plasma sodium in control mice; however, NHE3 loxloxCre mice were susceptible to low sodium chloride (about -4 mM) or high sodium chloride intake (about +2 mM) versus baseline, effects without differences in plasma aldosterone between groups. Blood pressure was significantly lower in NHE3 loxloxCre mice and was sodium chloride sensitive. In control mice, the expression of the sodium/phosphate co-transporter Npt2c was sodium chloride sensitive. However, lack of tubular NHE3 blunted Npt2c expression. Alterations in the abundances of sodium/chloride cotransporter and its phosphorylation at threonine 58 as well as the abundances of the α-subunit of the epithelial sodium channel, and its cleaved form, were also apparent in NHE3 loxloxCre mice. Thus, renal NHE3 is required to maintain blood pressure and steady-state plasma sodium levels when dietary sodium chloride intake is modified. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  19. Distal renal tubular acidosis as a cause of osteomalacia in a patient with primary Sjögren's syndrome

    Directory of Open Access Journals (Sweden)

    Jovelić Aleksandra

    2005-01-01

    Full Text Available Background. One half of the patients with primary Sjögren’s syndrome has extraglandular manifestations, including renal involvement. The most frequent renal lesion is tubulo-interstitial nephritis, which manifests clinically as distal tubular acidosis and may result in the development of osteomalacia. Case report. In a 29 - year-old female patient, with bilateral nephrolithiasis, the diagnosis of primary Sjögren’s syndrome, tubulo-interstitial nephritis, distal renal tubular acidosis, and hypokalemia were established. She was treated for hypokalemia. Two years later she developed bone pains and muscle weakness, she wasn’t able to walk, her proximal muscles and pelvic bones were painful, with radiological signs of pelvic bones osteopenia and pubic bones fractures. The diagnosis of osteomalacia was established and the treatment started with Schol’s solution, vitamin D and calcium. In the following two months, acidosis was corrected, and the patient started walking. Conclusion. In our patient with primary Sjögren’s syndrome and interstitial nephritis, osteomalacia was a result of the long time decompensate acidosis, so the correction of acidosis, and the supplementation of vitamin D and calcium were the integral part of the therapy.

  20. Dysfunction of the Lower Urinary Tract in Renal Transplant Children with Nephrological Disease

    NARCIS (Netherlands)

    Weide, M.J.A. van der; Cornelissen, E.A.M.; Achterberg, T. van; Smits, J.P.J.M.; Feitz, W.F.J.

    2006-01-01

    - OBJECTIVES: To investigate the relationship between dysfunction of the lower urinary tract after renal transplantation and renal transplant function in children with an underlying nephrologic disease. - METHODS: The research group consisted of 21 renal transplant children (12 girls and 9 boys,

  1. Early Allograft Dysfunction Is Associated With Higher Risk of Renal Nonrecovery After Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Hani M. Wadei, MD

    2018-04-01

    Full Text Available Abstract. Early allograft dysfunction (EAD identifies allografts with marginal function soon after liver transplantation (LT and is associated with poor LT outcomes. The impact of EAD on post-LT renal recovery, however, has not been studied. Data on 69 primary LT recipients (41 with and 28 without history of renal dysfunction who received renal replacement therapy (RRT for a median (range of 9 (13-41 days before LT were retrospectively analyzed. Primary outcome was renal nonrecovery defined as RRT requirement 30 days from LT. Early allograft dysfunction developed in 21 (30% patients, and 22 (32% patients did not recover renal function. Early allograft dysfunction was more common in the renal nonrecovery group (50% vs 21%, P = 0.016. Multivariate logistic regression analysis demonstrated that EAD (odds ratio, 7.25; 95% confidence interval, 2.0-25.8; P = 0.002 and baseline serum creatinine (odds ratio, 3.37; 95% confidence interval, 1.4-8.1; P = 0.007 were independently associated with renal nonrecovery. History of renal dysfunction, duration of renal dysfunction, and duration of RRT were not related to renal recovery (P > 0.2 for all. Patients who had EAD and renal nonrecovery had the worst 1-, 3-, and 5-year patient survival, whereas those without EAD and recovered renal function had the best outcomes (P < 0.001. Post-LT EAD was independently associated with renal nonrecovery in LT recipients on RRT for a short duration before LT. Furthermore, EAD in the setting of renal nonrecovery resulted in the worst long-term survival. Measures to prevent EAD should be undertaken in LT recipients on RRT at time of LT.

  2. Failure to thrive and nephrocalcinosis due to distal renal tubular acidosis: A rare presentation of pediatric lupus nephritis.

    Science.gov (United States)

    Nandi, Madhumita; Das, Mrinal Kanti; Nandi, Sukanta

    2016-01-01

    A 9-year-old female child was initially diagnosed of having nephrocalcinosis with distal renal tubular acidosis (dRTA) while investigating for short stature. She later on developed features of nephrotic syndrome (NS) while on treatment for RTA. Investigation for the cause of NS revealed very strong serological evidence in favor of systemic lupus erythematosus (SLE). Histopathological confirmation could not be done due to bilateral severely contracted kidneys. There are a few case reports of dRTA as the presentation of SLE, but nephrocalcinosis with dRTA with subsequent manifestation of SLE has hitherto not been reported in literature.

  3. Novel insights on the relationship between T-tubular defects and contractile dysfunction in a mouse model of hypertrophic cardiomyopathy.

    Science.gov (United States)

    Crocini, C; Ferrantini, C; Scardigli, M; Coppini, R; Mazzoni, L; Lazzeri, E; Pioner, J M; Scellini, B; Guo, A; Song, L S; Yan, P; Loew, L M; Tardiff, J; Tesi, C; Vanzi, F; Cerbai, E; Pavone, F S; Sacconi, L; Poggesi, C

    2016-02-01

    Abnormalities of cardiomyocyte Ca(2+) homeostasis and excitation-contraction (E-C) coupling are early events in the pathogenesis of hypertrophic cardiomyopathy (HCM) and concomitant determinants of the diastolic dysfunction and arrhythmias typical of the disease. T-tubule remodelling has been reported to occur in HCM but little is known about its role in the E-C coupling alterations of HCM. Here, the role of T-tubule remodelling in the electro-mechanical dysfunction associated to HCM is investigated in the Δ160E cTnT mouse model that expresses a clinically-relevant HCM mutation. Contractile function of intact ventricular trabeculae is assessed in Δ160E mice and wild-type siblings. As compared with wild-type, Δ160E trabeculae show prolonged kinetics of force development and relaxation, blunted force-frequency response with reduced active tension at high stimulation frequency, and increased occurrence of spontaneous contractions. Consistently, prolonged Ca(2+) transient in terms of rise and duration are also observed in Δ160E trabeculae and isolated cardiomyocytes. Confocal imaging in cells isolated from Δ160E mice reveals significant, though modest, remodelling of T-tubular architecture. A two-photon random access microscope is employed to dissect the spatio-temporal relationship between T-tubular electrical activity and local Ca(2+) release in isolated cardiomyocytes. In Δ160E cardiomyocytes, a significant number of T-tubules (>20%) fails to propagate action potentials, with consequent delay of local Ca(2+) release. At variance with wild-type, we also observe significantly increased variability of local Ca(2+) transient rise as well as higher Ca(2+)-spark frequency. Although T-tubule structural remodelling in Δ160E myocytes is modest, T-tubule functional defects determine non-homogeneous Ca(2+) release and delayed myofilament activation that significantly contribute to mechanical dysfunction. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All

  4. Evaluation of the potential interaction between tofacitinib and drugs that undergo renal tubular secretion using metformin, an in vivo marker of renal organic cation transporter 2.

    Science.gov (United States)

    Klamerus, Karen J; Alvey, Christine; Li, Lei; Feng, Bo; Wang, Rong; Kaplan, Irina; Shi, Haihong; Dowty, Martin E; Krishnaswami, Sriram

    2014-11-01

    Tofacitinib is a novel, oral Janus kinase inhibitor. The potential for drug-drug interactions (DDIs) between tofacitinib and drugs that undergo renal tubular secretion was evaluated using metformin as a probe transporter substrate, and genotyping for organic cation transporter (OCT) 1, OCT2 and multidrug and toxin extrusion 1 polymorphisms. Twenty-four healthy male subjects completed this open-label, fixed-sequence study. Subjects were administered a single oral metformin 500 mg dose on Days 1 and 4, and multiple oral tofacitinib 30 mg twice daily doses on Days 2, 3, and 4. Subjects underwent serial blood and urine samplings (Days 1 and 4) to estimate metformin pharmacokinetics. A single blood sample for tofacitinib was collected 2 hours after the morning dose (Day 4). The 90% confidence intervals for the ratios of maximum plasma concentration, area under the curve and renal clearance of metformin, with and without tofacitinib, were contained within the 80-125% acceptance range commonly used to establish a lack of DDI. No deaths, serious adverse events (AEs), severe AEs or discontinuations due to AEs were reported. The study confirms tofacitinib is unlikely to impact the pharmacokinetics of drugs that undergo renal tubular secretion, and concurs with its weak in vitro OCT2 inhibitory profile. © 2014, The American College of Clinical Pharmacology.

  5. The effects of cimetidine on creatinine excretion, glomerular filtration rate and tubular function in renal transplant recipients

    DEFF Research Database (Denmark)

    Olsen, N V; Ladefoged, S D; Feldt-Rasmussen, B

    1989-01-01

    The renal clearance of endogenous creatinine (CCr), sodium (CNa) and lithium (CLi) was determined before and after a single intravenous bolus of cimetidine in nine renal transplant recipients. The glomerular filtration rate (GFR) was measured with 125I-iothalamate clearance (CTh). The initial CCr...... of 65 ml/min (median) was reduced to a nadir of 46 ml/min (p less than 0.01) during the first 2 h after infusion of cimetidine. GFR remained unchanged, and thus the fractional clearance of creatinine (CCr/CTh) was reduced from 1.43 (median) to 1.03 (p less than 0.01). CNa and the fractional excretion...... of sodium decreased throughout the study (p less than 0.05); CLi was unchanged. In conclusion cimetidine, when measured during 1-h clearance periods, interferes with tubular creatinine secretion in the denervated kidney of transplant recipients without affecting the glomerular filtration rate or proximal...

  6. Specific estrogen-induced cell proliferation of cultured Syrian hamster renal proximal tubular cells in serum-free chemically defined media

    International Nuclear Information System (INIS)

    Oberley, T.D.; Lauchner, L.J.; Pugh, T.D.; Gonzalez, A.; Goldfarb, S.; Li, S.A.; Li, J.J.

    1989-01-01

    It has long been recognized that the renal proximal tubular epithelium of the hamster is a bona fide estrogen target tissue. The effect of estrogens on the growth of proximal tubule cell explants and dissociated single cells derived from these explant outgrowths has been studied in culture. Renal tubular cells were grown on a PF-HR-9 basement membrane under serum-free chemically defined culture conditions. At 7-14 days in culture, cell number was enhanced 3-fold in the presence of either 17β-estradiol or diethylstilbestrol. A similar 3-fold increase in cell number was also seen at 1 nM 17β-estradiol in subcultured dissociated single tubular cells derived from hamster renal tubular explant outgrowths at 21 days in culture. Concomitant exposure of tamoxifen at 3-fold molar excess in culture completely abolished the increase in cell number seen with 17β-estradiol. The proliferation effect of estrogens on proximal tubular cell growth appears to be species specific since 17β-estradiol did not alter the growth of either rat or guinea pig proximal tubules in culture. In addition, at 7-10 days in culture in the presence of 17β-estradiol, [ 3 H]thymidine labeling of hamster tubular cells was enhanced 3-fold. These results clearly indicate that estrogens can directly induce primary epithelial cell proliferation at physiologic concentrations and provide strong additional evidence for an important hormonal role in the neoplastic transformation of the hamster kidney

  7. Benazepril slows progression of renal dysfunction in patients with non-diabetic renal disease.

    Science.gov (United States)

    Ishimitsu, Toshihiko; Akashiba, Akira; Kameda, Tomoko; Takahashi, Toshiaki; Ohta, Satoshi; Yoshii, Masayoshi; Minami, Junichi; Ono, Hidehiko; Numabe, Atsushi; Matsuoka, Hiroaki

    2007-06-01

    The present study examined the effects of benazepril, an angiotensin-converting enzyme inhibitor, on the progression of renal insufficiency in patients with non-diabetic renal disease. Fifteen patients with non-diabetic renal disease whose serum creatinine (Cr) ranged from 1.5 to 3.0 mg/dL were given either benazepril (2.5-5 mg) or placebo once daily for 1 year in a random crossover manner. In both periods, antihypertensive medications were increased if blood pressure was greater than 130/85 mmHg. Blood sampling and urinalysis were performed bimonthly throughout the study period. Blood pressure was similar when comparing the benazepril and the placebo periods (128+/-12/83+/-6 vs 129+/-10/83+/-7 mmHg). Serum Cr significantly increased from 1.62+/-0.18 to 1.72+/-0.30 mg/dL (P=0.036) during the placebo period, while there was no statistically significant increase in serum Cr during the benazepril period (from 1.67+/-0.17 to 1.71+/-0.27 mg/dL). The slope of decrease of the reciprocal of serum Cr was steeper in the placebo period than in the benazepril period (-0.073+/-0.067 vs-0.025+/-0.096/year, P=0.014). Urinary protein excretion was lower during the benazepril period than during the placebo period (0.57+/-0.60 vs 1.00+/-0.85 g/gCr, P=0.006). Serum K was significantly higher in the benazepril period than in the placebo period (4.4+/-0.5 vs 4.2+/-0.5 mEq/L, Pbenazepril therapy as a result of hyperkalemia. Long-term benazepril treatment decreased the progression of renal dysfunction in patients with non-diabetic renal disease by a mechanism that is independent of blood pressure reduction.

  8. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Thomale, Jürgen [Institute of Cell Biology, University Duisburg-Essen, 45122 Essen (Germany); Schupp, Nicole [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany); Fritz, Gerhard, E-mail: fritz@uni-duesseldorf.de [Institute of Toxicology, Medical Faculty, Heinrich Heine University Düsseldorf, 40225 Düsseldorf (Germany)

    2016-02-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  9. Lovastatin prevents cisplatin-induced activation of pro-apoptotic DNA damage response (DDR) of renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Krüger, Katharina; Ziegler, Verena; Hartmann, Christina; Henninger, Christian; Thomale, Jürgen; Schupp, Nicole; Fritz, Gerhard

    2016-01-01

    The platinating agent cisplatin (CisPt) is commonly used in the therapy of various types of solid tumors. The anticancer efficacy of CisPt largely depends on the formation of bivalent DNA intrastrand crosslinks, which stimulate mechanisms of the DNA damage response (DDR), thereby triggering checkpoint activation, gene expression and cell death. The clinically most relevant adverse effect associated with CisPt treatment is nephrotoxicity that results from damage to renal tubular epithelial cells. Here, we addressed the question whether the HMG-CoA-reductase inhibitor lovastatin affects the DDR of renal cells by employing rat renal proximal tubular epithelial (NRK-52E) cells as in vitro model. The data show that lovastatin has extensive inhibitory effects on CisPt-stimulated DDR of NRK-52E cells as reflected on the levels of phosphorylated ATM, Chk1, Chk2, p53 and Kap1. Mitigation of CisPt-induced DDR by lovastatin was independent of the formation of DNA damage as demonstrated by (i) the analysis of Pt-(GpG) intrastrand crosslink formation by Southwestern blot analyses and (ii) the generation of DNA strand breaks as analyzed on the level of nuclear γH2AX foci and employing the alkaline comet assay. Lovastatin protected NRK-52E cells from the cytotoxicity of high CisPt doses as shown by measuring cell viability, cellular impedance and flow cytometry-based analyses of cell death. Importantly, the statin also reduced the level of kidney DNA damage and apoptosis triggered by CisPt treatment of mice. The data show that the lipid-lowering drug lovastatin extensively counteracts pro-apoptotic signal mechanisms of the DDR of tubular epithelial cells following CisPt injury. - Highlights: • Lovastatin blocks ATM/ATR-regulated DDR of tubular cells following CisPt treatment. • Lovastatin attenuates CisPt-induced activation of protein kinase ATM in vitro. • Statin-mediated DDR inhibition is independent of initial DNA damage formation. • Statin-mediated blockage of Cis

  10. Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

    2010-01-01

    Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (·O 2 ), nitric oxide (NO·), and peroxynitrite (ONOO - ), as well as nuclear factor-kappa B (NF-κB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, ·O 2 , NO·, ONOO - , the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-κB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation.

  11. Current strategies for preventing renal dysfunction in patients with heart failure: a heart failure stage approach

    Science.gov (United States)

    Issa, Victor Sarli; Andrade, Lúcia; Bocchi, Edimar Alcides

    2013-01-01

    Renal dysfunction is common during episodes of acute decompensated heart failure, and historical data indicate that the mean creatinine level at admission has risen in recent decades. Different mechanisms underlying this change over time have been proposed, such as demographic changes, hemodynamic and neurohumoral derangements and medical interventions. In this setting, various strategies have been proposed for the prevention of renal dysfunction with heterogeneous results. In the present article, we review and discuss the main aspects of renal dysfunction prevention according to the different stages of heart failure. PMID:23644863

  12. TWEAK activates the non-canonical NFkappaB pathway in murine renal tubular cells: modulation of CCL21.

    Directory of Open Access Journals (Sweden)

    Ana B Sanz

    2010-01-01

    Full Text Available TWEAK is a member of the TNF superfamily of cytokines that contribute to kidney tubulointerstitial injury. It has previously been reported that TWEAK induces transient nuclear translocation of RelA and expression of RelA-dependent cytokines in renal tubular cells. Additionally, TWEAK induced long-lasting NFkappaB activation suggestive of engagement of the non-canonical NFkappaB pathway. We now explore TWEAK-induced activation of NFkappaB2 and RelB, as well as expression of CCL21, a T-cell chemotactic factor, in cultured murine tubular epithelial cells and in healthy kidneys in vivo. In cultured tubular cells, TWEAK and TNFalpha activated different DNA-binding NFkappaB complexes. TWEAK-induced sustained NFkappaB activation was associated with NFkappaB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFalpha used as control, induced a delayed increase in CCL21a mRNA (3.5+/-1.22-fold over control and CCL21 protein (2.5+/-0.8-fold over control, which was prevented by inhibition of the proteasome, or siRNA targeting of NIK or RelB, but not by RelA inhibition with parthenolide. A second NFkappaB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFalpha. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h. In vivo, TWEAK induced nuclear NFkappaB2 and RelB translocation and CCL21a mRNA (1.5+/-0.3-fold over control and CCL21 protein (1.6+/-0.5-fold over control expression in normal kidney. Increased tubular nuclear RelB and tubular CCL21 expression in acute kidney injury were decreased by neutralization (2+/-0.9 vs 1.3+/-0.6-fold over healthy control or deficiency of TWEAK (2+/-0.9 vs 0.8+/-0.6-fold over healthy control. Moreover, anti-TWEAK treatment prevented the recruitment of T cells to the kidney in this model (4.1+/-1.4 vs 1.8+/-1-fold over healthy control. Our results thus identify TWEAK as a regulator of non-canonical NFkappa

  13. Dragon (Repulsive Guidance Molecule RGMb) Inhibits E-cadherin Expression and Induces Apoptosis in Renal Tubular Epithelial Cells*

    Science.gov (United States)

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y.; Xia, Yin

    2013-01-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45–66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo. PMID:24052264

  14. Dragon (repulsive guidance molecule RGMb) inhibits E-cadherin expression and induces apoptosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Wenjing; Li, Xiaoling; Zhao, Yueshui; Meng, Xiao-Ming; Wan, Chao; Yang, Baoxue; Lan, Hui-Yao; Lin, Herbert Y; Xia, Yin

    2013-11-01

    Dragon is one of the three members of the repulsive guidance molecule (RGM) family, i.e. RGMa, RGMb (Dragon), and RGMc (hemojuvelin). We previously identified the RGM members as bone morphogenetic protein (BMP) co-receptors that enhance BMP signaling. Our previous studies found that Dragon is highly expressed in the tubular epithelial cells of mouse kidneys. However, the roles of Dragon in renal epithelial cells are yet to be defined. We now show that overexpression of Dragon increased cell death induced by hypoxia in association with increased cleaved poly(ADP-ribose) polymerase and cleaved caspase-3 levels in mouse inner medullary collecting duct (IMCD3) cells. Dragon also inhibited E-cadherin expression but did not affect epithelial-to-mesenchymal transition induced by TGF-β in IMCD3 cells. Previous studies suggest that the three RGM members can function as ligands for the receptor neogenin. Interestingly, our present study demonstrates that the Dragon actions on apoptosis and E-cadherin expression in IMCD3 cells were mediated by the neogenin receptor but not through the BMP pathway. Dragon expression in the kidney was up-regulated by unilateral ureteral obstruction in mice. Compared with wild-type mice, heterozygous Dragon knock-out mice exhibited 45-66% reduction in Dragon mRNA expression, decreased epithelial apoptosis, and increased tubular E-cadherin expression and had attenuated tubular injury after unilateral ureteral obstruction. Our results suggest that Dragon may impair tubular epithelial integrity and induce epithelial apoptosis both in vitro and in vivo.

  15. EPIDEMIOLOGY AND ETIOLOGICAL FACTORS OF ERECTILE DYSFUNCTION IN PATIENTS ON DIALYSIS AND AFTER RENAL TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    E. A. Efremov

    2011-01-01

    Full Text Available Today the problem of better life quality of patients with end stage renal disease and after renal transplantation and their sexual adaptation is considered to be more impotent. The clinical part of the investigation is the obser- vation of 205 patients – men with terminal stage renal disease. Erectile dysfunction is represented in 91,4% (64 of patients getting haemodialysis, 92,3% (24 of patients getting peritoneal dialysis, 61,5% (67 of patients after renal transplantation. According to International Index of Erectile Function the mean score of erectile function is 16,7 ± 5,2 in haemodialysis patients, 19,46 ± 3,6 in peritoneal dialysis patients, 21,9 ± 5,6 in patients after renal transplantation. The analysis revealed great prevalence of erectile dysfunction and interest in improvement among the patients with end stage renal disease and after renal transplantation. 

  16. Circulating Markers of Endothelial Dysfunction Interact With Proteinuria in Predicting Mortality in Renal Transplant Recipients

    NARCIS (Netherlands)

    van Ree, Rutger M.; Oterdoom, Leendert H.; de Vries, Aiko P.J.; Homan van der Heide, Jaap J.; van Son, Willem J.; Navis, Gerjan; Gans, Reinold O.B.; Bakker, Stephan J L

    2008-01-01

    BACKGROUND: Proteinuria is associated with endothelial dysfunction (ED) and increased mortality. We investigated whether urinary protein excretion (UPE) is correlated with markers of ED and whether these markers affect the association of proteinuria with mortality in renal transplant recipients

  17. Circulating markers of endothelial dysfunction interact with proteinuria in predicting mortality in renal transplant recipients

    NARCIS (Netherlands)

    van Ree, Rutger M.; Oterdoom, Leendert H.; de Vries, Aiko P. J.; Homan van der Heide, Jaap J.; van Son, Willem J.; Navis, Gerjan; Gans, Reinold O. B.; Bakker, Stephan J. L.

    2008-01-01

    Proteinuria is associated with endothelial dysfunction (ED) and increased mortality. We investigated whether urinary protein excretion (UPE) is correlated with markers of ED and whether these markers affect the association of proteinuria with mortality in renal transplant recipients (RTR). Six

  18. The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine; Rossing, Kasper; Hess, Georg

    2012-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid......-binding protein (LFABP)....

  19. High risk of renal dysfunction in patients with fulminant type 1 diabetes

    OpenAIRE

    Takahashi, Nobuyuki; Tsujimoto, Tetsuro; Chujo, Daisuke; Kajio, Hiroshi

    2017-01-01

    Abstract Aims/Introduction To compare the incidence rate of renal dysfunction between patients with fulminant type 1 diabetes and those with acute‐onset type 1 diabetes. Materials and Methods The present retrospective cohort study included patients with fulminant type 1 diabetes and acute‐onset type 1 diabetes diagnosed during April 1993 to March 2016 at a national center in Japan. Glycated hemoglobin levels, incidence rates of renal dysfunction defined as an estimated glomerular filtration r...

  20. Long-Term Outcomes of Renal Transplant in Recipients With Lower Urinary Tract Dysfunction.

    Science.gov (United States)

    Wilson, Rebekah S; Courtney, Aisling E; Ko, Dicken S C; Maxwell, Alexander P; McDaid, James

    2018-01-02

    Lower urinary tract dysfunction can lead to chronic kidney disease, which, despite surgical intervention, will progress to end-stage renal disease, requiring dialysis. Urologic pathology may damage a transplanted kidney, limiting patient and graft survival. Although smaller studies have suggested that urinary tract dysfunction does not affect graft or patient survival, this is not universally accepted. Northern Ireland has historically had the highest incidence of neural tube defects in Europe, giving rich local experience in caring for patients with lower urinary tract dysfunction. Here, we analyzed outcomes of renal transplant recipients with lower urinary tract dysfunction versus control recipients. We identified 3 groups of kidney transplant recipients treated between 2001 and 2010; those in group 1 had end-stage renal disease due to lower urinary tract dysfunction with prior intervention (urologic surgery, long-term catheter, or intermittent self-catheterization), group 2 had end-stage renal disease secondary to lower urinary tract dysfunction without intervention, and group 3 had end-stage renal disease due to polycystic kidney disease (chosen as a relatively healthy control cohort without comorbid burden of other causes of end-stage renal disease such as diabetes). The primary outcome measured, graft survival, was death censored, with graft loss defined as requirement for renal replacement therapy or retransplant. Secondary outcomes included patient survival and graft function. In 150 study patients (16 patients in group 1, 64 in group 2, and 70 in group 3), 5-year death-censored graft survival was 93.75%, 90.6%, and 92.9%, respectively, with no significant differences in graft failure among groups (Cox proportional hazards model). Five-year patient survival was 100%, 100%, and 94.3%, respectively. Individuals with a history of lower urinary tract dysfunction had graft and patient survival rates similar to the control group. When appropriately treated, lower

  1. Effects of renal denervation on tubular sodium handling in rats with CBL-induced liver cirrhosis

    DEFF Research Database (Denmark)

    Jonassen, T.E.; Brond, L.; Torp, M.

    2003-01-01

    This study was designed to examine the effect of bilateral renal denervation (DNX) on thick ascending limb of Henle's loop (TAL) function in rats with liver cirrhosis induced by common bile duct ligation (CBL). The CBL rats had, as previously shown, sodium retention associated with hypertrophy...... renal sympathetic nerve activity known to be present in CBL rats plays a significant role in the formation of sodium retention by stimulating sodium reabsorption in the TAL via increased renal abundance of NKCC2....

  2. Effects of compound Shenhua tablet on renal tubular Na+-K+-ATPase in rats with acute ischemic reperfusion injury.

    Science.gov (United States)

    Yang, Yue; Wei, Ri-bao; Zheng, Xiao-yong; Qiu, Qiang; Cui, Shao-yuan; Yin, Zhong; Shi, Suo-zhu; Chen, Xiang-mei

    2014-03-01

    To observe the effect of Compound Shenhua Tablet (, SHT) on the sodium-potassium- exchanging adenosinetriphosphatase (Na(+)-K(+)-ATPase) in the renal tubular epithelial cells of rats with acute ischemic reperfusion and to investigate the mechanisms underlying the effects of SHT on renal ischemic reperfusion injury (RIRI). Fifty male Wistar rats were randomly divided into the sham surgery group, model group, astragaloside group [150 mg/(kg·d)], SHT low-dose group [1.5 g/(kg·d)] and SHT high-dose group [3.0 g/(kg·d)], with 10 rats in each group. After 1 week of continuous intragastric drug administration, surgery was performed to establish the model. At either 24 or 72 h after the surgery, 5 rats in each group were sacrificed, blood biochemistry, renal pathology, immunoblot and immunohistochemical examinations were performed, and double immunofluorescence staining was observed under a laser confocal microscope. Compared with the sham surgery group, the serum creatinine (SCr) and blood urea nitrogen (BUN) levels were significantly increased, Na(+)-K(+)-ATPase protein level was decreased, and kidney injury molecule-1 (KIM-1) protein level was increased in the model group after the surgery (P<0.01 or P<0.05). Compared with the model group, the SCr, BUN, pathological scores, Na(+)-K(+)-ATPase, and the KIM-1 protein level of the three treatment groups were significantly improved at 72 h after the surgery (P<0.05 or P<0.01). And the SCr, BUN of the SHT low- and high-dose groups, and the pathological scores of the SHT high-dose group were significantly lower than those of the astragaloside group (P<0.05). The localizations of Na(+)-K(+)-ATPase and megalin of the model group were disrupted, with the distribution areas overlapping with each other and alternately arranged. The severity of the disruption was slightly milder in three treatment groups compared with that of the model group. The results of immunofluorescence staining showed that the SHT high-dose group had a

  3. Atrial Natriuretic Peptide Stimulates Dopamine Tubular Transport by Organic Cation Transporters: A Novel Mechanism to Enhance Renal Sodium Excretion

    Science.gov (United States)

    Kouyoumdzian, Nicolás M.; Rukavina Mikusic, Natalia L.; Kravetz, María C.; Lee, Brenda M.; Carranza, Andrea; Del Mauro, Julieta S.; Pandolfo, Marcela; Gironacci, Mariela M.; Gorzalczany, Susana; Toblli, Jorge E.; Fernández, Belisario E.

    2016-01-01

    The aim of this study was to demonstrate the effects of atrial natriuretic peptide (ANP) on organic cation transporters (OCTs) expression and activity, and its consequences on dopamine urinary levels, Na+, K+-ATPase activity and renal function. Male Sprague Dawley rats were infused with isotonic saline solution during 120 minutes and randomized in nine different groups: control, pargyline plus tolcapone (P+T), ANP, dopamine (DA), D-22, DA+D-22, ANP+D-22, ANP+DA and ANP+DA+D-22. Renal functional parameters were determined and urinary dopamine concentration was quantified by HPLC. Expression of OCTs and D1-receptor in membrane preparations from renal cortex tissues were determined by western blot and Na+, K+-ATPase activity was determined using in vitro enzyme assay. 3H-DA renal uptake was determined in vitro. Compared to P+T group, ANP and dopamine infusion increased diuresis, urinary sodium and dopamine excretion significantly. These effects were more pronounced in ANP+DA group and reversed by OCTs blockade by D-22, demonstrating that OCTs are implied in ANP stimulated-DA uptake and transport in renal tissues. The activity of Na+, K+-ATPase exhibited a similar fashion when it was measured in the same experimental groups. Although OCTs and D1-receptor protein expression were not modified by ANP, OCTs-dependent-dopamine tubular uptake was increased by ANP through activation of NPR-A receptor and protein kinase G as signaling pathway. This effect was reflected by an increase in urinary dopamine excretion, natriuresis, diuresis and decreased Na+, K+-ATPase activity. OCTs represent a novel target that links the activity of ANP and dopamine together in a common mechanism to enhance their natriuretic and diuretic effects. PMID:27392042

  4. Renal albumin absorption in physiology and pathology.

    Science.gov (United States)

    Birn, H; Christensen, E I

    2006-02-01

    Albumin is the most abundant plasmaprotein serving multiple functions as a carrier of metabolites, hormones, vitamins, and drugs, as an acid/base buffer, as antioxidant and by supporting the oncotic pressure and volume of the blood. The presence of albumin in urine is considered to be the result of the balance between glomerular filtration and tubular reabsorption. Albuminuria has been accepted as an independent risk factor and a marker for renal as well as cardiovascular disease, and during the past decade, evidence has suggested that albumin itself may cause progression of renal disease. Thus, the reduction of proteinuria and, in particular, albuminuria has become a target in itself to prevent deterioration of renal function. Studies have shown albumin and its ligands to induce expression of inflammatory and fibrogenic mediators, and it has been hypothesized that increased filtration of albumin causes excessive tubular reabsorption, resulting in inflammation and fibrosis, resulting in the loss of renal function. In addition, it is known that tubular dysfunction in itself may cause albuminuria owing to decreased reabsorption of filtered albumin, and, recently, it has been suggested that significant amounts of albumin fragments are excreted in the urine as a result of tubular degradation. Thus, although both tubular and glomerular dysfunction influences renal handling of albumin, it appears that tubular reabsorption plays a central role in mediating the effects of albumin on renal function. The present paper will review the mechanisms for tubular albumin uptake and the possible implications for the development of renal disease.

  5. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats

    NARCIS (Netherlands)

    Waanders, Femke; Rienstra, Heleen; Boer, Mark Walther; Zandvoort, Andre; Rozing, Jan; Navis, Gerjan; van Goor, Harry; Hillebrands, Jan-Luuk

    Waanders F, Rienstra H, Walther Boer M, Zandvoort A, Rozing J, Navis G, van Goor H, Hillebrands JL. Spironolactone ameliorates transplant vasculopathy in renal chronic transplant dysfunction in rats. Am J Physiol Renal Physiol 296: F1072-F1079, 2009. First published February 25, 2009;

  6. Improved Structure and Function in Autosomal Recessive Polycystic Rat Kidneys with Renal Tubular Cell Therapy.

    Science.gov (United States)

    Kelly, K J; Zhang, Jizhong; Han, Ling; Kamocka, Malgorzata; Miller, Caroline; Gattone, Vincent H; Dominguez, Jesus H

    2015-01-01

    Autosomal recessive polycystic kidney disease is a truly catastrophic monogenetic disease, causing death and end stage renal disease in neonates and children. Using PCK female rats, an orthologous model of autosomal recessive polycystic kidney disease harboring mutant Pkhd1, we tested the hypothesis that intravenous renal cell transplantation with normal Sprague Dawley male kidney cells would improve the polycystic kidney disease phenotype. Cytotherapy with renal cells expressing wild type Pkhd1 and tubulogenic serum amyloid A1 had powerful and sustained beneficial effects on renal function and structure in the polycystic kidney disease model. Donor cell engraftment and both mutant and wild type Pkhd1 were found in treated but not control PCK kidneys 15 weeks after the final cell infusion. To examine the mechanisms of global protection with a small number of transplanted cells, we tested the hypothesis that exosomes derived from normal Sprague Dawley cells can limit the cystic phenotype of PCK recipient cells. We found that renal exosomes originating from normal Sprague Dawley cells carried and transferred wild type Pkhd1 mRNA to PCK cells in vivo and in vitro and restricted cyst formation by cultured PCK cells. The results indicate that transplantation with renal cells containing wild type Pkhd1 improves renal structure and function in autosomal recessive polycystic kidney disease and may provide an intra-renal supply of normal Pkhd1 mRNA.

  7. Regional anesthesia is safe and effective for lower limb orthopedic surgery in patient with renal tubular acidosis and hypokalemia

    Directory of Open Access Journals (Sweden)

    Indira Gurajala

    2018-01-01

    Full Text Available Renal tubular acidosis (RTA with hypokalemia may precipitate acute respiratory failure and potentially fatal arrhythmias like ventricular fibrillation. Though there are random reports of respiratory failure needing mechanical ventilation and sudden death in patients with RTA and hypokalemia, the anesthetic management of these patients has not been clearly elucidated. Acidosis and hypokalemia have significant interactions with both general and local anesthetics and alter their effect substantially. Proper preoperative planning and optimization are required for the safe conduct of anesthesia in this subset of patients. We describe a case of distal RTA, hypokalemia, and metabolic bone disease in whom central neuraxial anesthesia was effectively used for lower limb orthopedic surgery with no complications.

  8. Monoanionic 99mTc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: Radiosynthesis and evaluation as potential renal tubular tracers

    International Nuclear Information System (INIS)

    Lipowska, Malgorzata; Klenc, Jeffrey; Jarkas, Nashwa; Marzilli, Luigi G.; Taylor, Andrew T.

    2017-01-01

    Introduction: 99m Tc(CO) 3 -nitrilotriacetic acid, 99m Tc(CO) 3 (NTA), is a new renal tubular agent with pharmacokinetic properties comparable to those of 131 I-OIH but the clearance of 99m Tc(CO) 3 (NTA) and 131 I-OIH is still less than the clearance of PAH, the gold standard for the measurement of effective renal plasma flow. At physiological pH, dianionic 99m Tc(CO) 3 (NTA) has a mononegative inner metal-coordination sphere and a mononegative uncoordinated carboxyl group. To evaluate alternate synthetic approaches, we assessed the importance of an uncoordinated carboxyl group, long considered essential for tubular transport, by evaluating the pharmacokinetics of three analogs with the 99m Tc(CO) 3 (NTA) metal-coordination sphere but with uncharged pendant groups. Methods: 99m Tc(CO) 3 complexes with N-(2-acetamido)iminodiacetic acid (ADA), N-(2-hydroxyethyl)iminodiacetic acid (HDA) and N-(fluoroethyl)iminodiacetic acid (FEDA) were prepared using a tricarbonyl kit and isolated by HPLC. The pharmacokinetics were evaluated in Sprague–Dawley rats, with 131 I-OIH as an internal control; urine was analyzed for metabolites. Plasma protein binding and erythrocyte uptake were determined from the 10 min blood samples. Re(CO) 3 (FEDA), the analog of 99m Tc(CO) 3 (FEDA), was prepared and characterized. Results: 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA) were efficiently prepared as a single species with high radiochemical purities (>99%). These new monoanionic 99m Tc(CO) 3 tracers with uncharged dangling groups all showed rapid blood clearance and high specificity for renal excretion. Activity in the urine, as a percent of 131 I-OIH at 10 and 60 min, was 96% and 99% for ADA, 96% and 100% for HDA, and 100% and 99% for FEDA, respectively. Each new tracer was excreted unchanged in the urine. The Re(CO) 3 (FEDA) structure adds compelling evidence that such 99m Tc(CO) 3 (NTA) analogs have metal-coordination spheres identical to that of 99m Tc(CO) 3 (NTA

  9. Utility of intravenous nonionic contrast media for abdominal CT in patients with renal dysfunction

    International Nuclear Information System (INIS)

    Craig, B.M.; Alpern, M.B.; Sandler, M.A.; Pearlberg, J.L.; Swanson, D.P.

    1987-01-01

    The safety and efficacy of a nonionic contrast medium (NICM) for CT enhancements in patients with renal dysfunction were evaluated. Thirty consecutive patients referred for abdominal CT with a serum creatinine (SCr) level over 5 mg/dL or a SCr level of 2-5 mg/dL and another risk factor (e.g., diabetes, single kidney) received NICM. Each was matched with a control who received the same 150-mL bolus of a conventional medium. No adverse reactions or significant alterations in SCr values were found in the NICM patients. No significant differences between the patient groups were found in blinded subjective image quality ratings or measured attenuation values of a parenchymal organs and vascular structures (with the exception of less renal enhancement in the NICM patients, reflecting their renal dysfunction). Use of an NICM is a safe and effective method for contrast medium-enhanced CT in patients with renal dysfunction

  10. Effects of dopamine on renal haemodynamics tubular function and sodium excretion in normal humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1998-01-01

    The renal functional changes following infusion of dopamine are well documented. The most pronounced effect is the increase in renal blood flow and a marked natriuretic response. Due to its specific renal effects, dopamine has become one of the most frequently used drugs in the treatment...... of critically ill patients with low cardiac output states and/or acute oliguric renal failure. Pharmacological effects of dopamine are dose dependent. Low doses of dopamine predominantly stimulate dopaminergic receptors, but with increasing doses actions secondary to stimulation of adrenergic beta(1) and alpha...... indirectly may dilate the vessels by inhibition of norepinephrine release. Consistent with previous results in animals, the present haemodynamic studies revealed that dopamine in normal subjects elicits a dose dependent biphasic effect on the mean arterial blood pressure. With 1 and 2 micrograms...

  11. Distal Renal Tubular Acidosis (dRTA) Among Southeast Asian Ovalocytosis (SAO) Patients in Malaria Endemic Area of Sekotong, Lombok Island

    OpenAIRE

    Danuyanti, I Gusti Ayu Nyoman; -, Tasmini; Sadewa, Ahmad Hamim

    2014-01-01

    Introduction: Southeast Asian Ovalocytosis (SAO) is caused by 27 bp deletion of the band 3 protein gene in erythrocyte membrane and characterized by oval erythrocyte. The erythroid band 3 (AE1) gene isexpressed not only in erythrocyte membranes but also in the cell membrane of α-collecting renal tubular functions in the secretion of acid in renal tubules and HCO3 -/Cl- anion exchange. An alteration of the band 3 (AE1) gene functions in cell of α-collecting renal tubules reduces HCO3-/Cl- ion ...

  12. Chronic nitric oxide synthase inhibition exacerbates renal dysfunction in cirrhotic rats

    DEFF Research Database (Denmark)

    Graebe, M.; Brond, L.; Christensen, S.

    2004-01-01

    The present study investigated sodium balance and renal tubular function in cirrhotic rats with chronic blockade of the nitric oxide (NO) system. Rats were treated with the nonselective NO synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME) starting on the day of common bile duct ligation...... (CBL). Three weeks of daily sodium balance studies showed that CBL rats developed sodium retention compared with sham-operated rats and that l-NAME treatment dose dependently deteriorated cumulative sodium balance by reducing urinary sodium excretion. Five weeks after CBL, renal clearance studies were...

  13. Cisplatin toxicity reduced in human cultured renal tubular cells by oxygen pretreatment.

    Science.gov (United States)

    Kaeidi, Ayat; Rasoulian, Bahram; Hajializadeh, Zahra; Pourkhodadad, Soheila; Rezaei, Maryam

    2013-01-01

    Cisplatin is an effective and widely used chemotherapy agent and its side effects, particularly nephrotoxicity, limit its usage and related platinum-based drugs. Cisplatin nephrotoxicity is mainly due to extremely increase in reactive oxygen species (ROS) generation leading to kidney tubular cell death. Preconditioning with oxidative stress has been demonstrated to stimulate the cellular adaptation to subsequent severe oxidative stress. Short term oxygen pre-exposure as a mild oxidative stress may enhance some endogenous defense mechanisms, so its effect on Cisplatin induced cell death was investigated in present research. We studied the effects of hyperoxic environment pre-exposure on Cisplatin toxicity in an in-vitro model of cultured human embryonic tubular epithelial cells (AD293). Viability of AD293 cells, as evaluated by MTT-assay, was affected by Cisplatin in a time (1-4 h) dependent model. Biochemical markers of cell apoptosis were evaluated using immunoblotting. Pretreatment with nearly pure oxygen (≥90%) for 2 h significantly reduced the level of cell damage. Activated caspase 3 and Bax/Bcl-2 ratio were significantly increased in Cisplatin-treated cells. Oxygen pretreatment inhibited caspase 3 activation and decreased Bax/Bcl-2 ratio. Oxygen pre-treatment itself not showed any cytotoxicity in exposure times up to 3 h. Our data indicate that hyperoxic preconditioning reduces Cisplatin toxicity in cultured human tubular epithelial cells. The exact mechanism of protection is unclear, though enhancement of some endogenous defense mechanisms and subsequently scavenging of free oxygen radicals may play an important role.

  14. Changes in glomerular filtration rate after cardiac surgery with cardiopulmonary bypass in patients with mild preoperative renal dysfunction

    NARCIS (Netherlands)

    Loef, B. G.; Henning, R. H.; Navis, G.; Rankin, A. J.; Van Oeveren, W.; Ebels, T.; Epema, A. H.

    Background. Cardiac surgery with cardiopulmonary bypass (CPB) is commonly perceived as a risk factor for decline in renal function, especially in patients with preoperative renal dysfunction. There are few data on the effects of CPB on renal function in patients with mild preoperative renal

  15. Endolymphatic Sac Enlargement in a Girl with a Novel Mutation for Distal Renal Tubular Acidosis and Severe Deafness

    Directory of Open Access Journals (Sweden)

    Rink Nikki

    2012-01-01

    Full Text Available Hereditary distal renal tubular acidosis (dRTA is caused by mutations of genes encoding subunits of the H+-ATPase (ATP6V0A4 and ATP6V1B1 expressed in α-intercalated cells of the distal renal tubule and in the cochlea. We report on a 2-year-old girl with distal RTA and profound speech delay which was initially misdiagnosed as autism. Genetic analysis showed compound heterozygous mutations with one known and one novel mutation of the ATP6V1B1 gene; cerebral magnetic resonance imaging (MRI revealed bilateral enlargement of the endolymphatic sacs of the inner ear. With improved cooperation, audiometric testing showed that hearing loss was most profound on the right, where endolymphatic sac enlargement was greatest, demonstrating a clear link between the degree of deafness and the degree of inner ear abnormality. This case indicates the value of MRI for diagnosis of inner ear involvement in very young children with distal RTA. Although citrate therapy quickly corrects the acidosis and restores growth, early diagnosis of deafness is crucial so that hearing aids can be used to assist acquisition of speech and to provide enough auditory nerve stimulation to assure the affected infants remain candidates for cochlear implantation.

  16. Downregulation of miR-205 modulates cell susceptibility to oxidative and endoplasmic reticulum stresses in renal tubular cells.

    Directory of Open Access Journals (Sweden)

    Shiyo Muratsu-Ikeda

    Full Text Available BACKGROUND: Oxidative stress and endoplasmic reticulum (ER stress play a crucial role in tubular damage in both acute kidney injury (AKI and chronic kidney disease (CKD. While the pathophysiological contribution of microRNAs (miRNA to renal damage has also been highlighted, the effect of miRNA on renal damage under oxidative and ER stresses conditions remains elusive. METHODS: We assessed changes in miRNA expression in the cultured renal tubular cell line HK-2 under hypoxia-reoxygenation-induced oxidative stress or ER stress using miRNA microarray assay and real-time RT-PCR. The pathophysiological effect of miRNA was evaluated by cell survival rate, intracellular reactive oxygen species (ROS level, and anti-oxidant enzyme expression in miRNA-inhibited HK-2 or miRNA-overexpressed HK-2 under these stress conditions. The target gene of miRNA was identified by 3'-UTR-luciferase assay. RESULTS: We identified 8 and 10 miRNAs whose expression was significantly altered by oxidative and ER stresses, respectively. Among these, expression of miR-205 was markedly decreased in both stress conditions. Functional analysis revealed that decreased miR-205 led to an increase in cell susceptibility to oxidative and ER stresses, and that this increase was associated with the induction of intracellular ROS and suppression of anti-oxidant enzymes. While increased miR-205 by itself made no change in cell growth or morphology, cell viability under oxidative or ER stress conditions was partially restored. Further, miR-205 bound to the 3'-UTR of the prolyl hydroxylase 1 (PHD1/EGLN2 gene and suppressed the transcription level of EGLN2, which modulates both intracellular ROS level and ER stress state. CONCLUSIONS: miR-205 serves a protective role against both oxidative and ER stresses via the suppression of EGLN2 and subsequent decrease in intracellular ROS. miR-205 may represent a novel therapeutic target in AKI and CKD associated with oxidative or ER stress in tubules.

  17. Limitation of HIF-1α with pentoxifillyne on renal tubular ischemia result of hiperoxaluria and ESWL.

    Science.gov (United States)

    Erturhan, Sakip; Bayrak, Omer; Seckiner, Ilker; Celik, Mehmet; Karakok, Metin

    2014-03-01

    To evaluate hypoxia-inducible factor 1 subunit α (HIF-1α) expression during the performance of extracorporeal shock wave lithotripsy (ESWL) and to investigate the effects of pentoxyphylline on HIF-1α expression. One hundred New Zealand Albino rabbit were used in the study divided in 5 groups. There were 20 rabbits in each group. The groups were divided in two parts: early (7 days) and late period (14 days) according to follow up duration. Immunohistochemical analyses were performed using nuclear staining to show HIF-1α expression in rabbit renal tissue sample. HIF-1α expression was higher in rabbits undergoing ESWL (group 4). In the hyperoxaluria group taking pentoxyphylline before ESWL (group 5), HIF-1α expression was lower in both early and late period subgroups (p ESWL may cause renal cell injury. Our results suggest that pentoxyphylline, as a circulatory regulator agent, may prevent renal cell injury induced by ESWL.

  18. Utilidad de la recolección de orina de dos horas para el diagnóstico del tipo de acidosis tubular renal

    Directory of Open Access Journals (Sweden)

    Margarita Irene Rocha-Gómez

    2015-08-01

    Full Text Available La acidosis tubular renal se caracteriza por acidosis metabólica hiperclorémica. El diagnóstico del tipo de acidosis tubular renal se realiza mediante la medición del transporte tubular máximo de bicarbonato y de la capacidad de acidificación urinaria; sin embargo, estas pruebas son invasivas y requieren determinaciones especializadas. Objetivo: comparar la utilidad de la recolección urinaria de dos horas, una prueba relativamente simple y al alcance de muchos laboratorios, con la medición del transporte tubular máximo de bicarbonato y con la capacidad de acidificación urinaria (procedimientos de referencia para clasificar el tipo de acidosis tubular renal en pacientes pediátricos. Material y método: el estudio se realizó en niños con diagnóstico de acidosis tubular renal. El primer día se recolectó la muestra sérica y urinaria de dos horas. Al día siguiente se efectuaron los procedimientos de referencia administrando bicarbonato de sodio en 8 horas; las muestras se colectaron cada hora y se determinaron la reabsorción de bicarbonato y la acidificación urinaria.  Resultados: se incluyeron 19 pacientes y en 17 casos la colección urinaria de dos horas confirmó el diagnóstico de los procedimientos de referencia. La recolección urinaria de dos horas tuvo sensibilidad de 0.94 y especificidad de 0.67 para el diagnóstico de acidosis tubular renal distal. Conclusión: la recolección de orina de dos horas se realiza en forma menos invasiva y ofrece resultados semejantes a los procedimientos de referencia.

  19. Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney

    DEFF Research Database (Denmark)

    Abildgaard, U; Amtorp, O; Holstein-Rathlou, N H

    1988-01-01

    of [51Cr]EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments......This study was performed in order to quantify the effects of renal venous pressure (RVP) elevation on absolute and fractional reabsorption rates of sodium and water in proximal and distal segments of the nephron in dog kidneys. Renal blood flow (RBF) was measured electromagnetically. Clearance...

  20. Effects of intravenous bumetanide administration on renal haemodynamics and proximal and distal tubular sodium reabsorption in conscious rats

    Energy Technology Data Exchange (ETDEWEB)

    Shalmi, M.; Petersen, J.S.; Christensen, S. (Department of pharmacology, University of Copenhagen (Denmark))

    1989-01-01

    The renal effects of 0.02-62.5 mg/kg bumetanide given as intravenous bolus injections were studied in water diuretic conscious rats. Clearances of {sup 14}C-tetraethylammonium, {sup 3}H-inulin and lithium were used as markers for renal plasma flow (RPF), glomerular filtion rate (GFR) and proximal tubular output, respectively. Bumetanide caused biphasic, transient and dose-independent changes in the renal haemodynamics without significant alterations of the filtration fraction. At dose-levels above 0.02 mg/kg bumetanide increased urine flow, absolute and fractional Na excretion as well as the indices for fractional output of Na from the proximal tubules (C{sub Li}/C{sub I}n) and the distal nephron segments (C{sub Na}/C{sub Li}). The changes in C{sub Li}/C{sub In} became maximal at doses above 0.5 mg/kg, whereas C{sub Na}/C{sub Li} was increased with the dose up to 12.5 mg/kg. Paradoxically, doses above 12.5 mg/kg were less natriuretic due to a decrease of C{sub Na}/C{sub Li}. It is concluded that in rats bumetanide is an effective although short-acting diuretic when administered intravenously. When comparing peak responses bumetanide is equipotent to furosemide but has a lower maximal efficacy. Judged from the changes in fractional lithium excretion, the natriuretic effect of bumetanide is effected by inhibition of Na reabsorption in the proximal tubule in addition to the well-known effect on the distal nephron segment. (author).

  1. Clinical observation of calcium dobesilate in the treatment of chronic renal allograft dysfunction

    Institute of Scientific and Technical Information of China (English)

    Zheng Xue-yang; Han Shu; Zhou Mei-sheng; Fu Shang-xi; Wang Li-ming

    2014-01-01

    Abstract BACKGROUND: Calcium dobesilate (calcium dihydroxy-2, 5-benzenesulfonate) has been widely used to treat chronic venous insufficiency and diabetic retinopathy, especialy many clinical studies showed that calcium dobesilate as vasoprotective compound ameliorates renal lesions in diabetic nephropathy. However, there are few literatures reported calcium dobesilate in the treatment of chronic renal alograft dysfunction after renal transplantation. OBJECTIVE:To observe the efficacy and safety of calcium dobesilate on chronic renal dysfunction after renal transplantation. METHODS:A total of 152 patients with chronic renal alograft dysfunction after renal transplantation were enroled from the Military Institute of Organ Transplantation, Changzheng Hospital, Second Military Medical University of Chinese PLA. They were randomly divided into the treatment group (n=78) and the control group (n=74). Patients in the treatment group received 500 mg of calcium dobesilate three times daily for eight weeks. Al patients were treated with calcineurin inhibitor-based triple immunosuppressive protocols and comprehensive therapies. RESULTS AND CONCLUSION: For patients receiving calcium dobesilate, serum creatinine, blood urea nitrogen and uric acid decreased significantly at two weeks after treatment and maintained a stable level (P 0.05). Administration of calcium dobesilate did not change the general condition of patients with renal insufficiency, nor did it affect blood concentrations of the immunosuppressive agents. Calcium dobesilate may help to delay the progress of graft injury in patients with chronic renal graft dysfunction by conjugating with creatinine, ameliorating the impaired microcirculation and its antioxidant property. The decline in serum creatinine aleviates patients’ anxiety and concern arising from the elevation of creatinine. However, the negative interference with serum creatinine caused by calcium dobesilate should be cautious in order to avoid

  2. Hereditary tubular transport disorders: implications for renal handling of Ca2+ and Mg2+.

    NARCIS (Netherlands)

    Dimke, H.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2010-01-01

    The kidney plays an important role in maintaining the systemic Ca2+ and Mg2+ balance. Thus the renal reabsorptive capacity of these cations can be amended to adapt to disturbances in plasma Ca2+ and Mg2+ concentrations. The reabsorption of Ca2+ and Mg2+ is driven by transport of other electrolytes,

  3. Hyaluronan Biology and Regulation in Renal Tubular Epithelial Cells and its Role in Kidney Stone Disease

    NARCIS (Netherlands)

    M. Asselman (Marino)

    2008-01-01

    textabstractRenal stone disease is a widespread problem afflicting more and more people throughout the world. Epidemiological studies show an increase in incidence and prevalence rates. In North America and Europe the yearly incidence is estimated to be about 0.5% 1, 2. The prevalence of kidney

  4. Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

    Science.gov (United States)

    Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

    2018-06-01

    Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

  5. Comparison of four decontamination treatments on porcine renal decellularized extracellular matrix structure, composition, and support of human renal cortical tubular epithelium cells.

    Science.gov (United States)

    Poornejad, Nafiseh; Nielsen, Jeffery J; Morris, Ryan J; Gassman, Jason R; Reynolds, Paul R; Roeder, Beverly L; Cook, Alonzo D

    2016-03-01

    Engineering whole organs from porcine decellularized extracellular matrix and human cells may lead to a plentiful source of implantable organs. Decontaminating the porcine decellularized extracellular matrix scaffolds is an essential step prior to introducing human cells. However, decontamination of whole porcine kidneys is a major challenge because the decontamination agent or irradiation needs to diffuse deep into the structure to eliminate all microbial contamination while minimizing damage to the structure and composition of the decellularized extracellular matrix. In this study, we compared four decontamination treatments that could be applicable to whole porcine kidneys: 70% ethanol, 0.2% peracetic acid in 1 M NaCl, 0.2% peracetic acid in 4% ethanol, and gamma (γ)-irradiation. Porcine kidneys were decellularized by perfusion of 0.5% (w/v) aqueous solution of sodium dodecyl sulfate and the four decontamination treatments were optimized using segments (n = 60) of renal tissue to ensure a consistent comparison. Although all four methods were successful in decontamination, γ-irradiation was very damaging to collagen fibers and glycosaminoglycans, leading to less proliferation of human renal cortical tubular epithelium cells within the porcine decellularized extracellular matrix. The effectiveness of the other three optimized solution treatments were then all confirmed using whole decellularized porcine kidneys (n = 3). An aqueous solution of 0.2% peracetic acid in 1 M NaCl was determined to be the best method for decontamination of porcine decellularized extracellular matrix. © The Author(s) 2015.

  6. Effect of metabolic acidosis on renal tubular sodium handling in rats as determined by lithium clearance

    Directory of Open Access Journals (Sweden)

    Menegon L.F.

    1998-01-01

    Full Text Available Systemic metabolic acidosis is known to cause a decrease in salt and water reabsorption by the kidney. We have used renal lithium clearance to investigate the effect of chronic, NH4Cl-induced metabolic acidosis on the renal handling of Na+ in male Wistar-Hannover rats (200-250 g. Chronic acidosis (pH 7.16 ± 0.13 caused a sustained increase in renal fractional Na+ excretion (267.9 ± 36.4%, accompanied by an increase in fractional proximal (113.3 ± 3.6% and post-proximal (179.7 ± 20.2% Na+ and urinary K+ (163.4 ± 5.6% excretion when compared to control and pair-fed rats. These differences occurred in spite of an unchanged creatinine clearance and Na+ filtered load. A lower final body weight was observed in the acidotic (232 ± 4.6 g and pair-fed (225 ± 3.6 g rats compared to the controls (258 ± 3.7 g. In contrast, there was a significant increase in the kidney weights of acidotic rats (1.73 ± 0.05 g compared to the other experimental groups (control, 1.46 ± 0.05 g; pair-fed, 1.4 ± 0.05 g. We suggest that altered renal Na+ and K+ handling in acidotic rats may result from a reciprocal relationship between the level of metabolism in renal tubules and ion transport.

  7. Male gender and renal dysfunction are predictors of adverse outcome in nonpostoperative ischemic colitis patients.

    Science.gov (United States)

    Lee, Tsung-Chun; Wang, Hsiu-Po; Chiu, Han-Mo; Lien, Wan-Ching; Chen, Mei-Jyh; Yu, Linda C H; Sun, Chia-Tung; Lin, Jaw-Town; Wu, Ming-Shiang

    2010-01-01

    Ischemic colitis (IC) spans a broad spectrum from self-limiting illness to intestinal gangrene and mortality. Prognostic factors specifically for nonpostoperative IC were not fully characterized. We aim to focus on nonpostoperative IC in patients with renal dysfunction and try to identify prognostic factors for adverse outcomes. We conducted a retrospective analysis at a university-affiliated tertiary medical center in Taiwan. From January 2003 to August 2008, 25 men and 52 women (mean age: 66 y) had colonoscopic biopsy-proven IC without prior culprit surgery. We estimated glomerular filtration rate with simplified Modification of Diet in Renal Disease equation. Nine patients with glomerular filtration rate below 30 mL per minute per 1.73 m were classified as renal dysfunction group (including 7 dialysis patients). Adverse outcomes were defined as need for surgery and mortality. Predictors for adverse outcomes were captured by univariate and multivariate analysis. Research ethical committee approved the study protocol. Patients with renal dysfunction more often had: diabetes mellitus (56% vs. 16%, P=0.02), prolonged symptoms (6.8 d vs. 3.5 d, P=0.01), lower hemoglobin (11.1 g/dL vs. 13.4 g/dL, P=0.01), and more often right colonic involvement (56% vs. 19%, P=0.03). Renal dysfunction patients also had longer hospitalization days (median 15 d vs. 4 d, P=0.045). However, there was no statistical significance in the rate of either surgery or mortality between these 2 groups (P>0.05). Univariate analysis showed that renal dysfunction, sex, emergency department referral, presentation with abdominal pain were significant for adverse outcome (P<0.1). Multivariate analysis revealed that male sex conveyed 9.5-fold risk (P=0.01) and renal dysfunction conveyed 8.5-fold risk (P=0.03) for adverse outcomes. Nonpostoperative IC patients with concurrent renal dysfunction had distinct clinical profiles. Multivariate analysis showed that male patients had 9.5-fold and renal

  8. Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction

    DEFF Research Database (Denmark)

    Anavekar, Nagesh S; McMurray, John J V; Velazquez, Eric J

    2004-01-01

    BACKGROUND: The presence of coexisting conditions has a substantial effect on the outcome of acute myocardial infarction. Renal failure is associated with one of the highest risks, but the influence of milder degrees of renal impairment is less well defined. METHODS: As part of the Valsartan...... captopril, valsartan, or both. The glomerular filtration rate (GFR) was estimated by means of the four-component Modification of Diet in Renal Disease equation, and the patients were grouped according to their estimated GFR. We used a 70-candidate variable model to adjust and compare overall mortality...

  9. 4. Prevalence and Factors Associated with Renal Dysfunction in HIV ...

    African Journals Online (AJOL)

    Esem

    -Saharan Africa has limited data on HIV related kidney disease with most available data coming from the developed countries. Kidney disease is a recognised complication in HIV infected patients presenting with acute renal failure (ARF) or ...

  10. Mechanisms by which heme oxygenase rescue renal dysfunction in obesity

    Directory of Open Access Journals (Sweden)

    Joseph Fomusi Ndisang

    2014-01-01

    Collectively, these data suggest that hemin ameliorates nephropathy by potentiating the expression of proteins of repair/regeneration, abating oxidative/inflammatory mediators, reducing renal histo-pathological lesions, while enhancing nephrin, podocin, podocalyxin, CD2AP and creatinine clearance, with corresponding reduction of albuminuria/proteinuria suggesting improved renal function in hemin-treated ZFs. Importantly, the concomitant potentiation regeneration proteins and podocyte cytoskeletal proteins are novel mechanisms by which hemin rescue nephropathy in obesity.

  11. Decreases in renal functional reserve and proximal tubular fluid output in conscious oophorectomized rats

    DEFF Research Database (Denmark)

    Nielsen, Camilla Birch; Flyvbjerg, Allan; Bruun, Jens Meldgaard

    2003-01-01

    Age-dependent glomerulosclerosis with reduced GFR develops earlier among men than among women. Therefore, whether female sex hormones could prevent the age-dependent decrease in GFR was investigated. The kidney function in oophorectomized rats treated with placebo (OOX group), estrogen (OOX+E(2...... effects were prevented with administration of estrogen. Sham-operated rats demonstrated values for renal functional reserve and fractional lithium excretion that were between those observed for the OOX group and the groups treated with sex hormones....

  12. Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

    Directory of Open Access Journals (Sweden)

    Kohan Donald E

    2002-08-01

    Full Text Available Abstract Background The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx, the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. Methods Cultured human glomerular endothelial (HGEN, human glomerular visceral epithelial (HGEC and human proximal tubule (HPT cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. Results Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor by any cell type at any time point. Conclusion These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells.

  13. Acute renal dysfunction in a patient presenting with rhabdomyolysis due to Hypothyroidism attributed to Hashimoto's Disease

    OpenAIRE

    Nikolaidou, C; Gouridou, E; Ilonidis, G; Boudouris, G

    2010-01-01

    We describe a patient with rhabdomyolysis and acute renal dysfunction due to hypothyroidism, attributed to Hashimoto's disease. Though rhabdomyolysis could be life-threatening, it is a rare complication of hypothyroidism, especially when other precipitating factors, such as exercise, alcohol, medications or renal failure, are absent. Nevertheless, hypothyroidism can be an authentic cause of rhabdomyolysis and should always be considered when elevated creatine kinase (CK) and other muscle enzy...

  14. Renal dysfunction in patients with heart failure with preserved versus reduced ejection fraction

    DEFF Research Database (Denmark)

    McAlister, Finlay A; Ezekowitz, Justin; Tarantini, Luigi

    2012-01-01

    Prior studies in heart failure (HF) have used the Modification of Diet in Renal Disease (MDRD) equation to calculate estimated glomerular filtration rate (eGFR). The Chronic Kidney Disease-Epidemiology Collaboration Group (CKD-EPI) equation provides a more-accurate eGFR than the MDRD when compared...... against the radionuclide gold standard. The prevalence and prognostic import of renal dysfunction in HF if the CKD-EPI equation is used rather than the MDRD is uncertain....

  15. Renal dysfunction in liver cirrhosis and its correlation with Child-Pugh score and MELD score

    Science.gov (United States)

    Siregar, G. A.; Gurning, M.

    2018-03-01

    Renal dysfunction (RD) is a serious and common complication in a patient with liver cirrhosis. It provides a poor prognosis. The aim of our study was to evaluate the renal function in liver cirrhosis, also to determine the correlation with the graduation of liver disease assessed by Child-Pugh Score (CPS) and MELD score. This was a cross-sectional study included patients with liver cirrhosis admitted to Adam Malik Hospital Medan in June - August 2016. We divided them into two groups as not having renal dysfunction (serum creatinine SPSS 22.0 was used. Statistical methods used: Chi-square, Fisher exact, one way ANOVA, Kruskal Wallis test and Pearson coefficient of correlation. The level of significance was p<0.05. 55 patients with presented with renal dysfunction were 16 (29.1 %). There was statistically significant inverse correlation between GFR and CPS (r = -0.308), GFR and MELD score (r = -0.278). There was a statistically significant correlation between creatinine and MELD score (r = 0.359), creatinine and CPS (r = 0.382). The increase of the degree of liver damage is related to the increase of renal dysfunction.

  16. Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

    OpenAIRE

    Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

    2014-01-01

    In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin...

  17. Risk Factors for Lower Urinary Tract Dysfunction and Symptoms After Successful Renal Transplantation

    OpenAIRE

    Mitsui, Takahiko; Moriya, Kimihiko; Morita, Ken; Iwami, Daiki; Kitta, Takeya; Kanno, Yukiko; Takeda, Masayuki; Shinohara, Nobuo

    2015-01-01

    BACKGROUND: We investigated risk factors for lower urinary tract (LUT) dysfunction and LUT symptoms in patients who successfully underwent renal transplantation (RTX). MATERIAL AND METHODS: Ninety-five patients (54 males and 41 females) undergoing RTX (median age: 45 years old) at Hokkaido University Hospital were included in this study. Uroflowmetry (UFM), postvoid residual urine volume (PVR), and 24-h bladder diaries were performed. We analyzed risk factors for voiding dysfunction, urinary ...

  18. Quantifying cellular mechanics and adhesion in renal tubular injury using single cell force spectroscopy.

    Science.gov (United States)

    Siamantouras, Eleftherios; Hills, Claire E; Squires, Paul E; Liu, Kuo-Kang

    2016-05-01

    Tubulointerstitial fibrosis represents the major underlying pathology of diabetic nephropathy where loss of cell-to-cell adhesion is a critical step. To date, research has predominantly focussed on the loss of cell surface molecular binding events that include altered protein ligation. In the current study, atomic force microscopy single cell force spectroscopy (AFM-SCFS) was used to quantify changes in cellular stiffness and cell adhesion in TGF-β1 treated kidney cells of the human proximal tubule (HK2). AFM indentation of TGF-β1 treated HK2 cells showed a significant increase (42%) in the elastic modulus (stiffness) compared to control. Fluorescence microscopy confirmed that increased cell stiffness is accompanied by reorganization of the cytoskeleton. The corresponding changes in stiffness, due to F-actin rearrangement, affected the work of detachment by changing the separation distance between two adherent cells. Overall, our novel data quantitatively demonstrate a correlation between cellular elasticity, adhesion and early morphologic/phenotypic changes associated with tubular injury. Diabetes affects many patients worldwide. One of the long term problems is diabetic nephropathy. Here, the authors utilized atomic force microscopy single cell force spectroscopy (AFM- SCFS) to study cellular stiffness and cell adhesion after TGF1 treatment in human proximal tubule kidney cells. The findings would help further understand the overall disease mechanism in diabetic patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Monoanionic 99mTc-tricarbonyl-aminopolycarboxylate complexes with uncharged pendant groups: Radiosynthesis and evaluation as potential renal tubular tracers.

    Science.gov (United States)

    Lipowska, Malgorzata; Klenc, Jeffrey; Jarkas, Nashwa; Marzilli, Luigi G; Taylor, Andrew T

    2017-04-01

    99m Tc(CO) 3 -nitrilotriacetic acid, 99m Tc(CO) 3 (NTA), is a new renal tubular agent with pharmacokinetic properties comparable to those of 131 I-OIH but the clearance of 99m Tc(CO) 3 (NTA) and 131 I-OIH is still less than the clearance of PAH, the gold standard for the measurement of effective renal plasma flow. At physiological pH, dianionic 99m Tc(CO) 3 (NTA) has a mononegative inner metal-coordination sphere and a mononegative uncoordinated carboxyl group. To evaluate alternate synthetic approaches, we assessed the importance of an uncoordinated carboxyl group, long considered essential for tubular transport, by evaluating the pharmacokinetics of three analogs with the 99m Tc(CO) 3 (NTA) metal-coordination sphere but with uncharged pendant groups. 99m Tc(CO) 3 complexes with N-(2-acetamido)iminodiacetic acid (ADA), N-(2-hydroxyethyl)iminodiacetic acid (HDA) and N-(fluoroethyl)iminodiacetic acid (FEDA) were prepared using a tricarbonyl kit and isolated by HPLC. The pharmacokinetics were evaluated in Sprague-Dawley rats, with 131 I-OIH as an internal control; urine was analyzed for metabolites. Plasma protein binding and erythrocyte uptake were determined from the 10min blood samples. Re(CO) 3 (FEDA), the analog of 99m Tc(CO) 3 (FEDA), was prepared and characterized. 99m Tc(CO) 3 (ADA), 99m Tc(CO) 3 (HDA) and 99m Tc(CO) 3 (FEDA) were efficiently prepared as a single species with high radiochemical purities (>99%). These new monoanionic 99m Tc(CO) 3 tracers with uncharged dangling groups all showed rapid blood clearance and high specificity for renal excretion. Activity in the urine, as a percent of 131 I-OIH at 10 and 60min, was 96% and 99% for ADA, 96% and 100% for HDA, and 100% and 99% for FEDA, respectively. Each new tracer was excreted unchanged in the urine. The Re(CO) 3 (FEDA) structure adds compelling evidence that such 99m Tc(CO) 3 (NTA) analogs have metal-coordination spheres identical to that of 99m Tc(CO) 3 (NTA). New tracers lacking the negatively

  20. The effect of preoperative renal dysfunction with or without dialysis on early postoperative outcome following cardiac surgery.

    LENUS (Irish Health Repository)

    Al-Sarraf, Nael

    2011-01-01

    Although previous studies have shown increased mortality in renal dysfunction patients undergoing cardiac surgery, there is lack of data on the pattern of postoperative complications that occur in such patients and their distribution among dialysis and non-dialysis dependent renal dysfunction.

  1. Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

    Directory of Open Access Journals (Sweden)

    Francisco O'Valle

    Full Text Available UNLABELLED: Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD transplantation. Ischemia-reperfusion (IR injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1 activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN. MATERIALS AND METHODS: Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls and in murine Parp-1 knockout model of IR injury. RESULTS: PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603, time to effective diuresis (r = 0.770, serum creatinine levels at biopsy (r = 0.649, and degree of ATN (r = 0.810 (p = 0.001, Pearson test. In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

  2. A systematic review on renal and bladder dysfunction after endoscopic treatment of infravesical obstruction in boys.

    Directory of Open Access Journals (Sweden)

    Pauline M L Hennus

    Full Text Available BACKGROUND: Posterior urethral valves (PUV may cause subtle to severe obstruction of the urethra, resulting in a broad clinical spectrum. PUV are the most common cause of chronic renal disease in boys. Our purpose was to report the incidences of kidney and bladder dysfunction in boys treated with endoscopic valve resection for PUV. METHODOLOGY: We searched MEDLINE and EMBASE databases until 1st of July 2011, to identify original papers that described outcome of endoscopic valve resection (EVR in boys. We extracted information on (1 patient characteristics and clinical presentation of PUV related to outcomes and (2 the post-treatment absolute risks for kidney and bladder dysfunction. PRINCIPAL FINDINGS: Thirty-four studies describing renal function, vesicoureteral reflux (VUR, incontinence, and urodynamic bladder function after EVR in 1474 patients were retrieved. Patients treated for PUV show high percentages of chronic kidney disease (CKD or end stage renal disease (ESRD, 22% (0-32% and 11% (0-20%, respectively. Elevated nadir serum creatinine was the only independent factor associated with renal failure. Before treatment, VUR was present in 43% of boys and after EVR, VUR was present in 22%. Post treatment, 19% (0-70% was reported to suffer from urinary incontinence. Urodynamic bladder dysfunction was seen in many patients (55%, 0-72% after treatment of PUV. CONCLUSIONS: The reported cumulative incidence of renal and bladder dysfunction in patients with PUV after endoscopic PUV treatment varies widely. This may reflect a broad clinical spectrum, which relates to the lack of a standardised quantification of obstruction and its severity. Moreover, the risk of bias is rather high, and therefore we put little confidence in the reported estimates of effect. We found elevated nadir serum creatinine as a predictor for renal dysfunction. In order to be able to predict outcomes for patients with PUV, an objective classification of severity of

  3. Sida rhomboidea.Roxb leaf extract ameliorates gentamicin induced nephrotoxicity and renal dysfunction in rats.

    Science.gov (United States)

    Thounaojam, Menaka C; Jadeja, Ravirajsinh N; Devkar, Ranjitsinh V; Ramachandran, A V

    2010-10-28

    Sida rhomboidea.Roxb (SR) known as "Mahabala" in Ayurveda and marketed as "Shahadeyi" is used in ethnomedicine to treat ailments such as dysuria and urinary disorders. To evaluate nephroprotective potential of SR against gentamicin (GM) induced nephrotoxicity and renal dysfunction. Nephrotoxicity was induced in rats with GM (100 mg/kg bodyweight (i.p.) for 8 days) and were treated with SR extract (200 and 400 mg/kg bodyweight (p.o.) for 8 days) or 0.5% carboxymethyl cellulose (vehicle). Plasma and urine urea and creatinine, renal enzymatic and non-enzymatic antioxidants along with lipid peroxidation were evaluated in various experimental groups. GM treatment induced significant elevation (p<0.05) in plasma and urine urea, creatinine, renal lipid peroxidation along with significant decrement (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR treatment to GM treated rats (GM+SR) recorded significant decrement (p<0.05) in plasma and urine urea and creatinine, renal lipid peroxidation along with significant increment (p<0.05) in renal enzymatic and non-enzymatic antioxidants. SR leaf extract ameliorates GM induced nephrotoxicity and renal dysfunction and thus validates its ethnomedicinal use. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Enhancing the Detection of Dysmorphic Red Blood Cells and Renal Tubular Epithelial Cells with a Modified Urinalysis Protocol.

    Science.gov (United States)

    Chu-Su, Yu; Shukuya, Kenichi; Yokoyama, Takashi; Lin, Wei-Chou; Chiang, Chih-Kang; Lin, Chii-Wann

    2017-01-11

    Urinary sediment is used to evaluate patients with possible urinary tract diseases. Currently, numerous protocols are applied to detect dysmorphic red blood cells (RBCs) and renal tubular epithelial cells (RTECs) in urinary sediment. However, distinct protocols are used by nephrologists and medical technologists for specimen concentration and observation, which leads to major discrepancies in the differential counts of formed elements such as dysmorphic RBCs and RTECs and might interfere with an accurate clinical diagnosis. To resolve these problems, we first tested a modified urinalysis protocol with an increased relative centrifuge force and concentration factor in 20 biopsy-confirmed glomerulonephritis patients with haematuria. We successfully improved the recovery ratio of dysmorphic RBCs in clinical specimens from 34.7% to 42.0% (P dysmorphic RBCs were detected using a bright field microscope, with results comparable to those using a standard phase contrast microscope. Finally, we applied Sternheimer stain to enhance the contrast of RTECs in the urinary sediments. We concluded that this modified urinalysis protocol significantly enhanced the quality of urinalysis.

  5. Lithium clearance and renal tubular sodium handling during acute and long-term nifedipine treatment in essential hypertension

    DEFF Research Database (Denmark)

    Bruun, N E; Ibsen, H; Skøtt, P

    1988-01-01

    1. In two separate studies the lithium clearance method was used to evaluate the influence of acute and long-term nifedipine treatment on renal tubular sodium reabsorption. 2. In the acute study, after a 4 week placebo period two doses of 20 mg of nifedipine decreased supine blood pressure from 155...... were also unchanged, as were potassium clearance, urine flow and body weight. 3. In the long-term study, lithium clearance, glomerular filtration rate, sodium clearance, potassium clearance, urine flow and body fluid volumes were measured after a 4 weeks placebo period and after 6 and 12 weeks....../101 (20.6/13.5) +/- 11/4 (1.5/0.5) to 139/88 (18.5/11.7) +/- 16/9 (2.1/1.2) mmHg (kPa) (means +/- SD; P less than 0.01). Lithium clearance, glomerular filtration rate and sodium clearance did not change. Therefore the calculated values of absolute proximal and absolute distal sodium reabsorption rates...

  6. Is percutaneous microwave ablation of liver tumor safe for patients with renal dysfunction

    International Nuclear Information System (INIS)

    Liu Cun; Wang Yang; Yu Xiaoling; Dong Baowei; Zhou Pei; Ren He; Liang Ping

    2011-01-01

    Purpose: To determine the safety of percutaneous microwave ablation of primary and metastatic liver tumor for patients with renal dysfunction. Materials and methods: Fifty primary and metastatic liver tumors in 23 patients with renal dysfunction were retrospectively reviewed at our institution. Renal function was determined by measuring serum creatinine and serum urea before MWA as baseline, within 1 week and at last follow-up. The mean creatinine was 1.69 ± 0.32 mg/dL, 1.71 ± 0.33 mg/dL, and 1.71 ± 0.26 mg/dL respectively, there was not a statistically significant difference between baseline and at last follow-up (P = 0.26). The mean serum urea was 52.52 ± 6.48 mg/dL, 56.55 ± 14.72 mg/dL, and 57.90 ± 16.39 mg/dL respectively, there was not a statistically significant difference between baseline and within 1 week (P = 0.119), between within baseline and at last follow-up (P = 0.090). At the last follow-up examination, all patients had adequately functioning kidneys and did not require any form of renal replacement therapy. This is a small retrospectively study including highly selected patients treated. Therefore, further study should to determine the safety of percutaneous MWA for patients with renal dysfunction in the future. Conclusions: Percutaneous microwave ablation of primary and metastatic liver tumor is no adverse influence on renal function for patients with renal dysfunction in this preliminary series, which can be a minimally invasive alternative therapy.

  7. Urinary β2 microglobulin can predict tenofovir disoproxil fumarate-related renal dysfunction in HIV-1-infected patients who initiate tenofovir disoproxil fumarate-containing antiretroviral therapy.

    Science.gov (United States)

    Nishijima, Takeshi; Kurosawa, Takuma; Tanaka, Noriko; Kawasaki, Yohei; Kikuchi, Yoshimi; Oka, Shinichi; Gatanaga, Hiroyuki

    2016-06-19

    In nephrotoxicity induced by tenofovir disoproxil fumarate (TDF), tubular dysfunction precedes the decline in GFR, suggesting that tubular markers are more sensitive than estimated glomerular filtration rate (eGFR). The hypothesis that urinary β2 microglobulin (β2 M), a tubular function marker, can predict TDF-renal dysfunction in HIV-1-infected patients was tested. A single-center observational study. The inclusion criteria were: HIV-1-infected patients who started TDF-containing antiretroviral therapy from 2004 to 2013, urinary β2 M after and closest to the day of TDF initiation within 180 days (termed 'β2 M after TDF') was measured. The associations between 'β2 M after TDF' and four renal end points (>10 ml/min per 1.73 m decrement in eGFR relative to baseline, >20 decrement, >25% decrement, and eGFR model. The association between 'β2 M after TDF' and longitudinal changes in eGFR after initiation of TDF was estimated with a mixed-model. A total 655 study patients were analyzed (96% men, median age 38, median CD4 238 cells/μl, 63% treatment naïve). The median baseline eGFR was 117 ml/min per 1.73 m (IQR 110-125), and the median duration of TDF use was 3.32 years (IQR 2.02-5.31). 'β2 M after TDF' was significantly associated with more than 20 decrement in eGFR (P = 0.024) and more than 25% decrement (P = 0.014), and was marginally associated with eGFR less than 60 (P = 0.076). It was also significantly associated with the longitudinal eGFR after initiation of TDF (P < 0.0001). 'β2 M after TDF' of 1700 μg/l was identified as the optimal cutoff value for the prediction of longitudinal eGFR. Urinary β2 M measured within 180 days after initiation of TDF predicts renal dysfunction related to long-term TDF use.

  8. Prevalence and Factors Associated with Renal Dysfunction in HIV ...

    African Journals Online (AJOL)

    Background: Despite having the highest disease burden of HIV, Sub-Saharan Africa has limited data on HIV related kidney disease with most available data coming from the developed countries. Kidney disease is a recognised complication in HIV infected patients presenting with acute renal failure (ARF) or chronic kidney ...

  9. Comparing cystatin C and creatinine in the diagnosis of pediatric acute renal allograft dysfunction

    NARCIS (Netherlands)

    Slort, Pauline R.; Ozden, Nergiz; Pape, Lars; Offner, Gisela; Tromp, Wilma F.; Wilhelm, Abraham J.; Bokenkamp, Arend

    2012-01-01

    Allograft function following renal transplantation is commonly monitored using serum creatinine. Multiple cross-sectional studies have shown that serum cystatin C is superior to creatinine for detection of mild to moderate chronic kidney dysfunction. Recent data in adults indicate that cystatin C

  10. CD16(+) monocytes with smooth muscle cell characteristics are reduced in human renal chronic transplant dysfunction

    NARCIS (Netherlands)

    Boersema, M.; van den Born, Joost; van Ark, J.; Harms, Geertruida; Seelen, M. A.; van Dijk, M. C. R. F.; van Goor, H.; Navis, G. J.; Popa, E. R.; Hillebrands, J. L.

    In chronic transplant dysfunction (CTD), persistent (allo)immune-mediated inflammation eventually leads to tissue remodeling including neointima formation in intragraft arteries. We previously showed that recipient-derived neointimal alpha-SMA(+) smooth muscle-like cells are present in human renal

  11. A Systematic Review on Renal and Bladder Dysfunction after Endoscopic Treatment of Infravesical Obstruction in Boys

    NARCIS (Netherlands)

    Hennus, Pauline M. L.; van der Heijden, Geert J. M. G.; Bosch, J. L. H. Ruud; de Jong, Tom P. V. M.; de Kort, Laetitia M. O.

    2012-01-01

    Background: Posterior urethral valves (PUV) may cause subtle to severe obstruction of the urethra, resulting in a broad clinical spectrum. PUV are the most common cause of chronic renal disease in boys. Our purpose was to report the incidences of kidney and bladder dysfunction in boys treated with

  12. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism.

    Science.gov (United States)

    Zhang, Xiuli; Liang, Dan; Lian, Xu; Jiang, Yan; He, Hui; Liang, Wei; Zhao, Yue; Chi, Zhi-Hong

    2016-06-01

    Apoptosis of tubular epithelial cells is a major feature of diabetic kidney disease, and hyperglycemia triggers the generation of free radicals and oxidant stress in tubular cells. Berberine (BBR) is identified as a potential anti-diabetic herbal medicine due to its beneficial effects on insulin sensitivity, glucose metabolism and glycolysis. In this study, the underlying mechanisms involved in the protective effects of BBR on high glucose-induced apoptosis were explored using cultured renal tubular epithelial cells (NRK-52E cells) and human kidney proximal tubular cell line (HK-2 cells). We identified the pivotal role of phosphatidylinositol 3-kinase (PI3K)/Akt in BBR cellular defense mechanisms and revealed the novel effect of BBR on nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2) and heme oxygenase (HO)-1 in NRK-52E and HK-2 cells. BBR attenuated reactive oxygen species production, antioxidant defense (GSH and SOD) and oxidant-sensitive proteins (Nrf2 and HO-1), which also were blocked by LY294002 (an inhibitor of PI3K) in HG-treated NRK-52E and HK-2 cells. Furthermore, BBR improved mitochondrial function by increasing mitochondrial membrane potential. BBR-induced anti-apoptotic function was demonstrated by decreasing apoptotic proteins (cytochrome c, Bax, caspase3 and caspase9). All these findings suggest that BBR exerts the anti-apoptosis effects through activation of PI3K/Akt signal pathways and leads to activation of Nrf2 and induction of Nrf2 target genes, and consequently protecting the renal tubular epithelial cells from HG-induced apoptosis.

  13. Renal Dysfunction after Off-Pump Coronary Artery Bypass Surgery- Risk Factors and Preventive Strategies

    Directory of Open Access Journals (Sweden)

    Gaurab Maitra

    2009-01-01

    Full Text Available Postoperative renal dysfunction is a relatively common and one of the serious complications of cardiac surgery. Though off-pump coronary artery bypass surgery technique avoids cardiopulmonary bypass circuit induced adverse effects on renal function, multiple other factors cause postoperative renal dysfunction in these groups of patients. Acute kidney injury is generally defined as an abrupt and sustained decrease in kidney function. There is no consen-sus on the amount of dysfunction that defines acute kidney injury, with more than 30 definitions in use in the literature today. Although serum creatinine is widely used as a marker for changes in glomerular filtration rate, the criteria used to define renal dysfunction and acute renal failure is highly variable. The variety of definitions used in clinical studies may be partly responsible for the large variations in the reported incidence. Indeed, the lack of a uniform definition for acute kidney injury is believed to be a major impediment to research in the field. To establish a uniform definition for acute kidney injury, the Acute Dialysis Quality Initiative formulated the Risk, Injury, Failure, Loss, and End-stage Kidney (RIFLE classification. RIFLE , defines three grades of increasing severity of acute kidney injury -risk (class R, injury (class I and failure (class F - and two outcome classes (loss and end-stage kidney disease. Various perioperative risk factors for postoperative renal dysfunction and failure have been identified. Among the important preoperative factors are advanced age, reduced left ventricular function, emergency surgery, preoperative use of intraaortic balloon pump, elevated preoperative serum glucose and creatinine. Most important intraoperative risk factor is the intraoperative haemodynamic instability and all the causes of postoperative low output syndrome com-prise the postoperative risk factors. The most important preventive strategies are the identification of the

  14. Renal Dysfunction in the Presence of Normoalbuminuria in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Dwyer, Jamie P; Parving, Hans-Henrik; Hunsicker, Lawrence G

    2012-01-01

    population of patients with type 2 diabetes. Renal dysfunction was present in a large proportion of these patients without proteinuria, assessed by a single random albumin-to-creatinine ratio (ACR). We therefore undertook to characterize the nature of this association of non-proteinuric renal dysfunction...... in type 2 diabetes. METHODS: In the DEMAND (Developing Education on Microalbuminuria for Awareness of Renal and Cardiovascular Risk in Diabetes) study, a global, cross-sectional study which described the prevalence and risk factors for albuminuria in a clinic-based cohort, kidney function was assessed...... in 11,573 patients; ACR was measured using the Bayer reagent strip Multistix® 10SG. Normoalbuminuria was defined as ACR 300 mg/g. RESULTS: Among the patients with estimated kidney function determined, chronic kidney disease was noted in 17% of those with normoalbuminuria (stage 3-5), and significant...

  15. ER stress and basement membrane defects combine to cause glomerular and tubular renal disease resulting from Col4a1 mutations in mice

    Directory of Open Access Journals (Sweden)

    Frances E. Jones

    2016-02-01

    Full Text Available Collagen IV is a major component of basement membranes, and mutations in COL4A1, which encodes collagen IV alpha chain 1, cause a multisystemic disease encompassing cerebrovascular, eye and kidney defects. However, COL4A1 renal disease remains poorly characterized and its pathomolecular mechanisms are unknown. We show that Col4a1 mutations in mice cause hypotension and renal disease, including proteinuria and defects in Bowman's capsule and the glomerular basement membrane, indicating a role for Col4a1 in glomerular filtration. Impaired sodium reabsorption in the loop of Henle and distal nephron despite elevated aldosterone levels indicates that tubular defects contribute to the hypotension, highlighting a novel role for the basement membrane in vascular homeostasis by modulation of the tubular response to aldosterone. Col4a1 mutations also cause diabetes insipidus, whereby the tubular defects lead to polyuria associated with medullary atrophy and a subsequent reduction in the ability to upregulate aquaporin 2 and concentrate urine. Moreover, haematuria, haemorrhage and vascular basement membrane defects confirm an important vascular component. Interestingly, although structural and compositional basement membrane defects occurred in the glomerulus and Bowman's capsule, no tubular basement membrane defects were detected. By contrast, medullary atrophy was associated with chronic ER stress, providing evidence for cell-type-dependent molecular mechanisms of Col4a1 mutations. These data show that both basement membrane defects and ER stress contribute to Col4a1 renal disease, which has important implications for the development of treatment strategies for collagenopathies.

  16. No effect of dietary fish oil on renal hemodynamics, tubular function, and renal functional reserve in long-term renal transplant recipients

    DEFF Research Database (Denmark)

    Hansen, J M; Løkkegaard, H; Høy, Carl-Erik

    1995-01-01

    Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healt...... transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.......Dietary supplementation with fish oil rich in n-3 polyunsaturated fatty acids has been suggested to protect the kidney against cyclosporin A (CsA) toxicity. This study investigated the effects of a 10-wk dietary supplementation with fish oil on renal function and renal functional reserve in healthy...... volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR...

  17. Management of renal dysfunction following term perinatal hypoxia-ischaemia.

    LENUS (Irish Health Repository)

    Sweetman, Deirdre U

    2013-03-01

    Acute kidney injury frequently develops following the term perinatal hypoxia-ischaemia. Quantifying the degree of acute kidney injury is difficult, however, as the methods currently in use are suboptimal. Acute kidney injury management is largely supportive with little evidence basis for many interventions. This review discusses management strategies and novel biomarkers that may improve diagnosis and management of renal injury following perinatal hypoxia-ischaemia.

  18. The cholinergic pathway alleviates acute oxygen and glucose deprivation induced renal tubular cell injury by reducing the secretion of inflammatory medium of macrophages

    Directory of Open Access Journals (Sweden)

    Ming WU

    2017-10-01

    Full Text Available Objective To investigate the effects of cholinergic pathway on acute renal tubular cell injury induced by acute oxygen and glucose deprivation. Methods Rat kidney macrophages were isolated and cultured for constructing macrophages and renal epithelial cells co-cultivating model of oxygen-glucose deprivation (OGD, and the model cells were divided into three groups: OGD alone group, acetylcholine (ACh 100μmol/L+OGD group and ACh + galantamine (Gal 10μmol/L+OGD group. The cells underwent OGD treatment for 1 hour, and normally cultured for 24 hours. The expressions of TNF alpha, IL-1 beta, and IL-10 in supernatant fluid were detected by ELISA, the renal tubular cell viability was determined by MTT assay, the expression of acetylcholine esterase (AChE mRNA and protein were determined by RT-qPCR and Western blotting. The activity of AChE was determined by colorimetric method. Results The expressions of TNF alpha (pg/ml in OGD, Ach+OGD group, Ach+Gal+OGD groups were 140.2±44.81, 119.46±4.42 and 103.31±1.62 respectively (P0.05; The values of renal tubular cell proliferation were 55.02%±6.28%, 66.65%±6.47%, and 79.75%±4.22% respectively (P0.05; those of AchE protein were 0.66±0.07, 0.74±0.04 and 0.67±0.06 respectively (P>0.05; The activity of AChE (kU/L was 0.51±0.02, 0.35±0.05 and 0.32±0.04 respectively (P=0.001, 0.001 and 0.368. Conclusions ACh and Gal could inhibit the secretion of inflammatory mediators and cholinesterase activity and can reduce the acute hypoxic renal tubular cell injury. The modulation of the cholinergic pathway in macrophages may be the important treatment method for acute renal injury in the future. DOI: 10.11855/j.issn.0577-7402.2017.08.01

  19. Necesidad de estudio genético para el diagnóstico de algunos casos de acidosis tubular renal distal

    Directory of Open Access Journals (Sweden)

    Manuel Heras Benito

    2016-09-01

    Full Text Available Describimos el caso de una mujer joven, que fue diagnosticada de insuficiencia renal avanzada, con un hallazgo casual de una nefrocalcinosis sin una etiología clara, al haberse encontrado asintomática a lo largo de su vida. El estudio genético por paneles de genes conocidos asociados a enfermedad tubulointersticial permitió descubrir una acidosis tubular renal distal autosómica dominante, asociada a una mutación de novo en el exón 14 del gen SLC4A1, que hubiera sido imposible diagnosticar clínicamente por lo avanzado de la enfermedad renal cuando fue descubierta.

  20. [Decursin reduces reactive oxygen species and inhibits cisplatin-induced apoptosis in rat renal tubular epithelial cells].

    Science.gov (United States)

    Li, Cuiqiong; Li, Jianchun; Fan, Junming; Meng, Lifeng; Cao, Ling

    2017-10-01

    Objective To study the mechanism underlying the inhibitory effect of decursin on the apoptosis of rat renal tubular epithelial cells NRK-52E induced by cisplatin. Methods First, CCK-8 assay was used to detect the effects of 0, 10, 20, 40, 80, 100, 150, 200 μmol/L decursin and 0, 5, 10, 20, 30, 40, 50 μg/mL cispatin treatment for 24 hours on cell proliferation in NRK-52E cells via determining the half inhibitory concentration (IC 50 ). Then, NRK-52E cells were stimulated with 20 μg/mL cisplatin combined with 10, 50, 100 μmol/L decursin, and cell activity was detected by CCK-8 assay. The cells were divided into normal control group, 20 μg/mL cisplatin stimulation group, and 10, 50, 100 μmol/L decursin treated groups. Cell morphological changes was observed under inverted microscope, morphological changes of nucleus was detected by DAPI staining, cell apoptosis was detected by flow cytometry, the level of intracellular ROS was detected by DCFH-DA staining, and the apoptosis marker proteins cleaved-caspase-3 and cleaved-PARP were examined by Western blot analysis. Results Compared with the normal control group, cisplatin significantly inhibited the activity of the cells, and IC 50 was about 20 μg/mL; compared with the model group, in the decursin pretreatment groups, the level of intracellular ROS decreased remarkably, the expressions of cleaved-casspase-3 and cleaved-PARP proteins were reduced, and cell apoptosis was depressed. Conclusion Decursin can decrease the intracellular ROS level and inhibit the apoptosis of NRK-52E cells induced by cisplatin.

  1. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  2. Dahuang Fuzi Decoction Attenuates Renal Fibrosis and Ameliorates Mitochondrial Dysfunction in Chronic Aristolochic Acid Nephropathy

    Directory of Open Access Journals (Sweden)

    Guang-xing Shui

    2017-01-01

    Full Text Available Objectives. The effects of the traditional formula Dahuang Fuzi Decoction (DFD on chronic aristolochic acid nephropathy (AAN in mice and its underlying mechanisms were studied. Methods. Mice were randomly divided into the following six groups: the control group, the model group (AAN, the saline-treated group (AAN + vehicle, the normal dose DFD-treated group (AAN + NDFD, the high dose DFD-treated group (AAN + HDFD, and the rosiglitazone treated group (AAN + Rosi. After treating for 8 weeks, 24 h urine and blood samples were collected and the mice sacrificed to study the biochemical parameters associated with renal function. The samples were analyzed for renal fibrosis and mitochondrial dysfunction (MtD markers. To achieve that, collagen III, collagen I, mitochondrial DNA copy numbers (mtDNA, mitochondrial membrane potential (MMP, ATP content, and ROS production were evaluated. Results. Our results showed that proteinuria, kidney function, and the renal pathological characteristics were improved by DFD and rosiglitazone. The expression of collagen III and collagen I decreased after treating with either DFD or rosiglitazone. Mitochondrial dysfunction based on the increase in ROS production, decrease in mitochondrial DNA copy numbers, and reduction of MMP and ATP content was improved by DFD and rosiglitazone. Conclusions. DFD could protect against renal impairments and ameliorate mitochondrial dysfunction in chronic AAN mice.

  3. Endovascular management of renal transplant dysfunction secondary to hemodynamic effects related to ipsilateral femoral arteriovenous graft

    Science.gov (United States)

    Salsamendi, Jason; Pereira, Keith; Quintana, David; Bleicher, Drew; Tabbara, Marwan; Goldstein, Michael; Narayanan, Govindarajan

    2016-01-01

    Hemodialysis access options become complex in long-term treatment for patients with renal disease, while awaiting renal transplantation (RT). Once upper extremity sites are exhausted, lower extremities are used. RT is preferably in the contralateral iliac fossa, rarely ipsilateral. In current literature, RT dysfunction secondary to the hemodynamic effects of an ipsilateral femoral arteriovenous graft (AVG) has been rarely described. To our knowledge, AVG ligation is the only published technique for hemodynamic correction of an ipsilateral AVG. We present a simple, potentially reversible endovascular approach to manage the hemodynamic effects of an AVG, without potentially permanently losing future AVG access. PMID:26899147

  4. Urinary NGAL Ratio Is Not a Sensitive Biomarker for Monitoring Acute Tubular Injury in Kidney Transplant Patients: NGAL and ATI in Renal Transplant Patients

    Directory of Open Access Journals (Sweden)

    Jessica K. Kaufeld

    2012-01-01

    Full Text Available Urinary neutrophil gelatinase-associated lipocalin (uNGAL is known to predict the prolonged delayed graft function after kidney transplantation. We examined the relation of uNGAL with histological findings of acute tubular injury (ATI. Analyses were made in biopsies taken at 6 weeks, 3 months, and 6 months after kidney transplantation. uNGAL was measured in the spot urines, normalized to urinary creatinine excretion, and correlated to biopsy findings and clinical, laboratory, and demographic variables. Controls included healthy individuals, individuals after kidney donation and ICU patients with acute kidney failure. Renal transplant recipients without ATI did not display elevated uNGAL levels compared to the healthy controls. Transplant patients with ATI had a higher uNGAL excretion at 6 weeks than patients without ATI (27,435 versus 13,605 ng/g; P=0.031. This increase in uNGAL was minor compared to ICU patients with acute renal failure (2.05×106 ng/g. Patients with repeated findings of ATI or severe ATI did not have higher urinary NGAL levels compared to those with only one ATI finding or moderate ATI. Female recipient gender and urinary tract infection were identified as potential confounders. uNGAL has a relation with histological signs of acute tubular injury. The usability of this biomarker in renal allograft recipients is limited because of the low sensitivity.

  5. Inclusion and definition of acute renal dysfunction in critically ill patients in randomized controlled trials: a systematic review.

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    da Hora Passos, Rogerio; Ramos, Joao Gabriel Rosa; Gobatto, André; Caldas, Juliana; Macedo, Etienne; Batista, Paulo Benigno

    2018-04-24

    In evidence-based medicine, multicenter, prospective, randomized controlled trials (RCTs) are the gold standard for evaluating treatment benefits and ensuring the effectiveness of interventions. Patient-centered outcomes, such as mortality, are most often the preferred evaluated outcomes. While there is currently agreement on how to classify renal dysfunction in critically ill patients , the application frequency of this new classification system in RCTs has not previously been evaluated. In this study, we aim to assess the definition of renal dysfunction in multicenter RCTs involving critically ill patients that included mortality as a primary endpoint. A comprehensive search was conducted for publications reporting multicenter randomized controlled trials (RCTs) involving adult patients in intensive care units (ICUs) that included mortality as a primary outcome. MEDLINE and PUBMED were queried for relevant articles in core clinical journals published between May 2004 and December 2017. Of 418 articles reviewed, 46 multicenter RCTs with a primary endpoint related to mortality were included. Thirty-six (78.3%) of the trial reports provided information on renal function in the participants. Only seven articles (15.2%) included mean or median serum creatinine levels, mean creatinine clearance or estimated glomerular filtration rates. Sequential organ failure assessment (SOFA) score was the most commonly used definition of renal dysfunction (20 studies; 43.5%). Risk, Injury, Failure, Loss, End-stage renal disease (RIFLE), Acute Kidney Injury Network (AKIN) and Kidney Disease Improving Global Outcomes (KDIGO) criteria were used in five (10.9%) trials. In thirteen trials (28.3%), no renal dysfunction criteria were reported. Only one trial excluded patients with renal dysfunction, and it used urinary output or need for renal replacement therapy (RRT) as criteria for this diagnosis. The presence of renal dysfunction was included as a baseline patient characteristic in

  6. C-peptide increases Na,K-ATPase expression via PKC- and MAP kinase-dependent activation of transcription factor ZEB in human renal tubular cells.

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    Dana Galuska

    Full Text Available Replacement of proinsulin C-peptide in type 1 diabetes ameliorates nerve and kidney dysfunction, conditions which are associated with a decrease in Na,K-ATPase activity. We determined the molecular mechanism by which long term exposure to C-peptide stimulates Na,K-ATPase expression and activity in primary human renal tubular cells (HRTC in control and hyperglycemic conditions.HRTC were cultured from the outer cortex obtained from patients undergoing elective nephrectomy. Ouabain-sensitive rubidium ((86Rb(+ uptake and Na,K-ATPase activity were determined. Abundance of Na,K-ATPase was determined by Western blotting in intact cells or isolated basolateral membranes (BLM. DNA binding activity was determined by electrical mobility shift assay (EMSA. Culturing of HRTCs for 5 days with 1 nM, but not 10 nM of human C-peptide leads to increase in Na,K-ATPase α(1-subunit protein expression, accompanied with increase in (86Rb(+ uptake, both in normal- and hyperglycemic conditions. Na,K-ATPase α(1-subunit expression and Na,K-ATPase activity were reduced in BLM isolated from cells cultured in presence of high glucose. Exposure to1 nM, but not 10 nM of C-peptide increased PKCε phosphorylation as well as phosphorylation and abundance of nuclear ERK1/2 regardless of glucose concentration. Exposure to 1 nM of C-peptide increased DNA binding activity of transcription factor ZEB (AREB6, concomitant with Na,K-ATPase α(1-subunit mRNA expression. Effects of 1 nM C-peptide on Na,K-ATPase α(1-subunit expression and/or ZEB DNA binding activity in HRTC were abolished by incubation with PKC or MEK1/2 inhibitors and ZEB siRNA silencing.Despite activation of ERK1/2 and PKC by hyperglycemia, a distinct pool of PKCs and ERK1/2 is involved in regulation of Na,K-ATPase expression and activity by C-peptide. Most likely C-peptide stimulates sodium pump expression via activation of ZEB, a transcription factor that has not been previously implicated in C

  7. Role of IGFBP7 in Diabetic Nephropathy: TGF-β1 Induces IGFBP7 via Smad2/4 in Human Renal Proximal Tubular Epithelial Cells.

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    Jun Watanabe

    Full Text Available Tubular injury is one of the important determinants of progressive renal failure in diabetic nephropathy (DN, and TGF-β1 has been implicated in the pathogenesis of tubulointerstitial disease that characterizes proteinuric renal disease. The aim of this study was to identify novel therapeutic target molecules that play a role in the tubule damage of DN. We used an LC-MS/MS-based proteomic technique and human renal proximal epithelial cells (HRPTECs. Urine samples from Japanese patients with type 2 diabetes (n = 46 were used to quantify the candidate protein. Several proteins in HRPTECs in cultured media were observed to be driven by TGF-β1, one of which was 33-kDa IGFBP7, which is a member of IGFBP family. TGF-β1 up-regulated the expressions of IGFBP7 mRNA and protein in a dose- and time-dependent fashion via Smad2 and 4, but not MAPK pathways in HRPTECs. In addition, the knockdown of IGFBP7 restored the TGF-β1-induced epithelial to mesenchymal transition (EMT. In the immunohistochemical analysis, IGFBP7 was localized to the cytoplasm of tubular cells but not that of glomerular cells in diabetic kidney. Urinary IGFBP7 levels were significantly higher in the patients with macroalbuminuria and were correlated with age (r = 0.308, p = 0.037, eGFR (r = -0.376, p = 0.01, urinary β2-microglobulin (r = 0.385, p = 0.008, and urinary N-acetyl-beta-D-glucosaminidase (NAG (r = 0.502, p = 0.000. A multivariate regression analysis identified urinary NAG and age as determinants associated with urinary IGFBP7 levels. In conclusion, our data suggest that TGF-β1 enhances IGFBP7 via Smad2/4 pathways, and that IGFBP7 might be involved in the TGF-β1-induced tubular injury in DN.

  8. Idh2 deficiency accelerates renal dysfunction in aged mice.

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    Lee, Su Jeong; Cha, Hanvit; Lee, Seoyoon; Kim, Hyunjin; Ku, Hyeong Jun; Kim, Sung Hwan; Park, Jung Hyun; Lee, Jin Hyup; Park, Kwon Moo; Park, Jeen-Woo

    2017-11-04

    The free radical or oxidative stress theory of aging postulates that senescence is due to an accumulation of cellular oxidative damage, caused largely by reactive oxygen species (ROS) that are produced as by-products of normal metabolic processes in mitochondria. The oxidative stress may arise as a result of either increased ROS production or decreased ability to detoxify ROS. The availability of the mitochondrial NADPH pool is critical for the maintenance of the mitochondrial antioxidant system. The major enzyme responsible for generating mitochondrial NADPH is mitochondrial NADP + -dependent isocitrate dehydrogenase (IDH2). Depletion of IDH2 in mice (idh2 -/- ) shortens life span and accelerates the degeneration of multiple age-sensitive traits, such as hair grayness, skin pathology, and eye pathology. Among the various internal organs tested in this study, IDH2 depletion-induced acceleration of senescence was uniquely observed in the kidney. Renal function and structure were greatly deteriorated in 24-month-old idh2 -/- mice compared with wild-type. In addition, disruption of redox status, which promotes oxidative damage and apoptosis, was more pronounced in idh2 -/- mice. These data support a significant role for increased oxidative stress as a result of compromised mitochondrial antioxidant defenses in modulating life span in mice, and thus support the oxidative stress theory of aging. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Indomethacin reduces glomerular and tubular damage markers but not renal inflammation in chronic kidney disease patients: a post-hoc analysis.

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    Martin H de Borst

    Full Text Available Under specific conditions non-steroidal anti-inflammatory drugs (NSAIDs may be used to lower therapy-resistant proteinuria. The potentially beneficial anti-proteinuric, tubulo-protective, and anti-inflammatory effects of NSAIDs may be offset by an increased risk of (renal side effects. We investigated the effect of indomethacin on urinary markers of glomerular and tubular damage and renal inflammation. We performed a post-hoc analysis of a prospective open-label crossover study in chronic kidney disease patients (n = 12 with mild renal function impairment and stable residual proteinuria of 4.7±4.1 g/d. After a wash-out period of six wks without any RAAS blocking agents or other therapy to lower proteinuria (untreated proteinuria (UP, patients subsequently received indomethacin 75 mg BID for 4 wks (NSAID. Healthy subjects (n = 10 screened for kidney donation served as controls. Urine and plasma levels of total IgG, IgG4, KIM-1, beta-2-microglobulin, H-FABP, MCP-1 and NGAL were determined using ELISA. Following NSAID treatment, 24 h -urinary excretion of glomerular and proximal tubular damage markers was reduced in comparison with the period without anti-proteinuric treatment (total IgG: UP 131[38-513] vs NSAID 38[17-218] mg/24 h, p<0.01; IgG4: 50[16-68] vs 10[1-38] mg/24 h, p<0.001; beta-2-microglobulin: 200[55-404] vs 50[28-110] ug/24 h, p = 0.03; KIM-1: 9[5]-[14] vs 5[2]-[9] ug/24 h, p = 0.01. Fractional excretions of these damage markers were also reduced by NSAID. The distal tubular marker H-FABP showed a trend to reduction following NSAID treatment. Surprisingly, NSAID treatment did not reduce urinary excretion of the inflammation markers MCP-1 and NGAL, but did reduce plasma MCP-1 levels, resulting in an increased fractional MCP-1 excretion. In conclusion, the anti-proteinuric effect of indomethacin is associated with reduced urinary excretion of glomerular and tubular damage markers, but not with reduced excretion of renal

  10. Glutamyl aminopeptidase in microvesicular and exosomal fractions of urine is related with renal dysfunction in cisplatin-treated rats.

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    Andrés Quesada

    exosomal fractions of urine is an early and predictive biomarker of renal dysfunction in cisplatin-induced nephrotoxicity. Measurement of GluAp in these fractions can serve to detect proximal tubular damage independently of glomerular filtration status.

  11. Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

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    Andrés Quesada

    Full Text Available This study analyzes the fluorimetric determination of alanyl- (Ala, glutamyl- (Glu, leucyl-cystinyl- (Cys and aspartyl-aminopeptidase (AspAp urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG, albumin, and neutrophil gelatinase-associated lipocalin (NGAL. Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259 with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

  12. Prognostic impact of renal dysfunction does not differ according to the clinical profiles of patients: insight from the acute decompensated heart failure syndromes (ATTEND registry.

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    Taku Inohara

    Full Text Available BACKGROUND: Renal dysfunction associated with acute decompensated heart failure (ADHF is associated with impaired outcomes. Its mechanism is attributed to renal arterial hypoperfusion or venous congestion, but its prognostic impact based on each of these clinical profiles requires elucidation. METHODS AND RESULTS: ADHF syndromes registry subjects were evaluated (N = 4,321. Logistic regression modeling calculated adjusted odds ratios (OR for in-hospital mortality for patients with and without renal dysfunction. Renal dysfunction risk was calculated for subgroups with hypoperfusion-dominant (eg. cold extremities, a low mean blood pressure or a low proportional pulse pressure or congestion-dominant clinical profiles (eg. peripheral edema, jugular venous distension, or elevated brain natriuretic peptide to evaluate renal dysfunction's prognostic impact in the context of the two underlying mechanisms. On admission, 2,150 (49.8% patients aged 73.3 ± 13.6 years had renal dysfunction. Compared with patients without renal dysfunction, those with renal dysfunction were older and had dominant ischemic etiology jugular venous distension, more frequent cold extremities, and higher brain natriuretic peptide levels. Renal dysfunction was associated with in-hospital mortality (OR 2.36; 95% confidence interval 1.75-3.18, p0.05. CONCLUSIONS: Baseline renal dysfunction was significantly associated with in-hospital mortality in ADHF patients. The prognostic impact of renal dysfunction was the same, regardless of its underlying etiologic mechanism.

  13. Application of path analysis to urinary findings of cadmium-induced renal dysfunction.

    Science.gov (United States)

    Abe, T; Kobayashi, E; Okubo, Y; Suwazono, Y; Kido, T; Shaikh, Z A; Nogawa, K

    2001-01-01

    In order to identify some causal relations among various urinary indices of cadmium-induced renal dysfunction, such as glucose, total protein, amino nitrogen, beta 2-microglobulin (beta 2-m), metallothionein (MT), and cadmium (Cd), we applied path analysis method to previous epidemiological studies targeting the residents of the Cd-polluted Kakehashi River basin of Ishikawa Prefecture, Japan. We obtained a diagram-termed path model, representing some causal relations among the above urinary indices. It shows that urinary Cd is located at the beginning point in the diagram, and Cd-induced renal dysfunction develops in the following order: Cd exposure-->increase of beta 2-m and/or MT excretion-->increase of amino-N and/or total protein excretion-->increase of glucose excretion. It was proved mathematically, that in the case of both males and females, increased excretions of beta 2-m and/or MT were the most sensitive urinary indices of the early stage of chronic Cd-induced renal dysfunction.

  14. Hemodynamic and tubular changes induced by contrast media.

    Science.gov (United States)

    Caiazza, Antonella; Russo, Luigi; Sabbatini, Massimo; Russo, Domenico

    2014-01-01

    The incidence of acute kidney injury induced by contrast media (CI-AKI) is the third cause of AKI in hospitalized patients. Contrast media cause relevant alterations both in renal hemodynamics and in renal tubular cell function that lead to CI-AKI. The vasoconstriction of intrarenal vasculature is the main hemodynamic change induced by contrast media; the vasoconstriction is accompanied by a cascade of events leading to ischemia and reduction of glomerular filtration rate. Cytotoxicity of contrast media causes apoptosis of tubular cells with consequent formation of casts and worsening of ischemia. There is an interplay between the negative effects of contrast media on renal hemodynamics and on tubular cell function that leads to activation of renin-angiotensin system and increased production of reactive oxygen species (ROS) within the kidney. Production of ROS intensifies cellular hypoxia through endothelial dysfunction and alteration of mechanisms regulating tubular cells transport. The physiochemical characteristics of contrast media play a critical role in the incidence of CI-AKI. Guidelines suggest the use of either isoosmolar or low-osmolar contrast media rather than high-osmolar contrast media particularly in patients at increased risk of CI-AKI. Older age, presence of atherosclerosis, congestive heart failure, chronic renal disease, nephrotoxic drugs, and diuretics may multiply the risk of CI-AKI.

  15. Genome-wide analysis of murine renal distal convoluted tubular cells for the target genes of mineralocorticoid receptor

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    Ueda, Kohei [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Fujiki, Katsunori; Shirahige, Katsuhiko [Research Center for Epigenetic Disease, Institute of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo (Japan); Gomez-Sanchez, Celso E. [Endocrine Section, G.V. (Sonny) Montgomery VA Medical Center, MS (United States); Endocrinology, University of Mississippi Medical Center, MS (United States); Fujita, Toshiro [Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo (Japan); Nangaku, Masaomi [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Nagase, Miki, E-mail: mnagase-tky@umin.ac.jp [Department of Nephrology and Endocrinology, The University of Tokyo, Tokyo (Japan); Department of Anatomy and Life Structure, School of Medicine Juntendo University, Tokyo (Japan)

    2014-02-28

    Highlights: • We define a target gene of MR as that with MR-binding to the adjacent region of DNA. • We use ChIP-seq analysis in combination with microarray. • We, for the first time, explore the genome-wide binding profile of MR. • We reveal 5 genes as the direct target genes of MR in the renal epithelial cell-line. - Abstract: Background and objective: Mineralocorticoid receptor (MR) is a member of nuclear receptor family proteins and contributes to fluid homeostasis in the kidney. Although aldosterone-MR pathway induces several gene expressions in the kidney, it is often unclear whether the gene expressions are accompanied by direct regulations of MR through its binding to the regulatory region of each gene. The purpose of this study is to identify the direct target genes of MR in a murine distal convoluted tubular epithelial cell-line (mDCT). Methods: We analyzed the DNA samples of mDCT cells overexpressing 3xFLAG-hMR after treatment with 10{sup −7} M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10{sup −7} M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10{sup −9} M aldosterone. Twenty-five genes were indicated as the candidate target genes of MR by ChIP-seq and microarray analyses. Five genes, Sgk1, Fkbp5, Rasl12, Tns1 and Tsc22d3 (Gilz), were validated as the direct target genes of MR by quantitative RT-qPCR and ChIP-qPCR. MR binding regions adjacent to Ctgf and Serpine1 were also validated. Conclusions: We, for the first time, captured the genome-wide distribution of MR in mDCT cells and, furthermore, identified five MR target genes in the cell-line. These results will contribute to further studies on the mechanisms of kidney diseases.

  16. Renal Tubular Acidosis

    Science.gov (United States)

    ... is called transport. One researcher has theorized that Charles Dickens may have been describing a child with ... urine and the potassium level in the blood will help identify which type of RTA a person ...

  17. Renal Tubular Acidosis

    Science.gov (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... More on this topic for: Parents Kids Teens Definition: Kidney Living With Lupus Nephrotic Syndrome Vesicoureteral Reflux ( ...

  18. Proximal renal tubular acidosis

    Science.gov (United States)

    ... or decreased alertness Dehydration Fatigue Increased breathing rate Osteomalacia (softening of the bones) Muscle pain Weakness Other ... correct bone disorders and reduce the risk of osteomalacia and osteopenia in adults. Some adults may need ...

  19. Long-term bladder dysfunction and renal function in boys with posterior urethral valves based on urodynamic findings

    NARCIS (Netherlands)

    M.A.I. Ghanem (Mazen); K.P. Wolffenbuttel (Katja); A. de Vylder (Ann); R.J.M. Nijman (Rien)

    2004-01-01

    textabstractPurpose: Posterior urethral valves are the most common cause of congenital obstructive uropathy leading to renal failure in childhood. We investigate the influence of bladder dysfunction on renal function impairment. Materials and Methods: We retrospectively reviewed the records of 116

  20. Long-term bladder dysfunction and renal function in boys with posterior urethral valves based on urodynamic findings

    NARCIS (Netherlands)

    Ghanem, MA; Wolffenbuttel, KP; De Vylder, A; Nijman, RJ

    Purpose: Posterior urethral valves are the most common cause of congenital obstructive uropathy leading to renal failure in childhood. We investigate the influence of bladder dysfunction on renal function impairment. Materials and Methods: We retrospectively reviewed the records of 116 patients with

  1. Characterization of Organic Anion Transporter 2 (SLC22A7): A Highly Efficient Transporter for Creatinine and Species-Dependent Renal Tubular Expression.

    Science.gov (United States)

    Shen, Hong; Liu, Tongtong; Morse, Bridget L; Zhao, Yue; Zhang, Yueping; Qiu, Xi; Chen, Cliff; Lewin, Anne C; Wang, Xi-Tao; Liu, Guowen; Christopher, Lisa J; Marathe, Punit; Lai, Yurong

    2015-07-01

    The contribution of organic anion transporter OAT2 (SLC22A7) to the renal tubular secretion of creatinine and its exact localization in the kidney are reportedly controversial. In the present investigation, the transport of creatinine was assessed in human embryonic kidney (HEK) cells that stably expressed human OAT2 (OAT2-HEK) and isolated human renal proximal tubule cells (HRPTCs). The tubular localization of OAT2 in human, monkey, and rat kidney was characterized. The overexpression of OAT2 significantly enhanced the uptake of creatinine in OAT2-HEK cells. Under physiologic conditions (creatinine concentrations of 41.2 and 123.5 µM), the initial rate of OAT2-mediated creatinine transport was approximately 11-, 80-, and 80-fold higher than OCT2, multidrug and toxin extrusion protein (MATE)1, and MATE2K, respectively, resulting in approximately 37-, 1850-, and 80-fold increase of the intrinsic transport clearance when normalized to the transporter protein concentrations. Creatinine intracellular uptake and transcellular transport in HRPTCs were decreased in the presence of 50 µM bromosulfophthalein and 100 µM indomethacin, which inhibited OAT2 more potently than other known creatinine transporters, OCT2 and multidrug and toxin extrusion proteins MATE1 and MATE2K (IC50: 1.3 µM vs. > 100 µM and 2.1 µM vs. > 200 µM for bromosulfophthalein and indomethacin, respectively) Immunohistochemistry analysis showed that OAT2 protein was localized to both basolateral and apical membranes of human and cynomolgus monkey renal proximal tubules, but appeared only on the apical membrane of rat proximal tubules. Collectively, the findings revealed the important role of OAT2 in renal secretion and possible reabsorption of creatinine and suggested a molecular basis for potential species difference in the transporter handling of creatinine. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  2. Significance of downregulation of renal organic cation transporter (SLC47A1 in cisplatin-induced proximal tubular injury

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    Mizuno T

    2015-07-01

    Full Text Available Tomohiro Mizuno,1–3 Waichi Sato,2,3 Kazuhiro Ishikawa,4 Yuki Terao,1 Kazuo Takahashi,2 Yukihiro Noda,5 Yukio Yuzawa,2 Tadashi Nagamatsu1 1Department of Analytical Pharmacology, Meijo University Faculty of Pharmacy, Nagoya, 2Department of Nephrology, School of Medicine, Fujita Health University, Toyoake, 3Department of Nephrology, Nagoya University School of Medicine, Nagoya, 4Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, 5Division of Clinical Sciences and Neuropsychopharmacology, Meijo University Faculty of Pharmacy, Nagoya, Japan Background/aim: To elucidate the mechanism responsible for developing acute kidney injury in patients with diabetes mellitus, we also evaluated the issue of whether advanced glycation endproducts (AGEs influence the expressions of multi antimicrobial extrusion protein (MATE1/SLC47A1 in tubular cells. Materials and methods: To detect changing expression of MATE1/SLC47A1 in dose- and time-dependent manners, human proximal tubular epithelial cells were incubated with AGE-aggregated-human serum albumin. As a function assay for MATE1/SLC47A1, human proximal tubular epithelial cells were incubated with cisplatin or carboplatin. Results: On incubation with AGEs, the expressions of MATE1/SLC47A1 were decreased in tubular cells. In addition, the toxicities of cisplatin were increased in tubular cells that had been pretreated with AGEs. However, the toxicities of carboplatin were smaller than that of cisplatin in proximal tubular epithelial cells. Conclusion: The expression of the MATE1/SLC47A1 is decreased by AGEs, which increases the risk for proximal tubular injury. Keywords: advanced glycation endproducts, cisplatin, SLC47A1, diabetes mellitus, acute kidney injury

  3. Identification of genomic biomarkers for concurrent diagnosis of drug-induced renal tubular injury using a large-scale toxicogenomics database

    International Nuclear Information System (INIS)

    Kondo, Chiaki; Minowa, Yohsuke; Uehara, Takeki; Okuno, Yasushi; Nakatsu, Noriyuki; Ono, Atsushi; Maruyama, Toshiyuki; Kato, Ikuo; Yamate, Jyoji; Yamada, Hiroshi; Ohno, Yasuo; Urushidani, Tetsuro

    2009-01-01

    Drug-induced renal tubular injury is one of the major concerns in preclinical safety evaluations. Toxicogenomics is becoming a generally accepted approach for identifying chemicals with potential safety problems. In the present study, we analyzed 33 nephrotoxicants and 8 non-nephrotoxic hepatotoxicants to elucidate time- and dose-dependent global gene expression changes associated with proximal tubular toxicity. The compounds were administered orally or intravenously once daily to male Sprague-Dawley rats. The animals were exposed to four different doses of the compounds, and kidney tissues were collected on days 4, 8, 15, and 29. Gene expression profiles were generated from kidney RNA by using Affymetrix GeneChips and analyzed in conjunction with the histopathological changes. We used the filter-type gene selection algorithm based on t-statistics conjugated with the SVM classifier, and achieved a sensitivity of 90% with a selectivity of 90%. Then, 92 genes were extracted as the genomic biomarker candidates that were used to construct the classifier. The gene list contains well-known biomarkers, such as Kidney injury molecule 1, Ceruloplasmin, Clusterin, Tissue inhibitor of metallopeptidase 1, and also novel biomarker candidates. Most of the genes involved in tissue remodeling, the immune/inflammatory response, cell adhesion/proliferation/migration, and metabolism were predominantly up-regulated. Down-regulated genes participated in cell adhesion/proliferation/migration, membrane transport, and signal transduction. Our classifier has better prediction accuracy than any of the well-known biomarkers. Therefore, the toxicogenomics approach would be useful for concurrent diagnosis of renal tubular injury.

  4. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    Energy Technology Data Exchange (ETDEWEB)

    Ahad, Amjid [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Ganai, Ajaz Ahmad [Department of Biotechnology, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Mujeeb, Mohd [Department of Pharmacognosy and Phytochemistry, Faculty of Pharmacy, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India); Siddiqui, Waseem Ahmad, E-mail: was.sid121@gmail.com [Lipid Metabolism Laboratory, Department of Biochemistry, Faculty of Science, Jamia Hamdard, Hamdard Nagar, New Delhi 110062 (India)

    2014-08-15

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway.

  5. Chrysin, an anti-inflammatory molecule, abrogates renal dysfunction in type 2 diabetic rats

    International Nuclear Information System (INIS)

    Ahad, Amjid; Ganai, Ajaz Ahmad; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2014-01-01

    Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16 weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-kB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway. - Highlights: • Chrysin reduced renal oxidative stress and inflammation in diabetic rats. • Chrysin reduced serum levels of pro-inflammatory in diabetic rats. • Chrysin exhibited renal protective effect by suppressing the TNF-α pathway

  6. Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

    Science.gov (United States)

    Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

    2014-01-01

    In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

  7. Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

    Directory of Open Access Journals (Sweden)

    Xiaoyan Bai

    Full Text Available In view of increased vascular endothelial growth factor-A (VEGF-A expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM. In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II, angiotensin type II receptor 1 (ATR1 were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR, Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the

  8. Preproghrelin Leu72Met polymorphism predicts a lower rate of developing renal dysfunction in type 2 diabetic nephropathy.

    Science.gov (United States)

    Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang

    2006-07-01

    Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.

  9. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial.

    Directory of Open Access Journals (Sweden)

    Victoria K Snowdon

    2017-02-01

    Full Text Available Chronic liver scarring from any cause leads to cirrhosis, portal hypertension, and a progressive decline in renal blood flow and renal function. Extreme renal vasoconstriction characterizes hepatorenal syndrome, a functional and potentially reversible form of acute kidney injury in patients with advanced cirrhosis, but current therapy with systemic vasoconstrictors is ineffective in a substantial proportion of patients and is limited by ischemic adverse events. Serelaxin (recombinant human relaxin-2 is a peptide molecule with anti-fibrotic and vasoprotective properties that binds to relaxin family peptide receptor-1 (RXFP1 and has been shown to increase renal perfusion in healthy human volunteers. We hypothesized that serelaxin could ameliorate renal vasoconstriction and renal dysfunction in patients with cirrhosis and portal hypertension.To establish preclinical proof of concept, we developed two independent rat models of cirrhosis that were characterized by progressive reduction in renal blood flow and glomerular filtration rate and showed evidence of renal endothelial dysfunction. We then set out to further explore and validate our hypothesis in a phase 2 randomized open-label parallel-group study in male and female patients with alcohol-related cirrhosis and portal hypertension. Forty patients were randomized 1:1 to treatment with serelaxin intravenous (i.v. infusion (for 60 min at 80 μg/kg/d and then 60 min at 30 μg/kg/d or terlipressin (single 2-mg i.v. bolus, and the regional hemodynamic effects were quantified by phase contrast magnetic resonance angiography at baseline and after 120 min. The primary endpoint was the change from baseline in total renal artery blood flow. Therapeutic targeting of renal vasoconstriction with serelaxin in the rat models increased kidney perfusion, oxygenation, and function through reduction in renal vascular resistance, reversal of endothelial dysfunction, and increased activation of the AKT

  10. Renal dysfunction and chronic kidney disease in ischemic stroke and transient ischemic attack: A population-based study.

    Science.gov (United States)

    Hayden, Derek; McCarthy, Christine; Akijian, Layan; Callaly, Elizabeth; Ní Chróinín, Danielle; Horgan, Gillian; Kyne, Lorraine; Duggan, Joseph; Dolan, Eamon; O' Rourke, Killian; Williams, David; Murphy, Sean; O'Meara, Yvonne; Kelly, Peter J

    2017-10-01

    Background and purpose The prevalence of chronic kidney disease (estimated glomerular filtration rate (eGFR) chronic kidney disease (CKD)) in ischemic stroke and transient ischemic attack (TIA) is unknown, as estimates have been based on single-point estimates of renal function. Studies investigating the effect of renal dysfunction (eGFR < 60 mL/min per 1.73 m 2 , renal dysfunction) on post-stroke outcomes are limited to hospitalized cohorts and have provided conflicting results. Methods We investigated rates, determinants and outcomes of renal dysfunction in ischemic stroke and TIA in the North Dublin Population Stroke Study. We also investigate the persistence of renal dysfunction in 90-day survivors to determine the prevalence of CKD. Ascertainment included hot and cold pursuit using multiple overlapping sources. Survival analysis was performed using Kaplan-Meier survival curves and Cox proportional hazards modeling. Results In 547 patients (ischemic stroke in 76.4%, TIA in 23.6%), the mean eGFR at presentation was 63.7 mL/min/1.73 m 2 (SD 22.1). Renal dysfunction was observed in 44.6% (244/547). Among 90-day survivors, 31.2% (139/446) met criteria for CKD. After adjusting for age and stroke severity, eGFR < 45 mL/min/1.73 m 2 (hazard ratio 2.53, p = 0.01) independently predicted 28-day fatality but not at two years. Poor post-stroke functional outcome (Modified Rankin Scale 3-5) at two years was more common in those with renal dysfunction (52.5% vs. 20.6%, p < 0.001). After adjusting for age, stroke severity and pre-stroke disability, renal dysfunction (OR 2.17, p = 0.04) predicted poor functional outcome. Conclusion Renal dysfunction and CKD are common in ischemic stroke and TIA. Renal dysfunction is associated with considerable post-stroke morbidity and mortality. Further studies are needed to investigate if modifiable mechanisms underlie these associations.

  11. Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

    Science.gov (United States)

    Marcovecchio, M L; de Giorgis, T; Di Giovanni, I; Chiavaroli, V; Chiarelli, F; Mohn, A

    2017-06-01

    To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p 1). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI. Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Hypophosphatemia in a Malnourished Child: When Renal Fanconi Syndrome Does Not Stand for Refeeding Syndrome.

    Science.gov (United States)

    Runde, Joseph; Rivera-Rivera, Edgardo; Pompeii-Wolfe, Cecelia; Clardy, Christopher; Sentongo, Timothy

    2018-05-10

    Refeeding syndrome is diagnosed based on the onset of multiple laboratory abnormalities (most commonly hypophosphatemia) and clinical signs in the setting of nutrition rehabilitation of malnourished patients. Because definitions are not uniform, a broad differential diagnosis should always include renal tubular dysfunction. Our report details a 3 year-old child with undiagnosed renal tubular dysfunction who presented with the clinical picture of refeeding syndrome with refractory electrolyte abnormalities. A diagnosis of renal Fanconi syndrome was made after urinalysis that revealed glucosuria and urine electrolyte losses. Thus, urinalysis can aid in making a positive diagnosis of refeeding syndrome. © 2018 American Society for Parenteral and Enteral Nutrition.

  13. Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments.

    Science.gov (United States)

    Watanabe, Takao; Kusuhara, Hiroyuki; Watanabe, Tomoko; Debori, Yasuyuki; Maeda, Kazuya; Kondo, Tsunenori; Nakayama, Hideki; Horita, Shigeru; Ogilvie, Brian W; Parkinson, Andrew; Hu, Zhuohan; Sugiyama, Yuichi

    2011-06-01

    The present study investigated prediction of the overall renal tubular secretion and hepatic clearances of anionic drugs based on in vitro transport studies. The saturable uptake of eight drugs, most of which were OAT3 substrates (rosuvastatin, pravastatin, pitavastatin, valsartan, olmesartan, trichlormethiazide, p-aminohippurate, and benzylpenicillin) by freshly prepared human kidney slices underestimated the overall intrinsic clearance of the tubular secretion; therefore, a scaling factor of 10 was required for in vitro-in vivo extrapolation. We examined the effect of gemfibrozil and its metabolites, gemfibrozil glucuronide and the carboxylic metabolite, gemfibrozil M3, on pravastatin uptake by human kidney slices. The inhibition study using human kidney slices suggests that OAT3 plays a predominant role in the renal uptake of pravastatin. Comparison of unbound concentrations and K(i) values (1.5, 9.1, and 4.0 μM, for gemfibrozil, gemfibrozil glucuronide, and gemfibrozil M3, respectively) suggests that the mechanism of the interaction is due mainly to inhibition by gemfibrozil and gemfibrozil glucuronide. Furthermore, extrapolation of saturable uptake by cryopreserved human hepatocytes predicts clearance comparable with the observed hepatic clearance although fluvastatin and rosuvastatin required a scaling factor of 11 and 6.9, respectively. This study suggests that in vitro uptake assays using human kidney slices and hepatocytes provide a good prediction of the overall tubular secretion and hepatic clearances of anionic drugs and renal drug-drug interactions. It is also recommended that in vitro-in vivo extrapolation be performed in animals to obtain more reliable prediction.

  14. Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; de Vries, Aiko P. J.; Bakker, Stephan J. L.; Graaff, Reindert; van Son, Willem J.; van der Heide, Jaap J. Homan; Gans, Reinold O. B.; Wolffenbuttel, Bruce H. R.; de Jong, Paul E.; Smit, Andries J.

    Background. Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal

  15. Risk factors for chronic transplant dysfunction and cardiovascular disease are related to accumulation of advanced glycation end-products in renal transplant recipients

    NARCIS (Netherlands)

    Hartog, Jasper W. L.; de Vries, Aiko P. J.; Bakker, Stephan J. L.; Graaff, Reindert; van Son, Willem J.; Homan van der Heide, Jaap J.; Gans, Reinold O. B.; Wolffenbuttel, Bruce H. R.; de Jong, Paul E.; Smit, Andries J.

    2006-01-01

    Accumulation of advanced glycation end-products (AGEs) has been implicated in the pathogenesis of chronic transplant dysfunction and cardiovascular disease in renal transplant recipients. We aimed to investigate which factors are associated with tissue AGE accumulation in renal transplant

  16. [Renal dysfunction is a frequent complication in patients with advanced stage of Duchenne muscular dystrophy].

    Science.gov (United States)

    Matsumura, Tsuyoshi; Saito, Toshio; Fujimura, Harutoshi; Sakoda, Saburo

    2012-01-01

    Mechanical ventilation and cardioprotective therapy have significantly improved the prognosis and quality of life of patients with Duchenne muscular dystrophy (DMD). The incidence of congestive heart failure is on declining trend by meticulous care. Meanwhile, elongation of decreased cardiac function can provoke instability in circulation. Recently, we experienced six DMD patients who died from acute renal failure with preserved cardiac function (brain natriuretic peptide: BNP 15% and left ventricular diameter: LVD <50mm). In some patients, hypovolemia induced by low water intake, diarrhea or dose-up of diuretics was thought to be a trigger of renal failure. Since the value of creatinine (Crnn) decreased in amyotrophic patients, we evaluated renal function in 103 patients with DMD using cystatin C (CysC), which is a sensitive renal marker and unaffected by muscle volume. In addition, we assessed β2-microglobulin (b2MG) in 24 patients, because it is also unaffected by muscle volume. The correlation between logarithm of CysC (LogCysC) and logarithm of b2MG was quite high (r=0.954), though that between LogCysC and logarithm of Crnn was not adequate (r=0.623). The average of CysC increased along with age, and more than 30% of patients over 30 years old showed abnormal values. Hemoglobin and logCysC was also negatively associated (r=-0.519), and patients with hemoglobin less than 10 g/dl showed elevated values of CysC. Cardiac indices such as FS (r=-0.250) and logarithm of BNP (r=0.319) showed weak correlations with logCysC, though significant correlation was not detected between LVD and LogCysC. Since renal dysfunction is a common complication in advanced stage of DMD patients, proper managements of water balance and anemia is important. In the medical managements for DMD, we should pay attention to cardiac-renal-anemia association.

  17. Influence of renal dysfunction on the accuracy of procalcitonin for the diagnosis of postoperative infection after vascular surgery.

    Science.gov (United States)

    Amour, Julien; Birenbaum, Aurélie; Langeron, Olivier; Le Manach, Yannick; Bertrand, Michèle; Coriat, Pierre; Riou, Bruno; Bernard, Maguy; Hausfater, Pierre

    2008-04-01

    Procalcitonin has been advocated as a specific biomarker for bacterial infection. We performed this study to determine whether accuracy of procalcitonin for diagnosis of postoperative bacterial infection is affected by renal function after aortic surgery. Single-center prospective study. University hospital. Two hundred seventy-six patients scheduled for elective major aortic surgery. Blood samples were taken before surgery and each day over the 5-day postoperative period, and measurement of serum procalcitonin was performed. Diagnosis of infection was performed by a blinded expert panel. Renal function was assessed using an estimate of creatinine clearance with the Cockcroft formulas. Renal dysfunction was defined as a creatinine clearance <50 mL x min(-1). Infection was diagnosed in 67 patients. Seventy five patients (27%) had postoperative renal dysfunction. Procalcitonin was significantly higher in infected patients, with a peak reached at the fourth postoperative day, but it was significantly higher in patients with impaired renal function in both control and infected patients. The optimal threshold of procalcitonin markedly differed in patients with renal dysfunction compared with patients without renal dysfunction (2.57 vs. 0.80 ng x mL(-1), p < .05). The diagnostic accuracy of procalcitonin significantly increased (0.74 vs. 0.70, p < .05) when the threshold of procalcitonin was adapted to the renal function. The elevation of procalcitonin occurred 2 days before the medical team was able to diagnose infection. Procalcitonin is a valuable marker of bacterial infections after major aortic surgery, but renal function is a major determinant of procalcitonin levels and thus different thresholds should be applied according to renal function impairment.

  18. Advanced glycation end products overload might explain intracellular cobalamin deficiency in renal dysfunction, diabetes and aging.

    Science.gov (United States)

    Obeid, Rima; Shannan, Batool; Herrmann, Wolfgang

    2011-11-01

    Advanced glycation end products (AGEs) contribute to aging. Cobalamin (Cbl) is required for cell growth and functions, and its deficiency causes serious complications. Diabetics and renal patients show high concentrations of Cbl, but metabolic evidence of Cbl deficiency that is reversible after Cbl treatment. Cbl might be sequestered in blood and cannot be delivered to the cell. Megalin mediates the uptake of transcobalamin-Cbl complex into the proximal tubule cells. Megalin is involved in the uptake and degradation of AGEs. In aging, diabetes or renal dysfunction, AGEs might overload megalin thus lowering Cbl uptake. Transcobalamin-Cbl might retain in blood. Shedding of megalin and transcobalamin receptor under glycation conditions is also a possible mechanism of this phenomenon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  19. Elevation of plasma milrinone concentrations in stage D heart failure associated with renal dysfunction.

    Science.gov (United States)

    Cox, Zachary L; Calcutt, Marion W; Morrison, Thomas B; Akers, Wendell S; Davis, Mary Beth; Lenihan, Daniel J

    2013-09-01

    To determine steady state milrinone concentrations in patients with stage D heart failure (HF) with and without renal dysfunction We retrospectively identified patients with stage D HF at a single medical center on continuous milrinonein fusion at the time of plasma collection for entry into a research registry database. Milrinone was prescribed and titrated to improve hemodynamic and clinical status by a cardiologist. Plasma samples were obtained at steady state milrinone concentrations. Patients were stratified by creatinine clearance (CrCl) into 4 groups: group 1 (CrCl >60 mL/min), group 2 (CrCl 60-30 mL/min), group 3 (CrCl milrinone hemodynamic changes by cardiac catheterization and electrophysiologic changes by implantable cardiac defibrillator (ICD) interrogation. A total of 29 patients were identified: group 1 (n=14), group 2 (n=10), group 3(n=3), and group 4 (n = 2). The mean infusion rate (0.391+0.08 mg/kg/min) did not differ between groups (P=0.14). The mean milrinone concentration was 451+243 ng/mL in group 1, 591+293 ng/mL in group 2, 1575+962 ng/mL in group 3, and 6252+4409 ng/mL in group 4 (Pmilrinone hemodynamic improvements between the groups (P=0.41). The ICD interrogation revealed limited comparisons, but 6 of the 8 post milrinone ventricular tachycardia episodes requiring defibrillation occurred in group 4 patients. Patients with stage D HF having severe renal dysfunction have elevated milrinone concentrations. Future studies of milrinone concentrations are warranted to investigate the potential risk of life-threatening arrhythmias and potential dosing regimens in renal dysfunction.

  20. Aortic Blood Flow Reversal Determines Renal Function: Potential Explanation for Renal Dysfunction Caused by Aortic Stiffening in Hypertension.

    Science.gov (United States)

    Hashimoto, Junichiro; Ito, Sadayoshi

    2015-07-01

    Aortic stiffness determines the glomerular filtration rate (GFR) and predicts the progressive decline of the GFR. However, the underlying pathophysiological mechanism remains obscure. Recent evidence has shown a close link between aortic stiffness and the bidirectional (systolic forward and early diastolic reverse) flow characteristics. We hypothesized that the aortic stiffening-induced renal dysfunction is attributable to altered central flow dynamics. In 222 patients with hypertension, Doppler velocity waveforms were recorded at the proximal descending aorta to calculate the reverse/forward flow ratio. Tonometric waveforms were recorded to measure the carotid-femoral (aortic) and carotid-radial (peripheral) pulse wave velocities, to estimate the aortic pressure from the radial waveforms, and to compute the aortic characteristic impedance. In addition, renal hemodynamics was evaluated by duplex ultrasound. The estimated GFR was inversely correlated with the aortic pulse wave velocity, reverse/forward flow ratio, pulse pressure, and characteristic impedance, whereas it was not correlated with the peripheral pulse wave velocity or mean arterial pressure. The association between aortic pulse wave velocity and estimated GFR was independent of age, diabetes mellitus, hypercholesterolemia, and antihypertensive medication. However, further adjustment for the aortic reverse/forward flow ratio and pulse pressure substantially weakened this association, and instead, the reverse/forward flow ratio emerged as the strongest determinant of estimated GFR (P=0.001). A higher aortic reverse/forward flow ratio was also associated with lower intrarenal forward flow velocities. These results suggest that an increase in aortic flow reversal (ie, retrograde flow from the descending thoracic aorta toward the aortic arch), caused by aortic stiffening and impedance mismatch, reduces antegrade flow into the kidney and thereby deteriorates renal function. © 2015 American Heart Association

  1. Effect of all-trans retinoic acid treatment on prohibitin and renin-angiotensin-aldosterone system expression in hypoxia-induced renal tubular epithelial cell injury.

    Science.gov (United States)

    Zhou, Tian-Biao; Ou, Chao; Rong, Liang; Drummen, Gregor P C

    2014-09-01

    All-trans retinoic acid (ATRA) exerts various effects on physiological processes such as cell growth, differentiation, apoptosis and inflammation. Prohibitins (PHB), including prohibitin 1 (PHB1) and prohibitin 2 (PHB2), are evolutionary conserved and pleiotropic proteins implicated in various cellular functions, including proliferation, tumor suppression, apoptosis, transcription, and mitochondrial protein folding. The renin-angiotensin-aldosterone system plays a pivotal role in the regulation of blood pressure and volume homeostasis. All these factors and systems have been implicated in renal interstitial fibrosis. Therefore, the objective of this study was to investigate the effect of ATRA treatment on the renin-angiotensin-aldosterone system and expression of prohibitins to further understand its role in the processes leading to renal interstitial fibrosis. The hypoxic and oxidative stress conditions in obstructive renal disease were simulated in a hypoxia/reoxygenation model with renal tubular epithelial cells (RTEC) as a model system. Subsequently, the effect of ATRA on mRNA and protein expression levels was determined and correlations were established between factors involved in the renin-angiotensin-aldosterone system, the prohibitins, cellular redox status, renal interstitial fibrosis and ATRA treatment. Correlation analysis showed that both PHB1 and PHB2 protein levels were negatively correlated with angiotensin I, ACE1, angiotensin II, TGF-β1, Col-IV, FN, ROS, and MDA (PHB1: r = -0.792, -0.834, -0.805, -0.795, -0.778, -0.798, -0.751, -0.682; PHB2: r = -0.872, -0.799, -0.838, -0.773, -0.769, -0.841, -0.794, -0.826; each p system under hypoxia/reoxygenation conditions. © The Author(s) 2014.

  2. Positive correlations between cerebral choline and renal dysfunction in chronic renal failure

    International Nuclear Information System (INIS)

    Sasaki, Osamu; Nakahama, Hajime; Nakamura, Satoko; Inenaga, Takashi; Kawano, Yuhei; Hattori, Noriaki; Inoue, Noriko; Sawada, Tohru; Kohno, Shigeru

    2006-01-01

    Cerebral metabolism in chronic renal failure (CRF) patients has not been fully evaluated. This study examined cerebral metabolites in CRF, using proton magnetic resonance spectroscopy (MRS). Subjects comprised 19 CRF patients and 21 healthy volunteers. Spectra were acquired from voxels of interest positioned in the parietal gray and white matter, and concentrations of the following cerebral metabolites were measured: N-acetyl group (NA), creatine + phosphocreatine (Cr), choline-containing compounds (Cho), myo-inositol and glutamate + glutamine. Among the 19 CRF patients, 9 who were started on hemodialysis (HD) underwent careful follow-up. Proton MRS was performed before and about 2 weeks after starting HD. In six patients in whom follow-up was possible, a third MRS was performed after about 18 months. The NA/Cr ratio was not significantly changed in CRF. However, elevations in the Cho/Cr ratio were found in both gray and white matter compared with controls. To the best of our knowledge, this is the first report of positive correlations between the Cho/Cr ratio in both regions and serum osmotic pressure. (orig.)

  3. Resveratrol prevents high glucose-induced epithelial-mesenchymal transition in renal tubular epithelial cells by inhibiting NADPH oxidase/ROS/ERK pathway.

    Science.gov (United States)

    He, Ting; Guan, Xu; Wang, Song; Xiao, Tangli; Yang, Ke; Xu, Xinli; Wang, Junping; Zhao, Jinghong

    2015-02-15

    Resveratrol (RSV) is reported to have renoprotective activity against diabetic nephropathy, while the mechanisms underlying its function have not been fully elucidated. In this study, we investigate the effect and related mechanism of RSV against high glucose-induced epithelial to mesenchymal transition (EMT) in human tubular epithelial cells (HK-2). A typical EMT is induced by high glucose in HK-2 cells, accompanied by increased levels of reactive oxygen species (ROS). RSV exhibits a strong ability to inhibit high glucose-induced EMT by decreasing intracellular ROS levels via down-regulation of NADPH oxidase subunits NOX1 and NOX4. The activation of extracellular signal-regulated kinase (ERK1/2) is found to be involved in high glucose-induced EMT in HK-2 cells. RSV, like NADPH oxidase inhibitor diphenyleneiodonium, can block ERK1/2 activation induced by high glucose. Our results demonstrate that RSV is a potent agent against high glucose-induced EMT in renal tubular cells via inhibition of NADPH oxidase/ROS/ERK1/2 pathway. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Diffusion tensor imaging and tractography for assessment of renal allograft dysfunction - initial results

    Energy Technology Data Exchange (ETDEWEB)

    Hueper, Katja; Gutberlet, M.; Rodt, T.; Wacker, F.; Galanski, M.; Hartung, D. [Institute for Diagnostic and Interventional Radiology, Hannover Medical School - Germany, Hannover (Germany); Gwinner, W. [Clinic for Nephrology, Hannover Medical School - Germany, Hannover (Germany); Lehner, F. [Clinic for General, Abdominal and Transplant Surgery, Hannover Medical School - Germany, Hannover (Germany)

    2011-11-15

    To evaluate MR diffusion tensor imaging (DTI) as non-invasive diagnostic tool for detection of acute and chronic allograft dysfunction and changes of organ microstructure. 15 kidney transplanted patients with allograft dysfunction and 14 healthy volunteers were examined using a fat-saturated echo-planar DTI-sequence at 1.5 T (6 diffusion directions, b = 0, 600 s/mm{sup 2}). Mean apparent diffusion coefficient (ADC) and mean fractional anisotropy (FA) were calculated separately for the cortex and for the medulla and compared between healthy and transplanted kidneys. Furthermore, the correlation between diffusion parameters and estimated GFR was determined. The ADC in the cortex and in the medulla were lower in transplanted than in healthy kidneys (p < 0.01). Differences were more distinct for FA, especially in the renal medulla, with a significant reduction in allografts (p < 0.001). Furthermore, in transplanted patients a correlation between mean FA in the medulla and estimated GFR was observed (r = 0.72, p < 0.01). Tractography visualized changes in renal microstructure in patients with impaired allograft function. Changes in allograft function and microstructure can be detected and quantified using DTI. However, to prove the value of DTI for standard clinical application especially correlation of imaging findings and biopsy results is necessary. (orig.)

  5. Age features of myocardial remodeling in men with ischemic chronic heart failure and renal dysfunction

    Directory of Open Access Journals (Sweden)

    D. A. Lashkul

    2014-04-01

    Full Text Available In recent years, medicine has faced the problem of "dual epidemic" of heart and kidney failure. Regardless of the degree of heart failure, chronic kidney disease increases the risk of death and cardiac decompensation. Left ventricular hypertrophy (LVH is a well known option of cardiac remodeling and it has higher prevalence among people with impaired renal function. Types of myocardial remodeling identify mortality risk of patients with cardiovascular complications. We know that gender and age are important risk factors for cardiovascular disease. However, in most studies structural remodeling of the myocardium was analyzed without sex and age characteristics. The aim of research is to study the age features of the formation of different types of myocardial remodeling in men with ischemic chronic heart failure and renal dysfunction. Materials and methods. To investigate the age characteristics of cardiac remodeling in men with ischemic chronic heart failure and renal dysfunction structural and functional remodeling of left ventricular myocardium was studied in 277 men (mean age 58,1±9,3 years using Doppler echocardiography. Depending on the glomerular filtration rate, patients were divided into 3 groups: 58 with normal GFR (>90 ml/min/1.73m2, 182 with a slight decrease in GFR (60-90 ml/min/1.73m2 and 37 with moderately reduced GFR (<60 ml/min/1.73m2. Echocardiography was performed using the General Electric VIVID 3 system (General Electric Healthcare, USA with the 2.5–3.5 MHz transducer and Doppler technique. Descriptive statistics are presented as mean±standard deviation for continuous variables and as percentages for categorical variables. Depending on the distribution of the analyzed parameters unpaired Student's t-test or U-Mann-Whitney test were used. Comparisons among all groups for baseline clinical variables were performed with the Pearson χ2 or Fisher exact test for categorical variables. Differences were considered reliable for

  6. Total mercury levels in hair, toenail, and urine among women free from occupational exposure and their relations to renal tubular function

    International Nuclear Information System (INIS)

    Ohno, Tomoko; Sakamoto, Mineshi; Kurosawa, Tomoko; Dakeishi, Miwako; Iwata, Toyoto; Murata, Katsuyuki

    2007-01-01

    To investigate the relations among total mercury levels in hair, toenail, and urine, together with potential effects of methylmercury intake on renal tubular function, we determined their levels, and urinary N-acetyl-β-d-glucosaminidase activity (NAG) and α 1 -microglobulin (AMG) in 59 women free from occupational exposures, and estimated daily mercury intakes from fish and other seafood using a food frequency questionnaire. Mercury levels (mean+/-SD) in the women were 1.51+/-0.91μg/g in hair, 0.59+/-0.32μg/g in toenail, and 0.86+/-0.66μg/g creatinine in urine; and, there were positive correlations among them (P<0.001). The daily mercury intake of 9.15+/-7.84μg/day was significantly correlated with total mercury levels in hair, toenail, and urine (r=0.551, 0.537, and 0.604, P<0.001). Among the women, the NAG and AMG were positively correlated with both the daily mercury intake and mercury levels in hair, toenail, and urine (P<0.01); and, these relations were almost similar when using multiple regression analysis to adjust for possible confounders such as urinary cadmium (0.47+/-0.28μg/g creatinine) and smoking status. In conclusion, mercury resulting from fish consumption can explain total mercury levels in hair, toenail, and urine to some degree (about 30%), partly through the degradation into the inorganic form, and it may confound the renal tubular effect of other nephrotoxic agents. Also, the following equation may be applicable to the population neither with dental amalgam fillings nor with occupational exposures: [hair mercury (μg/g)]=2.44x[toenail mercury (μg/g)

  7. Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells.

    Science.gov (United States)

    Liu, Xiujuan; Hong, Quan; Wang, Zhen; Yu, Yanyan; Zou, Xin; Xu, Lihong

    2016-02-01

    Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor-β (TGF-β)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF-β-stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-β. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF-β by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), α-smooth muscle actin, and fibroblast-specific protein1 in TGF-β-treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF-β through activation of SphK1. Furthermore, it was observed that TGF-β-stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR2 also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF-β-stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR2 siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF-β-induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis. © 2015 by the Society for Experimental Biology and Medicine.

  8. A longitudinal study on urinary cadmium and renal tubular protein excretion of nickel-cadmium battery workers after cessation of cadmium exposure.

    Science.gov (United States)

    Gao, Yanhua; Zhang, Yanfang; Yi, Juan; Zhou, Jinpeng; Huang, Xianqing; Shi, Xinshan; Xiao, Shunhua; Lin, Dafeng

    2016-10-01

    This study aimed to predict the outcome of urinary cadmium (Cd) excretion and renal tubular function by analyzing their evolution through 10 years after Cd exposure ceased. Forty-one female, non-smoking workers were recruited from the year 2004 to 2009 when being removed from a nickel-cadmium battery factory, and they were asked to provide morning urine samples on three consecutive days at enrollment and in every follow-up year until 2014. Urinary Cd and renal tubular function biomarkers including urinary β2-microglobulin (β2-m) and retinol-binding protein (RBP) concentrations were determined with the graphite furnace atomic absorption spectrometry and the enzyme-linked immunosorbent assays, respectively. The medians of baseline Cd, β2-m and RBP concentrations at enrollment were 6.19, 105.38 and 71.84 μg/g creatinine, respectively. Urinary β2-m and RBP concentrations were both related to Cd concentrations over the years (β absolute-β2-m = 9.16, P = 0.008 and β absolute-RBP = 6.42, P < 0.001, respectively). Cd, β2-m and RBP concentrations in the follow-up years were all associated with their baseline concentrations (β absolute-Cd = 0.61, P < 0.001; β absolute-β2-m = 0.64, P < 0.001; and β absolute-RBP = 0.60, P < 0.001, respectively), and showed a decreasing tendency with the number of elapsed years relative to their baseline concentrations (β relative-Cd = -0.20, P = 0.010; β relative-β2-m = -17.19, P = 0.002; and β relative-RBP = -10.66, P < 0.001, respectively). Urinary Cd might eventually decrease to the general population level, and Cd-related tubular function would improve under the baseline conditions of this cohort.

  9. Toxicological Significance of Renal Bcrp: Another Potential Transporter in the Elimination of Mercuric Ions from Proximal Tubular Cells

    Science.gov (United States)

    Bridges, Christy C.; Zalups, Rudolfs K.; Joshee, Lucy

    2015-01-01

    Secretion of inorganic mercury (Hg2+) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg2+ was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg2+. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg2+-induced nephropathy, Sprague-Dawley and Bcrp knockout (bcrp−/−) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol • kg−1), a moderately nephrotoxic (1.5 μmol • kg−1) or a significantly nephrotoxic (2.0 μmol • kg−1) dose of HgCl2. In general, the accumulation of Hg2+ was greater in organs of bcrp−/− rats than in Sprague-Dawley rats, suggesting that Bcrp may play a role in the export of Hg2+ from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp−/− rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. PMID:25868844

  10. Toxicological significance of renal Bcrp: Another potential transporter in the elimination of mercuric ions from proximal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Bridges, Christy C., E-mail: bridges_cc@mercer.edu; Zalups, Rudolfs K.; Joshee, Lucy

    2015-06-01

    Secretion of inorganic mercury (Hg{sup 2+}) from proximal tubular cells into the tubular lumen has been shown to involve the multidrug resistance-associated protein 2 (Mrp2). Considering similarities in localization and substrate specificity between Mrp2 and the breast cancer resistance protein (Bcrp), we hypothesize that Bcrp may also play a role in the proximal tubular secretion of mercuric species. In order to test this hypothesis, the uptake of Hg{sup 2+} was examined initially using inside-out membrane vesicles containing Bcrp. The results of these studies suggest that Bcrp may be capable of transporting certain conjugates of Hg{sup 2+}. To further characterize the role of Bcrp in the handling of mercuric ions and in the induction of Hg{sup 2+}-induced nephropathy, Sprague–Dawley and Bcrp knockout (bcrp{sup −/−}) rats were exposed intravenously to a non-nephrotoxic (0.5 μmol·kg{sup −1}), a moderately nephrotoxic (1.5 μmol·kg{sup −1}) or a significantly nephrotoxic (2.0 μmol·kg{sup −1}) dose of HgCl{sub 2}. In general, the accumulation of Hg{sup 2+} was greater in organs of bcrp{sup −/−} rats than in Sprague–Dawley rats, suggesting that Bcrp may play a role in the export of Hg{sup 2+} from target cells. Within the kidney, cellular injury and necrosis was more severe in bcrp{sup −/−} rats than in controls. The pattern of necrosis, which was localized in the inner cortex and the outer stripe of the outer medulla, was significantly different from that observed in Mrp2-deficient animals. These findings suggest that Bcrp may be involved in the cellular export of select mercuric species and that its role in this export may differ from that of Mrp2. - Highlights: • Bcrp may mediate transport of mercury out of proximal tubular cells. • Hg-induced nephropathy was more severe in Bcrp knockout rats. • Bcrp and Mrp2 may differ in their ability to transport Hg.

  11. Renal scintigraphy in insulin-dependent diabetes mellitus: Early glomerular and urologic dysfunction

    International Nuclear Information System (INIS)

    Poirier, J.Y.; Moisan, A.; Le Cloirec, J.; Siemen, C.; Yaouanq, J.; Edan, G.; Herry, J.Y.

    1990-01-01

    Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by intravenous injection of 99mTc-diethylenetriaminepentaacetic acid (DTPA) and 131I-Hippuran in 115 insulin-dependent diabetic patients with albumin excretion rates (AER) less than 200 micrograms/min, and in 45 normal subjects. Separate kidney function and urinary elimination were estimated by renography. GFR was increased in the diabetic patients (152 +/- 24 ml/min/1.73 m2 vs. 128 +/- 15) and correlated significantly with RPF (r = 0.5; p less than 10(-9)). No relationship was found between GFR and the duration of diabetes, blood glucose, HbA1c, or AER. Fifty patients were hyperfiltering with RPF and filtration fraction higher than those in the normofiltering group. Slow intrarenal or pyeloureteral elimination, either unilateral or bilateral, was observed in 3 controls and 60 diabetic subjects (24 hyperfiltering; 36 normofiltering) and did not disappear with the patient in the standing position. In these 60 patients, mean age, duration of diabetes, blood glucose, HbA1c, 24 h albumin excretion rate, and frequency of peripheral or autonomic neuropathy did not differ from patients with normal scintigraphy; GFR was lower in the group with slow elimination, but not significantly so. 99mTc-DTPA renal uptake was symmetric in all the controls; asymmetric renal uptake with asymmetric GFR was observed in 13 patients (7 hyperfiltering; 6 normofiltering) and often associated with slower elimination. No evidence for renal stenotic atheroma or parenchymatous disease was found on the angiopyleoureterography. The results suggest that incipient uropathy is a very common phenomenon that occurs irrespective of glomerular dysfunction

  12. Manifestation of renal disease in obesity: pathophysiology of obesity-related dysfunction of the kidney

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    John A D’Elia

    2009-11-01

    reflex arc in humans. Further understanding of obesityrelated renal dysfunction has been accomplished recently using experimental models. Rapid weight loss following bariatric surgery may reverse renal pathology of obesity with restoration of normal blood pressure.Keywords: glomerulomegaly, podocyte hypertrophy, obesity, albuminuria, adiponectin, insulin, leptin

  13. Apparent diffusion coefficient of renal parenchyma and color Doppler ultrasound of intrarenal arteries in patients with cirrhosis related renal dysfunction

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    Mohamed M Hefeda

    2014-12-01

    Conclusion: Liver cirrhosis, even in the presence of refractory ascites, did not affect the ADC value of renal parenchyma, however ADC value is affected in renal parenchyma of patients with hepato-renal syndrome. Duplex-Doppler ultrasound of intrarenal arteries enables the early detection of renal hemodynamic disturbances in patients with liver cirrhosis.

  14. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

    Science.gov (United States)

    Jabbour, S A; Goldstein, B J

    2008-08-01

    The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

  15. Four siblings with distal renal tubular acidosis and nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial appearance: a possible new autosomal recessive syndrome.

    Science.gov (United States)

    Faqeih, Eissa; Al-Akash, Samhar I; Sakati, Nadia; Teebi, Prof Ahmad S

    2007-09-01

    We report on four siblings (three males, one female) born to first cousin Arab parents with the constellation of distal renal tubular acidosis (RTA), small kidneys, nephrocalcinosis, neurobehavioral impairment, short stature, and distinctive facial features. They presented with early developmental delay with subsequent severe mental, behavioral and social impairment and autistic-like features. Their facial features are unique with prominent cheeks, well-defined philtrum, large bulbous nose, V-shaped upper lip border, full lower lip, open mouth with protruded tongue, and pits on the ear lobule. All had proteinuria, hypercalciuria, hypercalcemia, and normal anion-gap metabolic acidosis. Renal ultrasound examinations revealed small kidneys, with varying degrees of hyperechogenicity and nephrocalcinosis. Additional findings included dilated ventricles and cerebral demyelination on brain imaging studies. Other than distal RTA, common causes of nephrocalcinosis were excluded. The constellation of features in this family currently likely represents a possibly new autosomal recessive syndrome providing further evidence of heterogeneity of nephrocalcinosis syndromes. Copyright 2007 Wiley-Liss, Inc.

  16. The Protective Effect of Omega-3 Against Thioacetamide Induced Lipid and Renal Dysfunction in Male Rats

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    Davood Moghadamnia

    2016-10-01

    Full Text Available Background Thioacetamide causes lipid and kidney dysfunction.Omega-3 unsaturated fatty acids prevent the progression of renal diseases. Objectives This study aimed to assess the protective effects of omega-3 fish oil supplement on thioacetamide induced lipid and kidney dysfunction in male rats. Methods In this experimental study, 42 male rats were divided into 6 groups of 7: control group sham group which received 0.4 mL olive oil as a solvent, Thioacetamide group receiving thioacetamide at a dose of 150 mg/kg once as intraperitoneal injection, Experimental groups of 1, 2 and 3 which received omega-3 fish oil supplement at the doses of 100, 200, 300 mg/kg orally for 3 months respectively and then they received thioacetamide at the dose of 150 mg/kg intraperitoneally for once. The levels of serum creatinine, BUN, total cholesterol, LDL, HDL, FBS, triglyceride, sodium and potassium were measured. The pathological changes of tissue samples of the kidneys were studied after hematoxylin-eosin staining. The data were analyzed by SPSS-18 software and using one way ANOVA and Tukey as post hoc test. Significant level was considered to be P < 0.05. Results The mean serum levels of potassium in the second experimental group significantly decreased (5.26 ± 0.02 compared to the group receiving thioacetamide (6.50 ± 0. The mean serum sodium in all experimental groups decreased significantly compared to the group receiving thioacetamide. The mean serum levels of total cholesterol in experimental group 3 (66.80 ± 1.46 significantly decreased compared to the group receiving thioacetamide (84 ± 0.57. No significant changes were observed in the mean serum levels of FBS, BUN, HDL, LDL, triglycerides and creatinine in all experimental groups compared to the group receiving thioacetamide. All the experimental groups improved renal histological changes induced by thioacetamide and these protective effects were dose-dependent (P ≤ 0.05. Conclusions The results of

  17. Preliminary study on application of urine amino acids profiling for monitoring of renal tubular injury using GLC-MS

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    Maja Kazubek-Zemke

    2014-11-01

    Full Text Available The early diagnosis of the nephrotoxic effect of xenobiotics and drugs is still an unsolved problem. Recent studies suggest a correlation between the nephrotoxic activity of xenobiotics and increased concentration of amino acids in urine. The presented study was focused on the application of GLC-MS method for amino acids profiling in human urine as a noninvasive method for monitoring of kidney condition and tubular injury level.The analytic method is based on the conversion of the amino acids present in the sample to tert-butyldimethylsilyl (TBDMS derivatives and their analysis by gas-liquid chromatography-mass spectrometry (GLC-MS. The procedure of urine sample preparation for chromatographic analysis was optimized.The presence of 12 amino acids in most of the tested healthy human urine samples was detected. The significant differences in the levels of particular amino acids between patients with tubular injury and healthy controls were found, especially for lysine, valine, serine, alanine and leucine (on average 30.0, 7.5, 3.6, 2.9 and 0.5 fold respectively.We found that this approach based on GLC-MS detection can be used in nephrotoxicity studies for urine amino acids monitoring in exposure to xenobiotics and drugs.

  18. Preliminary study on application of urine amino acids profiling for monitoring of renal tubular injury using GLC-MS.

    Science.gov (United States)

    Kazubek-Zemke, Maja; Rybka, Jacek; Marchewka, Zofia; Rybka, Wojciech; Pawlik, Krzysztof; Długosz, Anna

    2014-11-14

    The early diagnosis of the nephrotoxic effect of xenobiotics and drugs is still an unsolved problem. Recent studies suggest a correlation between the nephrotoxic activity of xenobiotics and increased concentration of amino acids in urine. The presented study was focused on the application of GLC-MS method for amino acids profiling in human urine as a noninvasive method for monitoring of kidney condition and tubular injury level. The analytic method is based on the conversion of the amino acids present in the sample to tert-butyldimethylsilyl (TBDMS) derivatives and their analysis by gas-liquid chromatography-mass spectrometry (GLC-MS). The procedure of urine sample preparation for chromatographic analysis was optimized. The presence of 12 amino acids in most of the tested healthy human urine samples was detected. The significant differences in the levels of particular amino acids between patients with tubular injury and healthy controls were found, especially for lysine, valine, serine, alanine and leucine (on average 30.0, 7.5, 3.6, 2.9 and 0.5 fold respectively). We found that this approach based on GLC-MS detection can be used in nephrotoxicity studies for urine amino acids monitoring in exposure to xenobiotics and drugs.

  19. Urotensin II Induces ER Stress and EMT and Increase Extracellular Matrix Production in Renal Tubular Epithelial Cell in Early Diabetic Mice

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    Xin-Xin Pang

    2016-07-01

    Full Text Available Background/Aims: Urotensin II (UII and its receptor are highly expressed in the kidney tissue of patients with diabetic nephropathy (DN. The aim of this study is to examine the roles of UII in the induction of endoplasmic reticulum stress (ER stress and Epithelial-mesenchymal transition (EMT in DN in vivo and in vitro. Methods: Kidney tissues were collected from patients with DN. C57BL/6 mice and mice with UII receptor knock out were injected with two consecutive doses of streptozotocin to induce diabetes and were sacrificed at 3th week for in vivo study. HK-2 cells in vitro were cultured and treated with UII. Markers of ER stress and EMT, fibronectin and type IV collagen were detected by immunohistochemistry, real time PCR and western blot. Results: We found that the expressions of protein of UII, GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were upregulated while E-cadherin protein was downregulated as shown by immunohistochemistry or western blot analysis in kidney of diabetic mice in comparison to normal control; moreover expressions of GRP78, CHOP, ALPHA-SMA, fibronectin and type IV collagen were inhibited while E-caherin expression was enhanced in kidney in diabetic mice with UII receptor knock out in comparison to C57BL/6 diabetic mice. In HK-2 cells, UII induced upregulation of GRP78, CHOP, ALPHA-SMA, fibroblast-specifc protein 1(FSP-1, fibronectin and type collagen and downregulation of E-cadherin. UII receptor antagonist can block UII-induced ER stress and EMT; moreover, 4-PBA can inhibit the mRNA expression of ALPHA-SMA and FSP1 induced by UII in HK-2 cells. Conclusions: We are the first to verify UII induces ER stress and EMT and increase extracellular matrix production in renal tubular epithelial cell in early diabetic mice. Moreover, UII may induce renal tubular epithelial EMT via triggering ER stress pathway in vitro, which might be the new pathogenic pathway for the development of renal fibrosis in DN.

  20. Evaluation of renal allograft dysfunction employing dynamic SPECT with 99mTc-MAG3 and graph plot analysis

    International Nuclear Information System (INIS)

    Akahira, Hideaki

    1996-01-01

    To estimate renal blood flow and tubular function in transplanted kidneys, we applied the 4 compartments model and the graphic analysis method to 99m Tc-MAG3 dynamic SPECT and calculated some parameters, i.e. K1 (renal influx rate constant), K3 (tubular transporting rate constant), Vd12 (intrarenal distribution volume), and others. Twenty-three renal transplant recipients were examined and divided into following 3 groups according to their serum creatinine levels (SCr); Group I: less than 13 mg/dl (1.1±0.3, n=7), Group II: 1.4-2.5 mg/dl (1.8±0.3, n=11), and Group III more than 2.6 mg/dl (3.9±0.9, n=5). The K3 value became lower in the order of Group I>II>III, and well correlated with blood urea nitrogen (BUN, r=-0.95, p 99m Tc-MAG3 uptake function, respectively. (author)

  1. Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

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    Shimada M

    2017-06-01

    Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

  2. MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5.

    Science.gov (United States)

    Du, Bin; Dai, Xiao-Meng; Li, Shuang; Qi, Guo-Long; Cao, Guang-Xu; Zhong, Ying; Yin, Pei-di; Yang, Xue-Song

    2017-08-10

    As a common anticancer drug, cisplatin has been widely used for treating tumors in the clinic. However, its side effects, especially its nephrotoxicity, noticeably restrict the application of cisplatin. Therefore, it is imperative to investigate the mechanism of renal injury and explore the corresponding remedies. In this study, we showed the phenotypes of the renal tubules and epithelial cell death as well as elevated cleaved-caspase3- and TUNEL-positive cells in rats intraperitoneally injected with cisplatin. Similar cisplatin-induced cell apoptosis was found in HK-2 and NRK-52E cells exposed to cisplatin as well. In both models of cisplatin-induced apoptosis in vivo and in vitro, quantitative PCR data displayed reductions in miR-30a-e expression levels, indicating that miR-30 might be involved in regulating cisplatin-induced cell apoptosis. This was further confirmed when the effects of cisplatin-induced cell apoptosis were found to be closely correlated with alterations in miR-30c expression, which were manipulated by transfection of either the miR-30c mimic or miR-30c inhibitor in HK-2 and NRK-52E cells. Using bioinformatics tools, including TargetScan and a gene expression database (Gene Expression Omnibus), Adrb1, Bnip3L, Hspa5 and MAP3K12 were predicted to be putative target genes of miR-30c in cisplatin-induced apoptosis. Subsequently, Bnip3L and Hspa5 were confirmed to be the target genes after determining the expression of these putative genes following manipulation of miR-30c expression levels in HK-2 cells. Taken together, our current experiments reveal that miR-30c is certainly involved in regulating the renal tubular cell apoptosis induced by cisplatin, which might supply a new strategy to minimize cisplatin-induced nephrotoxicity.

  3. The significance of determination of renal tubular markers before and after treatment in the primary nephrotic syndrome

    International Nuclear Information System (INIS)

    Xie Bing; Jiang Liping

    2011-01-01

    Objective: To evaluate the damage of renal tubule of patients with primary nephrotic syndrome (PNS) by detecting renal tubule markers and investigate the significance of different therapeutic effects. Methods: Serum levels of interleukin-6(IL-6), ET-1, α 1 -microglobulin(α 1 -m), β 2 -microglobulin(β 2 -m) and plasma level of ET-1 were determined with RIA, fibrinogen degradation product (FDP) with ELISA, automatic biochemistry analysis N-acetyl-β-D-glucosaminidase(NAG), CH 2 O was determined with physico-method respectively. Results: The concentrations of IL-6, ET-1, α 1 -m, β 2 -m, FDP, NAG were significantly decreased in cases of complete remission after therapy (P 2 O excepted (P>0.05), the decrease of IL-6, ET-1, α 1 -m, FDP were no significant in cases of invalid (P>0.05), the concentrations of renal tubule markers in cases of partial remission and invalid were higher than those in cases of complete and significant remission. Conclusion: The determination of several renal tubule markers can be used for diagnose, monitor and judge the therapeutic effects of PNS. (authors)

  4. Renal dysfunction and state of metabolic and hemodynamic factors in patients with arterial hypertension

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    Klochkov V.A.

    2011-12-01

    Full Text Available The aim of the investigation is to carry out comparative evaluation of metabolic and hemodynamic indices in patients with arterial hypertension (AH and renal dysfunction; to study the interrelation between arterial blood pressure level normalization and the presence or lack of microalbuminuria (MAU in the morning urine portion of patients with AH after therapy with antihypertensive preparations (APs of various groups. Methods. 121 persons have been investigated, 91 out — patients of both sexes, aged 33-55, with the diagnosis of arterial hypertension of stage II risk III, who have been taking Perindopril, Telmisartan and Bisoprolol for3 months. The control of arterial pressure level, biochemical analysis of metabolic indices and morning urine portion test for microalbuminuria has been carried out. Results. MAU has been revealed in 17,6% patients, occurring more frequently in men than in women. Microalbuminuria is accompanied by reliable decrease of total and ionized calcium and magnesium concentrations, an increase of potassium level in blood plasma, increase of cholesterol, triglycerides, glucose and levels. Patients with AH and renal dysfunction reliably demonstrate higher levels of systolic and diastolic arterial pressure in the morning and evening hours, their normalization effect after APs intake is significantly interconnected with MAU presence. Conclusion. In patients with AH and MAU the main risk factors of cardio-vascular diseases development are more expressed. Microalbuminuria is a risk factor in patients with arterial hypertension and may influence on the basic blood electrolyte balance. While carrying out antihypertensive therapy the presence of MAU should be taken into consideration

  5. Prophylactic furosemide infusion decreasing early major postoperative renal dysfunction in on-pump adult cardiac surgery: a randomized clinical trial

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    Fakhari S

    2017-01-01

    Full Text Available Solmaz Fakhari,1 Fariba Mirzaei Bavil,2 Eissa Bilehjani,1 Sona Abolhasani,3 Moussa Mirinazhad,2 Bahman Naghipour2 1Department of Anesthesiology, 2Department of Physiology, 3Tabriz University of Medical Sciences, Tabriz, Iran Introduction: Acute renal dysfunction is a common complication of cardiac surgery. Furosemide is used in prevention, or treatment, of acute renal dysfunction. This study was conducted to evaluate the protective effects of intra- and early postoperative furosemide infusion on preventing acute renal dysfunction in elective adult cardiac surgery. Methods: Eighty-one patients, candidates of elective cardiac surgery, were enrolled in this study in either the furosemide (n=41 or placebo (n=40 group. Furosemide (2 mg/h or 0.9% saline was administered and continued up to 12 hours postoperatively. We measured serum creatinine (Scr at preoperative and on the second and fifth postoperative days. Then calculated estimated glomerular filtration rate (eGFR at these times. An increase in Scr of >0.5 mg/dL and/or >25%–50%, compared to preoperative values, was considered as acute kidney injury (AKI. In contrast, an increase in Scr by >50% and/or the need for hemodialysis was regarded as acute renal failure (ARF. At the end we compared the AKI or ARF incidence between the two groups. Results: On the second and fifth postoperative days, Scr was lower, and the eGFR was higher in the furosemide group. AKI incidence was similar in the two groups (11 vs 12 cases; P-value 0.622; however, ARF rate was lower in furosemide group (1 vs 6 cases; P-value 0.044. During the study period, Scr was more stable in the furosemide group, however in the placebo group, Scr initially increased and then decreased to its preoperative value after a few days. Conclusion: This study showed that intra- and early postoperative furosemide infusion has a renal protective effect in adult cardiac surgery with cardiopulmonary bypass. Although this protective effect cannot

  6. Preclinical evaluation of nephroprotective potential of a probiotic formulation LOBUN on Cyclosporine-A induced renal dysfunction in Wistar rats

    Directory of Open Access Journals (Sweden)

    Kambham Venkateswarlu

    2017-06-01

    Full Text Available ABSTRACT The aim of present study was to evaluate the nephroprotective effect of probiotic formulation LOBUN on Cyclosporine A (CsA induced renal dysfunction in Wistar rats. CsA (20 mg/kg body weight s.c was administered for 15 days to cause renal dysfunction in Wistar rats. The probiotic formulation LOBUN was administered with the dose of 500 mg/kg body weight (p.o for twice (TGI and thrice a day (TGII. The samples were analyzed for the parameters like blood urine nitrogen (BUN, serum creatinine, serum uric acid, total serum protein and urine proteins, urine potassium, urine sodium. The renal functional and histopathological studies revealed that the oral administration of probiotic formulation LOBUN has provided appreciable renoprotection and possibly alleviated the symptoms of Chronic Kidney Disease (CKD at the dose of 500 mg/kg body weight administered thrice a day and also the results were supported by histopathological findings.

  7. Reversal of renal dysfunction by targeted administration of VEGF into the stenotic kidney: a novel potential therapeutic approach.

    Science.gov (United States)

    Chade, Alejandro R; Kelsen, Silvia

    2012-05-15

    Renal microvascular (MV) damage and loss contribute to the progression of renal injury in renovascular disease (RVD). Whether a targeted intervention in renal microcirculation could reverse renal damage is unknown. We hypothesized that intrarenal vascular endothelial growth factor (VEGF) therapy will reverse renal dysfunction and decrease renal injury in experimental RVD. Unilateral renal artery stenosis (RAS) was induced in 14 pigs, as a surrogate of chronic RVD. Six weeks later, renal blood flow (RBF) and glomerular filtration rate (GFR) were quantified in vivo in the stenotic kidney using multidetector computed tomography (CT). Then, intrarenal rhVEGF-165 or vehicle was randomly administered into the stenotic kidneys (n = 7/group), they were observed for 4 additional wk, in vivo studies were repeated, and then renal MV density was quantified by 3D micro-CT, and expression of angiogenic factors and fibrosis was determined. RBF and GFR, MV density, and renal expression of VEGF and downstream mediators such as p-ERK 1/2, Akt, and eNOS were significantly reduced after 6 and at 10 wk of untreated RAS compared with normal controls. Remarkably, administration of VEGF at 6 wk normalized RBF (from 393.6 ± 50.3 to 607.0 ± 45.33 ml/min, P < 0.05 vs. RAS) and GFR (from 43.4 ± 3.4 to 66.6 ± 10.3 ml/min, P < 0.05 vs. RAS) at 10 wk, accompanied by increased angiogenic signaling, augmented renal MV density, and attenuated renal scarring. This study shows promising therapeutic effects of a targeted renal intervention, using an established clinically relevant large-animal model of chronic RAS. It also implies that disruption of renal MV integrity and function plays a pivotal role in the progression of renal injury in the stenotic kidney. Furthermore, it shows a high level of plasticity of renal microvessels to a single-dose VEGF-targeted intervention after established renal injury, supporting promising renoprotective effects of a novel potential therapeutic intervention to

  8. Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

    Science.gov (United States)

    Kolic, Ivana; Purdell-Lewis, Jeremy; Taylor, Rachelle; Pearse, Rupert M.; Kirwan, Christopher J.

    2014-01-01

    Background and objectives AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness. Design, setting, participants, & measurements A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed. Results In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (Pcreatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFRcreatinine (a 135% increase in potential CKD diagnoses; Pcreatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings. PMID:24742481

  9. Decreased Polycystin 2 Levels Result in Non-Renal Cardiac Dysfunction with Aging.

    Science.gov (United States)

    Kuo, Ivana Y; Duong, Sophie L; Nguyen, Lily; Ehrlich, Barbara E

    2016-01-01

    Mutations in the gene for polycystin 2 (Pkd2) lead to polycystic kidney disease, however the main cause of mortality in humans is cardiac related. We previously showed that 5 month old Pkd2+/- mice have altered calcium-contractile activity in cardiomyocytes, but have preserved cardiac function. Here, we examined 1 and 9 month old Pkd2+/- mice to determine if decreased amounts of functional polycystin 2 leads to impaired cardiac function with aging. We observed changes in calcium handling proteins in 1 month old Pkd2+/- mice, and these changes were exacerbated in 9 month old Pkd2+/- mice. Anatomically, the 9 month old Pkd2+/- mice had thinner left ventricular walls, consistent with dilated cardiomyopathy, and the left ventricular ejection fraction was decreased. Intriguingly, in response to acute isoproterenol stimulation to examine β-adrenergic responses, the 9 month old Pkd2+/- mice exhibited a stronger contractile response, which also coincided with preserved localization of the β2 adrenergic receptor. Importantly, the Pkd2+/- mice did not have any renal impairment. We conclude that the cardiac-related impact of decreased polycystin 2 progresses over time towards cardiac dysfunction and altered adrenergic signaling. These results provide further evidence that polycystin 2 provides a critical function in the heart, independent of renal involvement.

  10. Influence of pre-hydration and pharmacogenetics on plasma methotrexate concentration and renal dysfunction following high-dose methotrexate therapy.

    Science.gov (United States)

    Yanagimachi, Masakatsu; Goto, Hiroaki; Kaneko, Tetsuji; Naruto, Takuya; Sasaki, Koji; Takeuchi, Masanobu; Tanoshima, Reo; Kato, Hiromi; Yokosuka, Tomoko; Kajiwara, Ryosuke; Fujii, Hisaki; Tanaka, Fumiko; Goto, Shoko; Takahashi, Hiroyuki; Mori, Masaaki; Kai, Sumio; Yokota, Shumpei

    2013-12-01

    High-dose methotrexate therapy (HD-MTX) has been well established for the treatment of childhood acute lymphoblastic leukemia (ALL). The aims of this study were to investigate whether clinical and pharmacogenetic factors influence plasma MTX concentration and renal dysfunction in patients treated with HD-MTX. In a total of 127 courses of HD-MTX in 51 patients with childhood ALL, influence of clinical and pharmacogenetic factors on plasma MTX concentration and HD-MTX-related renal dysfunction was evaluated. Clinical factors included age, gender, duration of HD-MTX continuous-infusion and duration of pre-hydration before HD-MTX. Pharmacogenetic factors included 5 gene polymorphisms within the MTX pathway genes, namely, SLC19A1, MTHFR, ABCC2 and ABCG2. Short duration of pre-hydration before HD-MTX is the most important risk factor for prolonged high MTX concentration (p < 0.001, OR 6.40, 95 % CI 2.39-17.16) and renal dysfunction (p = 0.013, OR 3.15, 95 % CI 1.27-7.80). The T allele at MTHFR C677T was the risk factor for prolonged high MTX concentration (p = 0.009, OR 5.54, 95 % CI 1.54-19.85), but not for renal dysfunction. We found the influence of MTHFR C677T polymorphism on prolonged high MTX concentration. We reconfirmed the importance of adequate pre-hydration before HD-MTX to prevent prolonged high MTX concentration and MTX-related renal dysfunction.

  11. Reactive Oxygen Species Modulation of Na/K-ATPase Regulates Fibrosis and Renal Proximal Tubular Sodium Handling

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    Jiang Liu

    2012-01-01

    Full Text Available The Na/K-ATPase is the primary force regulating renal sodium handling and plays a key role in both ion homeostasis and blood pressure regulation. Recently, cardiotonic steroids (CTS-mediated Na/K-ATPase signaling has been shown to regulate fibrosis, renal proximal tubule (RPT sodium reabsorption, and experimental Dahl salt-sensitive hypertension in response to a high-salt diet. Reactive oxygen species (ROS are an important modulator of nephron ion transport. As there is limited knowledge regarding the role of ROS-mediated fibrosis and RPT sodium reabsorption through the Na/K-ATPase, the focus of this review is to examine the possible role of ROS in the regulation of Na/K-ATPase activity, its signaling, fibrosis, and RPT sodium reabsorption.

  12. Predictors of mortality and the provision of dialysis in patients with acute tubular necrosis. The Auriculin Anaritide Acute Renal Failure Study Group.

    Science.gov (United States)

    Chertow, G M; Lazarus, J M; Paganini, E P; Allgren, R L; Lafayette, R A; Sayegh, M H

    1998-04-01

    To explore the natural history of critically ill patients with acute renal failure due to acute tubular necrosis, we evaluated 256 patients enrolled in the placebo arm of a randomized clinical trial. Death and the composite outcome, death or the provision of dialysis, were determined with follow-up to 60 d. The relative risks (RR) and 95% confidence intervals (95% CI) associated with routinely available demographic, clinical, and laboratory variables were estimated using proportional hazards regression. Ninety-three (36%) deaths were documented; an additional 52 (20%) patients who survived received dialysis. Predictors of mortality included male gender (RR, 2.01; 95% CI, 1.21 to 3.36), oliguria (RR, 2.25; 95% CI, 1.43 to 3.55), mechanical ventilation (RR, 1.86; 95% CI, 1.18 to 2.93), acute myocardial infarction (RR, 3.14; 95% CI, 1.85 to 5.31), acute stroke or seizure (RR, 3.08; 95% CI, 1.56 to 6.06), chronic immunosuppression (RR, 2.37; 95% CI, 1.16 to 4.88), hyperbilirubinemia (RR, 1.06; 95% CI, 1.03 to 1.08 per 1 mg/dl increase in total bilirubin) and metabolic acidosis (RR, 0.95; 95% CI, 0.90 to 0.99 per 1 mEq/L increase in serum bicarbonate concentration). Predictors of death or the provision of dialysis were oliguria (RR, 5.95; 95% CI, 3.96 to 8.95), mechanical ventilation (RR, 1.53; 95% CI, 1.07 to 2.21), acute myocardial infarction (RR, 1.95; 95% CI, 1.24 to 3.07), arrhythmia (RR, 1.51; 95% CI, 1.04 to 2.19), and hypoalbuminemia (RR, 0.56; 95% CI, 0.42 to 0.74 per 1 g/dl increase in serum albumin concentration). Neither mortality nor the provision of dialysis was related to patient age. These observations can be used to estimate risk early in the course of acute tubular necrosis. Furthermore, these and related models may be used to adjust for case-mix variation in quality improvement efforts, and to objectively stratify patients in future intervention trials aimed at favorably altering the course of hospital-acquired acute renal failure.

  13. Tubular combustion

    CERN Document Server

    Ishizuka, Satoru

    2014-01-01

    Tubular combustors are cylindrical tubes where flame ignition and propagation occur in a spatially confined, highly controlled environment, in a nearly flat, elongated geometry. This allows for some unique advantages where extremely even heat dispersion is required over a large surface while still maintaining fuel efficiency. Tubular combustors also allow for easy flexibility in type of fuel source, allowing for quick changeover to meet various needs and changing fuel pricing. This new addition to the MP sustainable energy series will provide the most up-to-date research on tubular combustion--some of it only now coming out of private proprietary protection. Plentiful examples of current applications along with a good explanation of background theory will offer readers an invaluable guide on this promising energy technology. Highlights include: * An introduction to the theory of tubular flames * The "how to" of maintaining stability of tubular flames through continuous combustion * Examples of both small-scal...

  14. Inhibition of WISE preserves renal allograft function.

    Science.gov (United States)

    Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

    2013-01-01

    Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

  15. Leptin Induces Oxidative Stress Through Activation of NADPH Oxidase in Renal Tubular Cells: Antioxidant Effect of L-Carnitine.

    Science.gov (United States)

    Blanca, Antonio J; Ruiz-Armenta, María V; Zambrano, Sonia; Salsoso, Rocío; Miguel-Carrasco, José L; Fortuño, Ana; Revilla, Elisa; Mate, Alfonso; Vázquez, Carmen M

    2016-10-01

    Leptin is a protein involved in the regulation of food intake and in the immune and inflammatory responses, among other functions. Evidences demonstrate that obesity is directly associated with high levels of leptin, suggesting that leptin may directly link obesity with the elevated cardiovascular and renal risk associated with increased body weight. Adverse effects of leptin include oxidative stress mediated by activation of NADPH oxidase. The aim of this study was to evaluate the effect of L-carnitine (LC) in rat renal epithelial cells (NRK-52E) exposed to leptin in order to generate a state of oxidative stress characteristic of obesity. Leptin increased superoxide anion (O2 (•) -) generation from NADPH oxidase (via PI3 K/Akt pathway), NOX2 expression and nitrotyrosine levels. On the other hand, NOX4 expression and hydrogen peroxide (H2 O2 ) levels diminished after leptin treatment. Furthermore, the expression of antioxidant enzymes, catalase, and superoxide dismutase, was altered by leptin, and an increase in the mRNA expression of pro-inflammatory factors was also found in leptin-treated cells. LC restored all changes induced by leptin to those levels found in untreated cells. In conclusion, stimulation of NRK-52E cells with leptin induced a state of oxidative stress and inflammation that could be reversed by preincubation with LC. Interestingly, LC induced an upregulation of NOX4 and restored the release of its product, hydrogen peroxide, which suggests a protective role of NOX4 against leptin-induced renal damage. J. Cell. Biochem. 117: 2281-2288, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  16. Fanconi Bickel Syndrome: Novel Mutations in GLUT 2 Gene Causing a Distinguished Form of Renal Tubular Acidosis in Two Unrelated Egyptian Families

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    Mohammad Al-Haggar

    2011-01-01

    Full Text Available Background. Fanconi-Bickel syndrome (FBS is an autosomal recessive disorder caused by defects in facilitative glucose transporter 2 (GLUT2 or SLC2A2 gene mapped on chromosome 3q26.1-26.3, that codes for the glucose transporter protein 2. Methods. Two unrelated Egyptian families having suspected cases of FBS were enrolled after taking a written informed consent; both had positive consanguinity, and index cases had evidences of proximal renal tubular defects with hepatomegaly; they were subjected to history taking, signs of rickets as well as anthropometric measurements. Laboratory workup included urinalysis, renal and liver function tests including fasting and postprandial blood sugar; serum calcium, phosphorus, alkaline phosphatase, sodium and potassium, lipid profile, and detailed blood gas. Imaging including bone survey and abdominal ultrasound, and liver biopsy were done to confirm diagnosis. Molecular analysis of the GLUT2 gene was done for DNA samples extracted from peripheral blood leukocyte. All coding sequences, including flanking introns in GLUT2 gene, were amplified using PCR followed by direct sequencing. Results. Two new mutations had been detected, one in each family, in exon 3 two bases (GA were deleted (c.253 254delGA and in exon 6 in the second family, G-to-C substitution at position-1 of the splicing acceptor site (c.776-1G>C or IVS5-1G>A. Conclusion. FBS is a rare disease due to mutation in GLUT2 gene; many mutations were reported, about half were novel mutations; yet none of these mutations is more frequent. A more extensive survey for the most frequent mutations among FBS has to be contemplated to allow for use of molecular screening tests like ARMS.

  17. [3H]AVP binding to rat renal tubular receptors during long-term treatment with an antagonist of arginine vasopressin

    International Nuclear Information System (INIS)

    Mah, S.C.; Whitebread, S.E.; De Gasparo, M.; Hofbauer, K.G.

    1988-01-01

    The interaction of an antagonist of arginine vasopressin (AVP), d(CH2)5-D-Tyr(Et)VAVP, with renal tubular V2 receptors were studied in medullary membrane preparations from kidneys of Sprague-Dawley and Brattleboro rats. In both rat strains, V2 receptors had comparable KD and Bmax values for binding of [3H]AVP. In vitro studies revealed that the V2-antagonist was more potent than cold AVP in displacing [3H]AVP. In vivo treatment of Sprague-Dawley rats with the antagonist over one week resulted only in a transient state of diabetes insipidus (DI). No specific [3H]AVP binding was detectable throughout the period of administration. Chronic treatment of Brattleboro rats resulted in a complete normalization of water intake. This agonistic effect was also associated with undetectable [3H]AVP binding. After stopping the infusion of d(CH2)5-D-Tyr(Et)VAVP, Bmax values tended to rise but had still not reached base line values after 6 days. In contrast, the chronic infusion of AVP in Brattleboro rats resulted in a reduction in water intake which was accompanied by a decreased Bmax. [3H]AVP binding remained detectable during the entire treatment period. Thereafter Bmax was restored to base line values within 2 days of stopping the infusion. These results suggest that d(CH2)5-D-Tyr(Et)VAVP has a high affinity for V2 receptors in both Sprague-Dawley and Brattleboro rats. Its rate of dissociation from the receptor appears to be much slower than that of AVP. In Brattleboro rats, the binding of d(CH2)5-D-Tyr(Et)VAVP leads to an antidiuretic response. In Sprague-Dawley rats, a transient diuretic response is followed by a progressive normalization in water intake. This occurs despite persistent and complete blockade of renal medullary V2 receptors

  18. Hypokalemic muscular paralysis causing acute respiratory failure due to rhabdomyolysis with renal tubular acidosis in a chronic glue sniffer.

    Science.gov (United States)

    Kao, K C; Tsai, Y H; Lin, M C; Huang, C C; Tsao, C Y; Chen, Y C

    2000-01-01

    A 34-year-old male was admitted to the emergency department with the development of quadriparesis and respiratory failure due to hypokalemia after prolonged glue sniffing. The patient was subsequently given mechanical ventilatory support for respiratory failure. He was weaned from the ventilator 4 days later after potassium replacement. Toluene is an aromatic hydrocarbon found in glues, cements, and solvents. It is known to be toxic to the nervous system, hematopoietic system, and causes acid-base and electrolyte disorders. Acute respiratory failure with hypokalemia and rhabdomyolysis with acute renal failure should be considered as potential events in a protracted glue sniffing.

  19. Effects of early changes in organ dysfunctions on the outcomes of critically ill patients in need of renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Elizabeth Maccariello

    2008-01-01

    Full Text Available INTRODUCTION: Acute kidney injury usually develops in critically ill patients in the context of multiple organ dysfunctions. OBJECTIVE: To evaluate the effect of changes in associated organ dysfunctions over the first three days of renal replacement therapy on the outcomes of patients with acute kidney injury. METHODS: Over a 19-month period, we evaluated 260 patients admitted to the intensive care units of three tertiary-care hospitals who required renal replacement therapy for > 48 h. Organ dysfunctions were evaluated by SOFA score (excluding renal points on the first (D1 and third (D3 days of renal replacement therapy. Absolute (A-SOFA and relative (D-SOFA changes in SOFA scores were also calculated. RESULTS: Hospital mortality rate was 75%. Organ dysfunctions worsened (A-SOFA>0 in 53%, remained unchanged (A-SOFA=0 in 17% and improved (A-SOFA<0 in 30% of patients; and mortality was lower in the last group (80% vs. 84% vs. 61%, p=0.003. SOFA on D1 (p<0.001, SOFA on D3 (p<0.001, A-SOFA (p=0.019 and D-SOFA (p=0.016 were higher in non-survivors. However, neither A-SOFA nor D-SOFA discriminated survivors from non-survivors on an individual basis. Adjusting for other covariates (including SOFA on D1, A-SOFA and D-SOFA were associated with increased mortality, and patients in whom SOFA scores worsened or remained unchanged had poorer outcomes. CONCLUSIONS: In addition to baseline values, early changes in SOFA score after the start of renal replacement therapy were associated with hospital mortality. However, no prognostic score should be used as the only parameter to predict individual outcomes.

  20. Hypermethylations of RASAL1 and KLOTHO is associated with renal dysfunction in a Chinese population environmentally exposed to cadmium

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Chen; Liang, Yihuai [School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032 (China); Key Laboratory of Public Health Safety, Ministry of Education, 130 DongAn Road, Shanghai 200032 (China); Lei, Lijian [Department of Epidemiology, School of Public Health, Shanxi Medical University, Shanxi (China); Zhu, Guoying; Chen, Xiao [Department of Bone Metabolism, Institute of Radiation Medicine, Fudan University, Shanghai (China); Jin, Taiyi, E-mail: tyjin@shmu.edu.cn [School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032 (China); Key Laboratory of Public Health Safety, Ministry of Education, 130 DongAn Road, Shanghai 200032 (China); Wu, Qing, E-mail: qingwu@fudan.edu.cn [School of Public Health, Fudan University, 130 DongAn Road, Shanghai 200032 (China); Key Laboratory of Public Health Safety, Ministry of Education, 130 DongAn Road, Shanghai 200032 (China)

    2013-08-15

    Exposure to cadmium (Cd) can affect both DNA methylation and renal function, but there are few examples of the association between epigenetic markers and Cd-induced kidney damage. It has been suggested that hypermethylation of the genes RASAL1 and KLOTHO is associated with renal fibrogenesis. To investigate whether hypermethylation of RASAL1 and KLOTHO in peripheral blood DNA can be associated with Cd exposure and/or Cd-induced renal dysfunction, the degrees of methylation of RASAL1 and KLOTHO in peripheral blood DNA from 81 residents in Cd-polluted and non-polluted areas were measured using bisulfate-PCR-pyrosequencing. Changes in blood cadmium (BCd), urinary cadmium (UCd), and kidney parameters were measured, and the glomerular filtration rate (eGFR) was estimated. The levels of BCd and UCd correlated positively with the levels of DNA methylation in RASAL1 and in KLOTHO. The more heavily exposed residents (BCd, 4.23–13.22 μg/L; UCd, 8.65–32.90 μg/g creatinine) exhibited obvious renal dysfunction. Notably, when Cd concentration in blood and urine was adjusted, the increased methylation level in RASAL1 was inversely correlated with eGFR (P < 0.01) but the relationship between hypermethylation of KLOTHO and eGFR was not statistically significant. The methylation of RASAL1 increased along with the increased abnormal prevalence of eGFR. Our findings suggest that Cd exposure can induce the hypermethylation of RASAL1 and KLOTHO. Hypermethylation of RASAL1 may be an indicator of the progress for chronic kidney disease. - Highlights: • A long term heavily Cd exposure induced renal dysfunction. • Cd exposure correlated positively with DNA methylation in RASAL1 and KLOTHO. • Hypermethylation of RASAL1 correlated with adjusted renal function indicators.

  1. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.

    Science.gov (United States)

    Lepist, Eve-Irene; Zhang, Xuexiang; Hao, Jia; Huang, Jane; Kosaka, Alan; Birkus, Gabriel; Murray, Bernard P; Bannister, Roy; Cihlar, Tomas; Huang, Yong; Ray, Adrian S

    2014-08-01

    Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition.

  2. Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat

    Science.gov (United States)

    Lepist, Eve-Irene; Zhang, Xuexiang; Hao, Jia; Huang, Jane; Kosaka, Alan; Birkus, Gabriel; Murray, Bernard P; Bannister, Roy; Cihlar, Tomas; Huang, Yong; Ray, Adrian S

    2014-01-01

    Many xenobiotics including the pharmacoenhancer cobicistat increase serum creatinine by inhibiting its renal active tubular secretion without affecting the glomerular filtration rate. This study aimed to define the transporters involved in creatinine secretion, applying that knowledge to establish the mechanism for xenobiotic-induced effects. The basolateral uptake transporters organic anion transporter OAT2 and organic cation transporters OCT2 and OCT3 were found to transport creatinine. At physiologic creatinine concentrations, the specific activity of OAT2 transport was over twofold higher than OCT2 or OCT3, establishing OAT2 as a likely relevant creatinine transporter and further challenging the traditional view that creatinine is solely transported by a cationic pathway. The apical multidrug and toxin extrusion transporters MATE1 and MATE2-K demonstrated low-affinity and high-capacity transport. All drugs known to affect creatinine inhibited OCT2 and MATE1. Similar to cimetidine and ritonavir, cobicistat had the greatest effect on MATE1 with a 50% inhibition constant of 0.99 μM for creatinine transport. Trimethoprim potently inhibited MATE2-K, whereas dolutegravir preferentially inhibited OCT2. Cimetidine was unique, inhibiting all transporters that interact with creatinine. Thus, the clinical observation of elevated serum creatinine in patients taking cobicistat is likely a result of OCT2 transport, facilitating intracellular accumulation, and MATE1 inhibition. PMID:24646860

  3. Renal Subcapsular Transplantation of PSC-Derived Kidney Organoids Induces Neo-vasculogenesis and Significant Glomerular and Tubular Maturation In Vivo

    Directory of Open Access Journals (Sweden)

    Cathelijne W. van den Berg

    2018-03-01

    Full Text Available Summary: Human pluripotent stem cell (hPSC-derived kidney organoids may facilitate disease modeling and the generation of tissue for renal replacement. Long-term application, however, will require transferability between hPSC lines and significant improvements in organ maturation. A key question is whether time or a patent vasculature is required for ongoing morphogenesis. Here, we show that hPSC-derived kidney organoids, derived in fully defined medium conditions and in the absence of any exogenous vascular endothelial growth factor, develop host-derived vascularization. In vivo imaging of organoids under the kidney capsule confirms functional glomerular perfusion as well as connection to pre-existing vascular networks in the organoids. Wide-field electron microscopy demonstrates that transplantation results in formation of a glomerular basement membrane, fenestrated endothelial cells, and podocyte foot processes. Furthermore, compared with non-transplanted organoids, polarization and segmental specialization of tubular epithelium are observed. These data demonstrate that functional vascularization is required for progressive morphogenesis of human kidney organoids. : In this article, Van den Berg and colleagues show that PSC-derived kidney organoids contain nephron structures but remain disorganized and immature after prolonged culture. Upon transplantation, the organoids develop host-derived vascularization, functional glomerular perfusion, and connection to pre-existing vascular networks. The authors conclude that patent vasculature is required for ongoing morphogenesis and maturation of these kidney organoids. Keywords: human pluripotent stem cells, directed differentiation, kidney organoids, transplantation, intravital microscopy, vascularization, maturation

  4. Contrast Media-Induced Renal Inflammation Is Mediated Through HMGB1 and Its Receptors in Human Tubular Cells.

    Science.gov (United States)

    Guan, Xiao-Feng; Chen, Qing-Jie; Zuo, Xiao-Cong; Guo, Ren; Peng, Xiang-Dong; Wang, Jiang-Lin; Yin, Wen-Jun; Li, Dai-Yang

    2017-01-01

    With the rapid development of imaging diagnosis and interventional therapy, contrast media (CM) are widely used in clinics. However, contrast-induced nephropathy (CIN) is the third leading cause of hospital-acquired acute renal failure accounting for 10-12% of all causes of hospital-acquired renal failure. Recent study found that inflammation may participate in the pathogenesis of CIN, but the role of it remains unclear. HK-2 cells were treated with Iohexol, Urografin, and mannitol. Two types of CM increased the release of HMGB1 in cell supernatant accompanied by increased expression of TLR2 and CXCR4. Iohexol and Urografin also caused a significant increase in NF-κB followed by the release of IL-6 and MCP-1. To clarify the role of HMGB1, TLR2, and CXCR4, glycyrrhizin, anti-TLR2-IgG, and AMD3100 were used to inhibit HMGB1, TLR2, and CXCR4, respectively. Significant decrease in the expression of TLR2, CXCR4, nuclear NF-κB, and the release of IL-6 and MCP-1 were observed. These results indicate that TLR2 and CXCR4 signaling are involved in CM-induced HK-2 cell injury model in an HMGB1-dependent pathway, which may provide a new target for the prevention and the treatment of CIN.

  5. Na+ pump in renal tubular cells is regulated by endogenous Na+-K+-ATPase inhibitor from hypothalamus

    International Nuclear Information System (INIS)

    Cantiello, H.F.; Chen, E.; Ray, S.; Haupert, G.T. Jr.

    1988-01-01

    Bovine hypothalamus contains a high affinity, specific, reversible inhibitor of mammalian Na + -K + -ATPase. Kinetic analysis using isolated membrane fractions showed binding and dissociation rates of the hypothalamic factor (HF) to be (like ouabain) relatively long (off rate = 60 min). To determine whether the kinetics of inhibition in intact cells might be more consistent with regulation of physiological processes in vivo, binding and dissociation reactions of HF in intact renal epithelial cells (LLC-PK 1 ) were studied using 86 Rb + uptake and [ 3 H]ouabain binding. As with membranes, a 60-min incubation with HF inhibited Na + -K + -ATPase in LLC-PK 1 cells. In contrast to membrane studies, no prolonged incubation with LLC-PK 1 was needed to observe inhibition of Na + -K + -ATPase. HF caused a 33% inhibition of ouabain-sensitive 86 Rb + influx within 10 min. Incubation of cells with HF followed by washout showed rapid reversal of pump inhibition and a doubling of pump activity. The dose-response curve for HF inhibition of LLC-PK 1 86 Rb + uptake showed a sigmoidal shape consistent with an allosteric binding reaction. Thus HF is a potent regulator of Na + -K + -ATPase activity in intact renal cells, with binding and dissociation reactions consistent with relevant physiological processes

  6. Na sup + pump in renal tubular cells is regulated by endogenous Na sup + -K sup + -ATPase inhibitor from hypothalamus

    Energy Technology Data Exchange (ETDEWEB)

    Cantiello, H.F.; Chen, E.; Ray, S.; Haupert, G.T. Jr. (Harvard medical School, Boston, MA (USA))

    1988-10-01

    Bovine hypothalamus contains a high affinity, specific, reversible inhibitor of mammalian Na{sup +}-K{sup +}-ATPase. Kinetic analysis using isolated membrane fractions showed binding and dissociation rates of the hypothalamic factor (HF) to be (like ouabain) relatively long (off rate = 60 min). To determine whether the kinetics of inhibition in intact cells might be more consistent with regulation of physiological processes in vivo, binding and dissociation reactions of HF in intact renal epithelial cells (LLC-PK{sup 1}) were studied using {sup 86}Rb{sup +} uptake and ({sup 3}H)ouabain binding. As with membranes, a 60-min incubation with HF inhibited Na{sup +}-K{sup +}-ATPase in LLC-PK{sub 1} cells. In contrast to membrane studies, no prolonged incubation with LLC-PK{sub 1} was needed to observe inhibition of Na{sup +}-K{sup +}-ATPase. HF caused a 33% inhibition of ouabain-sensitive {sup 86}Rb{sup +} influx within 10 min. Incubation of cells with HF followed by washout showed rapid reversal of pump inhibition and a doubling of pump activity. The dose-response curve for HF inhibition of LLC-PK{sub 1} {sup 86}Rb{sup +} uptake showed a sigmoidal shape consistent with an allosteric binding reaction. Thus HF is a potent regulator of Na{sup +}-K{sup +}-ATPase activity in intact renal cells, with binding and dissociation reactions consistent with relevant physiological processes.

  7. Different antidiabetic regimens and the development of renal dysfunction in US Veterans with type 2 diabetes mellitus.

    Science.gov (United States)

    Gosmanova, Elvira O; Canada, Robert B; Wan, Jim; Mangold, Therese A; Wall, Barry M

    2012-10-01

    The aim of this study was to evaluate the development of renal dysfunction in veterans with type 2 diabetes mellitus (T2DM) treated with different antidiabetic regimens. A retrospective cohort study involving 1715 patients with T2DM and baseline serum creatinine (SCr) of 1.5 mg/dL or lesser. The development of renal dysfunction, defined as 0.5 mg/dL or greater increase from baseline SCr during 4.8 years of follow-up with monotherapy metformin (M), 2 combination therapy groups: metformin + insulin (MI) and metformin + sulfonylurea (MS) users were compared with changes observed in sulfonylurea monotherapy users (S). Both MI and MS groups had higher mean baseline hemoglobin A1C (HbA1C) (9.0 and 8.6%, respectively) and higher rates of baseline macroalbuminuria (17.3 and 12.1%, respectively) as compared with M and S groups (mean HbA1C7.7% in both groups, and proteinuria M-5.1% and S-7.4%). In unadjusted analysis, the development of renal dysfunction was more frequent in MI and MS but not in M group as compared with sulfonylurea monotherapy (unadjusted HRs and [95% confidence interval (CI), 2.1[1.4-3.0], 1.4[1.1-1.9], and 1.0[0.6-1.7], respectively). However, differences in the development of renal dysfunction were not significant between the 4 groups after adjusting for baseline variables. Baseline macroalbuminuria was a strong predictor of Scr elevation of 0.5 mg/dL or greater during follow-up (adjusted HR, 3.1[1.9-4.7]). Unexpectedly, baseline use of renin-angiotensin-aldosterone system blockers was also associated with the development of renal dysfunction (adjusted HR, 1.9[1.3-2.8]). In this retrospective cohort study involving US predominantly male veterans with T2DM, baseline macroalbuminuria and use of RAAS blockers were associated with increased risk of development of renal dysfunction, whereas different antidiabetic regimens were not.

  8. Mucin 4 Gene Silencing Reduces Oxidative Stress and Calcium Oxalate Crystal Formation in Renal Tubular Epithelial Cells Through the Extracellular Signal-Regulated Kinase Signaling Pathway in Nephrolithiasis Rat Model

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    Ling Sun

    2018-05-01

    Full Text Available Background/Aims: Nephrolithiasis plagues a great number of patients all over the world. Increasing evidence shows that the extracellular signal-regulated kinase (ERK signaling pathway and renal tubular epithelial cell (RTEC dysfunction and attrition are central to the pathogenesis of kidney diseases. Mucin 4 (MUC4 is reported as an activator of ERK signaling pathway in epithelial cells. In this study, using rat models of calcium oxalate (CaOx nephrolithiasis, the present study aims to define the roles of MUC4 and ERK signaling pathway as contributors to oxidative stress and CaOx crystal formation in RTEC. Methods: Data sets of nephrolithiasis were searched using GEO database and a heat flow map was drawn. Then MUC4 function was predicted. Wistar rats were prepared for the purpose of model establishment of ethylene glycol and ammonium chloride induced CaOx nephrolithiasis. In order to assess the detailed regulatory mechanism of MUC4 silencing on the ERK signaling pathway and RTEC, we used recombinant plasmid to downregulate MUC4 expression in Wistar rat-based models. Samples from rat urine, serum and kidney tissues were reviewed to identify oxalic acid and calcium contents, BUN, Cr, Ca2+ and P3+ levels, calcium crystal formation in renal tubules and MUC4 positive expression rate. Finally, RT-qPCR, Western blot analysis, and ELISA were employed to access oxidative stress state and CaOx crystal formation in RTEC. Results: Initially, MUC4 was found to have an influence on the process of nephrolithiasis. MUC4 was upregulated in the CaOx nephrolithiasis model rats. We proved that the silencing of MUC4 triggered the inactivation of ERK signaling pathway. Following the silencing of MUC4 or the inhibition of ERK signaling pathway, the oxalic acid and calcium contents in rat urine, BUN, Cr, Ca2+ and P3+ levels in rat serum, p-ERK1/2, MCP-1 and OPN expressions in RTEC and H2O2 and MDA levels in the cultured supernatant were downregulated, but the GSH

  9. Management of oxidative stress by heme oxygenase-1 in cisplatin-induced toxicity in renal tubular cells.

    Science.gov (United States)

    Schaaf, G J; Maas, R F M; de Groene, E M; Fink-Gremmels, J

    2002-08-01

    Induction of heme oxygenase-1 (HO-1) may serve as an immediate protective response during treatment with the cytostatic drug cisplatin (CDDP). Oxidative pathways participate in the characteristic nephrotoxicity of CDDP. In the present study, cultured tubular cells (LLC-PK1) were used to investigate whether induction of HO provided protection against CDDP by maintaining the cellular redox balance. The antioxidants, alpha-tocopherol (TOCO) and N-acetylcysteine (NAC), were used to demonstrate that elevation of ROS levels contribute to the development of CDDP-induced cytotoxicity. Chemical modulators of HO activity were used to investigate the role of HO herein. Hemin was used to specifically induce HO-1, while exposure of the cells to tin-protoporphyrin (SnPP) was shown to inhibit HO activity. Hemin treatment prior to CDDP-exposure significantly decreased the generation of ROS to control levels, while inhibition of HO increased the ROS levels beyond the levels measured in cells treated with CDDP alone. Furthermore, HO induction protected significantly against the cytotoxicity of CDDP, although this protection was limited. Similar results were obtained when the cells were preincubated with TOCO, suggesting that mechanisms other than impairment of the redox ratio are important in CDDP-induced loss of cell viability in vitro. In addition, SnPP treatment exacerbated the oxidative response and cytotoxicity of CDDP, especially at low CDDP concentrations. We therefore conclude that HO is able to directly limit the CDDP-induced oxidative stress response and thus serves as safeguard of the cellular redox balance.

  10. Efecto citotóxico de la toxina shiga tipo 2 y su subunidad b en células epiteliales tubulares renales humanas en cultivo Cytotoxic effect of Shiga toxin type 2 and its B subunit on human renal tubular epithelial cell cultures

    Directory of Open Access Journals (Sweden)

    Virginia Pistone Creydt

    2005-04-01

    Full Text Available Escherichia coli enterohemorrágica productora de toxina Shiga (Stx causa diarrea acuosa, colitis hemorrágica y síndrome urémico hemolítico (SUH. En Argentina, el SUH es la principal causa de insuficiencia renal en niños. El objetivo de este trabajo fue estudiar la toxicidad de Stx tipo 2 (Stx2 y su subunidad B (Stx2B en células epiteliales tubulares renales humanas (CERH, en presencia y ausencia de factores inflamatorios. Los efectos citotóxicos se evaluaron como alteración de la funcionalidad del epitelio; daños histológicos; viabilidad celular; síntesis de proteínas y apoptosis celular. Los resultados muestran que Stx2 regula el pasaje de agua a través de CERH a tiempos menores de 1h de incubación. A tiempos mayores, hasta 72 hs, el estudio de la morfología, la viabilidad, la síntesis de proteínas y la apoptosis demostró que las CERH fueron sensibles a la acción citotóxica de Stx2 y Stx2B de una manera dosis y tiempo dependiente. Estos efectos fueron potenciados por lipopolisacáridos bacterianos (LPS, IL-1b, y butirato.Shiga toxin (Stx-producing E.coli causing watery diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome (HUS. In Argentina, HUS is the most common cause of acute renal failure in children. The purpose of the present study was to examine the cytotoxicity of Stx type 2 (Stx2 and its B subunit (Stx2B on human renal tubular epithelial cells (HRTEC, in the presence and absence of inflammatory factors. Cytotoxic effects were assessed in terms of functionality of the epithelium, histological damage, cell viability, protein synthesis and cellular apoptosis. Results show that Stx2 regulates the passage of water through the HRTEC within an incubation period of 1h. Within longer periods, up to 72 hours, the study of morphology, viability, protein synthesis and apoptosis shows that HRTEC were sensitive to the cytotoxic action of Stx2 and Stx2B in a dose- and time-dependent manner. These effects were potentiated by

  11. Grape Seed oil as Anti hepatic and Anti renal Dysfunction agent in Paracetamol Administrated Rats

    International Nuclear Information System (INIS)

    Farag, M.F.; Osman, N.N.; Darwish, M.M.

    2010-01-01

    The protection conferred by dietary grape seed oil (GSO) against paracetamol (PCL)-induced liver and kidney dysfunction have been evaluated in adult male albino Wistar rats. The animals (180-200 g) were randomly divided into four groups of seven rats each. Group l: normal control, group II: animals received GSO (3.7 g Kg-1 body wt/day orally), group III: animals received PCL (4 g Kg-1 body wt/day orally) and group IV: animals received PCL plus GSO. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AP), gamma glutamyl transferase (GGT), urea (U), creatinine (Cr) and albumin (A) levels in serum and blood urea nitrogen (BUN) were measured. In addition, the levels of thiobarbituric acid reactive substances (TBARS), reduced glutathione (GSH) and the activity of superoxide dismutase (SOD) and catalase (CAT) in the liver and kidney homogenates were chosen for assessing. The PCL induced a significant elevation in the serum AST, ALT, AP and GGT. Moreover, a significant increase in serum U, Cr, A and BUN were evident. Furthermore, a significant rise in TBARS, while a significant declined activity of SOD and CAT and GSH content in liver and kidney homogenates were also observed. Oral administration of GSO resulted in a significant reduction in liver and kidney markers in serum, BUN as well hepatic and renal TBARS accompanied by a significant improvement in the tissue antioxidants and A, when compared with PCL damaged rats. It was suggested that GSO has potent hepatic and renal protective effects against the oxidative damage induced in rats due to PCL treatment, perhaps by its antioxidative effects hence eliminating the deleterious effects of PCL.

  12. Mechanisms of endothelial dysfunction in resistance arteries from patients with end-stage renal disease.

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    Leanid Luksha

    Full Text Available The study focuses on the mechanisms of endothelial dysfunction in the uremic milieu. Subcutaneous resistance arteries from 35 end-stage renal disease (ESRD patients and 28 matched controls were studied ex-vivo. Basal and receptor-dependent effects of endothelium-derived factors, expression of endothelial NO synthase (eNOS, prerequisites for myoendothelial gap junctions (MEGJ, and associations between endothelium-dependent responses and plasma levels of endothelial dysfunction markers were assessed. The contribution of endothelium-derived hyperpolarizing factor (EDHF to endothelium-dependent relaxation was impaired in uremic arteries after stimulation with bradykinin, but not acetylcholine, reflecting the agonist-specific differences. Diminished vasodilator influences of the endothelium on basal tone and enhanced plasma levels of asymmetrical dimethyl L-arginine (ADMA suggest impairment in NO-mediated regulation of uremic arteries. eNOS expression and contribution of MEGJs to EDHF type responses were unaltered. Plasma levels of ADMA were negatively associated with endothelium-dependent responses in uremic arteries. Preserved responses of smooth muscle to pinacidil and NO-donor indicate alterations within the endothelium and tolerance of vasodilator mechanisms to the uremic retention products at the level of smooth muscle. We conclude that both EDHF and NO pathways that control resistance artery tone are impaired in the uremic milieu. For the first time, we validate the alterations in EDHF type responses linked to kinin receptors in ESRD patients. The association between plasma ADMA concentrations and endothelial function in uremic resistance vasculature may have diagnostic and future therapeutic implications.

  13. Adefovir nephrotoxicity in a renal allograft recipient

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    N George

    2015-01-01

    Full Text Available Adefovir dipivoxil, an oral prodrug of adefovir, is used in the treatment of lamivudine-resistant hepatitis B virus (HBV infection. Nephrotoxicity manifesting as proximal renal tubular dysfunction and acute tubular necrosis (ATN were commonly reported in the past, when higher doses were used for the treatment of human immunodeficiency virus infection. However, nephrotoxicity is rare at lower doses that are currently recommended for the treatment of HBV infection. A 31-year-old female was detected to be hepatitis B surface antigen positive months after a kidney transplant. The patient was initiated on lamivudine, but developed resistance after 1 year of treatment, at which time low-dose adefovir was added. The patient developed renal allograft dysfunction after 10 months of starting adefovir. Serum creatinine increased from 1.1 mg/dl to 1.9 mg/dl, along with progressively increasing sub-nephrotic proteinuria. Renal allograft biopsy revealed features of ATN. After discontinuation of adefovir, proteinuria resolved and renal dysfunction improved slowly over the next 2 years. Adefovir-induced nephrotoxicity, although uncommon at lower doses, needs to be considered in the differential diagnosis of renal dysfunction and sub-nephrotic proteinuria occurring in patients receiving adefovir for prolonged periods.

  14. Associations Between Neutrophil Gelatinase Associated Lipocalin, Neutrophil-to-Lymphocyte Ratio, Atrial Fibrillation and Renal Dysfunction in Chronic Heart Failure

    Science.gov (United States)

    Argan, Onur; Ural, Dilek; Kozdag, Guliz; Sahin, Tayfun; Bozyel, Serdar; Aktas, Mujdat; Karauzum, Kurtulus; Yılmaz, Irem; Dervis, Emir; Agir, Aysen

    2016-01-01

    Background Atrial fibrillation (AF) and renal dysfunction are two common comorbidities in patients with chronic heart failure with reduced ejection fraction (HFrEF). This study evaluated the effect of permanent AF on renal function in HFrEF and investigated the associations of atrial fibrillation, neutrophil gelatinase-associated lipocalin (NGAL), and neutrophil-to-lymphocyte ratio (NLR) with adverse clinical outcome. Material/Methods Serum NGAL levels measured by ELISA and NLR were compared between patients with sinus rhythm (HFrEF-SR, n=68), with permanent AF (HFrEF-AF, n=62), and a healthy control group (n=50). Results Mean eGFR levels were significantly lower, and NLR and NGAL levels were significantly higher in the HFrEF patients than in the control patients but the difference between HFrEF-SR and HFrEF-AF was not statistically significant (NGAL: 95 ng/mL in HFrEF-SR, 113 ng/mL in HFrEF-AF and 84 ng/mL in the control group; pfailure, C-reactive protein, NLR, triiodothyronine, and hemoglobin. In ROC analysis, a NLR >3 had a 68% sensitivity and 75% specificity to predict progression of kidney disease (AUC=0.72, 95% CI 0.58–0.85, p=0.001). Conclusions Presence of AF in patients with HFrEF was not an independent contributor of adverse clinical outcome (i.e., all-cause death, re-hospitalization) or progression of renal dysfunction. Renal dysfunction in HFrEF was associated with both NLR and NGAL levels, but systemic inflammation reflected by NLR seemed to be a more important determinant of progression of kidney dysfunction. PMID:27918494

  15. Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Ladefoged, S D

    1990-01-01

    of sodium and water during dopamine infusion (3 micrograms min-1 kg-1) were estimated in 12 normal volunteers. 2. CNa increased by 128% (P less than 0.001). Effective renal plasma flow and GFR increased by 43% (P less than 0.001) and 9% (P less than 0.01), respectively. CLi increased in all subjects by......, on average, 44% (P less than 0.001). Fractional proximal reabsorption [1-(CLi/GFR)] decreased by 13% after dopamine infusion (P less than 0.001), and estimated absolute proximal reabsorption rate (GFR-CLi) decreased by 8% (P less than 0.01). Absolute distal sodium reabsorption rate [(CLi-CNa) x PNa, where...... PNa is plasma sodium concentration] increased (P less than 0.001), and fractional distal sodium reabsorption [(CLi-CNa)/CLi] decreased (P less than 0.001). 3. It is concluded that natriuresis during low-dose dopamine infusion is caused by an increased outflow of sodium from the proximal tubules...

  16. Use of a “CNI holidays” strategy in acute renal dysfunction late after heart transplant. Report of two cases

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    Pau Alonso

    2014-12-01

    Full Text Available Background Acute renal dysfunction (ARD may appear in heart transplant (HTx patients both in the early postoperative period and during follow-up, even after several years. CD25 is a subunit of the interleukin-2 receptor which is found exclusively on activated CD4 T lymphocytes. CD25 is crucial for clonal expansion of anti-allograft host lymphocytes that mediate in acute rejection. There are experiences supporting the use of Anti-CD25 monoclonal antibodies (MAb immediately after HTx in patients with ARD as a bridge to renal function recovery, allowing the temporary suspension of treatment with CNI. Methods In this study we report two cases of successful use of weekly MAb (basiliximab in HTx patients who developed late ARD after HTx. Conclusions In coclusion, we think that in cases of ARD where CNI therapy plays a key role, the use of weekly doses of basiliximab allows CNI discontinuation until the restoration of renal function is achieved.

  17. Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction.

    Science.gov (United States)

    Palazzuoli, Alberto; Pellegrini, Marco; Franci, Beatrice; Beltrami, Matteo; Ruocco, Gaetano; Gonnelli, Stefano; Angelini, Gianni D; Nuti, Ranuccio

    2015-02-01

    Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p diuretics are responsible for worsening renal function and to define the best modality of administration.

  18. Regulation of renal NaPi-2 expression and tubular phosphate reabsorption by growth hormone in the juvenile rat.

    Science.gov (United States)

    Woda, Craig B; Halaihel, Nabil; Wilson, Paul V; Haramati, Aviad; Levi, Moshe; Mulroney, Susan E

    2004-07-01

    Growth hormone (GH) is an important factor in the developmental adaptation to enhance P(i) reabsorption; however, the nephron sites and mechanisms by which GH regulates renal P(i) uptake remain unclear and are the focus of the present study. Micropuncture experiments were performed after acute thyroparathyroidectomy in the presence and absence of parathyroid hormone (PTH) in adult (14- to 17-wk old), juvenile (4-wk old), and GH-suppressed juvenile male rats. While the phosphaturic effect of PTH was blunted in the juvenile rat compared with the adult, suppression of GH in the juvenile restored fractional P(i) excretion to adult levels. In the presence or absence of PTH, GH suppression in the juvenile rat caused a significant increase in the fractional P(i) delivery to the late proximal convoluted (PCT) and early distal tubule, so that delivery was not different from that in adults. These data were confirmed by P(i) uptake studies into brush-border membrane (BBM) vesicles. Immunofluorescence studies indicate increased BBM type IIa NaP(i) cotransporter (NaPi-2) expression in the juvenile compared with adult rat, and GH suppression reduced NaPi-2 expression to levels observed in the adult. GH replacement in the [N-acetyl-Tyr(1)-d-Arg(2)]-GRF-(1-29)-NH(2)-treated juveniles restored high NaPi-2 expression and P(i) uptake. Together, these novel results demonstrate that the presence of GH in the juvenile animal is crucial for the early developmental upregulation of BBM NaPi-2 and, most importantly, describe the enhanced P(i) reabsorption along the PCT and proximal straight nephron segments in the juvenile rat.

  19. Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury

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    Hideyuki Iwayama

    2011-10-01

    Full Text Available Background/Aims: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs and whether it regulates cyclosporine A (CyA-induced apoptosis in renal proximal tubular cells (RPTCs. Methods: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence and apoptosis (determined by Hoechst 33258 staining was examined in HK-2 cells. Results: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1–6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Conclusion: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.

  20. Serum Creatinine in Patients with Advanced Liver Disease Is of Limited Value for Identification of Moderate Renal Dysfunction: Are the Equations for Estimating Renal Function Better?

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    Jillian MacAulay

    2006-01-01

    Full Text Available BACKGROUND: The Cockcroft-Gault formula (CGF is used to estimate the glomerular filtration rate (GFR based on serum creatinine (Cr levels, age and sex. A new formula developed by the Modification of Diet in Renal Disease (MDRD Study Group, based on the patient’s Cr levels, age, sex, race and serum urea nitrogen and serum albumin levels, has shown to be more accurate. However, the best formula to identify patients with advanced liver disease (ALD and moderate renal dysfunction (GFR 60 mL/min/1.73 m2 or less is not known. The aim of the present study was to compare calculations of GFR, using published formulas (excluding those requiring urine collections with standard radionuclide measurement of GFR in patients with ALD.

  1. Heart Rate Variability in Patients with Acute Ischemic Stroke at Different Stages of Renal Dysfunction: A Cross-sectional Observational Study

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    Lin Wei

    2017-01-01

    Conclusions: Autonomic dysfunction is aggravated with the progression of eGFR stage in patients with acute ischemic stroke; the eGFR is an independent factor of LF/HF in the adjusted models. Stroke severity and a history of diabetes are more significantly associated with HRV in patients with acute ischemic stroke at different stages of renal dysfunction.

  2. Metabolic characteristics and renal dysfunction in 65 patients with tophi prior to gout.

    Science.gov (United States)

    Lu, Chuan-Chin; Wu, Shyi-Kuen; Chung, Wei-Sheng; Lin, Liang-Hung; Hung, Ta-Wei; Yeh, Chih-Jung

    2017-08-01

    Tophi typically occur many years after uncontrolled gout. Therefore, their development before gout remains unusual. Such patients might exhibit some characteristic differences compared with typical tophaceous gout patients. In this study, 65 tophaceous gout patients with tophi as the first sign of gout (tophi-first group) were enrolled. Their clinical characteristics were compared with those of 1421 patients whose tophi occurred after gout (tophi-after group). Compared with the tophi-after group, the tophi-first group had a significantly higher percentage of female patients and patients with elderly onset of disease and a lower percentage of patients with a positive family history; these patients had lower body mass indices, serum urate levels, and estimated glomerular filtration rates (eGFRs). Female sex and negative family history were identified as the principal determinants of tophi development before gout. The decreasing eGFR among the tophi-first group was not due to the group per se but was a result of older age, longer tophi duration, and hyperuricemia. The most common site of initial tophi occurrence in both groups was the toe. In the tophi-first group, the occurrence rates for initial tophi sites were significantly higher at the finger but were lower at the ankle. The tophi-first group exhibited distinct characteristics of age, gender, family history, BMI, serum urate levels, and initial tophi site. This group had fewer comorbidities but similar renal dysfunction compared with the tophi-after group. Thus, patients presenting with tophi should be treated promptly, even if they have no history of gout symptoms.

  3. Left ventricular diastolic dysfunction in chronic renal failure patients on chronic hemodialysis in Dr. Cipto-Mangunkusumo Hospital : the association with left ventricular mass

    Directory of Open Access Journals (Sweden)

    Idrus Alwi

    2006-06-01

    Full Text Available Fourty three patients with chronic renal failure undergoing chronic hemodialysis in Division of Nephrology and Hypertension, Faculty of Medicine, University of Indonesia/Cipto-Mangunkusumo Hospital, Jakarta, since October 2003 until February 2004, were examined for echocardiography (2-D, M-mode, Doppler imaging.Diastolic dysfunction was found in 58.1 % of chronic renal failure patients on hemodialysis. There was no significant difference between left ventricular mass in the group with or without left ventricular diastolic dysfunction. (Med J Indones 2006; 15:105-8Keywords: Left ventricular mass, diastolic function, chronic renal failure, hemodyalisis

  4. Long-term enzyme replacement therapy is associated with reduced proteinuria and preserved proximal tubular function in women with Fabry disease

    DEFF Research Database (Denmark)

    Prabakaran, Thaneas; Birn, Henrik; Bibby, Bo M

    2014-01-01

    dysfunction in women with Fabry disease treated with ERT. METHODS: A retrospective, single centre, cohort study evaluated the long-term association between ERT, albuminuria and eGFR in 13 women with Fabry disease and mild renal involvement. In particular, we analysed the changes in the proteinuric profile...... to end-stage renal failure. In women with Fabry disease, accumulation of GL-3 in the glomerular podocytes and other renal cells induces progressive, proteinuric nephropathy, but not as severe as in men. Enzyme replacement therapy (ERT) with recombinant α-Gal A reduces cellular GL-3 deposits in podocytes...... in albuminuria was paralleled by a decrease in both glomerular and tubular urine protein markers. CONCLUSIONS: The data indicate that long-term ERT is associated with a reduction in albuminuria and glomerular and tubular urinary protein markers in women with Fabry disease and mild renal manifestations....

  5. Urinary excretion of fatty acid-binding protein 4 is associated with albuminuria and renal dysfunction.

    Directory of Open Access Journals (Sweden)

    Yusuke Okazaki

    Full Text Available Fatty acid-binding protein 4 (FABP4/A-FABP/aP2 is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP, in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated.Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n = 392, male/female: 166/226 were enrolled. Urinary FABP4 (U-FABP4 and urinary albumin-to-creatinine ratio (UACR were measured. Change in estimated glomerular filtration rate (eGFR was followed up one year later.In 93 (23.7% of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4, triglycerides, hemoglobin A1c (HbA1c, urinary FABP1 (U-FABP1 and UACR (r = 0.360, p<0.001. Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile.Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

  6. Is a long term work in automotive industry a risk factor for renal dysfunction?

    Science.gov (United States)

    Assadi, Seyedeh Negar

    2015-01-01

    Disorders of renal system can cause renal failure; therefore screening is necessary especially in workers who are exposed to harmful materials. Hypertension, diabetes mellitus, and hazardous exposures are non-occupational and occupational risk factors for renal diseases. The objective of this study was to determine the effects of working in automotive industry on renal function in Iran. In a historical cohort study, workers of automotive industry who worked in production and had low exposure to metal fumes were selected and divided to three groups with 5-10, 11-20, and 21-30 years work duration. risk factors for renal diseases were collected and analyzed with SPSS using one-way ANOVA, correlation coefficient and with P automotive Industry with low exposure to toxic metals and solvents has no significant effect on GFR, creatinine clearance, uric acid, and mean blood pressure.

  7. Impact of Small Body Weight on Tenofovir-Associated Renal Dysfunction in HIV-Infected Patients: A Retrospective Cohort Study of Japanese Patients

    Science.gov (United States)

    Nishijima, Takeshi; Komatsu, Hirokazu; Gatanaga, Hiroyuki; Aoki, Takahiro; Watanabe, Koji; Kinai, Ei; Honda, Haruhito; Tanuma, Junko; Yazaki, Hirohisa; Tsukada, Kunihisa; Honda, Miwako; Teruya, Katsuji; Kikuchi, Yoshimi; Oka, Shinichi

    2011-01-01

    Background Treatment with tenofovir is sometimes associated with renal dysfunction. Limited information is available on this side effect in patients with small body weight, although the use of tenofovir will spread rapidly in Asia and Africa, where patients are likely to be of smaller body weight. Methods In a single-center cohort, Japanese patients with HIV infection who started tenofovir-containing antiretroviral therapy were retrospectively analyzed. The incidence of tenofovir-associated renal dysfunction, defined as more than 25% decrement of estimated glomerular filtration rate (eGFR) from the baseline, was determined. The effects of small body weight and body mass index (BMI) on tenofovir-associated renal dysfunction, respectively, were estimated in univariate and multivariate Cox hazards models as the primary exposure. Other possible risk factors were evaluated by univariate analysis and those found significant were entered into the multivariate analysis. Results The median weight of 495 patients was 63 kg. Tenofovir-related renal dysfunction occurred in 97 (19.6%) patients (incidence: 10.5 per 100 person-years). Univariate analysis showed that the incidence of tenofovir-related renal dysfunction was significantly associated with smaller body weight and BMI, respectively (per 5 kg decrement, HR = 1.23; 95% CI, 1.10–1.37; pdecrement, HR = 1.14; 95% CI, 1.05–1.23; p = 0.001). Old age, high baseline eGFR, low serum creatinine, low CD4 count, high HIV viral load, concurrent nephrotoxic drugs, hepatitis C infection, and current smoking were also associated with tenofovir-related renal dysfunction. Multivariate analysis identified small body weight as a significant risk (adjusted HR = 1.13; 95% CI, 1.01–1.27; p = 0.039), while small BMI had marginal significance (adjusted HR = 1.07; 95% CI 1.00–1.16; p = 0.058). Conclusion The incidence of tenofovir-associated renal dysfunction in Japanese patients was high. Small body weight

  8. The Use of Fibrous, Supramolecular Membranes and Human Tubular Cells for Renal Epithelial Tissue Engineering : Towards a Suitable Membrane for a Bioartificial Kidney

    NARCIS (Netherlands)

    Dankers, Patricia Y. W.; Boomker, Jasper M.; Huizinga-van der Vlag, Ali; Smedts, Frank M. M.; Harmsen, Martin C.; van Luyn, Marja J. A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We

  9. The use of fibrous, supramolecular membranes and human tubular cells for renal epithelial tissue engineering: towards a suitable membrane for a bioartificial kidney,

    NARCIS (Netherlands)

    Dankers, P.Y.W.; Boomker, J.M.; Huizinga-van der Vlag, A.; Smedts, F.M.M.; Harmsen, M.C.; Luyn, van M.J.A.

    2010-01-01

    A bioartificial kidney, which is composed of a membrane cartridge with renal epithelial cells, can substitute important kidney functions in patients with renal failure. A particular challenge is the maintenance of monolayer integrity and specialized renal epithelial cell functions ex vivo. We

  10. Tributyltin chloride induces renal dysfunction by inflammation and oxidative stress in female rats.

    Science.gov (United States)

    Coutinho, João V S; Freitas-Lima, Leandro C; Freitas, Frederico F C T; Freitas, Flávia P S; Podratz, Priscila L; Magnago, Rafaella P L; Porto, Marcella L; Meyrelles, Silvana S; Vasquez, Elisardo C; Brandão, Poliane A A; Carneiro, Maria T W D; Paiva-Melo, Francisca D; Miranda-Alves, Leandro; Silva, Ian V; Gava, Agata L; Graceli, Jones B

    2016-10-17

    Tributyltin chloride (TBT) is an organometallic pollutant that is used as a biocide in antifouling paints. TBT induces several toxic and endocrine-disrupting effects. However, studies evaluating the effects of TBT on renal function are rare. This study demonstrates that TBT exposure is responsible for improper renal function as well as the development of abnormal morphophysiology in mammalian kidneys. Female rats were treated with TBT, and their renal morphophysiology was assessed. Morphophysiological abnormalities such as decreased glomerular filtration rate and increased proteinuria levels were observed in TBT rats. In addition, increases in inflammation, collagen deposition and α-smooth muscle actin (α-SMA) protein expression were observed in TBT kidneys. A disrupted cellular redox balance and apoptosis in kidney tissue were also observed in TBT rats. TBT rats demonstrated reduced serum estrogen levels and estrogen receptor-α (ERα) protein expression in renal cortex. Together, these data provide in vivo evidence that TBT is toxic to normal renal function and that these effects may be associated with renal histopathology complications, such as inflammation and fibrosis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Exercise induced renal dysfunction demonstrated both in hypertensives and normotensive controls studies by Tc-99m-DTPA

    International Nuclear Information System (INIS)

    Mizuiri, S.; Hayashi, I.; Ohara, T.; Hirata, K.; Sasaki, Y.

    1985-01-01

    It was previously reported that the hippurate transport disturbance after exercise is a specific phenomenon to patients with hypertension. The authors' study with Tc-99m-DTPA revealed exercise induced renal dysfunction not only in hypertensives (H) but also in normotensive controls (N). The details of the investigation is presented. Tc-99m-DTPA was intravenously injected at rest and during bicycle ergometric stress to 14 H and 14 N in sitting position. Serial dynamic renal images were taken, of which data were simultaneously stored in a data processor for later analysis. The renogram was drawn setting ROI on each kidney. Peak counts (PC) of vascular phase, peak time (PT) of secretory phase and radioisotope retention rate (RR) at 10 minutes were the parameters being compared between at rest and at exercise. GFR of each kidney was determined. Blood samples were obtained at rest and at the end of exercise for the measurement of aldosterone (ALD), plasma renin activity (PRA) and catecholamines (A, NA). Exercise caused significant lowering of PC, prolongation of PT and increase in RR (10 min. counts/peak counts) both in H and N. GFR (miota/min.) during exercise was significantly lower than at rest in both H (80 +- 22 vs 93.8 +- 16.9, p<0.02) and N (84 +- 17 vs 102 +- 15, p<0.01). ALD, PRA, A and NA are all elevated during exercise both in H and N. None of the rest-exercise differences significantly differed between H and N. The data indicate the exercise induced renal dysfunction demonstrated by Tc-99m-DTPA renograms is not specified to H but can also be observed in N, which may be resulted from the common changes in H and N of GFR and humoral factors

  12. Blood urea nitrogen to creatinine ratio is associated with congestion and mortality in heart failure patients with renal dysfunction.

    Science.gov (United States)

    Parrinello, Gaspare; Torres, Daniele; Testani, Jeffrey M; Almasio, Piero Luigi; Bellanca, Michele; Pizzo, Giuseppina; Cuttitta, Francesco; Pinto, Antonio; Butler, Javed; Paterna, Salvatore

    2015-12-01

    Renal dysfunction (RD) and venous congestion are related and common in heart failure (HF). Studies suggest that venous congestion may be the primary driver of RD in HF. In this study, we sought to investigate retrospectively the relationship between common measures of renal function with caval congestion and mortality among outpatients with HF and RD. We reviewed data from 103 HF outpatients (45 males, mean age 74 years, ejection fraction 41.8 ± 11.6 %) with estimated glomerular filtration rate (eGFR) of 25.5 (adjusted OR 2.98, p 0.015) and eGFR ≤ 45.8 (adjusted OR 5.38, p 0.002) identify patients at risk for caval congestion; a BUN/Cr > 23.7 was the best predictor of impaired collapsibility (adjusted OR 4.41, p 0.001). a BUN/Cr > 25.5 (HR 2.19, 95 % CI 1.21-3.94, p < 0.001) and NYHA class 3 (HR 2.91, 95 % CI 1.60-5.31, p < 0.0005) were independent risk factors associated with all-cause death during a median follow-up of 31 months. In outpatients with HF and RD, a higher BUN/Cr and lower eGFR are reliable renal biomarkers for caval congestion. The BUN/Cr is associated with long-term mortality and may help to stratify HF severity.

  13. Stage-to-stage progression of chronic kidney disease in renal transplantation with chronic allograft dysfunction

    Directory of Open Access Journals (Sweden)

    Khalkhali H

    2009-11-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Although the short-term results of kidney transplantation have improved greatly during the past decades, the long-term results have not improved according. Graft loss due to chronic allograft dysfunction (CAD is a major concern in renal transplant recipients (RTRs. There is little data about disease progression in this patient population. In this paper, we investigated history of kidney function as the pattern, waiting time and rate of pass from intermediate stages in RTR with CAD."n"nMethods: In a single-center retrospective study, 214 RTRs with CAD investigated at the Urmia University Hospital urmia, Iran from 1997 to 2005. Kidney function at each visit assessed with GFR. We apply NKF and K/DOQI classification of chronic kidney disease (CKD staging system to determine pattern of disease progression per stage in this group of patients. "n"nResults: The pure death-censored graft loss was 26% with mean waiting time 81.7 months. 100% of RTRs passed from stage I to II in mean waiting time 26.3 months. The probability of prognostic factors transition from stage II to III was 88.9% with mean waiting time 25.5 months, transition from III to IV was 55.7% with mean waiting time of 24.9 months and transition for

  14. Diglycolic acid, the toxic metabolite of diethylene glycol, chelates calcium and produces renal mitochondrial dysfunction in vitro.

    Science.gov (United States)

    Conrad, Taylor; Landry, Greg M; Aw, Tak Yee; Nichols, Royce; McMartin, Kenneth E

    2016-07-01

    Diethylene glycol (DEG) has caused many cases of acute kidney injury and deaths worldwide. Diglycolic acid (DGA) is the metabolite responsible for the renal toxicity, but its toxic mechanism remains unclear. To characterize the mitochondrial dysfunction produced from DGA by examining several mitochondrial processes potentially contributing to renal cell toxicity. The effect of DGA on mitochondrial membrane potential was examined in normal human proximal tubule (HPT) cells. Isolated rat kidney mitochondria were used to assess the effects of DGA on mitochondrial function, including respiratory parameters (States 3 and 4), electron transport chain complex activities and calcium-induced opening of the mitochondrial permeability transition pore. DGA was compared with ethylene glycol tetraacetic acid (EGTA) to determine calcium chelating ability. DGA cytotoxicity was assessed using lactate dehydrogenase leakage from cultured proximal tubule cells. DGA decreased the mitochondrial membrane potential in HPT cells. In rat kidney mitochondria, DGA decreased State 3 respiration, but did not affect State 4 respiration or the ADP/O ratio. DGA reduced glutamate/malate respiration at lower DGA concentrations (0.5 mmol/L) than succinate respiration (100 mmol/L). DGA inhibited Complex II activity without altering Complex I, III or IV activities. DGA blocked calcium-induced mitochondrial swelling, indicating inhibition of the calcium-dependent mitochondrial permeability transition. DGA and EGTA reduced the free calcium concentration in solution in an equimolar manner. DGA toxicity and mitochondrial dysfunction occurred as similar concentrations. DGA inhibited mitochondrial respiration, but without uncoupling oxidative phosphorylation. The more potent effect of DGA on glutamate/malate respiration and the inhibition of mitochondrial swelling was likely due to its chelation of calcium. These results indicate that DGA produces mitochondrial dysfunction by chelating calcium to

  15. Structural and functional changes of the heart in patients with chronic ischemic heart failure, associated with renal dysfunction

    Directory of Open Access Journals (Sweden)

    D. A. Lashkul

    2014-04-01

    Full Text Available Kidney disease is a frequent complication of congestive heart failure (CHF and may contribute to the progression of ventricular dysfunction. Regardless of the degree of heart failure, chronic kidney disease (CKD increases the risk of death and cardiac decompensation. Left ventricular hypertrophy (LVH is a known parameter of cardiac remodelling and has a higher prevalence and incidence among people with impaired kidney function. LVH is an early subclinical marker of cardiovascular disease and heart failure risk, and is probably an intermediary step in the pathway leading from kidney dysfunction to heart failure and its complications. The effects of CKD on other left ventricular and myocardial parameters, however, have been less characterized. The aim of the study was to examine the structural and functional changes, geometric remodeling of the heart in patients with ischemic chronic heart failure, being hospitalized, according to the presence of renal dysfunction. Materials and methods. The study involved 333 patients with ischemic CHF (277 men and 56 women, mean age 59,3±9,4 years. The functional class of heart failure was assessed on the recommendations of the New York Heart Association (NYHA. The etiology of heart failure in 288 (86.5% patients had a combination of coronary artery disease and essential hypertension, in 45 (13.5% – only CAD. 1 FC of heart failure was diagnosed in 9 (2.7% patients, 2 FC - in 106 (31.8%, 3 FC - in 199 (59.8% and 4 FC - 19 (5.7% patients. Diabetes was in 61 (18.3%, myocardial infarction history was in 240 (72.1% patients. Depending on the glomerular filtration rate, patients were divided into 3 groups: 72 with normal GFR (>90 ml/min/1.73m2, 218 with a slight decrease in GFR (60-90 ml/min/1.73m2 and 43 with moderate reduced GFR (<60 ml/min/1.73m2. Echocardiography was performed using the General Electric VIVID 3 system (General Electric Healthcare, USA with the 2.5–3.5 MHz transducer and Doppler technique

  16. Ectopic germinal center and megalin defect in primary Sjogren syndrome with renal Fanconi syndrome.

    Science.gov (United States)

    Wang, Jing; Wen, Yubing; Zhou, Mengyu; Shi, Xiaoxiao; Jiang, Lanping; Li, Mingxi; Yu, Yang; Li, Xuemei; Li, Xuewang; Zhang, Wen; Lundquist, Andrew L; Chen, Limeng

    2017-06-02

    This study reports the clinical and pathological features of 12 cases of primary Sjogren syndrome (pSS) with renal involvement presenting with proximal tubular dysfunction in a single center, and investigates the possible correlation of ectopic germinal center formation and megalin/cubilin down-expression. Clinical and pathological records were reviewed. Immunohistochemistry was carried out to detect megalin, cubilin, CD21 and IL-17 expression. Patients presented with different degrees of proximal renal tubule lesion and decreased estimated glomerular filtration rate (eGFR). Renal biopsy revealed tubulointerstitial nephritis, with tubular epithelial cell degeneration, tubular atrophy, interstitial inflammation and focal fibrosis. Immunohistochemistry revealed decreased expression of megalin and cubilin, two important multiligand protein receptors on the brush border of proximal tubular epithelial cells. IL-17 secreted by Th17 subtype effector T cells was diffusely detected in the renal proximal tubule, with a negative correlation of IL-17 and megalin expression. In addition, ectopic germinal centers characterized by CD21 + follicular dendritic cells were present in the renal interstitium. In patients with a decreased eGFR, treatment with 4 weeks of glucocorticoid therapy resulted in an improved eGFR in 75% of patients. We report 12 cases of pSS characterized by Fanconi syndrome. The decreased megalin and cubilin expression may contribute to the proximal tubular reabsorption defect, possibly secondary to Th17 infiltration and formation of ectopic germinal centers.

  17. Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

    Science.gov (United States)

    Fricke, Lisa; Petroff, David; Desch, Steffen; Lurz, Philipp; Reinhardt, Sebastian; Sonnabend, Melanie; Classen, Joseph; Baum, Petra

    2017-01-01

    Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1) and normal or enhanced in nine patients (group 2). The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1-21 mmHg, p = 0.035) and from 166 to 145 mmHg (8-34 mmHg, p = 0.005), respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3-22 mmHg) greater in group 2 than in group 1 (p = 0.045). Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

  18. Prognostic importance of renal function in patients with early heart failure and mild left ventricular dysfunction

    NARCIS (Netherlands)

    Smilde, Tom; Hillege, Hans; Voors, Adriaan; Dunselman, P.H.J.; Van Veldhuisen, D.J.

    2004-01-01

    We evaluated the prognostic value of renal function in an initially “untreated” population with mild heart failure and compared the prognosis of this population with a matched controlled population. During a follow-up of 13 years (mean 11.7), 90 patients (56%) died. Mortality was higher compared

  19. P-glycoprotein-deficient mice have proximal tubule dysfunction but are protected against ischemic renal injury

    NARCIS (Netherlands)

    Huls, M.; Kramers, C.; Levtchenko, E.N.; Wilmer, M.J.G.; Dijkman, H.B.P.M.; Kluijtmans, L.A.J.; Hoorn, J.W.A. van der; Russel, F.G.M.; Masereeuw, R.

    2007-01-01

    The multidrug resistance gene 1 product, P-glycoprotein (P-gp), is expressed in several excretory organs, including the apical membrane of proximal tubules. After inducing acute renal failure, P-gp expression is upregulated and this might be a protective function by pumping out toxicants and harmful

  20. A case of ceftriaxone-associated biliary pseudolithiasis in an elderly patient with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Shuichi Abe

    2017-01-01

    Full Text Available Prior literature suggests that ceftriaxone causes formation of gallbladder stones at a relatively high frequency, and when abdominal symptoms occur, prompt investigation of the gallbladder is required with institution of appropriate treatment. Aging, malnutrition, renal impairment, and sepsis are risk factors for pseudolithiasis, and prevention of these is important to suppress gallstone development.

  1. Does dysfunction of the autonomic nervous system affect success of renal denervation in reducing blood pressure?

    Directory of Open Access Journals (Sweden)

    Lisa Fricke

    2017-04-01

    Full Text Available Objectives: Renal denervation is an interventional approach aiming to reduce high blood pressure. Its efficacy is subject of controversial debate. We analyzed autonomic function in patients undergoing renal denervation to identify responders. Methods: A total of 21 patients with treatment-resistant hypertension scheduled for renal denervation were included. Heart rate variability, pupillary function and sympathetic skin response were examined prior to intervention. Before and 1 or 3 months after intervention, 24-h ambulatory blood pressure readings were taken. Results: Patients were stratified according to sympathetic nervous system function. Sympathetic activity was reduced in 12 participants (group 1 and normal or enhanced in nine patients (group 2. The mean of daytime systolic blood pressure decreased in groups 1 and 2 from 168 to 157 mmHg (95% confidence interval for difference, 1–21 mmHg, p = 0.035 and from 166 to 145 mmHg (8–34 mmHg, p = 0.005, respectively. In a linear model, blood pressure reduction was 11.3 mmHg (0.3–22 mmHg greater in group 2 than in group 1 (p = 0.045. Conclusion: Patients with preexisting reduced activity of the sympathetic nervous system benefited less from renal denervation.

  2. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  3. Taurine Ameliorates Renal Oxidative Damage and Thyroid Dysfunction in Rats Chronically Exposed to Fluoride.

    Science.gov (United States)

    Adedara, Isaac A; Ojuade, Temini Jesu D; Olabiyi, Bolanle F; Idris, Umar F; Onibiyo, Esther M; Ajeigbe, Olufunke F; Farombi, Ebenezer O

    2017-02-01

    Excessive exposure to fluoride poses several detrimental effects to human health particularly the kidney which is a major organ involved in its elimination from the body. The influence of taurine on fluoride-induced renal toxicity was investigated in a co-exposure paradigm for 45 days using five groups of eight rats each. Group I rats received normal drinking water alone, group II rats were exposed to sodium fluoride (NaF) in drinking water at 15 mg/L alone, group III received taurine alone at a dose of 200 mg/kg group IV rats were co-administered with NaF and taurine (100 mg/kg), while group V rats were co-administered with NaF and taurine (200 mg/kg). Administration of taurine significantly reversed the fluoride-mediated decrease in absolute weight and organo-somatic index of the kidney in the exposed rats. Taurine significantly prevented fluoride-induced elevation in plasma urea and creatinine levels in the exposed rats. Moreover, taurine restored fluoride-mediated decrease in the circulatory concentrations of triiodothyronine, thyroxine, and the ratio of triiodothyronine to thyroxine. Taurine ameliorated fluoride-mediated decrease in renal antioxidant status by significantly enhancing the antioxidant enzyme activities as well as glutathione level in the exposed rats. Additionally, taurine inhibited fluoride-induced renal oxidative damage by markedly decreasing the hydrogen peroxide and malondialdehyde levels as well as improved the kidney architecture in the treated rats. Collectively, taurine protected against fluoride-induced renal toxicity via enhancement of thyroid gland function, renal antioxidant status, and histology in rats.

  4. Infection related renal impairment: a major cause of acute allograft dysfunction.

    Science.gov (United States)

    Nampoory, Mangalathillam R N; Johny, Kaivilayil V; Costandy, Jamal N; Nair, Madhavan P; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, Mustafa

    2003-06-01

    We prospectively analyzed the impact of post-transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40+14 years). During the follow-up period, 52 patients expired and 64 lost on followup. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100+90.2) than that of acute rejection (166+127.1), but was more than that in cyclosporine toxicity (50+42.2). Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=orEcoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR.

  5. Plasma cystatin C is a predictor of renal dysfunction, acute-on-chronic liver failure, and mortality in patients with acutely decompensated liver cirrhosis

    DEFF Research Database (Denmark)

    Markwardt, Daniel; Holdt, Lesca; Steib, Christian

    2017-01-01

    The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. We investigated whether cystatin C (Cys...

  6. Glyoxalase-1 overexpression reduces endothelial dysfunction and attenuates early renal impairment in a rat model of diabetes

    DEFF Research Database (Denmark)

    Brouwers, Olaf; Niessen, Petra M G; Miyata, Toshio

    2014-01-01

    AIMS/HYPOTHESIS: In diabetes, advanced glycation end-products (AGEs) and the AGE precursor methylglyoxal (MGO) are associated with endothelial dysfunction and the development of microvascular complications. In this study we used a rat model of diabetes, in which rats transgenically overexpressed...... the MGO-detoxifying enzyme glyoxalase-I (GLO-I), to determine the impact of intracellular glycation on vascular function and the development of early renal changes in diabetes. METHODS: Wild-type and Glo1-overexpressing rats were rendered diabetic for a period of 24 weeks by intravenous injection...... podocyte number and diabetes-induced elevation of urinary markers albumin, osteopontin, kidney-inflammation-molecule-1 and nephrin) were attenuated by Glo1 overexpression. In line with this, downregulation of Glo1 in cultured endothelial cells resulted in increased expression of inflammation...

  7. Prevalence of renal dysfunction and its influence on functional capacity in elderly patients with stable chronic heart failure

    Directory of Open Access Journals (Sweden)

    Stanojević Dragana

    2012-01-01

    Full Text Available Bacground/Aim. Chronic heart failure (CHF is highly prevalent and constitutes an important public health problem around the world. In spite of a large number of pharmacological agents that successfully decrease mortality in CHF, the effects on exercise tolerance and quality of life are modest. Renal dysfunction is extremely common in patients with CHF and it is strongly related not only to increased mortality and morbidity but to a significant decrease in exercise tolerance, as well. The aim of our study was to investigate the prevalence and influence of the renal dysfunction on functional capacity in the elderly CHF patients. Methods. We included 127 patients aged over 65 years in a stable phase of CHF. The diagnosis of heart failure was based on the latest diagnostic principles of the European Society of Cardiology. The estimated glomerular filtration rate (eGRF was determined by the abbreviated Modification of Diet in Renal Disease (MDRD2 formula, and patients were categorized using the Kidney Disease Outcomes Quality Initiative (K/DOQI classification system. Functional capacity was determined by the 6 minute walking test (6MWT. Results. Among 127 patients, 90 were men. The average age was 72.5 ± 4.99 years and left ventricular ejection fraction (LVEF was 40.22 ± 9.89%. The average duration of CHF was 3.79 ± 4.84 years. Ninty three (73.2% patients were in New York Heart Association (NYHA class II and 34 (26.8% in NYHA class III. Normal renal function (eGFR ≥ 90 mL/min had 8.9% of participants, 57.8% had eGFR between 60-89 mL/min (stage 2 or mild reduction in GFR according to K/DOQI classification, 32.2% had eGFR between 30-59 mL/min (stage 3 or moderate reduction in GFR and 1.1% had eGFR between 15-29 mL/min (stage 4 or severe reduction in GFR. We found statistically significant correlation between eGFR and 6 minute walking distance (6MWD (r = 0.390, p < 0.001, LVEF (r = 0.268, p < 0.05, NYHA class (ς = -0.269, p < 0.05 and age (r = - 0

  8. Association between in-hospital mortality and renal dysfunction in 186,219 patients hospitalized for acute stroke in the Emilia-Romagna region of Italy.

    Science.gov (United States)

    Fabbian, Fabio; Gallerani, Massimo; Pala, Marco; De Giorgi, Alfredo; Salmi, Raffaella; Dentali, Francesco; Ageno, Walter; Manfredini, Roberto

    2014-11-01

    Using a regional Italian database, we evaluated the relationship between renal dysfunction and in-hospital mortality (IHM) in patients with acute stroke (ischemic/hemorrhagic). Patients were classified on the basis of renal damage: without renal dysfunction, with chronic kidney disease (CKD), and with end-stage renal disease (ESRD). Of a total of 186,219 patients with a first episode of stroke, 1626 (0.9%) had CKD and 819 (0.4%) had ESRD. Stroke-related IHM (total cases) was independently associated with CKD, ESRD, atrial fibrillation (AF), age, and Charlson comorbidity index (CCI). In patients with ischemic stroke (n=154,026), IHM remained independently associated with CKD, ESRD, AF, and CCI. In patients with hemorrhagic stroke (n=32,189), variables that were independently associated with IHM were CKD, ESRD, and AF. Renal dysfunction is associated with IHM related to stroke, both ischemic and hemorrhagic, with even higher odds ratios than those of other established risk factors, such as age, comorbidities, and AF. © The Author(s) 2013.

  9. Plantar fascia thickness is longitudinally associated with retinopathy and renal dysfunction: a prospective study from adolescence to adulthood.

    Science.gov (United States)

    Benitez-Aguirre, Paul Z; Craig, Maria E; Jenkins, Alicia J; Gallego, Patricia H; Cusumano, Janine; Duffin, Anthony C; Hing, Stephen; Donaghue, Kim C

    2012-03-01

    The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997-2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). Median (interquartile range) age at baseline was 15.1 (13.4-16.8) years, and median follow-up was 8.3 (7.0-9.5) years, with 4 (3-6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p 7.5 μg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd-4th quartiles, χ(2) = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0-10.3] and early renal dysfunction (OR 3.2, CI 1.3-8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation. © 2012 Diabetes Technology Society.

  10. Life after placental dysfunction : the mother's renal function and her child's health

    NARCIS (Netherlands)

    Paauw, N.D.

    2018-01-01

    Introduction: over the last decades it has become apparent that implications of pregnancy complications are not limited to the pregnancy itself, but extend to later life, not only for the exposed mother, but also for the exposed child. After placental dysfunction, characterized by the development of

  11. Radionuclide evaluation of renal transplants

    International Nuclear Information System (INIS)

    Yang Hong; Zhao Deshan

    2000-01-01

    Radionuclide renal imaging and plasma clearance methods can quickly quantitate renal blood flow and function in renal transplants. They can diagnose acute tubular necrosis and rejection, renal scar, surgical complications such as urine leaks, obstruction and renal artery stenosis after renal transplants. At the same time they can assess the therapy effect of renal transplant complications and can also predict renal transplant survival from early post-operative function studies

  12. Effects of statin therapy on clinical outcomes after acute myocardial infarction in patients with advanced renal dysfunction: A propensity score-matched analysis.

    Science.gov (United States)

    Kim, Jin Sug; Kim, Weon; Park, Ji Yoon; Woo, Jong Shin; Lee, Tae Won; Ihm, Chun Gyoo; Kim, Yang Gyun; Moon, Ju-Young; Lee, Sang Ho; Jeong, Myung Ho; Jeong, Kyung Hwan

    2017-01-01

    Lipid lowering therapy is widely used for the prevention of cardiovascular complications after acute myocardial infarction (AMI). However, some studies show that this benefit is uncertain in patients with renal dysfunction, and the role of statins is based on the severity of renal dysfunction. In this study, we investigated the impact of statin therapy on major adverse cardiac events (MACEs) and all-cause mortality in patients with advanced renal dysfunction undergoing percutaneous coronary intervention (PCI) after AMI. This study was based on the Korea Acute Myocardial Infarction Registry database. We included 861 patients with advanced renal dysfunction from among 33,205 patients who underwent PCI after AMI between November 2005 and July 2012. Patients were divided into two groups: a statin group (n = 537) and a no-statin group (n = 324). We investigated the 12-month MACEs (cardiac death, myocardial infarction, repeated PCI or coronary artery bypass grafting) and all-cause mortality of each group. Subsequently, a propensity score-matched analysis was performed. In the total population studied, no significant differences were observed between the two groups with respect to the rate of recurrent MI, repeated PCI, coronary artery bypass grafting (CABG), or all-cause mortality. However, the cardiac death rate was significantly lower in the statin group (p = 0.009). Propensity score-matched analysis yielded 274 pairs demonstrating, results similar to those obtained from the total population. However, there was no significant difference in the cardiac death rate in the propensity score-matched population (p = 0.103). Cox-regression analysis revealed only left ventricular ejection fraction to be an independent predictor of 12-month MACEs (Hazard ratio [HR] of 0.979, 95% confidence interval [CI], 0962-0.996, p = 0.018). Statin therapy was not significantly associated with a reduction in the 12-month MACEs or all-cause mortality in patients with advanced renal dysfunction

  13. Detection and prognostic impact of renal dysfunction in patients with chronic heart failure and normal serum creatinine.

    Science.gov (United States)

    Scrutinio, Domenico; Passantino, Andrea; Lagioia, Rocco; Santoro, Daniela; Cacciapaglia, Erasmo

    2011-03-03

    Accurate identification of renal dysfunction (RD) is crucial to risk stratification in chronic heart failure (CHF). Patients with CHF are at special risk of having RD despite normal serum creatinine (SCr), owing to a decreased Cr generation. At low levels of SCr, the equations estimating renal function are less accurate. This study was aimed to assess and compare the prognostic value of formulas estimating renal function in CHF patients with normal SCr. We studied 462 patients with systolic CHF and normal SCr. Creatinine clearance was estimated by the Cockcroft-Gault (eCrCl) and glomerular filtration rate by the 4-variable MDRD equation (eGFR); eCrCl normalized for body-surface area (eCrCl(BSA)) was calculated. The primary outcome was all-cause mortality at 2 years. Seventy five patients died. At multivariate Cox regression analysis, only eCrCl(BSA) was significantly associated with mortality (p = 0.006); eGFR (p = 0.24), eCrCl (p = 0.09) and BUN (p = 0.14) were not statistically significant predictors. The patients in the lowest eCrCl(BSA) quartile had an adjusted 2.1-fold (CI: 1.06-4.1) increased risk of mortality, compared with those in the referent quartile. Two-year survival was 70.4% in the lowest eCrCl(BSA) quartile and 89.7% in the referent quartile. Other independent predictors of mortality were ischemic etiology (RR: 2.16 [CI: 1.3-3.5], p = 0.0017), NYHA III/IV class (RR: 2.45 [CI: 1.51-3.97], p = 0.0003), LVEF high-risk subgroup and can more accurately be identified by the CG formula corrected for BSA than the MDRD. Copyright © 2009 Elsevier B.V. All rights reserved.

  14. Exercise renogram. A new approach documents renal involvement in systemic hypertension

    International Nuclear Information System (INIS)

    Clorius, J.H.; Schmidlin, P.

    1983-01-01

    Hippurate functional scintiscans were obtained in 51 hypertensive patients and in 15 controls. The authors investigated the influence that posture and exercise have on hippurate kinetics in patients with hypertension. A posture- or exercise-induced disturbance of renal hippurate transport was sought. All persons were examined in prone and standing positions, as well as during exercise. When prone and upright renograms were compared, 24% of the hypertensives demonstrated bilateral orthostatic renal dysfunction. Exercise caused the hippurate transport disturbance to increase. Fifty-seven percent of all hypertensives developed evidence of marked, bilateral, renal dysfunction during ergometric stress, so that exercise renography was shown to be a more sensitive test of the presence of transient tubular dysfunction in hypertension than the standing renogram. In normotensive controls the hippurate functional scintigram failed to be influenced by posture and exercise. The results suggest presence in hypertension of transient, posture- and exercise-mediated alterations of renal cortical blood flow

  15. The exercise renogram. A new approach documents renal involvement in systemic hypertension

    International Nuclear Information System (INIS)

    Clorius, J.H.; Schmidlin, P.

    1983-01-01

    Hippurate functional scintiscans were obtained in 51 hypertensive patients and in 15 controls. We investigated the influence that posture and exercise have on hippurate kinetics in patients with hypertension. A posture- or exercise-induced disturbance of renal hippurate transport was sought. All persons were examined in prone and standing positions, as well as during exercise. When prone and upright renograms were compared, 24% of the hypertensives demonstrated bilateral orthostatic renal dysfunction. Exercise caused the hippurate transport disturbance to increase. Fifty-seven percent of all hypertensives developed evidence of marked, bilateral, renal dysfunction during ergometric stress, so that exercise renography was shown to be a more sensitive test of the presence of transient tubular dysfunction in hypertension than the standing renogram. In normotensive controls the hippurate functional scintigram failed to be influenced by posture and exercise. The results suggest presence in hypertension of transient, posture- and exercise-mediated alterations of renal cortical blood flow

  16. Evaluation of chronic kidney disease in chronic heart failure: From biomarkers to arterial renal resistances

    Science.gov (United States)

    Iacoviello, Massimo; Leone, Marta; Antoncecchi, Valeria; Ciccone, Marco Matteo

    2015-01-01

    Chronic kidney disease and its worsening are recurring conditions in chronic heart failure (CHF) which are independently associated with poor patient outcome. The heart and kidney share many pathophysiological mechanisms which can determine dysfunction in each organ. Cardiorenal syndrome is the condition in which these two organs negatively affect each other, therefore an accurate evaluation of renal function in the clinical setting of CHF is essential. This review aims to revise the parameters currently used to evaluate renal dysfunction in CHF with particular reference to the usefulness and the limitations of biomarkers in evaluating glomerular dysfunction and tubular damage. Moreover, it is reported the possible utility of renal arterial resistance index (a parameter associated with abnormalities in renal vascular bed) for a better assesment of kidney disfunction. PMID:25610846

  17. Cardiac and renal dysfunction is associated with progressive hearing loss in patients with Fabry disease.

    Directory of Open Access Journals (Sweden)

    Maria Köping

    Full Text Available Fabry disease (FD is an X-linked recessive hereditary lysosomal storage disorder which results in the accumulation of globotriaosylceramid (Gb3 in tissues of kidney and heart as well as central and peripheral nervous system. Besides prominent renal and cardiac organ involvement, cochlear symptoms like high-frequency hearing loss and tinnitus are frequently found with yet no comprehensive data available in the literature.To examine hearing loss in patients with FD depending on cardiac and renal function.Single-center study with 68 FD patients enrolled between 2012 and 2016 at the Department of Oto-Rhino-Laryngology, Plastic, Aesthetic and Reconstructive Head and Neck Surgery of the University of Würzburg. Every subject underwent an oto-rhino-laryngological examination as well as behavioral, electrophysiological and electroacoustical audiological testing. High-frequency thresholds were evaluated by using a modified PTA6 (0.5, 1, 2, 4, 6, 8 and HF-PTA (6, 8 kHz. Renal function was measured by eGFR, cardiac impairment was graduated by NYHA class.Sensorineural hearing loss was detected in 58.8% of the cohort, which occurred typically in sudden episodes and affected especially high frequencies. Hearing loss is asymmetric, beginning unilaterally and affecting the contralateral ear later. Tinnitus was reported by 41.2%. Renal and cardiac impairment influenced the severity of hearing loss (p < 0.05.High frequency hearing loss is a common problem in patients with FD. Although not life-threatening, it can seriously reduce quality of life and should be taken into account in diagnosis and therapy. Optimized extensive hearing assessment including higher frequency thresholds should be used.

  18. Role Of Adhesion Molecules Vcam-1 And Ve-Cadherin In Endothelium Dysfunction Development At Hemorrhagic Fever With Renal Syndrome

    Directory of Open Access Journals (Sweden)

    А.А. Baygildina

    2009-12-01

    Full Text Available The research goal is to determine the changes in concentration of both sVCAM-1 and VE-cadherin in blood serum of patients suffered from hemorrhagic fever with renal syndrome (HFRS. 87 patients aged 15-65 were examined. Concentrations of both sVCAM-1 and VE- cadherin in blood serum by means of "Bender MedSystems" (Austria ELISA test were determined. It was shown that in both medium severe and severe forms of HFRS statistically the significant rise of sVCAM-1 concentration in blood with high indices in oliguric period took place. Complicated form was characterized by high indices of sVCAM-1 level in fever period, extremely decreasing in concentration in oliguric period and tendency to normalizing in clinical convalescence period. VE-cadherin level in blood was predominantly lower than control in all the observed groups with the exception of fever period in group with medium severe disease form. Negative correlation of normal intensity between adhesion molecules levels in blood was revealed. In conclusion it is necessary to point out that high VCAM-1 expression by endotheliocytes evidences the development of an adhesion form of endothelial dysfunction, low VE-cadherin production in a base for development of angiogenic form of endothelial dysfunction and changes in expression of these adhesion molecules that have adaptive metabolic response to macroorganism of HFRS pathogenic action

  19. Telmisartan, a possible PPAR-δ agonist, reduces TNF-α-stimulated VEGF-C production by inhibiting the p38MAPK/HSP27 pathway in human proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Kimura, Hideki, E-mail: hkimura@u-fukui.ac.jp [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Mikami, Daisuke; Kamiyama, Kazuko [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Sugimoto, Hidehiro [Department of Clinical Laboratories and Nephrology, University of Fukui Hospital, Fukui (Japan); Kasuno, Kenji; Takahashi, Naoki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Yoshida, Haruyoshi [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan); Division of Nephrology, Obama Municipal Hospital, Obama, Fukui (Japan); Iwano, Masayuki [Division of Nephrology, Department of General Medicine, School of Medicine, Faculty of Medical Sciences, University of Fukui, Fukui (Japan)

    2014-11-14

    Highlights: • TNF-α increased VEGF-C expression by enhancing phosphorylation of p38MAPK and HSP27. • Telmisartan decreased TNF-α-stimulated expression of VEGF-C. • Telmisartan suppressed TNF-α-induced phosphorylation of p38MAPK and HSP27. • Telmisartan activated endogenous PPAR-δ protein. • Telmisartan suppressed p38MAPK phosphorylation in a PPAR-δ-dependent manner. - Abstract: Vascular endothelial growth factor-C (VEGF-C) is a main inducer of inflammation-associated lymphangiogenesis in various inflammatory disorders including chronic progressive kidney diseases, for which angiotensin II receptor type 1 blockers (ARBs) are widely used as the main treatment. Although proximal renal tubular cells may affect the formation of lymphatic vessels in the interstitial area by producing VEGF-C, the molecular mechanisms of VEGF-C production and its manipulation by ARB have not yet been examined in human proximal renal tubular epithelial cells (HPTECs). In the present study, TNF-α dose-dependently induced the production of VEGF-C in HPTECs. The TNF-α-induced production of VEGF-C was mediated by the phosphorylation of p38MAPK and HSP27, but not by that of ERK or NFkB. Telmisartan, an ARB that can activate the peroxisome proliferator-activated receptor (PPAR), served as a PPAR-δ activator and reduced the TNF-α-stimulated production of VEGF-C. This reduction was partially attributed to a PPAR-δ-dependent decrease in p38MAPK phosphorylation. Our results indicate that TNF-α induced the production of VEGF-C in HPTECs by activating p38MAPK/HSP27, and this was partially inhibited by telmisartan in a PPAR-δ dependent manner. These results provide a novel insight into inflammation-associated lymphangiogenesis.

  20. Downregulation of the S1P Transporter Spinster Homology Protein 2 (Spns2 Exerts an Anti-Fibrotic and Anti-Inflammatory Effect in Human Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Olivier Blanchard

    2018-05-01

    Full Text Available Sphingosine kinase (SK catalyses the formation of sphingosine 1-phosphate (S1P, which acts as a key regulator of inflammatory and fibrotic reactions, mainly via S1P receptor activation. Here, we show that in the human renal proximal tubular epithelial cell line HK2, the profibrotic mediator transforming growth factor β (TGFβ induces SK-1 mRNA and protein expression, and in parallel, it also upregulates the expression of the fibrotic markers connective tissue growth factor (CTGF and fibronectin. Stable downregulation of SK-1 by RNAi resulted in the increased expression of CTGF, suggesting a suppressive effect of SK-1-derived intracellular S1P in the fibrotic process, which is lost when SK-1 is downregulated. In a further approach, the S1P transporter Spns2, which is known to export S1P and thereby reduces intracellular S1P levels, was stably downregulated in HK2 cells by RNAi. This treatment decreased TGFβ-induced CTGF and fibronectin expression, and it abolished the strong induction of the monocyte chemotactic protein 1 (MCP-1 by the pro-inflammatory cytokines tumor necrosis factor (TNFα and interleukin (IL-1β. Moreover, it enhanced the expression of aquaporin 1, which is an important water channel that is expressed in the proximal tubules, and reverted aquaporin 1 downregulation induced by IL-1β/TNFα. On the other hand, overexpression of a Spns2-GFP construct increased S1P secretion and it resulted in enhanced TGFβ-induced CTGF expression. In summary, our data demonstrate that in human renal proximal tubular epithelial cells, SK-1 downregulation accelerates an inflammatory and fibrotic reaction, whereas Spns2 downregulation has an opposite effect. We conclude that Spns2 represents a promising new target for the treatment of tubulointerstitial inflammation and fibrosis.

  1. Acute Kidney Injury in Heart Failure Revisited-The Ameliorating Impact of "Decongestive Diuresis" on Renal Dysfunction in Type 1 Acute Cardiorenal Syndrome: Accelerated Rising Pro B Naturetic Peptide Is a Predictor of Good Renal Prognosis.

    Science.gov (United States)

    Onuigbo, Macaulay Amechi Chukwukadibia; Agbasi, Nneoma; Sengodan, Mohan; Rosario, Karen Flores

    2017-08-29

    There is mounting evidence that forward heart failure as manifested by low cardiac output alone does not define the degree of renal dysfunction in cardiorenal syndrome. As a result, the term "congestive renal failure" was coined in 2012 by Ross to depict the role of renal venous hypertension in type 1 acute cardiorenal syndrome. If so, aggressive decongestive therapies, either through mechanical ultrafiltration with dialysis machines or pharmacologic ultrafiltration with potent diuretics, would lead to improved cardio and renal outcomes. Nevertheless, as recently as 2012, a review of this literature had concluded that a renal venous hypertension-directed approach using diuretics to manage cardio-renal syndrome was yet to be fully investigated. We, in this review, with three consecutive case series, describe our experience with pharmacologic decongestive diuresis in this paradigm of care and argue for studies of such therapeutic interventions in the management of cardiorenal syndrome. Finally, based on our observations in the Renal Unit, Mayo Clinic Health System, in Northwestern Wisconsin, we have hypothesized that patients with cardiorenal syndrome presenting with accelerated rising Pro B Naturetic Peptide levels appear to represent a group that would have good cardio- and renal-outcomes with such decongestive pharmacologic therapies.

  2. Expanding the pool of kidney donors: use of kidneys with acute renal dysfunction

    OpenAIRE

    Matos, Ana Cristina Carvalho de; Requião-Moura, Lúcio Roberto; Clarizia, Gabriela; Durão Junior, Marcelino de Souza; Tonato, Eduardo José; Chinen, Rogério; Arruda, Érika Ferraz de; Filiponi, Thiago Corsi; Pires, Luciana Mello de Mello Barros; Bertocchi, Ana Paula Fernandes; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Given the shortage of organs transplantation, some strategies have been adopted by the transplant community to increase the supply of organs. One strategy is the use of expanded criteria for donors, that is, donors aged >60 years or 50 and 59 years, and meeting two or more of the following criteria: history of hypertension, terminal serum creatinine >1.5mg/dL, and stroke as the donor´s cause of death. In this review, emphasis was placed on the use of donors with acute renal failure, ...

  3. Chronic Heart Failure and Comorbid Renal Dysfunction - A Focus on Type 2 Cardiorenal Syndrome

    Science.gov (United States)

    Preeti, Jois; Alexandre, Mebazaa; Pupalan, Iyngkaran; Merlin, Thomas C.; Claudio, Ronco

    2016-01-01

    The most important advancements in the Cardiorenal syndrome (CRS) are its definition and subsequent classifications. When the predominant pathology and pathophysiology is the heart, i.e. chronic heart failure (CHF), and where any renal impairment (RI) subsequent to this is secondary, the classification is type 2 CRS. There are unique differences in the pathophysiology and progression of individual subclasses. It is important to understand the evolution of CHF and consequences of subsequent RI as they are becoming increasingly prevalent, aggravate morbidity and mortality and limit many therapeutic options. In this paper we discuss the significance of the type 2 CRS patients in the context of the thematic series. PMID:27280302

  4. Renal Oxidative Stress Induced by Long-Term Hyperuricemia Alters Mitochondrial Function and Maintains Systemic Hypertension

    Directory of Open Access Journals (Sweden)

    Magdalena Cristóbal-García

    2015-01-01

    Full Text Available We addressed if oxidative stress in the renal cortex plays a role in the induction of hypertension and mitochondrial alterations in hyperuricemia. A second objective was to evaluate whether the long-term treatment with the antioxidant Tempol prevents renal oxidative stress, mitochondrial alterations, and systemic hypertension in this model. Long-term (11-12 weeks and short-term (3 weeks effects of oxonic acid induced hyperuricemia were studied in rats (OA, 750 mg/kg BW, OA+Allopurinol (AP, 150 mg/L drinking water, OA+Tempol (T, 15 mg/kg BW, or vehicle. Systolic blood pressure, renal blood flow, and vascular resistance were measured. Tubular damage (urine N-acetyl-β-D-glucosaminidase and oxidative stress markers (lipid and protein oxidation along with ATP levels were determined in kidney tissue. Oxygen consumption, aconitase activity, and uric acid were evaluated in isolated mitochondria from renal cortex. Short-term hyperuricemia resulted in hypertension without demonstrable renal oxidative stress or mitochondrial dysfunction. Long-term hyperuricemia induced hypertension, renal vasoconstriction, tubular damage, renal cortex oxidative stress, and mitochondrial dysfunction and decreased ATP levels. Treatments with Tempol and allopurinol prevented these alterations. Renal oxidative stress induced by hyperuricemia promoted mitochondrial functional disturbances and decreased ATP content, which represent an additional pathogenic mechanism induced by chronic hyperuricemia. Hyperuricemia-related hypertension occurs before these changes are evident.

  5. Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction).

    Science.gov (United States)

    Schroten, Nicolas F; Damman, Kevin; Hemmelder, Marc H; Voors, Adriaan A; Navis, Gerjan; Gaillard, Carlo A J M; van Veldhuisen, Dirk J; Van Gilst, Wiek H; Hillege, Hans L

    2015-05-01

    We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF are associated with increased mortality. Aliskiren can provide additional renin-angiotensin-aldosterone system inhibition and increases RBF in healthy individuals. Patients with left ventricular ejection fraction ≤45% and estimated GFR 30 to 75 mL/min per 1.73 m(2) on optimal medical therapy were randomized 2:1 to receive aliskiren 300 mg once daily or placebo. Renal blood flow and GFR were measured using radioactive-labeled (125)I-iothalamate and (131)I-hippuran at baseline and 26 weeks. After 41 patients were included, the trial was halted based on an interim safety analysis showing futility. Mean age was 68 ± 9 years, 82% male, GFR (49 ± 16 mL/min per 1.73 m(2)), RBF (294 ± 77 mL/min per 1.73 m(2)), and NT-proBNP 999 (435-2040) pg/mL. There was a nonsignificant change in RBF after 26 weeks in the aliskiren group compared with placebo (-7.1 ± 30 vs +14 ± 54 mL/min per 1.73 m(2); P = .16). However, GFR decreased significantly in the aliskiren group compared with placebo (-2.8 ± 6.0 vs +4.4 ± 9.6 mL/min per 1.73 m(2); P = .01) as did filtration fraction (-2.2 ± 3.3 vs +1.1 ± 3.1%; P = .01). There were no significant differences in plasma aldosterone, NT-proBNP, urinary tubular markers, or adverse events. Plasma renin activity was markedly reduced in the aliskiren group versus placebo throughout the treatment phase (P = .007). Adding aliskiren on top of optimal HFREF medical therapy did not improve RBF and was associated with a reduction of GFR and filtration fraction. Copyright © 2015 Mosby, Inc. All rights reserved.

  6. Duration of streptozotocin-induced diabetes differentially affects p38-mitogen-activated protein kinase (MAPK phosphorylation in renal and vascular dysfunction

    Directory of Open Access Journals (Sweden)

    Gupta Akanksha

    2005-03-01

    Full Text Available Abstract Background In the present study we tested the hypothesis that progression of streptozotocin (STZ-induced diabetes (14-days to 28-days would produce renal and vascular dysfunction that correlate with altered p38- mitogen-activated protein kinase (p38-MAPK phosphorylation in kidneys and thoracic aorta. Methods Male Sprague Dawley rats (350–400 g were randomized into three groups: sham (N = 6, 14-days diabetic (N = 6 and 28-days diabetic rats (N = 6. Diabetes was induced using a single tail vein injection of STZ (60 mg/kg, I.V. on the first day. Rats were monitored for 28 days and food, water intake and plasma glucose levels were noted. At both 14-days and 28-days post diabetes blood samples were collected and kidney cortex, medulla and aorta were harvested from each rat. Results The diabetic rats lost body weight at both 14-days (-10% and 28-days (-13% more significantly as compared to sham (+10% group. Glucose levels were significantly elevated in the diabetic rats at both 14-days and 28-days post-STZ administration. Renal dysfunction as evidenced by renal hypertrophy, increased plasma creatinine concentration and reduced renal blood flow was observed in 14-days and 28-days diabetes. Vascular dysfunction as evidenced by decreased carotid blood flow was observed in 14-days and 28-days diabetes. We observed an up-regulation of inducible nitric oxide synthase (iNOS, prepro endothelin-1 (preproET-1 and phosphorylated p38-MAPK in thoracic aorta and kidney cortex but not in kidney medulla in 28-days diabetes group. Conclusion The study provides evidence that diabetes produces vascular and renal dysfunction with a profound effect on signaling mechanisms at later stage of diabetes.

  7. Low prevalence of renal dysfunction in HIV-infected pregnant women: implications for guidelines for the prevention of mother-to-child transmission of HIV.

    Science.gov (United States)

    Myer, Landon; Kamkuemah, Monika; Kaplan, Richard; Bekker, Linda-Gail

    2013-11-01

    Emerging international guidelines for the prevention of mother-to-child transmission of HIV infection across sub-Saharan Africa call for the initiation of a triple-drug antiretroviral regimen containing tenofovir, a potentially nephrotoxic agent, in all HIV-infected pregnant women at the first antenatal clinic visit. While there are significant benefits to the rapid initiation of antiretroviral therapy (ART) in pregnancy, there are few data on the prevalence of pre-existing renal disease in HIV-infected pregnant women and in turn, the potential risks of this approach are not well understood. We analysed data on renal function in consecutive patients eligible for ART at a large primary healthcare clinic in Cape Town. All individuals were screened for renal dysfunction via serum creatinine and estimation of creatinine clearance via the Cockroft-Gault equation. Over a 2-year period, 238 pregnant women, 1014 non-pregnant women and 609 men were screened to initiate ART. Pregnant women eligible were significantly younger, in earlier stages of HIV disease, had higher CD4 cell counts and lower HIV viral loads, than non-pregnant adults. The median serum creatinine in pregnant women (46 µmol/L) was significantly lower and the median creatinine clearance (163 ml/min/1.73 m(2) ) was significantly higher than other groups (P pregnant women had moderate renal dysfunction before ART initiation, with no instances of severe dysfunction observed, compared to 7% moderate or severe renal dysfunction in non-pregnant women or men (P HIV-infected pregnant women is significantly less common than in other HIV-infected adults eligible for ART. The risks associated with initiating tenofovir immediately in pregnant women before reviewing serum creatinine results may be limited, and the benefits of rapid ART initiation in pregnancy may outweigh possible risks of nephrotoxicity. © 2013 John Wiley & Sons Ltd.

  8. Drug-induced renal injury

    African Journals Online (AJOL)

    The kidney receives a rich blood flow of 25% of resting cardiac output ... Drugs can cause acute renal failure by causing pre-renal, intrinsic or .... tubular epithelial cells causing cell swelling ... the dose as required or prescribe alternative drugs.

  9. Effects of aging and uninephrectomy on renal changes in Tsukuba hypertensive mice.

    Science.gov (United States)

    Inui, Yosuke; Mochida, Hideki; Yamairi, Fumiko; Okada, Miyoko; Ishida, Junji; Fukamizu, Akiyoshi; Arakawa, Kenji

    2013-05-01

    Renal dysfunction is accelerated by various factors such as hypertension, aging and diabetes. Glomerular hyper-filtration, considered one of the major risk factors leading to diabetic nephropathy, is often encountered in diabetic patients. However, the interrelationship of these risk factors during the course and development of renal dysfunction has not been fully elucidated. In this study, the effects of aging and uninephrectomy (UNx)-induced hyperfiltration on renal changes were investigated in Tsukuba hypertensive mice (THM) carrying both human renin and angiotensinogen genes. In THM, the urinary albumin/creatinine (Alb/Cr) ratio was elevated with age without a concomitant increase in the plasma Cr concentration. Moreover, the urinary neutrophil gelatinase-associated lipocalin/Cr (NGAL/Cr) ratio, the renal monocyte chemoattractant protein-1 (MCP-1) mRNA expression and the renal collagen type I α 2 (COL1A2) mRNA expression were also increased with age. Age-related albuminuria in THM is likely caused by renal tubular damage, enhanced inflammatory response and tubulointerstitial fibrosis. Furthermore, following UNx, the urinary Alb/Cr ratio and the plasma Cr concentration were increased in THM. The urinary NGAL/Cr ratio and the renal MCP-1 and COL1A2 mRNA expression were not affected by UNx. These results suggested that UNx-induced albuminuria in THM was caused by glomerular dysfunction, rather than renal tubular injury. In conclusion, this study demonstrated for the first time the effects of aging and UNx on renal changes in THM. These findings strongly reinforce the significance of applying a diversity of therapeutic approaches to the management of renal dysfunction.

  10. The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Sung Min Ju

    2015-01-01

    Full Text Available Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2 cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.

  11. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

    Science.gov (United States)

    Ajibade, Temitayo Olabisi; Omobowale, Temidayo Olutayo; Asenuga, Ebunoluwa Racheal; Afolabi, Jeremiah Moyinoluwa; Adedapo, Adeolu Alex

    2016-01-01

    Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN) alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA) in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (pgallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened. PMID:28652848

  12. Bromide supplementation exacerbated the renal dysfunction, injury and fibrosis in a mouse model of Alport syndrome.

    Science.gov (United States)

    Yokota, Tsubasa; Omachi, Kohei; Suico, Mary Ann; Kojima, Haruka; Kamura, Misato; Teramoto, Keisuke; Kaseda, Shota; Kuwazuru, Jun; Shuto, Tsuyoshi; Kai, Hirofumi

    2017-01-01

    A seminal study recently demonstrated that bromide (Br-) has a critical function in the assembly of type IV collagen in basement membrane (BM), and suggested that Br- supplementation has therapeutic potential for BM diseases. Because salts of bromide (KBr and NaBr) have been used as antiepileptic drugs for several decades, repositioning of Br- for BM diseases is probable. However, the effects of Br- on glomerular basement membrane (GBM) disease such as Alport syndrome (AS) and its impact on the kidney are still unknown. In this study, we administered daily for 16 weeks 75 mg/kg or 250 mg/kg (within clinical dosage) NaBr or NaCl (control) via drinking water to 6-week-old AS mice (mouse model of X-linked AS). Treatment with 75 mg/kg NaBr had no effect on AS progression. Surprisingly, compared with 250 mg/kg NaCl, 250 mg/kg NaBr exacerbated the progressive proteinuria and increased the serum creatinine and blood urea nitrogen in AS mice. Histological analysis revealed that glomerular injury, renal inflammation and fibrosis were exacerbated in mice treated with 250 mg/kg NaBr compared with NaCl. The expressions of renal injury markers (Lcn2, Lysozyme), matrix metalloproteinase (Mmp-12), pro-inflammatory cytokines (Il-6, Il-8, Tnf-α, Il-1β) and pro-fibrotic genes (Tgf-β, Col1a1, α-Sma) were also exacerbated by 250 mg/kg NaBr treatment. Notably, the exacerbating effects of Br- were not observed in wild-type mice. These findings suggest that Br- supplementation needs to be carefully evaluated for real positive health benefits and for the absence of adverse side effects especially in GBM diseases such as AS.

  13. The metabolic and renal effects of adrenaline and milrinone in patients with myocardial dysfunction after coronary artery bypass grafting

    Science.gov (United States)

    Heringlake, Matthias; Wernerus, Marit; Grünefeld, Julia; Klaus, Stephan; Heinze, Hermann; Bechtel, Matthias; Bahlmann, Ludger; Poeling, Jochen; Schön, Julika

    2007-01-01

    Introduction Myocardial dysfunction necessitating inotropic support is a typical complication after on-pump cardiac surgery. This prospective, randomized pilot study analyzes the metabolic and renal effects of the inotropes adrenaline and milrinone in patients needing inotropic support after coronary artery bypass grafting (CABG). Methods During an 18-month period, 251 patients were screened for low cardiac output upon intensive care unit (ICU) admission after elective, isolated CABG surgery. Patients presenting with a cardiac index (CI) of less than 2.2 liters/minute per square meter upon ICU admission – despite adequate mean arterial (titrated with noradrenaline or sodium nitroprusside) and filling pressures – were randomly assigned to 14-hour treatment with adrenaline (n = 7) or milrinone (n = 11) to achieve a CI of greater than 3.0 liters/minute per square meter. Twenty patients not needing inotropes served as controls. Hemodynamics, plasma lactate, pyruvate, glucose, acid-base status, insulin requirements, the urinary excretion of alpha-1-microglobuline, and creatinine clearance were determined during the treatment period, and cystatin-C levels were determined up to 48 hours after surgery (follow-up period). Results After two to four hours after ICU admission, the target CI was achieved in both intervention groups and maintained during the observation period. Plasma lactate, pyruvate, the lactate/pyruvate ratio, plasma glucose, and insulin doses were higher (p milrinone or control conditions. The urinary excretion of alpha-1-microglobuline was higher in the adrenaline than in the control group 6 to 14 hours after admission (p milrinone or the control group after 48 hours (p milrinone – is associated with unwarranted metabolic and renal effects. Clinical trials registration: ClinicalTrials.gov NCT00446017. PMID:17470271

  14. Original article. Mitigation of diazinon-induced cardiovascular and renal dysfunction by gallic acid

    Directory of Open Access Journals (Sweden)

    Ajibade Temitayo Olabisi

    2016-06-01

    Full Text Available Studies of the link between environmental pollutants and cardiovascular dysfunction, neglected for decades, have recently provided new insights into the pathology and consequences of these killers. In this study, rats were divided into four groups, each containing 10 rats. The rats in group one served as controls and were administered normal saline, whereas the rats in group two were orally gavaged with 3 mg/kg of diazinon (DZN alone for twenty one consecutive days. The rats in groups 3 and 4 were administered respective 60 mg/kg and 120 mg/kg gallic acid (GA in addition to DZN for twenty one consecutive days. Exposure of rats to diazinon significantly (p<0.05 reduced the activities of superoxide dismutase (SOD, catalase (CAT, glutathione peroxidase (GPx, glutathione-S-transferase (GST and reduced glutathione (GSH content. Malondialdehyde, hydrogen peroxide (H2O2 and nitric oxide (NO contents were also significantly (p<0.05 elevated following DZN exposure. DZN further caused a significant (p<0.05 decrease of heart rate and QT interval prolongation. Hematologic analysis revealed significant reduction (p<0.05 in packed cell volume (PCV, hemoglobin concentration (Hb, red blood cell (RBC count, and total white blood cell count of rats administered only DZN. Observations in this study suggest a modulatory role of gallic acid in diazinon-induced anemia and associated cardiovascular dysfunction in rats. Treatment with gallic acid reversed the oxidative stress markers studied, increased the antioxidant defence system and reduced deleterious effects on hematological parameters in rats. Pathologic findings of the heart and kidney were also found to be lessened.

  15. Renal disease and mitochondrial genetics.

    Science.gov (United States)

    Rötig, Agnès

    2003-01-01

    Respiratory chain (RC) deficiencies have long been regarded as neuromuscular diseases mainly originating from mutations in the mitochondrial DNA. Oxidative phosphorylation, i.e. adenosine triphosphate (ATP) synthesis-coupled electron transfer from substrate to oxygen through the RC, does not occur only in the neuromuscular system. Therefore, a RC deficiency can theoretically give rise to any symptom, in any organ or tissue, at any age and with any mode of inheritance, owing to the dual genetic origin of RC enzymes (nuclear DNA and mitochondrial DNA). Mitochondrial diseases can give rise to various syndromes or association, namely, neurologic and neuromuscular diseases, cardiac, renal, hepatic, hematological and endocrin or dermatological presentations. The most frequent renal symptom is proximal tubular dysfunction with a more or less complete de Toni-Debre-Fanconi Syndrome. A few patients have been reported with tubular acidosis, Bartter Syndrome, chronic tubulointerstitial nephritis or nephrotic syndrome. The diagnosis of a RC deficiency is difficult when only renal symptoms are present, but should be easier when another, seemingly unrelated symptom is observed. Metabolic screening for abnormal oxidoreduction status in plasma, including lactate/pyruvate and ketone body molar ratios, can help to identify patients for further investigations. These include the measurement of oxygen consumption by mitochondria and the assessment of mitochondrial respiratory enzyme activities by spectrophotometric studies. Any mode of inheritance can be observed: sporadic, autosomal dominant or recessive, or maternal inheritance.

  16. Attenuation of hyperlipidemia- and diabetes-induced early-stage apoptosis and late-stage renal dysfunction via administration of fibroblast growth factor-21 is associated with suppression of renal inflammation.

    Directory of Open Access Journals (Sweden)

    Chi Zhang

    Full Text Available BACKGROUND: Lipotoxicity is a key feature of the pathogenesis of diabetic kidney disease, and is attributed to excessive lipid accumulation (hyperlipidemia. Increasing evidence suggests that fibroblast growth factor (FGF21 has a crucial role in lipid metabolism under diabetic conditions. OBJECTIVE: The present study investigated whether FGF21 can prevent hyperlipidemia- or diabetes-induced renal damage, and if so, the possible mechanism. METHODS: Mice were injected with free fatty acids (FFAs, 10 mg/10 g body weight or streptozotocin (150 mg/kg to establish a lipotoxic model or type 1 diabetic model, respectively. Simultaneously the mice were treated with FGF21 (100 µg/kg for 10 or 80 days. The kidney weight-to-tibia length ratio and renal function were assessed. Systematic and renal lipid levels were detected by ELISA and Oil Red O staining. Renal apoptosis was examined by TUNEL assay. Inflammation, oxidative stress, and fibrosis were assessed by Western blot. RESULTS: Acute FFA administration and chronic diabetes were associated with lower kidney-to-tibia length ratio, higher lipid levels, severe renal apoptosis and renal dysfunction. Obvious inflammation, oxidative stress and fibrosis also observed in the kidney of both mice models. Deletion of the fgf21 gene further enhanced the above pathological changes, which were significantly prevented by administration of exogenous FGF21. CONCLUSION: These results suggest that FFA administration and diabetes induced renal damage, which was further enhanced in FGF21 knock-out mice. Administration of FGF21 significantly prevented both FFA- and diabetes-induced renal damage partially by decreasing renal lipid accumulation and suppressing inflammation, oxidative stress, and fibrosis.

  17. Renal dysfunction and barttin expression in Bartter syndrome Type IV associated with a G47R mutation in BSND in a family.

    Science.gov (United States)

    Park, C W; Lim, J H; Youn, D-Y; Chung, S; Lim, M-H; Kim, Y K; Chang, Y S; Lee, J-H

    2011-02-01

    Bartter syndrome (BS) Type IV, associated with a G47R mutation in the BSND gene, is known to result in a mild renal phenotype. However, we report here on three brothers with varying degrees of renal dysfunction from mild to end-stage renal disease associated with renal barttin and ClC-K expression. The brothers had histories of polyhydramnios, prematurity, polyuria, deafness, and small body size. Laboratory findings showed hypokalemic metabolic alkalosis, normotensive hyperreninemic hyperaldosteronism, and an increased urinary excretion of sodium, potassium and chloride, consistent with BS Type IV. Microscopic examination of renal tissue showed hyperplasia of cells at the juxtaglomerular apparatus with dilated atrophic tubules and tubulointerstitial fibrosis. A weak barttin signal related to CIC-K expression in the cytoplasm of tubule cells, but not the basement membrane, was noted. A sequence analysis of the BSND gene showed that the affected males were homozygous for a missense G47R mutation in exon 1 of BSND. These findings suggest that the G47R mutation results in a dramatic decrease in barttin expression, which appears to be related to the location of CIC-K being changed from the basement membrane to the cytoplasm in the tubule and might have varying effects on renal function associated with factors other than this gene.

  18. High Avidity dsDNA Autoantibodies in Brazilian Women with Systemic Lupus Erythematosus: Correlation with Active Disease and Renal Dysfunction

    Directory of Open Access Journals (Sweden)

    Rodrigo C. Oliveira

    2015-01-01

    Full Text Available We investigated in Brazilian women with SLE the prevalence and levels of high avidity (HA dsDNA antibodies and tested their correlation with lupus activity and biomarkers of renal disease. We also compared these correlations to those observed with total dsDNA antibodies and antibodies against nucleosome (ANuA. Autoantibodies were detected by ELISA, while C3 and C4 levels were determined by nephelometry. Urine protein/creatinine ratio was determined, and lupus activity was measured by SLEDAI-2K. The prevalence of total and HA dsDNA antibodies was similar to but lower than that verified for ANuA. The levels of the three types of antibodies were correlated, but the correlation was more significant between HA dsDNA antibodies and ANuA. High avidity dsDNA antibodies correlated positively with ESR and SLEDAI and inversely with C3 and C4. Similar correlations were observed for ANuA levels, whereas total dsDNA antibodies only correlated with SLEDAI and C3. The levels of HA dsDNA antibodies were higher in patients with proteinuria, but their levels of total dsDNA antibodies and ANuA were unaltered. High avidity dsDNA antibodies can be found in high prevalence in Brazilian women with SLE and are important biomarkers of active disease and kidney dysfunction.

  19. Protective effect of Petroselinum crispum extract in abortion using prostadin-induced renal dysfunction in female rats

    Directory of Open Access Journals (Sweden)

    Maryam Rezazad

    2014-09-01

    Full Text Available Objective: Present study investigated the effects of parsley extract on pregnant rat kidneys which have undergone clinical abortion using prostaglandins. The renal protective effect of parsley extract was evaluated in pregnant rats which had an abortion. Parsley was used due to its antioxidant properties. Materials and Methods:  Fifty-four female rats were divided in 9 groups of 6: control pregnant, two pregnant groups which received parsley extract and prostadin, two non-pregnant groups treated with parsley extract and prostadin, a group administered with both treatments, and three groups which received parsley extract in pre-implantation, implantation, and post-implantation periods of embryos. Ethanolic extract (5 mg/kg was given daily to animals for 18 days of pregnancy period. Parameters such as malondialdehyde (MDA, total antioxidant statues (TAS, creatinine, and urea were measured using biochemical assays. Histopathologic studies were also done with Hematoxylin-Eosin staining method. Results: After 18 days of treatment, significant differences were observed in serum creatinine, urea, and MDA and TAS levels. Kidney cross-sections showed edema in prostadin-treated rats while improvements in parsley + prostadin -treated rats were observed. Conclusion: These results suggested that ethanolic extract of Petroselinum crispum reduced the dysfunction in rats kidney caused by prostadin-induced abortion and could have beneficial effect in reducing the progression of prostaglandin-induced edema.

  20. Graphene Oxide/Ag Nanoparticles Cooperated with Simvastatin as a High Sensitive X-Ray Computed Tomography Imaging Agent for Diagnosis of Renal Dysfunctions.

    Science.gov (United States)

    Li, Zhan; Tian, Longlong; Liu, Jianli; Qi, Wei; Wu, Qiang; Wang, Haijing; Ali, Mohammad Chand; Wu, Wangsuo; Qiu, Hongdeng

    2017-09-01

    Graphene oxides (GO) are attracting much attention in the diagnosis and therapy of the subcutaneous tumor as a novel biomaterial, but its diagnosis to tissue dysfunction is yet to be found. Here, a novel application of GO for diagnosis of renal dysfunction via contrast-enhanced computed tomography (CT) is proposed. In order to serve as contrast-enhanced agent, Ag nanoparticles (AgNPs) are composited on the surface of GO to promote its X-ray absorption, and then simvastatin is coinjected for eliminating in vivo toxicity induced by AgNPs. It is found that GO/AgNPs can enhance the imaging of CT into the lung, liver, and kidney of mice for a long circulation time (≈24 h) and a safety profile in vivo in the presence of simvastatin. Interestingly, the lower dose of GO/AgNPs (≈0.5 mg per kg bw) shows an excellent performance for CT imaging of renal perfusion, and visually exhibits the right renal dysfunction in model mice. Hence, this work suggests that graphene nanoparticles will play a vital role for the future medical translational development including drug carrier, biosensing, and disease therapy. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Relationship of endothelial dysfunction with degree of renal function damage and lipidemic profile in patients with type 2 diabetes mellitus and hypertension

    Directory of Open Access Journals (Sweden)

    Pertseva N.O.

    2014-09-01

    Full Text Available In the article defining relationship between endothelial dysfunction, the degree of renal and lipidemic profile damage in 234 patients with type 2 diabetes mellitus with hypertension was carried depending on the quality of glycemic control. It is shown that the deepening of endothelial dysfunction in patients with insufficient and poor compensation tightly correlates with the degree of renal and lipidemic disorders. In these patients there was a significant increase in the level of albuminuria, reduction in glomerular filtration rate, increase of concentrations of urea and creatinine. Against the background of poor hyperglycemia, compensation total cholesterol, low density lipoprotein content increases by 73,3% (p<0.05, hype¬rtriglyceridemia twice exceeds the control values. In patients with type 2 diabetes mellitus with poor compensation the most significant correlation links were observed between the concentration of endothelin-1 and the level of microalbuminuria (r=+0,79, as well as the content of low density lipoprotein cholesterol (r=+0.81. Thrombomodulin concentration is in direct correlation with microalbuminuria (r=+0.76, hypercholesterolemia (r=+0.80 and hypertriglyceridemia (r=+0.83, indicating to increasing interaction between the pathogenetic mechanisms which cause depression of endothelial dysfunction, renal and dyslipidemic disorders with increasing hyperglycemia.

  2. Silymarin and Nigella sativa extract ameliorate paracetamol induced oxidative stress and renal dysfunction in male mice

    Directory of Open Access Journals (Sweden)

    Reham Zakaria Hamza

    2015-06-01

    Full Text Available Objective: To evaluate the ameliorative role of silymarin or/and Nigella sativa (N. sativa water extract against N-acetyl-p-aminophenol (APAP-induced renal function deterioration in male mice at the biochemical levels. Methods: The mice were divided into seven groups (10/group. The first group was served as control. The second group was treated with dose of APAP. The third and fourth groups were treated with silymarin alone and N. sativa water extract alone, respectively. The fifth and sixth groups were treated with combination of APAP with silymarin and APAP with N. sativa water extract, respectively. The seventh group was treated with a combination of both ameliorative compounds (silymarin and N. sativa water extract with APAP and all animals were treated for a period of 30 days. Results: Exposure to APAP at the treated dose for mice led to an alteration of kidney function parameters, increase in the level of serum urea and creatinine. Also, paracetamol administration induced oxidative stress in kidney homogenates by increasing malondialdhyde level and decreasing superoxide dismutase and catalase activities and this stress was ameliorated by administration of either silymarin or N. sativa water extract. Conclusions: Administration of silymarin or/and N. sativa water extract to APAP-treated mice alleviate the toxicity of APAP, and this appeared clearly by biochemical improvement of kidney function parameters and antioxidant parameters. But, the alleviation is more pronounced with the both antioxidants. Thus, the pronounce effect of silymarin and N. sativa water extract is most effective in reducing the toxicity induced by APAP and improving the kidney function parameters and antioxidant status of kidney of male mice.

  3. A Randomized, Controlled Trial of Rituximab in IgA Nephropathy with Proteinuria and Renal Dysfunction.

    Science.gov (United States)

    Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C

    2017-04-01

    IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.

  4. Renal cysteine conjugate C-S lyase mediated toxicity of halogenated alkenes in primary cultures of human and rat proximal tubular cells.

    Science.gov (United States)

    McGoldrick, Trevor A; Lock, Edward A; Rodilla, Vicente; Hawksworth, Gabrielle M

    2003-07-01

    Proximal tubular cells from human (HPT) and rat (RPT) kidneys were isolated, grown to confluence and incubated with S-(1,2-dichlorovinyl)- l-cysteine (DCVC), S-(1,2,2-trichlorovinyl)- l-cysteine (TCVC), S-(1,1,2,2-tetrafluoroethyl)- l-cysteine (TFEC) and S-(2-chloro-1,1-difluorethyl)- l-cysteine (CDFEC), the cysteine conjugates of nephrotoxicants. The cultures were exposed to the conjugates for 12, 24 and 48 h and the toxicity determined using the MTT assay. All four conjugates caused dose-dependent toxicity to RPT cells over the range 50-1,000 microM, the order of toxicity being DCVC>TCVC>TFEC=CDFEC. The inclusion of aminooxyacetic acid (AOAA; 250 microM), an inhibitor of pyridoxal phosphate-dependent enzymes such as C-S lyase, afforded protection, indicating that C-S lyase has a role in the bioactivation of these conjugates. In HPT cultures only DCVC caused significant time- and dose-dependent toxicity. Exposure to DCVC (500 microM) for 48 h decreased cell viability to 7% of control cell values, whereas co-incubation of DCVC (500 microM) with AOAA (250 microM) resulted in cell viability of 71%. Human cultures were also exposed to S-(1,2-dichlorovinyl)-glutathione (DCVG). DCVG was toxic to HPT cells, but the onset of toxicity was delayed compared with the corresponding cysteine conjugate. AOAA afforded almost complete protection from DCVG toxicity. Acivicin (250 microM), an inhibitor of gamma-glutamyl transferase (gamma-GT), partially protected against DCVG (500 microM)-induced toxicity at 48 h (5% viability and 53% viability in the absence and presence of acivicin, respectively). These results suggest that DCVG requires processing by gamma-GT prior to bioactivation by C-S lyase in HPT cells. The activity of C-S lyase, using TFEC as a substrate, and glutamine transaminase K (GTK) was measured in rat and human cells with time in culture. C-S lyase activity in RPT and HPT cells decreased to approximately 30% of fresh cell values by the time the cells reached

  5. Carnitine Profile and Effect of Suppletion in Children with Renal Fanconi Syndrome due to Cystinosis

    OpenAIRE

    Besouw, M.; Cornelissen, E.; Cassiman, D.; Kluijtmans, L.; van den Heuvel, L.; Levtchenko, E.

    2014-01-01

    Background: Cystinosis is an autosomal recessive disorder marked by intralysosomal cystine accumulation. Patients present with generalized proximal tubular dysfunction called renal Fanconi syndrome. Urinary carnitine loss results in plasma and muscle carnitine deficiency, but no clinical signs of carnitine deficiency have been described. Also, the optimal dose of carnitine supplementation is undefined. This study aimed to determine whether currently recommended carnitine doses result in adequ...

  6. Protective role of cabbage extract versus cadmium-induced oxidative renal and thyroid hormones dysfunctions in rats

    International Nuclear Information System (INIS)

    FARAG, M. F. S.; OSMAN, N. N.; DARWISH, M.M.

    2011-01-01

    Cadmium (Cd) is an environmental and industrial pollutant that affects various organs in human and experimental animals. A body of evidence has accumulated implicating the free radical generation with subsequent oxidative stress in the biochemical and molecular mechanisms of Cd damage. Cabbage is economically an important cole crop grown and consumed worldwide. It belongs the Cruciferous vegetables (Brassica), which have been reported to have a wide range of pharmacological properties. Since kidney is the critical target organ of chronic Cd damage, we carried out this study to investigate the effects of cabbage extract (C.E.) on Cd-induced dysfunction in the kidney of rats. The thyroid hormones values were also determined. Male Wistar rats were provided with cadmium chloride (100 mg/ L water) as the only drinking fluid and/or cabbage extract (C.E.) (5 ml/ kg body weight /day) for 4 weeks. Oral administration of Cd significantly induced the renal damage which was evident from the significantly (p < 0.05) increased levels of serum urea, uric acid and creatinine with a significant (p < 0.05) decrease in creatinine clearance. It also significantly declined the levels of urea, uric acid and creatinine in urine. Intoxication of Cd to rats reduced serum triiodothyronine (T3) and thyroxine (T4) concentrations. Reduced glutathione (GSH), and enzymatic antioxidants (superoxide dismutase (SOD) and catalase (CAT) were also significantly (p < 0.05) depressed with a concomitant marked enhancement in lipid peroxidation marker (thiobarbituric acid reactive substances, TBARS). Co-administration of C.E. along with Cd resulted in a reversal of the Cd-induced biochemical variables in kidney accompanied by a significant reduction in lipid peroxidation and a higher levels of renal antioxidant defense system. However, incorporation of C.E. to rats whether applied alone or in combination with Cd did not reveal any change in the thyroid hormones levels, which reflect significant drop in

  7. 2-Methoxyestradiol Reduces Angiotensin II-Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice.

    Science.gov (United States)

    Pingili, Ajeeth K; Davidge, Karen N; Thirunavukkarasu, Shyamala; Khan, Nayaab S; Katsurada, Akemi; Majid, Dewan S A; Gonzalez, Frank J; Navar, L Gabriel; Malik, Kafait U

    2017-06-01

    Cytochrome P450 1B1 protects against angiotensin II (Ang II)-induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II-induced hypertension, renal dysfunction, and end-organ damage in intact Cyp1b1 -/- , ovariectomized female, and Cyp1b1 +/+ male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II-induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female Cyp1b1 -/- and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II-induced increase in blood pressure, water intake, urine output, and proteinuria in Cyp1b1 +/+ male mice. Treatment with 2-methoxyestradiol attenuated Ang II-induced end-organ damage in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice and Cyp1b1 +/+ male mice. 2-Methoxyestradiol mitigated Ang II-induced increase in urinary excretion of angiotensinogen in intact Cyp1b1 -/- and ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice but not in Cyp1b1 +/+ male mice. The G protein-coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II-induced increases in blood pressure and renal function in Cyp1b1 +/+ female mice. These data suggest that 2-methoxyestradiol reduces Ang II-induced hypertension and associated end-organ damage in intact Cyp1b1 -/- , ovariectomized Cyp1b1 +/+ and Cyp1b1 -/- female mice, and Cyp1b1 +/+ male mice independent of G protein-coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males. © 2017 American Heart Association, Inc.

  8. Activation of PI3K-Akt-GSK3β pathway mediates hepatocyte growth factor inhibition of RANTES expression in renal tubular epithelial cells

    International Nuclear Information System (INIS)

    Gong Rujun; Rifai, Abdalla; Dworkin, Lance D.

    2005-01-01

    Hepatocyte growth factor (HGF) was recently reported to ameliorate renal inflammation in a rat model of chronic renal failure. HGF exerted its action through suppression of RANTES expression in renal tubules. In the present study, we utilized an in vitro model of human kidney proximal tubule epithelial cells (HKC) to elucidate the mechanisms of RANTES suppression by HGF. HGF significantly suppressed basal and TNF-α-induced mRNA and protein expression of RANTES in a time and dose dependent fashion. HGF elicited PI3K-Akt activation and inhibited GSK3, a downstream transducer of PI3K-Akt, by inhibitory phosphorylation at Ser-9. When the PI3K-Akt pathway was blocked by wortmannin, HGF inhibition of RANTES was abrogated, demonstrating that the PI3K-Akt pathway is necessary for HGF action. In addition, specific inhibition of GSK3 activity by lithium ion suppressed basal and TNF-α-induced RANTES expression, reminiscent of the action of HGF. To further investigate the role of GSK3 in modulating RANTES expression, we examined the effect of forced expression of wild type GSK3β or an uninhibitable mutant GSK3β, in which the regulatory Ser-9 residue is changed to alanine (S9A-GSK3β) in HKC. Overexpression of wild type GSK3β did not alter the inhibitory action of HGF on RANTES. In contrast, expression of S9A-GSK3β abolished HGF inhibition of basal and TNF-α stimulated RANTES expression. These findings suggest that PI3K-Akt activation and subsequent inhibitory phosphorylation of GSK3β are required for HGF-induced suppression of RANTES in HKC

  9. Generation of Urinary Albumin Fragments Does Not Require Proximal Tubular Uptake

    OpenAIRE

    Weyer, K.; Nielsen, R.; Christensen, E. I.; Birn, H.

    2012-01-01

    Urinary albumin excretion is an important diagnostic and prognostic marker of renal function. Both animal and human urine contain large amounts of albumin fragments, but whether these fragments originate from renal tubular degradation of filtered albumin is unknown. Here, we used mice with kidneys lacking megalin and cubilin, the coreceptors that mediate proximal tubular endocytosis of albumin, to determine whether proximal tubular degradation of albumin forms the detectable urinary albumin f...

  10. Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

    Science.gov (United States)

    Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

    2006-07-01

    Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

  11. Sustained oxidative stress causes late acute renal failure via duplex regulation on p38 MAPK and Akt phosphorylation in severely burned rats.

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    Yafei Feng

    Full Text Available BACKGROUND: Clinical evidence indicates that late acute renal failure (ARF predicts high mortality in severely burned patients but the pathophysiology of late ARF remains undefined. This study was designed to test the hypothesis that sustained reactive oxygen species (ROS induced late ARF in a severely burned rat model and to investigate the signaling mechanisms involved. MATERIALS AND METHODS: Rats were exposed to 100°C bath for 15 s to induce severe burn injury (40% of total body surface area. Renal function, ROS generation, tubular necrosis and apoptosis, and phosphorylation of MAPK and Akt were measured during 72 hours after burn. RESULTS: Renal function as assessed by serum creatinine and blood urea nitrogen deteriorated significantly at 3 h after burn, alleviated at 6 h but worsened at 48 h and 72 h, indicating a late ARF was induced. Apoptotic cells and cleavage caspase-3 in the kidney went up slowly and turned into significant at 48 h and 72 h. Tubular cell ROS production shot up at 6 h and continuously rose during the 72-h experiment. Scavenging ROS with tempol markedly attenuated tubular apoptosis and renal dysfunction at 72 h after burn. Interestingly, renal p38 MAPK phosphorylation elevated in a time dependent manner whereas Akt phosphorylation increased during the first 24 h but decreased at 48 h after burn. The p38 MAPK specific inhibitor SB203580 alleviated whereas Akt inhibitor exacerbated burn-induced tubular apoptosis and renal dysfunction. Furthermore, tempol treatment exerted a duplex regulation through inhibiting p38 MAPK phosphorylation but further increasing Akt phosphorylation at 72 h postburn. CONCLUSIONS: These results demonstrate that sustained renal ROS overproduction induces continuous tubular cell apoptosis and thus a late ARF at 72 h after burn in severely burned rats, which may result from ROS-mediated activation of p38 MAPK but a late inhibition of Akt phosphorylation.

  12. alpha-Adducin mutations increase Na/K pump activity in renal cells by affecting constitutive endocytosis: implications for tubular Na reabsorption.

    Science.gov (United States)

    Torielli, Lucia; Tivodar, Simona; Montella, Rosa Chiara; Iacone, Roberto; Padoani, Gloria; Tarsini, Paolo; Russo, Ornella; Sarnataro, Daniela; Strazzullo, Pasquale; Ferrari, Patrizia; Bianchi, Giuseppe; Zurzolo, Chiara

    2008-08-01

    Genetic variation in alpha-adducin cytoskeletal protein is implicated in the polymerization and bundling of actin and alteration of the Na/K pump, resulting in abnormal renal sodium transport and hypertension in Milan hypertensive rats and humans. To investigate the molecular involvement of alpha-adducin in controlling Na/K pump activity, wild-type or mutated rat and human alpha-adducin forms were, respectively, transfected into several renal cell lines. Through multiple experimental approaches (microscopy, enzymatic assays, coimmunoprecipitation), we showed that rat and human mutated forms increased Na/K pump activity and the number of pump units; moreover, both variants coimmunoprecipitate with Na/K pump. The increased Na/K pump activity was not due to changes in its basolateral localization, but to an alteration of Na/K pump residential time on the plasma membrane. Indeed, both rat and human mutated variants reduced constitutive Na/K pump endocytosis and similarly affected transferrin receptor trafficking and fluid-phase endocytosis. In fact, alpha-adducin was detected in clathrin-coated vesicles and coimmunoprecipitated with clathrin. These results indicate that adducin, besides its modulatory effects on actin cytoskeleton dynamics, might play a direct role in clathrin-dependent endocytosis. The constitutive reduction of the Na/K pump endocytic rate induced by mutated adducin variants may be relevant in Na-dependent hypertension.

  13. Nuclear medicine in the management of renal vein thrombosis post renal transplantation - a case study

    International Nuclear Information System (INIS)

    Waran, L.; Unger, S.

    2005-01-01

    Renal scintigraphy allows the assessment of both perfusion and function of the transplanted kidney. Treatment of renal dysfunction depends on its cause. Nuclear medicine plays an important role in determining the cause of renal dysfunction, thereby providing appropriate intervention. Renal vein thrombosis (RVT) is a rare occurrence (1-2%) in renal transplants, and constitutes a surgical emergency. Early detection of RVT is critical in order to prevent infarction and subsequent loss of the graft. A 43-year-old woman with end stage renal disease as a result of diabetic nephropathy underwent transplantation of a living-related-donor kidney. The patient underwent a post operative Tc-MAG, scan that demonstrated good perfusion to the graft. Three days post-transplantation, the patient complained of acute pain and swelling. Creatinine increased from 0.13 to 0.16. and urine output decreased. The m Tc-MAG, scan revealed dramatic deterioration, with absent perfusion to the kidney. Immediate allograft exploration was performed in theatre and RVT was revealed, followed by thrombectomy. A follow-up renal scan performed the next day demonstrated a viable kidney with improved but patchy perfusion throughout, indicating patchy cortical infarction as well as acute tubular necrosis. On day 19. the patient again complained of severe pain over the graft, and the 99 mTc-MAG, scan again revealed absent perfusion, this time with residual function. Further surgical exploration confirmed re-thrombosis of the renal vein, and subsequent genetic analysis revealed that the patient had a rare mutation of her clotting Factor V gene, leading to an increased thrombogenic tendency. Following full anticoagulation, the patient was finally discharged on day 58. This case illustrates a rare case of renal allograft infarction secondary to renal vein thrombosis. The ability of nuclear medicine to provide immediate functional information helped confirm the diagnosis, and salvage the kidney

  14. Effect of Unripe Plantain (Musa paradisiaca) and Ginger (Zingiber officinale) on Renal Dysfunction in Streptozotocin-Induced Diabetic Rats.

    Science.gov (United States)

    Iroaganachi, Mercy; Eleazu, Chinedum; Okafor, Polycarp

    2015-03-20

    Although unripe plantain (Musa paradisiaca) and ginger (Zingiber officinale) are used as single plants to manage diabetes mellitus in Nigeria, the possibility of combining them in a typical diabetic diet and the glycemic response elicited as a result of such combination has not been investigated. To determine the effect of unripe plantain and ginger on serum total proteins, albumin, creatinine and urea levels of streptozotocin induced diabetic rats. Twenty four male albino rats were used and were divided into 4 groups of 6 rats each. Group 1 (non-diabetic) received standard rat feeds; Group 2 (diabetic) received standard rat feeds; Group 3 received unripe plantain pellets and Group 4 received unripe plantain+ginger pellets. There were significant increases (P=0.045) of both serum urea and creatinine, but significant decreases (P=0.045) of both serum total protein and albumin levels, in Group 2 rats compared with Group 1. There were significant decreases (P=0.033) of both serum urea and creatinine levels of Group 3 and 4 rats compared with Group 2. In addition, there were significant increases of both serum total protein and albumin levels (P=0.033) in Group 3 rats compared with Group 2, but the comparison of serum total protein and albumin levels between Group 4 and Group 2 did not reach the significant level (P=0.056 and P=0.065 for serum total protein and albumin levels, respectively. Combination of unripe plantain and ginger at the ratio used in the management of renal dysfunction in diabetics was not very effective compared with unripe plantain alone.

  15. CD44-deficiency attenuates the immunologic responses to LPS and delays the onset of endotoxic shock-induced renal inflammation and dysfunction.

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    Elena Rampanelli

    Full Text Available Acute kidney injury (AKI is a common complication during systemic inflammatory response syndrome (SIRS, a potentially deadly clinical condition characterized by whole-body inflammatory state and organ dysfunction. CD44 is a ubiquitously expressed cell-surface transmembrane receptor with multiple functions in inflammatory processes, including sterile renal inflammation. The present study aimed to assess the role of CD44 in endotoxic shock-induced kidney inflammation and dysfunction by using CD44 KO and WT mice exposed intraperitoneally to LPS for 2, 4, and 24 hours . Upon LPS administration, CD44 expression in WT kidneys was augmented at all time-points. At 2 and 4 hours, CD44 KO animals showed a preserved renal function in comparison to WT mice. In absence of CD44, the pro-inflammatory cytokine levels in plasma and kidneys were lower, while renal expression of the anti-inflammatory cytokine IL-10 was higher. The cytokine levels were associated with decreased leukocyte influx and endothelial activation in CD44 KO kidneys. Furthermore, in vitro assays demonstrated a role of CD44 in enhancing macrophage cytokine responses to LPS and leukocyte migration. In conclusion, our study demonstrates that lack of CD44 impairs the early pro-inflammatory cytokine response to LPS, diminishes leukocyte migration/chemotaxis and endothelial activation, hence, delays endotoxic shock-induced AKI.

  16. Nicotine protects kidney from renal ischemia/reperfusion injury through the cholinergic anti-inflammatory pathway.

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    Claude Sadis

    Full Text Available Kidney ischemia/reperfusion injury (I/R is characterized by renal dysfunction and tubular damages resulting from an early activation of innate immunity. Recently, nicotine administration has been shown to be a powerful inhibitor of a variety of innate immune responses, including LPS-induced toxaemia. This cholinergic anti-inflammatory pathway acts via the alpha7 nicotinic acetylcholine receptor (alpha7nAChR. Herein, we tested the potential protective effect of nicotine administration in a mouse model of renal I/R injury induced by bilateral clamping of kidney arteries. Renal function, tubular damages and inflammatory response were compared between control animals and mice receiving nicotine at the time of ischemia. Nicotine pretreatment protected mice from renal dysfunction in a dose-dependent manner and through the alpha7nAChR, as attested by the absence of protection in alpha7nAChR-deficient mice. Additionally, nicotine significantly reduced tubular damages, prevented neutrophil infiltration and decreased productions of the CXC-chemokine KC, TNF-alpha and the proinflammatory high-mobility group box 1 protein. Reduced tubular damage in nicotine pre-treated mice was associated with a decrease in tubular cell apoptosis and proliferative response as attested by the reduction of caspase-3 and Ki67 positive cells, respectively. All together, these data highlight that nicotine exerts a protective anti-inflammatory effect during kidney I/R through the cholinergic alpha7nAChR pathway. In addition, this could provide an opportunity to overcome the effect of surgical cholinergic denervation during kidney transplantation.

  17. Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance

    Science.gov (United States)

    Jin, Jianliang; Lv, Xianhui; Chen, Lulu; Zhang, Wei; Li, Jinbo; Wang, Qian; Wang, Rong; Lu, Xiang; Miao, Dengshun

    2014-01-01

    To determine whether Bmi-1 deficiency could lead to renal tubulointerstitial injury by mitochondrial dysfunction and increased oxidative stress in the kidney, 3-week-old Bmi-1-/- mice were treated with the antioxidant N-acetylcysteine (NAC, 1 mg mL−1) in their drinking water, or pyrro-quinoline quinone (PQQ, 4 mg kg−1 diet) in their diet for 2 weeks, and their renal phenotypes were compared with vehicle-treated Bmi1-/- and wild-type mice. Bmi-1 was knocked down in human renal proximal tubular epithelial (HK2) cells which were treated with 1 mm NAC for 72 or 96 h, and their phenotypes were compared with control cells. Five-week-old vehicle-treated Bmi-1-/- mice displayed renal interstitial fibrosis, tubular atrophy, and severe renal function impairment with decreased renal cell proliferation, increased renal cell apoptosis and senescence, and inflammatory cell infiltration. Impaired mitochondrial structure, decreased mitochondrial numbers, and increased oxidative stress occurred in Bmi-1-/- mice; subsequently, this caused DNA damage, the activation of TGF-β1/Smad signaling, and the imbalance between extracellular matrix synthesis and degradation. Oxidative stress-induced epithelial-to-mesenchymal transition of renal tubular epithelial cells was enhanced in Bmi-1 knocked down HK2 cells. All phenotypic alterations caused by Bmi-1 deficiency were ameliorated by antioxidant treatment. These findings indicate that Bmi-1 plays a critical role in protection from renal tubulointerstitial injury by maintaining redox balance and will be a novel therapeutic target for preventing renal tubulointerstitial injury. PMID:24915841

  18. Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia.

    Science.gov (United States)

    Vidal-Petiot, Emmanuelle; Rea, Delphine; Serrano, Fidéline; Stehlé, Thomas; Gardin, Claude; Rousselot, Philippe; Peraldi, Marie-Noëlle; Flamant, Martin

    2016-03-01

    Monitoring renal function is important in imatinib-treated patients with chronic myeloid leukemia because serum creatinine may increase during the course of therapy. The mechanism of this increase and its reversibility on treatment cessation have never been investigated. We retrospectively analyzed data from imatinib-treated patients explored in our renal physiology unit with measurement of glomerular filtration rate (urinary clearance of (51)CrEDTA) and of urinary clearance and tubular secretion of creatinine. Results were compared with those of controls matched for measured glomerular filtration rate, age, gender, and ethnicity. We also analyzed variations of serum creatinine before and during imatinib cessation and after imatinib resumption in patients enrolled in imatinib discontinuation studies. In 4 imatinib-treated patients who underwent thorough renal exploration, the part of creatinine clearance due to tubular secretion was negligible (2.4, 3.1, -1.3, and 2.8 mL/min) and significantly lower than that measured in their respective controls (17.7 ± 5.6, 43.0 ± 18.0, 23.1 ± 6.7, and 18.6 ± 5.6 mL/min, P creatinine tubular secretion (20.3 vs. 17.9 ± 5.2 mL/min in the control population, P = .2). In 15 patients of imatinib discontinuation studies, a median decrease in serum creatinine of 17.9% was observed after imatinib cessation. Resumption of treatment in 6 patients led to a median increase in serum creatinine of 18.8%. Imatinib completely blunts tubular secretion of creatinine, a previously unreported pharmacologic property. This inhibition increases serum creatinine independently of any glomerular dysfunction and is fully reversible on imatinib cessation. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Association of renal biochemical parameters with left ventricular diastolic dysfunction in a community-based elderly population in China: a cross-sectional study.

    Directory of Open Access Journals (Sweden)

    Jingmin Zhou

    Full Text Available BACKGROUND: Relationship of left ventricular diastolic dysfunction (LVDD with parameters that could provide more information than hemodynamic renal indexes has not been clarified. We aimed to explore the association of comprehensive renal parameters with LVDD in a community-based elderly population. METHODS: 1,166 community residents (aged ≥ 65 years, 694 females participating in the Shanghai Heart Health Study with complete data of renal parameters were investigated. Echocardiography was used to evaluate diastolic function with conventional and tissue Doppler imaging techniques. Serum urea, creatinine, urea-to-creatinine ratio, estimated glomerular filtration rate (eGFR and urinary albumin-to-creatinine ratio (UACR were analyzed on their associations with LVDD. RESULTS: The prevalence of LVDD increased in proportion to increasing serum urea, urea-to-creatinine ratio and UACR. These three renal parameters were found negatively correlated to peak early (E to late (A diastolic velocities ratio (E/A, and positively to left atrial volume index; UACR also positively correlated with E to peak early (E' diastolic mitral annular velocity ratio (E/E'. Serum urea, urea-to-creatinine ratio and UACR correlated with LVDD in logistic univariate regression analysis, and urea-to-creatinine ratio remained independently correlated to LVDD [Odds ratio (OR 2.82, 95% confidence interval (CI 1.34-5.95] after adjustment. Serum urea (OR 1.18, 95%CI 1.03-1.34, creatinine (OR 6.53, 95%CI 1.70- -25.02, eGFR (OR 0.22, 95%CI 0.07-0.65 and UACR (OR 2.15, 95%CI 1.42-3.24 were revealed independent correlates of advanced (moderate and severe LVDD. CONCLUSIONS: Biochemical parameters of renal function were closely linked with LVDD. This finding described new cardio-renal relationship in the elderly population.

  20. Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris

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    A. Aggarwal

    2010-08-01

    Full Text Available PURPOSE: Recurrence and persistent side effects of present day treatment for urolithiasis restrict their use, so an alternate solution, using phytotherapy is being sought. The present study attempted to evaluate the antilithiatic properties of Tribulus terrestris commonly called as “gokhru” which is often used in ayurveda to treat various urinary diseases including urolithiasis. MATERIALS AND METHODS: The activity of Tribulus terrestris was investigated on nucleation and the growth of the calcium oxalate (CaOx crystals as well as on oxalate induced cell injury of NRK 52E renal epithelial cells. RESULTS: Tribulus terrestris extract exhibited a concentration dependent inhibition of nucleation and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. CONCLUSION: The current data suggests that Tribulus terrestris extract not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role. Our results indicate that it could be a potential candidate for phytotherapy against urolithiasis.

  1. Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris.

    Science.gov (United States)

    Aggarwal, A; Tandon, S; Singla, S K; Tandon, C

    2010-01-01

    Recurrence and persistent side effects of present day treatment for urolithiasis restrict their use, so an alternate solution, using phytotherapy is being sought. The present study attempted to evaluate the antilithiatic properties of Tribulus terrestris commonly called as "gokhru" which is often used in ayurveda to treat various urinary diseases including urolithiasis. The activity of Tribulus terrestris was investigated on nucleation and the growth of the calcium oxalate (CaOx) crystals as well as on oxalate induced cell injury of NRK 52E renal epithelial cells. Tribulus terrestris extract exhibited a concentration dependent inhibition of nucleation and the growth of CaOx crystals. When NRK-52E cells were injured by exposure to oxalate for 72 h, Tribulus terrestris extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and lactate dehydrogenase release decreased in a concentration dependent manner. The current data suggests that Tribulus terrestris extract not only has a potential to inhibit nucleation and the growth of the CaOx crystals but also has a cytoprotective role. Our results indicate that it could be a potential candidate for phytotherapy against urolithiasis.

  2. Correction of renal dysfunction under the influence of dietary management, exercises and lisinopril in patients with abdominal obesity and hypertension

    Directory of Open Access Journals (Sweden)

    Rokutova М.К.

    2015-11-01

    Full Text Available The purpose of research is to assess the impact of diet therapy, physical activity and an ACE inhibitor (lisinopril on renal dysfunction in patients with abdominal obesity and hypertension. The study involved 14 patients with abdominal obesity, 2-3 degrees in BMI, hypertension, I-II stage, 1 degree, and severe insulin resistance. Men were 9 (64.3% patients, women - 5 (35.7% persons. The average age of the patients was 37,0±1,7 years, mean BMI - 44.7 [35.5; 46.5] kg/m2. BP was between 140-158/90-98 mm Hg. Diroton (lisinopril, Richter Gedeon Ltd, Hungary was administered 1 time per day in the morning at a dose of 10 mg. The effect of diet therapy, exercise and lisinopril on parameteres of renal function (glomerular filtration rate, urine protein, urine albumin, urine І2 microglobulin, urine albumin / creatinine ratio, І2- microglobulin / urine creatinine ratio. After 6 months of treatment there was a significant decrease in body weight (p<0.001 from 123.5 [110.0; 154.0] to 120.0 [105.0; 142.0] kg, with a BMI from 44.7 [35.5; 46.5] to 42.7 [33.9; 45.2] kg/m2 (p <0.001 and waist from 118.0 [105.0; 142.0] to 116.0 [105.0; 135.0] cm (p<0.05. Normalization of blood pressure was achieved in 71,4% (n=10 patients and a significant decrease in blood pressure - in 28,7% (n=4 persons in the 6th week of treatment. The level of GFR was significantly (p<0.01 decreased from 202.2 [156.1; 254.6] to 200.3 [148.8; 220.6] ml/min, the level of І2-mg decreased from 3.4 [1.1, 4.8] to 2.8 [1.4; 3.6] mg/24 h, the І2-mg / Cr urine ratio - from 2.3 [0.9, 4.0] to 1.9 [1.0, 2.7] mg/g, which is a positive point prognosis of obesity-associated nephropathy in these patients. GFR normalized in 2 (14.3% patients, І2-mg and І2-mg / Сr ratio - only in 1 (7.1% patients. GFR decreased in 10 (71.4% patients, І2-mg and І2-mg / Cr ratio – in 12 (85.7% patients. It is the result of complex treatment of diet, exercises and lisinopril. A significant reduction (p<0.01 of leptin

  3. Renal Dysfunction Induced by Kidney-Specific Gene Deletion of Hsd11b2 as a Primary Cause of Salt-Dependent Hypertension.

    Science.gov (United States)

    Ueda, Kohei; Nishimoto, Mitsuhiro; Hirohama, Daigoro; Ayuzawa, Nobuhiro; Kawarazaki, Wakako; Watanabe, Atsushi; Shimosawa, Tatsuo; Loffing, Johannes; Zhang, Ming-Zhi; Marumo, Takeshi; Fujita, Toshiro

    2017-07-01

    Genome-wide analysis of renal sodium-transporting system has identified specific variations of Mendelian hypertensive disorders, including HSD11B2 gene variants in apparent mineralocorticoid excess. However, these genetic variations in extrarenal tissue can be involved in developing hypertension, as demonstrated in former studies using global and brain-specific Hsd11b2 knockout rodents. To re-examine the importance of renal dysfunction on developing hypertension, we generated kidney-specific Hsd11b2 knockout mice. The knockout mice exhibited systemic hypertension, which was abolished by reducing salt intake, suggesting its salt-dependency. In addition, we detected an increase in renal membrane expressions of cleaved epithelial sodium channel-α and T53-phosphorylated Na + -Cl - cotransporter in the knockout mice. Acute intraperitoneal administration of amiloride-induced natriuresis and increased urinary sodium/potassium ratio more in the knockout mice compared with those in the wild-type control mice. Chronic administration of amiloride and high-KCl diet significantly decreased mean blood pressure in the knockout mice, which was accompanied with the correction of hypokalemia and the resultant decrease in Na + -Cl - cotransporter phosphorylation. Accordingly, a Na + -Cl - cotransporter blocker hydrochlorothiazide significantly decreased mean blood pressure in the knockout mice. Chronic administration of mineralocorticoid receptor antagonist spironolactone significantly decreased mean blood pressure of the knockout mice along with downregulation of cleaved epithelial sodium channel-α and phosphorylated Na + -Cl - cotransporter expression in the knockout kidney. Our data suggest that kidney-specific deficiency of 11β-HSD2 leads to salt-dependent hypertension, which is attributed to mineralocorticoid receptor-epithelial sodium channel-Na + -Cl - cotransporter activation in the kidney, and provides evidence that renal dysfunction is essential for developing the

  4. Genetic polymorphisms of angiotensin-2 type 1 receptor and angiotensinogen and risk of renal dysfunction and coronary heart disease in type 2 diabetes mellitus

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    Hu Frank B

    2009-03-01

    Full Text Available Abstract Background Increased activation of the renin-angiotensin system (RAS may be important in promoting coronary heart disease (CHD and renal dysfunction, but limited data are available on associations between angiotensin type 1 receptor (AGT1R and angiotensinogen (AGT genotypes in type 2 diabetes. Methods Study participants were diabetics from the Health Professionals Follow-Up Study (HPFS and the Nurses' Health Study (NHS. We analyzed single nucleotide polymorphisms (SNPs associated with cardiovascular pathophysiology (including AGT1R T573C, AGT1R A1166C, and AGT M235T and presence of renal dysfunction (eGFR2 or history of CHD. Results The AGT1R 1166 C-allele was associated with eGFR2 (multivariable OR 1.63 [1.01, 2.65] in the HPFS men (n = 733 and in the combined dataset (n = 1566 (OR 1.42 [1.02, 1.98]. The AGT1R 1166 C-allele was also associated with CHD in men (OR 1.57 [1.10, 2.24]. In NHS women (n = 833, AGT 235T-allele was associated with CHD (OR 1.72 [1.20, 2.47]. Removal of hypertension from the fully adjusted models did not influence results, suggesting that the associations may not be mediated by hypertension. There were significant interactions between sex and AGT1R 1166 C-allele (p = 0.008 and AGT M235T (p = 0.03 in models for CHD. No significant associations were seen between AGT1R T573 C-allele and renal dysfunction or CHD. Conclusion Polymorphisms in AGT1R and AGT genes are associated with renal dysfunction and CHD in type 2 diabetes and further support the important role of the RAS in these complications. Sex may modify associations between AGT1R 1166 C-allele and AGT 235T and CHD in type 2 diabetes.

  5. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  6. Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase.

    Science.gov (United States)

    Nie, Huibin; Xue, Xia; Liu, Gang; Guan, Guangju; Liu, Haiying; Sun, Lina; Zhao, Long; Wang, Xueling; Chen, Zhixin

    2016-01-01

    Nitroalkene derivative of oleic acid (OA-NO 2 ), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO 2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO 2 in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO 2 (1.25 μM, 45 min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO 2 promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO 2 inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22 phox up-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO 2 reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.

  7. TUBULAR DISORDERS WITH RICKETS-LIKE SYNDROME

    Directory of Open Access Journals (Sweden)

    N.N. Kartamysheva

    2011-01-01

    Full Text Available Often under the guise of «ordinary» Rickets are more severe kidney diseases, developing as a result of inherited or acquired, primary or secondary defects in the renal tubules. Incorrect diagnosis leads to an inadequate therapy, rapid progression of disease and renal failure. The article describes the main approaches to the diagnosis and treatment of disorders of tubular rachitis similar syndrome, presents a number of clinical cases in author's practice.Key words: tubulopathy, acidosis, electrolyte disorders, rickets, rickets-like syndrome, diagnostics, treatment, children.

  8. Association between left ventricular dysfunction, anemia, and chronic renal failure. Analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) cohort.

    Science.gov (United States)

    Kepez, A; Mutlu, B; Degertekin, M; Erol, C

    2015-06-01

    Anemia and chronic renal failure (CRF) are frequent comorbidities in patients with heart failure (HF), and they have been reported to be associated with increased mortality and hospitalization rates. HF, anemia, and CRF have been reported to interact with each other forming a vicious cycle termed cardio-renal-anemia syndrome. The aim of the present study was to evaluate the association of HF, anemia, and CRF using data from the large-scale"Heart Failure Prevalence and Predictors in Turkey (HAPPY)" study. Among the HAPPY cohort, 3,369 subjects who had either left ventricular dysfunction (LVD) or normal left ventricular function on echocardiography or normal serum NT-proBNP levels were included in this analysis. The prevalence of anemia and CRF was significantly higher in patients with LVD compared with subjects with normal ventricular function (20.7 % vs. 4.0 % and 19.0 % vs. 3.7 %, respectively; p renal-anemia syndrome and the necessity of treating these comorbidities in patients with HF.

  9. Upregulation of microRNA 142-3p in the peripheral blood and urinary cells of kidney transplant recipients with post-transplant graft dysfunction.

    Science.gov (United States)

    Domenico, T D; Joelsons, G; Montenegro, R M; Manfro, R C

    2017-04-03

    We analyzed microRNA (miR)-142-3p expression in leucocytes of the peripheral blood and urinary sediment cell samples obtained from kidney transplant recipients who developed graft dysfunction. Forty-one kidney transplant recipients with kidney graft dysfunction and 8 stable patients were included in the study. The groups were divided according to histological analysis into acute rejection group (n=23), acute tubular necrosis group (n=18) and stable patients group used as a control for gene expression (n=8). Percutaneous biopsies were performed and peripheral blood samples and urine samples were obtained. miR-142-3p was analyzed by real-time polymerase chain reaction. The group of patients with acute tubular necrosis presented significantly higher expressions in peripheral blood (Ptransplantation and may potentially be used as a non-invasive biomarker for renal graft dysfunction.

  10. Reliability of Tubular Joints

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle

    In this paper the preliminary results obtained by tests on tubular joints are presented. The joints are T-joints and the loading is static. It is the intention in continuation of these tests to perform tests on other types of joints (e.g. Y-joints) and also with dynamic loading. The purpose...... of the test is partly to obtain empirical data for the ultimate load-carrying capacity of tubular T-joints and partly to obtain some experience in performing tests with tubular joints. It is well known that tubular joints are usually designed in offshore engineering on the basis of empirical formulas obtained...... by experimental test results. Therefore, there is a need for performing experimental tests in this area....

  11. High-fat diet amplifies renal renin angiotensin system expression, blood pressure elevation, and renal dysfunction caused by Ceacam1 null deletion.

    Science.gov (United States)

    Li, Caixia; Culver, Silas A; Quadri, Syed; Ledford, Kelly L; Al-Share, Qusai Y; Ghadieh, Hilda E; Najjar, Sonia M; Siragy, Helmy M

    2015-11-01

    Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAMl), a substrate of the insulin receptor tyrosine kinase, regulates insulin action by promoting insulin clearance. Global null mutation of Ceacam1 gene (Cc1(-/-)) results in features of the metabolic syndrome, including insulin resistance, hyperinsulinemia, visceral adiposity, elevated blood pressure, and albuminuria. It also causes activation of the renal renin-angiotensin system (RAS). In the current study, we tested the hypothesis that high-fat diet enhances the expression of RAS components. Three-month-old wild-type (Cc1(+/+)) and Cc1(-/-) mice were fed either a regular or a high-fat diet for 8 wk. At baseline under regular feeding conditions, Cc1(-/-) mice exhibited higher blood pressure, urine albumin-to-creatinine ratio (UACR), and renal expression of angiotensinogen, renin/prorenin, angiotensin-converting enzyme, (pro)renin receptor, angiotensin subtype AT1 receptor, angiotensin II, and elevated PI3K phosphorylation, as detected by p85α (Tyr(508)) immunostaining, inflammatory response, and the expression of collagen I and collagen III. In Cc1(+/+) mice, high-fat diet increased blood pressure, UACR, the expression of angiotensin-converting enzyme and angiotensin II, PI3K phosphorylation, inflammatory response, and the expression of collagen I and collagen III. In Cc1(-/-) mice, high-fat intake further amplified these parameters. Immunohistochemical staining showed increased p-PI3K p85α (Tyr(508)) expression in renal glomeruli, proximal, distal, and collecting tubules of Cc1(-/-) mice fed a high-fat diet. Together, this demonstrates that high-fat diet amplifies the permissive effect of Ceacam1 deletion on renal expression of all RAS components, PI3K phosphorylation, inflammation, and fibrosis. Copyright © 2015 the American Physiological Society.

  12. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion

    Directory of Open Access Journals (Sweden)

    Fausto Chiazza

    2015-01-01

    Full Text Available Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO- donor furoxan moiety (NO-EDV. Male Wistar rats were subjected to renal ischemia (45 minutes, followed by reperfusion (6 hours. Administration of either EDV (1.2–6–30 µmol/kg, i.v. or NO-EDV (0.3–1.2–6 µmol/kg, i.v. dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2. NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-α overproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools.

  13. G Protein-Coupled Receptor-G-Protein βγ-Subunit Signaling Mediates Renal Dysfunction and Fibrosis in Heart Failure.

    Science.gov (United States)

    Kamal, Fadia A; Travers, Joshua G; Schafer, Allison E; Ma, Qing; Devarajan, Prasad; Blaxall, Burns C

    2017-01-01

    Development of CKD secondary to chronic heart failure (CHF), known as cardiorenal syndrome type 2 (CRS2), clinically associates with organ failure and reduced survival. Heart and kidney damage in CRS2 results predominantly from chronic stimulation of G protein-coupled receptors (GPCRs), including adrenergic and endothelin (ET) receptors, after elevated neurohormonal signaling of the sympathetic nervous system and the downstream ET system, respectively. Although we and others have shown that chronic GPCR stimulation and the consequent upregulated interaction between the G-protein βγ-subunit (Gβγ), GPCR-kinase 2, and β-arrestin are central to various cardiovascular diseases, the role of such alterations in kidney diseases remains largely unknown. We investigated the possible salutary effect of renal GPCR-Gβγ inhibition in CKD developed in a clinically relevant murine model of nonischemic hypertrophic CHF, transverse aortic constriction (TAC). By 12 weeks after TAC, mice developed CKD secondary to CHF associated with elevated renal GPCR-Gβγ signaling and ET system expression. Notably, systemic pharmacologic Gβγ inhibition by gallein, which we previously showed alleviates CHF in this model, attenuated these pathologic renal changes. To investigate a direct effect of gallein on the kidney, we used a bilateral ischemia-reperfusion AKI mouse model, in which gallein attenuated renal dysfunction, tissue damage, fibrosis, inflammation, and ET system activation. Furthermore, in vitro studies showed a key role for ET receptor-Gβγ signaling in pathologic fibroblast activation. Overall, our data support a direct role for GPCR-Gβγ in AKI and suggest GPCR-Gβγ inhibition as a novel therapeutic approach for treating CRS2 and AKI. Copyright © 2016 by the American Society of Nephrology.

  14. Radiological evaluation of renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Dorph, S [Herlev University Hospital, Copenhagen (Denmark). Dept. of Radiology

    1996-12-31

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.).

  15. Radiological evaluation of renal transplantation

    International Nuclear Information System (INIS)

    Dorph, S.

    1995-01-01

    Briefly discussed the nephrologic complications, episodes of rejection, acute tubular necrosis, cyclosporine, urologic complications, perirenal fluid collections, small asymptomatic hematomas, urinomas, abscesses, lymphocele, ureteral obstruction, cascular complications, imaging of the renal allograft, radionuclide imaging, ultrasonography, conventional radiography, cystograhy (8 refs.)

  16. Effect of additive renin inhibition with aliskiren on renal blood flow in patients with Chronic Heart Failure and Renal Dysfunction (Additive Renin Inhibition with Aliskiren on renal blood flow and Neurohormonal Activation in patients with Chronic Heart Failure and Renal Dysfunction)

    NARCIS (Netherlands)

    Schroten, Nicolas F.; Damman, Kevin; Hemmelder, Marc H.; Voors, Adriaan A.; Navis, Gerjan; Gaillard, Carlo A. J. M.; van Veldhuisen, Dirk J.; van Gilst, Wiek H.; Hillege, Hans L.

    AIMS: We examined the effect of the renin inhibitor, aliskiren, on renal blood flow (RBF) in patients with heart failure with reduced ejection fraction (HFREF) and decreased glomerular filtration rate (GFR). Renal blood flow is the main determinant of GFR in HFREF patients. Both reduced GFR and RBF

  17. Dietary exposure to cadmium at close to the current provisional tolerable weekly intake does not affect renal function among female Japanese farmers

    International Nuclear Information System (INIS)

    Horiguchi, Hyogo; Oguma, Etsuko; Sasaki, Satoshi; Miyamoto, Kayoko; Ikeda, Yoko; Machida, Munehito; Kayama, Fujio

    2004-01-01

    Dietary cadmium (Cd) exposure and renal tubular function were investigated in 1381 female farmers from five districts in Japan (Japanese Multi-centered Environmental Toxicant Study project; JMETS). Dietary Cd exposure of the five populations was assessed from the individual Cd concentrations of the rice consumed by the study participants and the quantities of rice consumed daily. The populations showed a sequential difference in dietary Cd exposure, ranging from a level as low as that of the general Japanese population to one close to the current provisional tolerable weekly intake (PTWI). The levels of urinary Cd excretion, an indicator of Cd accumulation in the kidneys, increased along the same sequential pattern as dietary Cd exposure. However, no differences were observed among the populations in levels of urinary α 1 -microglobulin and β 2 -microglobulin excretion, which are indicators of renal tubular function. These results indicate that the current PTWI is sufficient to prevent Cd-induced renal dysfunction among the general population

  18. Drug-interaction-induced hemodynamically mediated acute renal failure in postsurgical patient

    Directory of Open Access Journals (Sweden)

    Arup K Misra

    2014-01-01

    Full Text Available Acute renal failure is a life threatening condition. Nonsteroidal antiinflammatory drugs (NSAIDs and cephalosporins are widely used postoperative drugs. NSAID-induced acute renal failure has been reported in the past. In this case, drug interaction and decompensated state of the patient precipitate the condition. NSAIDs inhibit prostaglandins synthesis and thus aggravate ischemia to the kidney that is already facing volume crisis due to surgery. Due to renal dysfunction, plasma ceftriaxone level increases due to decrease clearance and it also acts as nephrotoxic by unknown mechanism. On the other hand, ceftriaxone on its interaction with diclofenac for renal tubular clearance also increases the level of diclofenac and thus further aggravate the ischemia. It is a reversible condition with excluding diclofenac from the treatment regimen and giving adequate hydration to the patient. This highlights the importance of hydration and knowledge of drugs interactions in a postsurgical patient.

  19. Heavy metals toxicity after acute exposure of cultured renal cells. Intracellular accumulation and repartition

    International Nuclear Information System (INIS)

    Khodja, Hicham; Carriere, Marie; Avoscan, Laure; Gouget, Barbara

    2005-01-01

    Lead (Pb), cadmium (Cd) and uranium (U) present no known biological function but are toxic in various concentration ranges. Pb and Cd lead generally to nephrotoxicity consisting in proximal renal tubular dysfunction and accumulation while U has been reported to induce chemical kidney toxicity, functional and histological damages being as well mainly observed in proximal tubule cells. This work address the question of Cd, Pb, and U cytotoxicity, intracellular accumulation and repartition after acute intoxication of renal proximal tubule epithelial cells. After cells exposure to different concentrations of metals for various times, morphological changes were observed and intracellular concentrations and distributions of toxic metals were specified by PIXE coupled to RBS. Cell viability, measured by biochemical tests, was used as toxicity indicator. A direct correlation between cytotoxicity and intracellular accumulation in renal epithelial cells have been established. Finally, intracellular Pb and U localizations were detected while Cd was found to be uniformly distributed in renal cells. (author)

  20. Age, renal dysfunction, cardiovascular disease, and antihyperglycemic treatment in type 2 diabetes mellitus: findings from the Renal Insufficiency and Cardiovascular Events Italian Multicenter Study.

    Science.gov (United States)

    Solini, Anna; Penno, Giuseppe; Bonora, Enzo; Fondelli, Cecilia; Orsi, Emanuela; Trevisan, Roberto; Vedovato, Monica; Cavalot, Franco; Cignarelli, Mauro; Morano, Susanna; Ferrannini, Ele; Pugliese, Giuseppe

    2013-08-01

    To assess the distribution of antihyperglycemic treatments according to age and renal function and its relationship with cardiovascular disease in type 2 diabetes mellitus (T2DM). Cross-sectional analysis. Nineteen hospital-based diabetes mellitus clinics in 2007 and 2008. Fifteen thousand seven hundred thirty-three individuals with T2DM from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study. Current antihyperglycemic treatments were recorded. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Albuminuria was measured using immunonephelometry or immunoturbidimetry. Prevalence of major acute cardiovascular events was calculated according to age quartiles, treatments, and categories of eGFR (1 = ≥90; 2 = 60-89; 3 = 30-59; and 4 = metformin or glitazones fell; percentage taking sulphonylureas and repaglinide rose, and percentage taking insulin remained stable. In eGFR categories 3 and 4, use of metformin was 41.4% and 14.5%, respectively, and that of sulphonylureas was 34.2% and 18.1%, respectively. Inappropriate prescription of these agents, especially sulphonylureas, increased with age. Metformin was independently associated with lower prevalence of cardiovascular disease for any age quartile and eGFR category than all other treatments. In real-life conditions, use of agents that are not recommended in elderly adults with diabetes mellitus with moderate to severe renal impairment is frequent, but metformin is associated with lower cardiovascular event rates even in these individuals. © 2013, Copyright the Authors Journal compilation © 2013, The American Geriatrics Society.

  1. Nephrotic Syndrome and Acute Renal Failure Apparently Induced by Sunitinib

    Directory of Open Access Journals (Sweden)

    Ying-Shou Chen

    2009-10-01

    Full Text Available We report a case of nephrotic syndrome and acute renal failure apparently induced by sunitinib. A 67-year-old man with a history of metastatic renal cell carcinoma presented with progressive kidney dysfunction with proteinuria, general edema, and body weight gain of 21 kg after undergoing 3 weeks of sunitinib therapy. The patient had taken no other over-the-counter medications, and all other possible causes of nephrotic syndrome were excluded. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 6, indicating a high probability that the observed presentations were associated with use of the drug. However, despite the discontinuation of sunitinib, his condition deteriorated, and hemodialysis was initiated for respiratory distress. A renal biopsy was performed, which revealed ischemic acute tubular necrosis with minimal change nephropathy. In conclusion, nephrologists and oncologists should be aware that nephrotic syndrome with ischemic acute tubular necrosis is a possible adverse effect of sunitinib. For early diagnosis of this condition and to avoid renal damage, we recommend differential diagnosis of serum creatinine and proteinuria in patients undergoing sunitinib therapy.

  2. Hepatocyte growth factor in renal failure: promise and reality.

    Science.gov (United States)

    Vargas, G A; Hoeflich, A; Jehle, P M

    2000-04-01

    Can science discover some secrets of Greek mythology? In the case of Prometheus, we can now suppose that his amazing hepatic regeneration was caused by a peptide growth factor called hepatocyte growth factor (HGF). Increasing evidence indicates that HGF acts as a multifunctional cytokine on different cell types. This review addresses the molecular mechanisms that are responsible for the pleiotropic effects of HGF. HGF binds with high affinity to its specific tyrosine kinase receptor c-met, thereby stimulating not only cell proliferation and differentiation, but also cell migration and tumorigenesis. The three fundamental principles of medicine-prevention, diagnosis, and therapy-may be benefited by the rational use of HGF. In renal tubular cells, HGF induces mitogenic and morphogenetic responses. In animal models of toxic or ischemic acute renal failure, HGF acts in a renotropic and nephroprotective manner. HGF expression is rapidly up-regulated in the remnant kidney of nephrectomized rats, inducing compensatory growth. In a mouse model of chronic renal disease, HGF inhibits the progression of tubulointerstitial fibrosis and kidney dysfunction. Increased HGF mRNA transcripts were detected in mesenchymal and tubular epithelial cells of rejecting kidney. In transplanted patients, elevated HGF levels may indicate renal rejection. When HGF is considered as a therapeutic agent in human medicine, for example, to stimulate kidney regeneration after acute injury, strategies need to be developed to stimulate cell regeneration and differentiation without an induction of tumorigenesis.

  3. Angiotensin II and Renal Tubular Ion Transport

    Directory of Open Access Journals (Sweden)

    Patricia Valles

    2005-01-01

    Evidence for the regulation of H+-ATPase activity in vivo and in vitro by trafficking/exocytosis has been provided. An additional level of H+-ATPase regulation via protein synthesis may be important as well. Recently, we have shown that both aldosterone and angiotensin II provide such a mechanism of regulation in vivo at the level of the medullary collecting tubule. Interestingly, in this part of the nephron, the effects of aldosterone and angiotensin II are not sodium dependent, whereas in the cortical collecting duct, both aldosterone and angiotensin II, by contrast, affect H+ secretion by sodium-dependent mechanisms.

  4. Genetics Home Reference: renal tubular dysgenesis

    Science.gov (United States)

    ... next step, angiotensin-converting enzyme (produced from the ACE gene) converts angiotensin I to angiotensin II. Angiotensin II ... proximal tubules) and other tissues. Mutations in the ACE , AGT , AGTR1 , or REN gene impair the production or function of angiotensin II, ...

  5. Central Diabetes Insipidus, Central Hypothyroidism, Renal Tubular ...

    African Journals Online (AJOL)

    readmitted to the hospital because of jaundice and failure to thrive, for which he was investigated and diagnosed to have central congenital hypothyroidism. Shortly thereafter, he was admitted to our institute with a history of vomiting, decreased oral intake, polyuria, and dehydration having lasted 5 days. He was investigated ...

  6. Preventive effect of pretreatment with intravenous nicorandil on contrast-induced nephropathy in patients with renal dysfunction undergoing coronary angiography (PRINCIPLE Study).

    Science.gov (United States)

    Ko, Young-Guk; Lee, Byoung-Kwon; Kang, Woong Chol; Moon, Jae-Youn; Cho, Yun Hyeong; Choi, Seong Hun; Hong, Myeong-Ki; Jang, Yangsoo; Kim, Jong-Youn; Min, Pil-Ki; Kwon, Hyuck-Moon

    2013-07-01

    To investigate the effect of pretreatment with intravenous nicorandil on the incidence of contrast-induced nephropathy (CIN) in patients with renal dysfunction undergoing coronary angiography. This randomized controlled multicenter study enrolled a total of 166 patients (nicorandil n=81; control n=85) with an estimated glomerular filtration rate 0.5 mg/dL increase or >25% rise in serum creatinine (SCr) concentration within 48 hours of contrast exposure compared to baseline. The final analysis included 149 patients (nicorandil n=73; control n=76). The baseline characteristics and the total volume of the used contrast (Iodixanol, 125.6±69.1 mL vs. 126.9±74.6 mL, p=0.916) were similar between the two groups. The incidence of CIN also did not differ between the nicorandil and control groups (6.8% vs. 6.6%, p=0.794). There was no difference between the two groups in the relative change in SCr from baseline to peak level within 48 hours after coronary angiography (-1.58±24.07% vs. 0.96±17.49%, p=0.464), although the nicorandil group showed less absolute change in SCr than the control group (-0.01±0.43 mg/mL vs. 0.02±0.31 mg/mL, p=0.005). Prophylactic intravenous infusion of nicorandil did not decrease the incidence of CIN in patients with renal dysfunction undergoing coronary angiography.

  7. Fanconi syndrome and chronic renal failure in a chronic hepatitis B monoinfected patient treated with tenofovir

    Directory of Open Access Journals (Sweden)

    Pedro Magalhães-Costa

    Full Text Available Tenofovir disoproxil fumarate (TDF is one of the first-line treatment options in chronic hepatitis B (CHB. Despite its efficacy in suppressing viral load and a high resistance barrier, long life maintenance therapy is required. Registration studies demonstrated TDF to be a safe drug. However, post-marketing experience reported cases of serious nephrotoxicity associated with hypophosphatemia, osteomalacia and, even more recently, Fanconi syndrome associated with TDF therapy in CHB monoinfected patients. Here the authors report a case of a 40 year-old male, with a CHB monoinfection, that, three years after TDF therapy, developed a progressive chronic kidney disease with a serious hypophosphatemia and a secondary osteomalacia that was manifested by bone pain and multiple bone fractures. Further investigational analyses unveiled a proximal renal tubular dysfunction, which fulfilled most of the diagnostic criteria for a Fanconi syndrome. After TDF withdrawal and oral supplementation with phosphate and calcitriol, his renal function stabilized (despite not returning to normal, proximal renal tubular dysfunction abnormalities resolved as well as osteomalacia. In conclusion, physicians should be aware that, in CHB monoinfected patients under TDF therapy, serious renal damage is possible and preventable by timely monitoring serum creatinine and phosphate.

  8. Blood transfusion improves renal oxygenation and renal function in sepsis-induced acute kidney injury in rats.

    Science.gov (United States)

    Zafrani, Lara; Ergin, Bulent; Kapucu, Aysegul; Ince, Can

    2016-12-20

    The effects of blood transfusion on renal microcirculation during sepsis are unknown. This study aimed to investigate the effect of blood transfusion on renal microvascular oxygenation and renal function during sepsis-induced acute kidney injury. Twenty-seven Wistar albino rats were randomized into four groups: a sham group (n = 6), a lipopolysaccharide (LPS) group (n = 7), a LPS group that received fluid resuscitation (n = 7), and a LPS group that received blood transfusion (n = 7). The mean arterial blood pressure, renal blood flow, and renal microvascular oxygenation within the kidney cortex were recorded. Acute kidney injury was assessed using the serum creatinine levels, metabolic cost, and histopathological lesions. Nitrosative stress (expression of endothelial (eNOS) and inducible nitric oxide synthase (iNOS)) within the kidney was assessed by immunohistochemistry. Hemoglobin levels, pH, serum lactate levels, and liver enzymes were measured. Fluid resuscitation and blood transfusion both significantly improved the mean arterial pressure and renal blood flow after LPS infusion. Renal microvascular oxygenation, serum creatinine levels, and tubular damage significantly improved in the LPS group that received blood transfusion compared to the group that received fluids. Moreover, the renal expression of eNOS was markedly suppressed under endotoxin challenge. Blood transfusion, but not fluid resuscitation, was able to restore the renal expression of eNOS. However, there were no significant differences in lactic acidosis or liver function between the two groups. Blood transfusion significantly improved renal function in endotoxemic rats. The specific beneficial effect of blood transfusion on the kidney could have been mediated in part by the improvements in renal microvascular oxygenation and sepsis-induced endothelial dysfunction via the restoration of eNOS expression within the kidney.

  9. Methylmercury inhibits gap junctional intercellular communication in primary cultures of rat proximal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Minoru; Sumi, Yawara [Department of Chemistry, St. Marianna University School of Medicine, Kawasagi (Japan); Kujiraoka, Toru [Department of Physiology, St. Marianna University School of Medicine, Kawasagi (Japan); Hara, Masayuki [Department of Anatomy, St. Marianna University School of Medicine, Kawasagi (Japan); Nakazawa, Hirokazu [Department of Chemistry, Faculty of Sciences, Meisei University (Japan)

    1998-03-01

    Methylmercury (MeHg) causes renal injury in addition to central and peripheral neuropathy. To clarify the mechanism of nephrotoxicity by MeHg, we investigated the effect of this compound on intercellular communication through gap junction channels in primary cultures of rat renal proximal tubular cells. Twenty minutes after exposure to 30 {mu}M MeHg, gap junctional intercellular communication (GJIC), which was assessed by dye coupling, was markedly inhibited before appearance of cytotoxicity. When the medium containing MeHg was exchanged with MeHg-free medium, dye coupling recovered abruptly. However, the dye-coupling was abolished again 30 min after replacement with control medium, and the cells were damaged. Intracellular calcium concentration, [Ca{sup 2+}]{sub i}, which modulates the function of gap junctions, significantly increased following exposure of the cells to 30 {mu}M MeHg and returned to control level following replacement with MeHg-free medium. These results suggest that the inhibiting effect of MeHg on GJIC is related to the change in [Ca{sup 2+}]{sub i}, and may be involved in the pathogenesis of renal dysfunction. (orig.) With 5 figs., 23 refs.

  10. Renal sonographic findings of type I glycogen storage disease in infancy and early childhood

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Chun-Chen; Lin, Shuan-Pei [Mackay Memorial Hospital, Department of Pediatrics, Taipei (Taiwan); Tsai, Jeng-Daw; Lee, Hung-Chang [Mackay Memorial Hospital, Department of Pediatrics, Taipei (Taiwan); Taipei Medical University, Department of Pediatrics, Taipei (Taiwan)

    2005-08-01

    Type I glycogen storage disease (GSD-I) is an inherited disorder affecting glycogenolysis and gluconeogenesis. The characteristic manifestations are hepatomegaly, hypoglycemia, hyperlacticacidemia, hyperuricemia, and hyperlipidemia. Renal disease is regarded as a long-term complication and is reported mainly in older patients. We report the renal manifestations and renal ultrasonographic findings of GSD-I in infancy and early childhood in order to assess the role of renal sonography in the diagnosis of GSD-I. We retrospectively reviewed our hospital's database for patients with GSD-I from January 1993 to September 2004. The records of five patients were reviewed for this study. These five patients were diagnosed when they were younger than 3 years old. Data extracted from the charts included the initial extrarenal and renal manifestations, laboratory data, and imaging studies. We analyzed the indications for, and results of, renal sonography. In addition to the clinical presentations and laboratory abnormalities, all five children had nephromegaly and increased echogenicity on ultrasonography on their first visit, although only a minor degree of tubular dysfunction was noted clinically. Three of these five patients had nephrocalcinosis or renal stones or both. Hyperechoic large kidneys, nephrocalcinosis, and renal stones are common in GSD-I. They can be present in early infancy. Abnormalities on renal sonography might suggest GSD-I in a patient with suspected inborn errors of metabolism. (orig.)

  11. The crosstalk between the kidney and the central nervous system: the role of renal nerves in blood pressure regulation.

    Science.gov (United States)

    Nishi, Erika E; Bergamaschi, Cássia T; Campos, Ruy R

    2015-04-20

    What is the topic of this review? This review describes the role of renal nerves as the key carrier of signals from the kidneys to the CNS and vice versa; the brain and kidneys communicate through this carrier to maintain homeostasis in the body. What advances does it highlight? Whether renal or autonomic dysfunction is the predominant contributor to systemic hypertension is still debated. In this review, we focus on the role of the renal nerves in a model of renovascular hypertension. The sympathetic nervous system influences the renal regulation of arterial pressure and body fluid composition. Anatomical and physiological evidence has shown that sympathetic nerves mediate changes in urinary sodium and water excretion by regulating the renal tubular water and sodium reabsorption throughout the nephron, changes in the renal blood flow and the glomerular filtration rate by regulating the constriction of renal vasculature, and changes in the activity of the renin-angiotensin system by regulating the renin release from juxtaglomerular cells. Additionally, renal sensory afferent fibres project to the autonomic central nuclei that regulate blood pressure. Hence, renal nerves play a key role in the crosstalk between the kidneys and the CNS to maintain homeostasis in the body. Therefore, the increased sympathetic nerve activity to the kidney and the renal afferent nerve activity to the CNS may contribute to the outcome of diseases, such as hypertension. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

  12. Tubular closure device

    International Nuclear Information System (INIS)

    Klahn, F.C.; Nolan, J.H.; Wills, C.

    1982-01-01

    This invention relates to a closure mechanism for closing openings such as the bore of a conduit and for releasably securing members within the bore. More particularly, this invention relates to a closure mechanism for tubular irradiation surveillance specimen assembly holders used in nuclear reactors

  13. Chronic kidney disease and worsening renal function in acute heart failure: different phenotypes with similar prognostic impact?

    Science.gov (United States)

    Palazzuoli, Alberto; Lombardi, Carlo; Ruocco, Gaetano; Padeletti, Margherita; Nuti, Ranuccio; Metra, Marco; Ronco, Claudio

    2016-12-01

    Nearly a third of patients with acute heart failure experience concomitant renal dysfunction. This condition is often associated with increased costs of care, length of hospitalisation and high mortality. Although the clinical impact of chronic kidney disease (CKD) has been well established, the exact clinical significance of worsening renal function (WRF) during the acute and post-hospitalisation phases is not completely understood. Therefore, it is still unclear which of the common laboratory markers are able to identify WRF at an early stage. Recent studies comparing CKD with WRF showed contradictory results; this could depend on a different WRF definition, clinical characteristics, haemodynamic disorders and the presence of prior renal dysfunction in the population enrolled. The current definition of acute cardiorenal syndrome focuses on both the heart and kidney but it lacks precise laboratory marker cut-offs and a specific diagnostic approach. WRF and CKD could represent different pathophysiological mechanisms in the setting of acute heart failure; the traditional view includes reduced cardiac output with systemic and renal vasoconstriction. Nevertheless, it has become a mixed model that encompasses both forward and backward haemodynamic dysfunction. Increased central venous pressure, renal congestion with tubular obliteration, tubulo-glomerular feedback and increased abdominal pressure are all potential additional contributors. The impact of WRF on patients who experience preserved renal function and individuals affected with CKD is currently unknown. Therefore it is extremely important to understand the origins, the clinical significance and the prognostic impact of WRF on CKD. © The European Society of Cardiology 2015.

  14. Cardio-renal syndrome

    OpenAIRE

    Gnanaraj, Joseph; Radhakrishnan, Jai

    2016-01-01

    Cardio-renal syndrome is a commonly encountered problem in clinical practice. Its pathogenesis is not fully understood. The purpose of this article is to highlight the interaction between the cardiovascular system and the renal system and how their interaction results in the complex syndrome of cardio-renal dysfunction. Additionally, we outline the available therapeutic strategies to manage this complex syndrome.

  15. 1H magnetic resonance spectroscopy of urine for the assessment of renal dysfunction in healthy pregnant women

    International Nuclear Information System (INIS)

    Majewska, A. K.; Ronin-Walknowska, E.; Plonka, T.; Borowiak, K. S.; Janus, T.

    2010-01-01

    Background. Pregnancy is associated with adaptive alterations affecting almost all organs and systems of the female body and is also a time when pathologies appear which would otherwise remain asymptomatic for many years. 1H Magnetic Resonance Spectroscopy ( 1H -MRS) of urine, a modern diagnostic method, can disclose discrete changes in organ function. It seemed interesting to search for pregnancy-dependent renal pathology in healthy women and thus prognosticate progression to overt disease after pregnancy. Objectives. To determine whether physiological pregnancy is accompanied by alterations in renal structures detectable by 1H-MRS of urine and to assess the type and reversibility of alterations. Material and Methods. Eighty women were enrolled in two groups: a study group (B) consisting of 40 healthy pregnant women and a control group (K) of 40 healthy nulligravida women. Enrollment criteria included normal health status, unrevealing physical and gynecological examination, and normal results of laboratory tests (complete blood count, urea, creatinine, uric acid, urinalysis). MRS of urine and laboratory tests were done in group B during each trimester (B1, B2, and B3, i.e. the 1 st , 2 nd , and 3 rd trimesters, respectively) and six weeks after delivery (BP). In group K, the tests were done only once. The spectra were processed with MestReC software and then multidimensional statistical analysis using Unscrambler software was performed. The results were presented as the distribution of the variables in multidimensional space. Results. The patterns in multidimensional space revealed a clustering of points when comparing the first and third trimesters of pregnancy and comparing the third trimester and the healthy non-pregnant women. Also, a partial clustering of points comparing healthy non-pregnant and pregnant women after the puerperium was noticeable. Conclusions. Differences in 1H -MRS profiles of urine between healthy pregnant and non-pregnant women reflect

  16. Ectopia renal cruzada con fusión, reflujo vesicoureteral y riñón ectópico afuncional:: informe de un caso Crossed renal ectopia with fusion, vesicoureteral reflux and dysfunctional ectopic kidney:: A case report

    Directory of Open Access Journals (Sweden)

    Sandalio Durán Álvarez

    2010-03-01

    due to the no-obstructive pelvic dilation or right kidney, crossed renal ectopia with fusion of dysfunctional left kidney and II degree bilateral vesicoureteral reflux from right kidney and of V degree from the crossed ectopic left kidney. At eleven months life he undergoes a lumbotomy and the hydronephrosis big sac was fused with lower pole of the right kidney. This big sac was resected and a low ureter ligature was carried out.

  17. Tubular transport and metabolism of cimetidine in chicken kidneys

    International Nuclear Information System (INIS)

    Rennick, B.; Ziemniak, J.; Smith, I.; Taylor, M.; Acara, M.

    1984-01-01

    Renal tubular transport and renal metabolism of [ 14 C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [ 14 C]CIM was actively transported at a rate 88% that of simultaneously infused p-aminohippuric acid, and its transport was saturable. The following organic cations competitively inhibited the tubular transport of [ 14 C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [ 14 C]thiamine, [ 14 C]amiloride and [ 14 C]tetraethylammonium. During CIM infusion, two renal metabolites, CIM sulfoxide and hydroxymethylcimetidine, were found in urine. When CIM sulfoxide was infused, its transport efficiency was 32% and not saturable. CIM sulfoxide did ot inhibit the simultaneous renal tubular transport of p-aminohippuric acid or tetraethylammonium. CIM is transported by the organic cation transport system and the kidney metabolizes CIM. Transport of CIM and other cationic drugs could produce a drug interaction to alter drug excretion

  18. The efficacy and safety of dual blockage of the renin-angiotensin-aldosterone system in patients with type 2 diabetes, hypertension and obesity without renal dysfunction

    Directory of Open Access Journals (Sweden)

    2012-09-01

    Full Text Available The purpose of the study was to evaluate the clinical efficacy and safety of dual RAAS blockage during treatment with angiotensin-converting enzyme (ACE inhibitors in combination with a direct renin inhibitor (PIR aliskiren versus combination therapy with ACE inhibitors and angiotensin receptor blocker II (ARB valsartan in patients with type 2 diabetes mellitus (T2DM, arterial hypertension (AH and obesity, without renal dysfunction. Materials and methods. The study included 26 patients with T2DM (10 men and 16 women, mean age 59,0±6,2 years with inadequate control of blood pressure (over 130 and/or 80 mm Hg on prior antihypertensive therapy and without renal dysfunctions (glomerular filtration rate (GFR> 60 ml/min/1, 73 m2 and the of albumin/creatinine (A/C ratio in the morning urine sample <10 mg/mol. After screening with the continuation of the initial therapy, including ACE inhibitors, 14 patients were added aliskiren 150–300 mg/day, 12 patients – valsartan 80–160 mg/day. Evaluation of the treatment effectiveness in terms of blood pressure (mean of three consecutive measurements in the sitting position and the parameters of renal function (serum creatinine and potassium, GFR, A/C ratio in the urine was performed at 4, 12 and 24 weeks of therapy. Results. In the group of patients treated with aliskiren, after 4 weeks of treatment a significant decrease in systolic and diastolic blood pressure (SBP and DBP, respectively was noted as compared to baseline: 146,1 and 138,9 mm Hg, p<0,05, 87,1 and 81,1 mm Hg, p <0,05, respectively; with systolic BP after 24 weeks of treatment decreased to 127,8 (-18,2 mm Hg, p<0,05, diastolic BP to 75,0 (-12, 1 mm Hg, p<0,05, the target blood pressure (≤130/80 mm Hg was achieved in 83% of patients. The group of patients treated with valsartan, after 4 weeks of therapy showed a significant reduction in systolic BP 148 and 141,6 mm Hg, p <0,05, diastolic BP - to 85,8 and 81,7 mm Hg, p=0,059; after 24 weeks

  19. Acute tubular necrosis in a patient with paroxysmal nocturnal hemoglobinuria

    Directory of Open Access Journals (Sweden)

    Eranga S Wijewickrama

    2013-01-01

    Full Text Available Acute renal failure (ARF is a well-recognized complication of paroxysmal nocturnal hemoglobinuria (PNH. The predominant mechanism is intravascular hemolysis resulting in massive hemoglobinuria ARF. We report a case of acute tubular necrosis (ATN developed in the absence of overwhelming evidence of intravascular hemolysis in a 21-year-old man with anemia, who was eventually diagnosed to have PNH. The patient presented with rapidly deteriorating renal functions in the background of iron deficiency anemia, which was attributed to reflux esophagitis. There was no clinical or laboratory evidence of intravascular hemolysis. Renal biopsy revealed ATN with deposition of hemosiderin in the proximal tubular epithelial cells. Diagnosis of PNH was confirmed with a positive Ham′s test and flow cytometry. Our case emphasizes the need to consider ATN as a possible cause for ARF in patients suspected to have PNH even in the absence of overwhelming evidence of intravascular hemolysis.

  20. Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

    Science.gov (United States)

    García-Blas, Sergio; Bonanad, Clara; Llàcer, Pau; Ventura, Silvia; Núñez, José María; Sánchez, Ruth; Chamorro, Carlos; Fácila, Lorenzo; de la Espriella, Rafael; Vaquer, Juana María; Cordero, Alberto; Roqué, Mercè; Ortiz, Víctor; Racugno, Paolo; Bodí, Vicent; Valero, Ernesto; Santas, Enrique; Moreno, María Del Carmen; Miñana, Gema; Carratalá, Arturo; Bondanza, Lourdes; Payá, Ana; Cardells, Ingrid; Heredia, Raquel; Pellicer, Mauricio; Valls, Guillermo; Palau, Patricia; Bosch, María José; Raso, Rafael; Sánchez, Andrés; Bertomeu-González, Vicente; Bertomeu-Martínez, Vicente; Montagud-Balaguer, Vicente; Albiach-Montañana, Cristina; Pendás-Meneau, Jezabel; Marcaida, Goitzane; Cervantes-García, Sonia; San Antonio, Rodolfo; de Mingo, Elisabet; Chorro, Francisco J; Sanchis, Juan; Núñez, Julio

    2017-12-01

    The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will inc