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Sample records for acidosis renal tubular

  1. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... are neutralized by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate ...

  2. Distal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA ... blood and excreting it into the urine. Distal renal tubular acidosis (Type I RTA) is caused by ...

  3. Renal tubular acidosis type 4 in pregnancy.

    Science.gov (United States)

    Jakes, Adam Daniel; Baynes, Kevin; Nelson-Piercy, Catherine

    2016-03-17

    We describe the clinical course of renal tubular acidosis (RTA) type 4 in pregnancy, which has not been previously published. Renal tubular acidosis type 4 is a condition associated with increased urinary ammonia secondary to hypoaldosteronism or pseudohypoaldosteronism. Pregnancy may worsen the hyperkalaemia and acidosis of renal tubular acidosis type 4, possibly through an antialdosterone effect. We advise regular monitoring of potassium and pH throughout pregnancy to ensure safe levels are maintained.

  4. 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...... (1.1%) had complete distal renal tubular acidosis and 14 (15.5%) incomplete distal renal tubular acidosis. Our results confirm that distal renal tubular acidification defects are associated with a more severe form of stone disease and make distal renal tubular acidosis one of the most frequent...... metabolic disturbances in renal stone formers. Distal renal tubular acidosis (dRTA) was relatively more common in female stone formers and most often found in patients with bilateral stone disease (36%). Since prophylactic treatment in renal stone formers with renal acidification defects is available...

  5. Distal Renal Tubular Acidosis and Calcium Nephrolithiasis

    Science.gov (United States)

    Moe, Orson W.; Fuster, Daniel G.; Xie, Xiao-Song

    2008-09-01

    Calcium stones are commonly encountered in patients with congenital distal renal tubular acidosis, a disease of renal acidification caused by mutations in either the vacuolar H+-ATPase (B1 or a4 subunit), anion exchanger-1, or carbonic anhydrase II. Based on the existing database, we present two hypotheses. First, heterozygotes with mutations in B1 subunit of H+-ATPase are not normal but may harbor biochemical abnormalities such as renal acidification defects, hypercalciuria, and hypocitraturia which can predispose them to kidney stone formation. Second, we propose at least two mechanisms by which mutant B1 subunit can impair H+-ATPase: defective pump assembly and defective pump activity.

  6. Type IV renal tubular acidosis associated with Alport's syndrome.

    OpenAIRE

    Tkácová, R.; Roland, R.; Böör, A.; Kovácová, A.; Lazúrová, I.; Tkác, I.; Hildebrand, T.; Sefara, P.

    1993-01-01

    A case of hereditary nephritis with mild reduction of renal function associated with renal tubular acidosis type IV is described. The patient was admitted with life-threatening hyperkalaemia. To our knowledge, type IV renal tubular acidosis has not been reported previously in association with Alport's syndrome in an adult patient.

  7. Renal histology and immunopathology in distal renal tubular acidosis.

    Science.gov (United States)

    Feest, T G; Lockwood, C M; Morley, A R; Uff, J S

    1978-11-01

    Renal biospy studies are reported from 10 patients with distal renal tubular acidosis (DRTA). On the biopsies from 6 patients who had associated immunological abnormalities immunofluorescent studies for immunoglobulins, complement, and fibrin were performed. Interstitial cellular infiltration and fibrosis were common findings in patients with and without immunological abnormalities, and were usually associated with nephrocalcinosis and/or recurrent urinary infection. No immune deposits were demonstrated in association with the renal tubules. This study shows that DRTA in immunologically abnormal patients is not caused by tubular deposition of antibody or immune complexes. The possibility of cell mediated immune damage is discussed.

  8. A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

    OpenAIRE

    C. Ripoli; Pinna, A.; Marras, S.; M.L. Fenu; Nurchi, A M

    2012-01-01

    Introduction: distal renal tubular acidosis (dRTA) presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions...

  9. 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......; 13 had incomplete and 1 had complete distal RTA. Distal RTA was found particularly in recurrent stone formers (17%), and especially in those with bilateral stone disease, where a distal renal tubular acidification defect was found in 50%. We have been unable to differentiate primary from secondary...... 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...

  10. [Primary distal renal tubular acidosis: a case report].

    Science.gov (United States)

    Abdallah, Jihene Ben; Charfeddine, Bassem; Braham, Imen; Neffati, Souhir; Othmen, Leila Ben; Letaief, Affef; Smach, Mohamed Ali; Bourfifa, Zoheier; Dridi, Hedi; Limem, Khalifa

    2011-01-01

    The primary distal renal tubular acidosis is characterized biochemically by the inability of the kidney to produce appropriately acid urine in the presence of systemic metabolic acidosis or after acid loading (e.g. ammonium chloride). It is secondary to defective excretion of H(+) by the cells of the collecting duct. We report the observation of the child MC, 4-year-old, for whom the association of polyuria-polydipsia syndrome, a failure to thrive, nephrolithiasis, hypercalciuria, and especially a high urine pH in the presence of metabolic acidosis did evoke diagnosis of distal renal tubular acidosis. An urine acidification test with ammonium chloride was performed, the urinary pH was always higher than 5.5, thus confirming the diagnosis. PMID:21464016

  11. Type 4 renal tubular acidosis in a kidney transplant recipient.

    Science.gov (United States)

    Kulkarni, Manjunath

    2016-02-01

    We report a case of a 66-year-old diabetic patient who presented with muscle weakness 2 weeks after kidney transplantation. Her immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and steroids. She was found to have hyperkalemia and normal anion gap metabolic acidosis. Tacrolimus levels were in therapeutic range. All other drugs such as beta blockers and trimethoprim - sulfamethoxazole were stopped. She did not respond to routine antikalemic measures. Further evaluation revealed type 4 renal tubular acidosis. Serum potassium levels returned to normal after starting sodium bicarbonate and fludrocortisone therapy. Though hyperkalemia is common in kidney transplant recipients, determining exact cause can guide specific treatment. PMID:27105603

  12. A distal renal tubular acidosis showing hyperammonemia and hyperlactacidemia

    Directory of Open Access Journals (Sweden)

    C. Ripoli

    2012-08-01

    Full Text Available Introduction: distal renal tubular acidosis (dRTA presents itself with variable clinical manifestations and often with late expressions that impact on prognosis. Case report: A 45-day-old male infant was admitted with stopping growth, difficult feeding and vomiting after meals. Clinical tests and labs revealed a type 1 renal tubular acidosis, even if the first blood tests showed ammonium and lactate increase. We had to exclude metabolic diseases before having a certain diagnosis. Conclusions: blood and urine investigations and genetic tests are fundamental to formulate dRTA diagnosis and to plan follow-up, according to possible phenotypic expressions of recessive and dominant autosomal forms in patients with dRTA.

  13. Late Metabolic Acidosis Caused by Renal Tubular Acidosis in Acute Salicylate Poisoning.

    Science.gov (United States)

    Sakai, Norihiro; Hirose, Yasuo; Sato, Nobuhiro; Kondo, Daisuke; Shimada, Yuko; Hori, Yasushi

    2016-01-01

    A 16-year-old man was transferred to our emergency department seven hours after ingesting 486 aspirin tablets. His blood salicylate level was 83.7 mg/dL. He was treated with fluid resuscitation and sodium bicarbonate infusion, and his condition gradually improved, with a decline in the blood salicylate level. However, eight days after admission, he again reported nausea, a venous blood gas revealed metabolic acidosis with a normal anion gap. The blood salicylate level was undetectable, and a urinalysis showed glycosuria, proteinuria and elevated beta-2 microglobulin and n-acetyl glucosamine levels, with a normal urinary pH despite the acidosis. We diagnosed him with relapse of metabolic acidosis caused by renal tubular acidosis. PMID:27181539

  14. 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. PMID:25193912

  15. Type IV renal tubular acidosis and spironolactone therapy in the elderly.

    OpenAIRE

    O'Connell, J. E.; Colledge, N. R.

    1993-01-01

    Spironolactone therapy is a well-known cause of hyperkalaemia, but in susceptible patient, it may also be associated with metabolic acidosis. We report a case of severe renal tubular acidosis (Type IV) with life-threatening hyperkalaemia caused by spironolactone, and discuss the mechanisms by which this may occur.

  16. Genetics Home Reference: renal tubular acidosis with deafness

    Science.gov (United States)

    ... Prevention: Hearing Loss in Children Centre for Genetics Education (Australia): Deafness and Hearing Loss Gallaudet University: Laurent Clerc National Deaf Education Center KidsHealth: What's Hearing Loss? MalaCards: renal tubular ...

  17. Medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome

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    Karunarathne Suneth

    2012-07-01

    Full Text Available Abstract Background Medullary nephrocalcinosis and distal renal tubular acidosis are closely associated and each can lead to the other. These clinical entities are rare in patients with nephrotic syndrome and polycythaemia is an unusual finding in such patients. We describe the presence of medullary nephrocalcinosis, distal renal tubular acidosis and polycythaemia in a patient with nephrotic syndrome due to minimal change disease. Proposed mechanisms of polycythaemia in patients with nephrotic syndrome and distal renal tubular acidosis include, increased erythropoietin production and secretion of interleukin 8 which in turn stimulate erythropoiesis. Case presentation A 22 year old Sri Lankan Sinhala male with nephrotic syndrome due to minimal change disease was investigated for incidentally detected polycythaemia. Investigations revealed the presence of renal tubular acidosis type I and medullary nephrocalcinosis. Despite extensive investigation, a definite cause for polycythaemia was not found in this patient. Treatment with potassium and bicarbonate supplementation with potassium citrate led to correction of acidosis thereby avoiding the progression of nephrocalcinosis and harmful effects of chronic acidosis. Conclusion The constellation of clinical and biochemical findings in this patient is unique but the pathogenesis of erythrocytosis is not clearly explained. The proposed mechanisms for erythrocytosis in other patients with proteinuria include increased erythropoietin secretion due to renal hypoxia and increased secretion of interleukin 8 from the kidney. This case illustrates that there may exist hitherto unknown connections between tubular and glomerular dysfunction in patients with nephrotic syndrome.

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

    OpenAIRE

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

    2010-01-01

    Background and Purpose: 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. Objectives: To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s) of action. Materials and Methods: Rats were anesthetized and the carotid artery was cannulated. Electrocardiogram ...

  19. Relationship between rickets and incomplete distal renal tubular acidosis in children

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    Oduwole Abiola O

    2010-08-01

    Full Text Available Abstract Background In the Sub Saharan Africa Rickets has now been established to be due primarily to calcium deficiency and sometimes in combination with vitamin D deficiency. The main thrust of management is calcium supplementation with or without vitamin D. An observation was made that some children with nutritional rickets do not respond to this management modality. The recently reported high prevalence of Incomplete Distal Renal Tubular Acidosis (idRTA in adults with osteoporosis as brought to fore the possibility of this being a possible cause of calcium wastage and therefore the poor response in these group of children with rickets. Aim To determine the prevalence of idRTA amongst a cohort of subjects with rickets To show a relationship between rickets and incomplete distal renal acidosis To determine the response of children with rickets and idRTA to addition of Shohl's solution to therapy Methodology Two separate cohorts of children with rickets performed the ammonium chloride loading test to detect those with incomplete renal tubular acidosis. Following identification for idRTA, Shohl's solution was added to therapy of calcium and vitamin D supplementation and their response compared to those without idRTA on calcium and vitamin D supplementation solely. Results 50 children with rickets aged from two to six years of age and composed of 29 females and 21males were investigated. Incomplete renal tubular acidosis was found in 38% of them. Prevalence of idRTA was highest amongst those aged 3-6 years of age. Those with idRTA had worse limb deformities, biochemical and radiological parameters than those who hadn't. Rate of response on those with idRTA treated with Shohl's solution was at par with those without idRTA. Conclusion Incomplete idRTA exist amongst children with rickets and should be looked out for in severe rickets and older children. Treatment of idRTA will lead to optimal response and healing of rickets.

  20. A case of quadriparesis due to renal tubular acidosis accompanied by vitamin D deficiency in Sjogren's syndrome

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    Can Huzmeli

    2016-08-01

    Full Text Available Renal tubular acidosis (RTA is metabolic acidosis disorder with a normal anion gap that occurs resulting from bicarbonate reabsorption or disorder in the hydrogen excretion from the kidney. A variety of tests are required to be administered in a stepwise fashion for the diagnosis and characterization of RTA. Correct diagnosis involves careful evaluation, including exclusion of other entities causing acidosis. The patients were treated with potassium and bicarbonate supplementation. A fifty-one years old female patient presented to the emergency department with quadriparesis dependent on hypokalemia and vitamin D deficiency, was diagnosed with distal renal tubular acidosis (dRTA combined with Sjogrens Syndrome (SS. We submitted this case in order to draw attention to the presentation of the RTA with SS. [Int J Res Med Sci 2016; 4(8.000: 3625-3628

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

    Directory of Open Access Journals (Sweden)

    Maneksh Delinda

    2010-01-01

    Full Text Available Background and Purpose : 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. Objectives : To demonstrate features of C. collinus toxicity in a rat model and to identify its mechanism(s of action. Materials and Methods : 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. Results : 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. Conclusions and Implications : 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.

  2. 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......-carbonic acidosis during fasting may be a pathophysilogical factor of both nephrolithiasis and disturbed bone metabolism in stone formers with iRTA....... significantly increased in iRTA compared with NUA and NC (P <0.01), indicating increased bone turnover in stone formers with iRTA. Stone formers with iRTA thus presented with disturbed calcium, bone and citrate metabolism--the same metabolic abnormalities which characterize classic type 1 RTA. Mild non...

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    Rink Nikki; Bitzan Martin; O'Gorman Gus; Nagel Mato; Torban Elena; Goodyer Paul

    2012-01-01

    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) r...

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

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    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. Ibuprofen-Induced Hypokalemia and Distal Renal Tubular Acidosis: A Patient’s Perceptions of Over-the-Counter Medications and Their Adverse Effects

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    Mark D. Salter

    2013-01-01

    Full Text Available We highlight a case of distal renal tubular acidosis secondary to ibuprofen and codeine use. Of particular interest in this case are the patient’s perception of over-the-counter (OTC medication use, her own OTC use prior to admission, and her knowledge of adverse reactions or side effects of these medications prior to taking them.

  8. 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.

  9. Endolymphatic sac enlargement in a girl with a novel mutation for distal renal tubular acidosis and severe deafness.

    Science.gov (United States)

    Nikki, Rink; Martin, Bitzan; Gus, O'Gorman; Mato, Nagel; Elena, Torban; Paul, Goodyer

    2012-01-01

    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. PMID:22966473

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

    DEFF Research Database (Denmark)

    Andersen, NN; Ladefoged, NN

    1991-01-01

    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...

  11. A single nucleotide polymorphism in kidney anion exchanger 1 gene is associated with incomplete type 1 renal tubular acidosis

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    Takeuchi, Takumi; Hattori-Kato, Mami; Okuno, Yumiko; Kanatani, Atsushi; Zaitsu, Masayoshi; Mikami, Koji

    2016-01-01

    Various conditions including distal renal tubular acidosis (dRTA) can induce stone formation in the kidney. dRTA is characterized by an impairment of urine acidification in the distal nephron. dRTA is caused by variations in genes functioning in intercalated cells including SLC4A1/AE1/Band3 transcribing two kinds of mRNAs encoding the Cl−/HCO3− exchanger in erythrocytes and that expressed in α-intercalated cells (kAE1). With the acid-loading test, 25% of urolithiasis patients were diagnosed with incomplete dRTA. In erythroid intron 3 containing the promoter region of kAE1, rs999716 SNP showed a significantly higher minor allele A frequency in incomplete dRTA compared with non-dRTA patients. The promoter regions of the kAE1 gene with the minor allele A at rs999716 downstream of the TATA box showed reduced promoter activities compared that with the major allele G. Patients with the A allele at rs999716 may express less kAE1 mRNA and protein in the intercalated cells, developing incomplete dRTA. PMID:27767102

  12. Atp6v0a4 knockout mouse is a model of distal renal tubular acidosis with hearing loss, with additional extrarenal phenotype

    OpenAIRE

    Elizabeth E. Norgett; Golder, Zoe J.; Lorente-Cánovas, Beatriz; Ingham, Neil; Steel, Karen P; Karet Frankl, Fiona E.

    2012-01-01

    Autosomal recessive distal renal tubular acidosis (dRTA) is a severe disorder of acid–base homeostasis, often accompanied by sensorineural deafness. We and others have previously shown that mutations in the tissue-restricted a4 and B1 subunits of the H+-ATPase underlie this syndrome. Here, we describe an Atp6v0a4 knockout mouse, which lacks the a4 subunit. Using β-galactosidase as a reporter for the null gene, developmental a4 expression was detected in developing bone, nose, eye, and skin, i...

  13. A novel heterozygous mutation in the ATP6V0A4 gene encoding the V-ATPase a4 subunit in an adult patient with incomplete distal renal tubular acidosis.

    Science.gov (United States)

    Imai, Eri; Kaneko, Shuzo; Mori, Takayasu; Okado, Tomokazu; Uchida, Shinichi; Tsukamoto, Yusuke

    2016-06-01

    A 40-year-old Japanese man who had a medical history of hypokalemic periodic paralysis 4 months prior was hospitalized to undergo a cholecystectomy. Hypokalemia, nephrocalcinosis and alkaluria suggesting distal renal tubular acidosis (dRTA) were detected, but metabolic acidosis was not evident. An ammonium chloride/furosemide-fludrocortisone/bicarbonate loading test demonstrated a remarkable disability in urinary H(+) excretion. A novel heterozygous mutation in the ATP6V0A4 gene encoding the vacuolar H(+)-ATPase (V-ATPase) a4 subunit p.S544L was detected. Among cases of V-ATPase a4 mutations, this is the first case in which a heterozygous mutation developed to an incomplete or latent form of dRTA. PMID:27274828

  14. 肾小管性酸中毒骨骼并发症的临床分析%Clinical analysis of bone complications in renal tubular acidosis

    Institute of Scientific and Technical Information of China (English)

    马毓华; 谢静远; 张春丽; 李晓; 沈平雁; 任红; 陈楠

    2013-01-01

    Objectives This study aims to investigate the features of bone complications secondary to renal tubular acidosis(RTA) and to further discuss the differences and characteristics of clinical manifestations between patients with primary RTA (PRTA) or RTA Secondary to Sj? gren's syndrome (SRTA) patients.Methods We retrospectively recruited 109 SRTA patients and 144 PRTA patients who admitted to our clinical center during 1996 and 2010.Baseline demographic,clinical features,laboratory examinations,outcomes and isotope bone density examination were collected and analyzed.Results The study included 144 PRTA and 109 SRTA patients.In PRTA group,there were 63 men and 81 women,the average age was 38 years; In SRTA group,there were 10 men and 99 women,the average age was 42 years..Within the PRTA group,bone pain and joint pain occured in 22 cases (15.3%),reduced bone mass was observed in 3 cases (2.1%),osteoporosis was found in 17 cases (11.8%).While in SRTA group,25 patients (22.9%) were reported to have bone pain and joint pain,and reduced bone mass was found in 10 cases (9.2%),9 cases (8.3%) of the patients had osteoporosis.Accordingly,more patients with bone disease were detected in SRTA group than in PRTA group (37.6% vs 24.3%,p < 0.05).The isotope bone density with lumbar spine T value of 9 PRTA patients is more than the SRTA patients.Additionally,SRTA patients had a lower lumber spine T value than PRTA patients (-0.53 ± 0.97 vs-1.65 ± 1.29,P < 0.05) by isotope bone density test which indicated a higher frequency and more severe bone disease occurred in RTA patients with Sj? gren 's syndrome than primary RTA patients.Conclusions Sjgren's syndrome is the most common cause of secondary RTA,the incidence and severity of bone disease was higher in RTA patients secondary to Sj? gren's syndrome than primary RTA patients,which aroused early diagnosis and clinical attentions.%目的 总结肾小管酸中毒(Renal Tubular Acidosis,RTA)骨骼并发症的特

  15. 儿童远端肾小管酸中毒1例%1 Case of Children With Distal Renal Tubular Acidosis

    Institute of Scientific and Technical Information of China (English)

    王瑞彬

    2015-01-01

    在儿科临床工作中,如果小儿有烦渴,多饮,多尿,腹泻,乏力,低钾血症,不明原因的代谢性酸中毒,生长发育落后,佝偻病,要考虑到本病,进一步检查血离子,血气,肾功能,尿常规,双肾超声,腕骨 X 线片。注意酸碱度,有无高氯性酸中毒,电解质紊乱,活动性佝偻病,肾结石,肾钙化。%In pediatric clinical work if the child has thirst, polydipsia, polyuria, diarrhea, fatigue, hypokalemia, metabolic acidosis, unexplained, growth retardation, rickets, taking into account the disease, further examination of blood ions, blood gas, kidney function, urine routine, renal ultrasound, Carpale x-ray. Note that the pH is hyperchloremic acidosis, electrolyte disorder, activity of rickets, kidney stones, renal calcification.

  16. Dietary Acid Load and Metabolic Acidosis in Renal Transplant Recipients

    NARCIS (Netherlands)

    Berg, van den Else; Engberink, M.F.; Brink, E.J.; Baak, van M.A.; Joosten, M.M.; Gans, R.O.B.; Navis, G.; Bakker, S.J.L.

    2012-01-01

    Background and objectives Acidosis is prevalent among renal transplant recipients (RTRs) and adversely affects cardiometabolic processes. Factors contributing to acidosis are graft dysfunction and immunosuppressive drugs. Little is known about the potential influence of diet on acidosis in RTRs. Thi

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Calcium citrate improves the epithelial-to-mesenchymal transition induced by acidosis in proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Maria José Rodriguez Cabalgante

    2012-12-01

    Full Text Available INTRODUCTION: Epithelial-to-mesenchymal transition (EMT is a key event in renal fibrosis. The aims of the study were to evaluate acidosis induced EMT, transforming-growth-factor (TGF β1 role and citrate effect on it. METHODS: HK2 cells (ATCC 2290 were cultured in DMEM/HAM F12 medium, pH 7.4. At 80% confluence, after 24 hr under serum free conditions, cells were distributed in three groups (24 hours: A Control: pH 7.4, B Acidosis: pH 7.0 and C Calcium citrate (0.2 mmol/L + pH 7.0. Change (Δ of intracellular calcium concentration, basal and after Angiotensin II (10-6M exposition, were measured to evaluate cellular performance. EMT was evaluated by the expression of α-smooth muscle actin (α-SMA and E-cadherin by immunocytochemistry and/or Western blot. TGF-β1 secretion was determined by ELISA in cell supernatant. RESULTS: At pH 7.0 HK2 cells significantly reduced E-cadherin and increased α-SMA expression (EMT. Supernatant TGF-β1 levels were higher than in control group. Calcium citrate decreased acidosis induced EMT and improved cells performance, without reduction of TGF-β production. CONCLUSIONS: Acidosis induces EMT and secretion of TGF-β1 in tubular proximal cells in culture and citrate improves cellular performance and ameliorates acidosis induced EMT.

  19. Differential uptake of Tc-99m DMSA and Tc-99m EC in renal tubular disorders: Report of two cases and review of the literature

    International Nuclear Information System (INIS)

    Tc-99m DMSA and Tc-99m EC studies are invaluable functional imaging modalities for renal structural and functional assessment. Normally, the relative renal function estimated by the two methods correlates well with each other. We here present two patients with renal tubular acidosis who showed impaired/altered DMSA uptake with normal EC renal dynamic study depicting the pitfall of DMSA imaging in tubular disorders. The two presented cases also depict distinct pattern of Tc-99m DMSA scintigraphic findings in patients with proximal and distal renal tubular acidosis, thus highlighting the factors affecting DMSA kinetics

  20. 桥本甲状腺炎合并干燥综合征肾小管酸中毒致低钾血症的临诊应对%Approach to the patient with hypokalemia caused by Hashimoto′s thyroiditis associated with primary Sjogren′s syndrome and renal tubular acidosis

    Institute of Scientific and Technical Information of China (English)

    张洪梅; 张伟伟; 李晓永; 陈寒蓓; 杨震; 钮忆欣; 苏青

    2016-01-01

    Hypokalemia is a common clinical symptom. It is quite important to clarify the cause of hypokalemia. Autoimmune thyroid disease and primary Sjogren syndrome ( pSS ) have a common genetic predisposition. The coexistence of both diseases is frequent. Renal tubular acidosis ( RTA) is one of the causes of hypokalemia, which can be primary and secondary to other diseases in etiology. Primary RTA is more common in children. As for adults, RTA is often secondary to pSS. In this paper, we reported a case of hypokalemia caused by Hashimoto’s thyroiditis associated with primary Sjogren’s syndrome and renal tubular acidosis in order to call attention to the special cause and treatment of hypokalemia.%低钾血症临床上较为常见,明确低血钾的原因至关重要。自身免疫性甲状腺疾病及干燥综合征有共同的遗传易感性,往往同时发生,肾小管性酸中毒为低钾血症病因之一,按病因分原发性和继发性,原发性多见于儿童,成人以继发性肾小管酸中毒多见,多继发于原发性干燥综合征。本文详细描述了1例桥本甲状腺炎合并干燥综合征肾小管酸中毒导致低钾血症的诊疗过程,以使临床医生重视低钾血症的病因,及时诊治。

  1. Inherited renal tubular defects with hypokalemia

    OpenAIRE

    Muthukrishnan J; Modi K; Kumar P; Jha Ratan

    2009-01-01

    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 hy...

  2. Sodium Bicarbonate Therapy in Patients with Metabolic Acidosis

    OpenAIRE

    Adeva-Andany, María M.; Carlos Fernández-Fernández; David Mouriño-Bayolo; Elvira Castro-Quintela; Alberto Domínguez-Montero

    2014-01-01

    Metabolic acidosis occurs when a relative accumulation of plasma anions in excess of cations reduces plasma pH. Replacement of sodium bicarbonate to patients with sodium bicarbonate loss due to diarrhea or renal proximal tubular acidosis is useful, but there is no definite evidence that sodium bicarbonate administration to patients with acute metabolic acidosis, including diabetic ketoacidosis, lactic acidosis, septic shock, intraoperative metabolic acidosis, or cardiac arrest, is beneficial ...

  3. Inherited renal tubular defects with hypokalemia

    Directory of Open Access Journals (Sweden)

    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.

  4. 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 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...... 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....

  5. 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

    showed impaired capacity for acidification of urine. The lowest urinary pH was 5.53 +/- 0.10 in 10 bypass patients and 4.76 +/- 0.06 in 6 controls. The corresponding values for standard bicarbonate in plasma were 15.0 +/- 0.3 mM and 15.8 +/- 0.3 mM. Glomerular filtration rate was identical in the two...

  6. 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.

  7. 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. PMID:26936872

  8. Renal pathophysiologic role of cortical tubular inclusion bodies.

    Science.gov (United States)

    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.

  9. 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 ...... of NaCl at the macula densa. This review describes the relevant aspects of local, intrarenal purinergic signaling and outlines its integrative concepts....

  10. The glomerulo-tubular junction: a target in renal diseases.

    Science.gov (United States)

    Lindop, G B M; Gibson, I W; Downie, T T; Vass, D; Cohen, E P

    2002-05-01

    Both global and segmental glomerulopathies may damage specific areas of the renal glomerulus. Diseases associated with glomerular hyperperfusion cause lesions at the vascular pole, while diseases associated with proteinuria often damage the tubular pole. Atubular glomeruli are now known to be plentiful in a variety of common renal diseases. These glomeruli are disconnected from their tubule at the tubular pole and therefore cannot participate in the production of urine. It is widely believed that the disconnection is a result of external compression by periglomerular fibrosis. However, the variable anatomy and cell populations within both the glomerulus and the beginning of the proximal tubule at the glomerulo-tubular junction may also have important roles to play in the response to damage at this sensitive site of the nephron.

  11. Acidosis láctica por metformina desencadenada por una insuficiencia renal aguda Metformin-induced lactic acidosis due to acute renal failure

    Directory of Open Access Journals (Sweden)

    M.D. Macías-Robles

    2011-04-01

    Full Text Available La acidosis láctica es una complicación grave pero infrecuente asociada al empleo de metformina. Se discuten los mecanismos fisiopatológicos implicados en la acidosis láctica, con especial atención al papel potencial del fármaco. Presentamos un caso severo de este efecto secundario de la metformina en una paciente con diabetes tipo 2 que ingresó en el Servicio de Urgencias Hospitalario por un cuadro de insuficiencia renal aguda. El diagnóstico quedó apoyado por unos niveles séricos elevados de la biguanida, procedimiento escasamente utilizado en la práctica clínica. El tratamiento consiste en suspender la administración del fármaco e iniciar de forma inmediata la hemodiálisis con bicarbonato, lo cual proporciona un tratamiento sintomático y etiológico al eliminar del suero tanto el lactato como el antidiabético oral. Los síntomas de la acidosis láctica por metformina son inespecíficos y el comienzo es sutil, lo que hace necesario un alto nivel de sospecha para establecer un diagnostico precoz.Lactic acidosis is a serious but uncommon side effect of metformin use. We discuss the pathophysiological mechanisms of lactic acidosis with particular regard to the role played by the drug as a potential cause of the entity. We report on a severe case of this kind of drug toxicity in a patient with type 2 diabetes mellitus, admitted to the emergency department with acute renal failure symptoms. The diagnosis was supported by elevated serum levels of the biguanide, a procedure scarcely used in clinical practice. The management of this complication consists in drug discontinuation and hemodialysis with bicarbonate that provides symptomatic and ethiological treatment by removing both the lactate and the hypoglycemic agent from the serum. Since the symptoms of metformin-associated lactic acidosis are unspecific and its onset is subtle, a high level of suspicion is needed to establish an early diagnosis.

  12. 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 demonstr

  13. Changes at the glomerulo-tubular junction in renal transplants.

    Science.gov (United States)

    Lee, S J; Howie, A J

    1988-12-01

    We studied by microscopy 377 biopsies, nephrectomies, and necropsy kidneys from 123 human renal transplants. We discovered two common abnormalities of the renal corpuscle, both affecting the glomerulo-tubular junction. Adhesion of the tip of the glomerular tuft to the origin of the tubule, as reported in various non-transplant glomerulopathies, was seen in 197 specimens (52 per cent). This change was common in material showing acute or chronic vascular rejection and glomerulopathy, and was almost universal in transplants that had been in place for over 1 year. Another change at the glomerulo-tubular junction, not previously highlighted, consisted of an infiltrate of lymphocytes or neutrophil polymorphs into the epithelium at the tubular origin. This change was seen in 145 specimens (38 per cent) and was associated with cellular rejection and ascending infection. These changes are of importance because they show two responses of the kidney to injury that involve the glomerulo-tubular junction and thus suggest that this part of the kidney has some specific properties that have been largely neglected up to now.

  14. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

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

    1988-01-01

    Thirteen patients with medullary sponge kidney underwent a short ammonium chloride loading test to investigate their renal acidification capacity. All but 1 presented with a history of recurrent renal calculi and showed bilateral widespread renal medullary calcification on X-ray examination. Nine...... patients had some form of renal acidification defect; 8 had the distal type of renal tubular acidosis, 2 the complete and 6 the incomplete form. One patient had proximal renal tubular acidosis. These findings, which suggest that renal acidification defects play an important role in the pathogenesis...... of renal calculi in medullary sponge kidney, have considerable therapeutic implications....

  15. Differentiation between renal allograft rejection and acute tubular necrosis by renal scan

    Energy Technology Data Exchange (ETDEWEB)

    Delmonico, F.L.; McKusick, K.A.; Cosimi, A.B.; Russell, P.S.

    1977-04-01

    The usefulness of the renal scan in diagnosing technical complications in the transplant patient is well established. However, the ability of the renal scan to differentiate between acute rejection and acute tubular necrosis has remained uncertain. We have evaluated the effectiveness of the /sup 99m/Tc DTPA computer-derived time-activity curve of renal cortical perfusion, as well as data obtained from scintillation camera images, in making such diagnoses. Fifteen patients with a clinical diagnosis of either acute rejection or acute tubular necrosis, or both, were studied retrospectively. Technetium scan diagnoses did not agree with the clinical assessment in nine of the patients. Thus selection of a course of treatment should not be based on data obtained from the scan alone.

  16. Spectrum of mutations in the renin-angiotensin system genes in autosomal recessive renal tubular dysgenesis

    DEFF Research Database (Denmark)

    Gribouval, Olivier; Morinière, Vincent; Pawtowski, Audrey;

    2012-01-01

    Autosomal recessive renal tubular dysgenesis (RTD) is a severe disorder of renal tubular development characterized by early onset and persistent fetal anuria leading to oligohydramnios and the Potter sequence, associated with skull ossification defects. Early death occurs in most cases from anuri...... and histological analyses and the characterization of the genetic defects allow genetic counseling and early prenatal diagnosis....

  17. Losartan attenuates renal interstitial fibrosis and tubular cell apoptosis in a rat model of obstructive nephropathy.

    Science.gov (United States)

    He, Ping; Li, Detian; Zhang, Beiru

    2014-08-01

    Ureteral obstruction leads to renal injury and progresses to irreversible renal fibrosis, with tubular cell atrophy and apoptosis. There is conflicting evidence concerning whether losartan (an angiotensin II type I receptor antagonist) mitigates renal interstitial fibrosis and renal tubular epithelial cell apoptosis following unilateral ureteral obstruction (UUO) in animal models. The aim of this study was to investigate the effect and mechanism of losartan on renal tubular cell apoptosis and renal fibrosis in a rat model of UUO. The rats were subjected to UUO by ureteral ligation and were treated with dimethyl sulfoxide (control) or losartan. The controls underwent sham surgery. The renal tissues were collected 3, 5, 7 and 14 days after surgery for measurement of various indicators of renal fibrosis. UUO increased the expression levels of α‑smooth muscle actin and collagen I, and the extent of renal tubular fibrosis and apoptosis in a time‑dependent manner. Losartan treatment partially attenuated these responses. Progression of renal interstitial fibrosis was accompanied by phosphorylation of signal transducer and activator of transcription 3 (STAT3) and altered the expression levels of two apoptosis‑related proteins (Bax and Bcl2). Losartan treatment also partially attenuated these responses. The results indicated that losartan attenuated renal fibrosis and renal tubular cell apoptosis in a rat model of UUO. This effect appeared to be mediated by partial blockage of STAT3 phosphorylation.

  18. 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...... capacities associated with increased renal vascular resistance. The polyuria seems to be due to the impaired reabsorption rate in the distal nephron segments....

  19. 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.

  20. Human embryonic stem cells differentiate into functional renal proximal tubular-like cells.

    Science.gov (United States)

    Narayanan, Karthikeyan; Schumacher, Karl M; Tasnim, Farah; Kandasamy, Karthikeyan; Schumacher, Annegret; Ni, Ming; Gao, Shujun; Gopalan, Began; Zink, Daniele; Ying, Jackie Y

    2013-04-01

    Renal cells are used in basic research, disease models, tissue engineering, drug screening, and in vitro toxicology. In order to provide a reliable source of human renal cells, we developed a protocol for the differentiation of human embryonic stem cells into renal epithelial cells. The differentiated stem cells expressed markers characteristic of renal proximal tubular cells and their precursors, whereas markers of other renal cell types were not expressed or expressed at low levels. Marker expression patterns of these differentiated stem cells and in vitro cultivated primary human renal proximal tubular cells were comparable. The differentiated stem cells showed morphological and functional characteristics of renal proximal tubular cells, and generated tubular structures in vitro and in vivo. In addition, the differentiated stem cells contributed in organ cultures for the formation of simple epithelia in the kidney cortex. Bioreactor experiments showed that these cells retained their functional characteristics under conditions as applied in bioartificial kidneys. Thus, our results show that human embryonic stem cells can differentiate into renal proximal tubular-like cells. Our approach would provide a source for human renal proximal tubular cells that are not affected by problems associated with immortalized cell lines or primary cells.

  1. Cadmium and cisplatin damage erythropoietin-producing proximal renal tubular cells

    Energy Technology Data Exchange (ETDEWEB)

    Horiguchi, Hyogo; Oguma, Etsuko; Kayama, Fujio [Jichi Medical School, Division of Environmental Medicine, Center for Community Medicine, Tochigi (Japan); Core Research for Evolutional Science and Technology, Japan Science Technology Corporation (CREST-JST), Saitama (Japan)

    2006-10-15

    The concomitant manifestations of proximal renal tubular dysfunction and anemia with erythropoietin (Epo) deficiency observed in chronic cadmium (Cd) intoxication, such as Itai-itai disease, suggest a close local correlation between the Cd-targeted tubular cells and Epo-producing cells in the kidney. Therefore, we investigated the local relationship between hypoxia-induced Epo production and renal tubular injury in rats injected with Cd at 2 mg/kg twice a week for 8 months. Anemia due to insufficient production of Epo was observed in Cd-intoxicated rats. In situ hybridization detected Epo mRNA expression in the proximal renal tubular cells of hypoxic rats without Cd intoxication, and the Cd-intoxicated rats showed atrophy of Epo-expressing renal tubules and replacement of them with fibrotic tissue. A single dose of cisplatin at 8 mg/kg, which can induce clinical manifestations similar to those of Cd including renal tubular damage along with Epo-deficient anemia, resulted in Epo-expressing renal tubule destruction on day 4. These data indicate that Cd and cisplatin would induce anemia through the direct injury of the proximal renal tubular cells that are responsible for Epo production. (orig.)

  2. Low-flow CO2 removal integrated into a renal-replacement circuit can reduce acidosis and decrease vasopressor requirements

    Science.gov (United States)

    2013-01-01

    Introduction Lung-protective ventilation in patients with ARDS and multiorgan failure, including renal failure, is often paralleled with a combined respiratory and metabolic acidosis. We assessed the effectiveness of a hollow-fiber gas exchanger integrated into a conventional renal-replacement circuit on CO2 removal, acidosis, and hemodynamics. Methods In ten ventilated critically ill patients with ARDS and AKI undergoing renal- and respiratory-replacement therapy, effects of low-flow CO2 removal on respiratory acidosis compensation were tested by using a hollow-fiber gas exchanger added to the renal-replacement circuit. This was an observational study on safety, CO2-removal capacity, effects on pH, ventilator settings, and hemodynamics. Results CO2 elimination in the low-flow circuit was safe and was well tolerated by all patients. After 4 hours of treatment, a mean reduction of 17.3 mm Hg (−28.1%) pCO2 was observed, in line with an increase in pH. In hemodynamically instable patients, low-flow CO2 elimination was paralleled by hemodynamic improvement, with an average reduction of vasopressors of 65% in five of six catecholamine-dependent patients during the first 24 hours. Conclusions Because no further catheters are needed, besides those for renal replacement, the implementation of a hollow-fiber gas exchanger in a renal circuit could be an attractive therapeutic tool with only a little additional trauma for patients with mild to moderate ARDS undergoing invasive ventilation with concomitant respiratory acidosis, as long as no severe oxygenation defects indicate ECMO therapy. PMID:23883472

  3. Perfluorooctanesulfonate Mediates Renal Tubular Cell Apoptosis through PPARgamma Inactivation.

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    Li-Li Wen

    Full Text Available Perfluorinated chemicals (PFCs are ubiquitously distributed in the environments including stainless pan-coating, raincoat, fire extinguisher, and semiconductor products. The PPAR family has been shown to contribute to the toxic effects of PFCs in thymus, immune and excretory systems. Herein, we demonstrated that perfluorooctanesulfonate (PFOS caused cell apoptosis through increasing ratio of Bcl-xS/xL, cytosolic cytochrome C, and caspase 3 activation in renal tubular cells (RTCs. In addition, PFOS increased transcription of inflammatory cytokines (i.e., TNFα, ICAM1, and MCP1 by NFκB activation. Conversely, PFOS reduced the mRNA levels of antioxidative enzymes, such as glutathione peroxidase, catalase, and superoxide dismutase, as a result of reduced PPARγ transactivational activity by using reporter and chromatin immuoprecipitation (ChIP assays. PFOS reduced the protein interaction between PPARγ and PPARγ coactivator-1 alpha (PGC1α by PPARγ deacetylation through Sirt1 upregulation, of which the binding of PPARγ and PGC1α to a peroxisome proliferator response element (PPRE in the promoter regions of these antioxidative enzymes was alleviated in the ChIP assay. Furthermore, Sirt1 also deacetylated p53 and then increased the binding of p53 to Bax, resulting in increased cytosolic cytochrome C. The effect of PPARγ inactivation by PFOS was validated using the PPARγ antagonist GW9662, whereas the adverse effects of PFOS were prevented by PPARγ overexpression and activators, rosiglitozone and L-carnitine, in RTCs. The in vitro finding of protective effect of L-carnitine was substantiated in vivo using Balb/c mice model subjected to PFOS challenge. Altogether, we provide in vivo and in vitro evidence for the protective mechanism of L-carnitine in eliminating PFOS-mediated renal injury, at least partially, through PPARγ activation.

  4. Pathology of the idiopathic renal tubular proteinuria evaluated by the renal scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takeshi; Saotome, Yumiko; Fuse, Tomoko [Tokyo Fussa Hospital (Japan)] [and others

    1998-03-01

    In 10 patients matching to the temporal standards of the idiopathic renal tubular proteinuria disease, renal scintigrams using {sup 99m}Tc-dimercaptosuccinic acid (DMSA) and {sup 99m}Tc-mercaptoacetyl-glycylglycylglycine (MAG3) were performed. All patients were boys with age of 11.9 years and the median concentration of {beta}{sub 2}-macroglobulin in urea was 69,150 {mu}g/l. In the DMSA scintigram, there was no abnormalities of accumulation in the morphology, but %uptake of DMSA in all patients decreased, and that ranges from 2.8 to 10.9% per kidney, equivalent to 1/3 to 1/5 of the normal healthy controls. On the other hand, in the MAG3 scintigram, the vessel and the functional phases seemed to be normal except one case, but the excretion phase was delayed except one case. This disease had the impairment in the active transport on the vessel cavity side of the distal renal tubular cells, and will show in future symptoms other than the low molecular weight proteinuria. It is important to observe carefully the development of symptoms. (K.H.)

  5. 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

  6. Reality of severe metformin-induced lactic acidosis in the absence of chronic renal impairment.

    NARCIS (Netherlands)

    Bruijstens, L.A.; Luin, M. van; Buscher-Jungerhans, P.M.; Bosch, F.H.

    2008-01-01

    BACKGROUND: Lactic acidosis in metformin use is a widely recognised but rare side effect. Case reports usually describe elderly patients with conditions which in themselves can cause lactic acidosis or with known contraindications to metformin. We present cases of an elderly woman, a younger woman a

  7. Intragraft Tubular Vimentin and CD44 Expression Correlate With Long-Term Renal Allograft Function and Interstitial Fibrosis and Tubular Atrophy

    NARCIS (Netherlands)

    J. Kers; Y.C. Xu-Dubois; E. Rondeau; N. Claessen; M.M. Idu; J.J.T.H. Roelofs; F.J. Bemelman; R.J.M. ten Berge; S. Florquin

    2010-01-01

    Background. Development of interstitial fibrosis and tubular atrophy (IF/TA) is the main histologic feature involved in renal allograft deterioration. The aim of this study was to validate whether de novo tubular expression of CD44 (transmembrane glycoprotein) and vimentin (mesenchymal cell marker),

  8. Renal Cortical Lactate Dehydrogenase: A Useful, Accurate, Quantitative Marker of In Vivo Tubular Injury and Acute Renal Failure.

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    Richard A Zager

    Full Text Available Studies of experimental acute kidney injury (AKI are critically dependent on having precise methods for assessing the extent of tubular cell death. However, the most widely used techniques either provide indirect assessments (e.g., BUN, creatinine, suffer from the need for semi-quantitative grading (renal histology, or reflect the status of residual viable, not the number of lost, renal tubular cells (e.g., NGAL content. Lactate dehydrogenase (LDH release is a highly reliable test for assessing degrees of in vitro cell death. However, its utility as an in vivo AKI marker has not been defined. Towards this end, CD-1 mice were subjected to graded renal ischemia (0, 15, 22, 30, 40, or 60 min or to nephrotoxic (glycerol; maleate AKI. Sham operated mice, or mice with AKI in the absence of acute tubular necrosis (ureteral obstruction; endotoxemia, served as negative controls. Renal cortical LDH or NGAL levels were assayed 2 or 24 hrs later. Ischemic, glycerol, and maleate-induced AKI were each associated with striking, steep, inverse correlations (r, -0.89 between renal injury severity and renal LDH content. With severe AKI, >65% LDH declines were observed. Corresponding prompt plasma and urinary LDH increases were observed. These observations, coupled with the maintenance of normal cortical LDH mRNA levels, indicated the renal LDH efflux, not decreased LDH synthesis, caused the falling cortical LDH levels. Renal LDH content was well maintained with sham surgery, ureteral obstruction or endotoxemic AKI. In contrast to LDH, renal cortical NGAL levels did not correlate with AKI severity. In sum, the above results indicate that renal cortical LDH assay is a highly accurate quantitative technique for gauging the extent of experimental acute ischemic and toxic renal injury. That it avoids the limitations of more traditional AKI markers implies great potential utility in experimental studies that require precise quantitation of tubule cell death.

  9. p-Cresol mediates autophagic cell death in renal proximal tubular cells.

    Science.gov (United States)

    Lin, Hsin-Hung; Huang, Chiu-Ching; Lin, Tze-Yi; Lin, Ching-Yuang

    2015-04-01

    Higher serum level of p-cresol (PC) in chronic kidney disease (CKD) patients has been linked with CKD progression. The toxic effect of PC on diverse cells has been reported by prior studies, except for renal tubular cells. Both autophagy and apoptosis contribute to renal tubular cell death, yet evidence of its response to PC is limited and their crosstalk is still unclear. Autophagy is an important cellular process involved in toxin-induced cell death. Renal tubular cell death in tubular injury is thought to be one of the key events causing the progression of CKD. Thus, we treated rat (NRK-52E) and human (HRPTEC) renal proximal tubular cells (RPTC) with PC and found the cell proliferation was significantly decreased. Cell apoptosis was significantly increased and accompanied with the activation of autophagy as evidenced by increases in LC3-II, beclin 1 and Atg 4. We also found an increase of p62 by c-Jun activation. p62 accumulation could mediate the activation of caspase 8-dependent cell apoptosis. Conversely, knockdown of p62 by siRNA of p62 had the opposite effect by arresting LC3-II accumulation and promoting increasing cell viability. We conclude that PC triggered autophagic RPTC death via JNK-mediated p62 accumulation and then activated caspase 8-dependent cell death pathway. PC can be considered as one of the key events causing progression of CKD, which might affect drug disposition in CKD cases. PMID:25668154

  10. 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

  11. Metabolic acidosis

    Science.gov (United States)

    Acidosis - metabolic ... Metabolic acidosis occurs when the body produces too much acid. It can also occur when the kidneys are not ... the body. There are several types of metabolic acidosis. Diabetic acidosis develops when acidic substances, known as ...

  12. 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 tubulo-interstitia

  13. Gender Difference of Cadmium-induced Renal Tubular Dysfunction for Inhabitants in Toyama,Japan

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Objective The aim of the present study was to compare the gender differencefor cadmium-induced renal tubular dysfunction between the male and female inhabitants. MethodsUrinary β2-microglobulin was measured in 299 male (94%) and 342 female (92%) inhabitants aged54 - 72 years,and the development of renal tubular dysfunction for 11 years was studied in the 62married couples from them. Results A significantly higher cumulative incidence was found in bothmen and women in cudmium-polluted area,showing 68. 4% in men and 64.8% in women compared to15.3 % in men and 5.9 % in women in the reference areas. Relative risk of renal tubular dysfunctionin females (11.0) was higher than males (4.5). The ratios of urinary β2-nicroglobulin and glucosewere higher in women than those in men in both the cadmium-polluted areas and the reference areas.Conclusion Although almost identical incidences were detected between men and wonen, the changesin excretion of β2-microglobulin and glucose was greater in women than those in men. These findings sug-gest that renal tubular dysfunction might be more progressive in women than that in men.

  14. Effect of adrenomedullin on rat renal tubular epithelial cell apoptosis induced by hypoxiareoxygenation and its mechanism

    Institute of Scientific and Technical Information of China (English)

    苏晓乐

    2013-01-01

    Objective To investigate the effect of adrenomedullin on rat renal tubular epithelial cell line (NRK-52E) apoptosis induced by hypoxia-reoxygenation (HR) injury and its mechanism.Methods NRK-52E cells were cultured and randomly allotted to the following 4 groups:control group,HR group,empty plasmid+HR group,

  15. Nephrotic syndrome and multiple tubular defects in children: an early sign of focal segmental glomerulosclerosis.

    Science.gov (United States)

    McVicar, M; Exeni, R; Susin, M

    1980-12-01

    The nephrotic syndrome is rarely associated with renal tubular defects, and the combination has been reported only in association with advanced renal insufficiency. We report here five children with nephrotic syndrome and multiple tubular defects which evolved when glomular filtration rate ranged between 56 and 90 ml/minute/1.73 m2. The tubular defects were first noted at 3, 4, 4, 7, and 22 months after the onset of the nephrotic syndrome, and renal glycosuria was the first sign in all five children. Glycosuria was intermittent in three patients, constant in two, and ceased with loss of kidney function. Four patients had hyperaminoaciduria and renal tubular acidosis (two of four tested had distal renal tubular acidosis). Three patients had decreased tubular reabsorption of phosphorus and defective maximum concentrating capacity. All five had focal segmental glomerulosclerosis proven by renal biopsy. Over a follow-up period of seven years, all of the children have developed advanced renal insufficiency, four of the five have required dialysis or transplantation within 21 to 72 months after onset, and one has stabilized renal function at 35 ml/minute/1.73 m2. The one patient receiving a kidney transplant has had recurrence of focal segmental glomerulosclerosis in the transplanted kidney and became nephrotic with three subsequent transplants. Our experience suggests that the nephrotic syndrome associated with tubular defects in children forms a subgroup of focal segmental glomerulosclerosis, with rapid progression to renal insufficiency and the potential for recurrence of the lesion in the transplanted kidney.

  16. 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.

  17. Protection of Renal Tubular Cells by Antioxidants: Current Knowledge and New Trends

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    Azar Baradaran

    2015-01-01

    Full Text Available Acute renal damage mainly develops following toxic or ischemic insults and is defined as acute. These damages have largely been attributed to oxidative stress. Recently much attention has been directed toward decreased renal tubular cell regeneration during tubular cell injury. Antioxidants have recently been the focus of researchers and scientists for prevention and treatment of various oxidative stress-related conditions, including renal toxicities. Although free radicals are known to contribute in kidney injury and abundant researches, particularly laboratory trials, have shown the beneficial effects of antioxidants against these complications, long term clinical trials do not uniformly confirm this matter,especially for single antioxidant consumption such as vitamin C. The aim of this paper is to discuss the possible explanation of this matter.

  18. Renal hyperconcentration of /sup 99m/Tc-HEDP in experimental acute tubular necrosis

    International Nuclear Information System (INIS)

    The effect of transient renal ischemia on renal concentration and distribution of /sup 99m/Tc-HEDP, /sup 99m/Tc-DMSA, and /sup 99m/Tc-DTPA was compared in rabbits with acute tubular necrosis. Scintigrams were obtained after injection in normal rabbits or ones with unilateral or bilateral ischemia. /sup 99m/Tc-HEDP concentration in ischemic tissue was 8 to 18 times normal 1 to 4 hrs after injection, and the resulting images delineated the morphological changes in the ischemic kidneys more accurately than those obtained with DMSA or DTPA. Calcium concentration in the ischemic kidneys increased sixfold. /sup 99m/Tc-HEDP may be useful in evaluation of renal failure secondary to tubular injury

  19. Shear Stress-Induced Alteration of Epithelial Organization in Human Renal Tubular Cells.

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    Damien Maggiorani

    Full Text Available Tubular epithelial cells in the kidney are continuously exposed to urinary fluid shear stress (FSS generated by urine movement and recent in vitro studies suggest that changes of FSS could contribute to kidney injury. However it is unclear whether FSS alters the epithelial characteristics of the renal tubule. Here, we evaluated in vitro and in vivo the influence of FSS on epithelial characteristics of renal proximal tubular cells taking the organization of junctional complexes and the presence of the primary cilium as markers of epithelial phenotype. Human tubular cells (HK-2 were subjected to FSS (0.5 Pa for 48 h. Control cells were maintained under static conditions. Markers of tight junctions (Claudin-2, ZO-1, Par polarity complex (Pard6, adherens junctions (E-Cadherin, β-Catenin and the primary cilium (α-acetylated Tubulin were analysed by quantitative PCR, Western blot or immunocytochemistry. In response to FSS, Claudin-2 disappeared and ZO-1 displayed punctuated and discontinuous staining in the plasma membrane. Expression of Pard6 was also decreased. Moreover, E-Cadherin abundance was decreased, while its major repressors Snail1 and Snail2 were overexpressed, and β-Catenin staining was disrupted along the cell periphery. Finally, FSS subjected-cells exhibited disappeared primary cilium. Results were confirmed in vivo in a uninephrectomy (8 months mouse model where increased FSS induced by adaptive hyperfiltration in remnant kidney was accompanied by both decreased epithelial gene expression including ZO-1, E-cadherin and β-Catenin and disappearance of tubular cilia. In conclusion, these results show that proximal tubular cells lose an important number of their epithelial characteristics after long term exposure to FSS both in vitro and in vivo. Thus, the changes in urinary FSS associated with nephropathies should be considered as potential insults for tubular cells leading to disorganization of the tubular epithelium.

  20. Mesenchymal stem cells modulate albumin-induced renal tubular inflammation and fibrosis.

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    Hao Jia Wu

    Full Text Available Bone marrow-derived mesenchymal stem cells (BM-MSCs have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF and TNFα-stimulating gene (TSG-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6.

  1. Mesenchymal Stem Cells Modulate Albumin-Induced Renal Tubular Inflammation and Fibrosis

    Science.gov (United States)

    Wu, Hao Jia; Yiu, Wai Han; Li, Rui Xi; Wong, Dickson W. L.; Leung, Joseph C. K.; Chan, Loretta Y. Y.; Zhang, Yuelin; Lian, Qizhou; Lin, Miao; Tse, Hung Fat; Lai, Kar Neng; Tang, Sydney C. W.

    2014-01-01

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) have recently shown promise as a therapeutic tool in various types of chronic kidney disease (CKD) models. However, the mechanism of action is incompletely understood. As renal prognosis in CKD is largely determined by the degree of renal tubular injury that correlates with residual proteinuria, we hypothesized that BM-MSCs may exert modulatory effects on renal tubular inflammation and epithelial-to-mesenchymal transition (EMT) under a protein-overloaded milieu. Using a co-culture model of human proximal tubular epithelial cells (PTECs) and BM-MSCs, we showed that concomitant stimulation of BM-MSCs by albumin excess was a prerequisite for them to attenuate albumin-induced IL-6, IL-8, TNF-α, CCL-2, CCL-5 overexpression in PTECs, which was partly mediated via deactivation of tubular NF-κB signaling. In addition, albumin induced tubular EMT, as shown by E-cadherin loss and α-SMA, FN and collagen IV overexpression, was also prevented by BM-MSC co-culture. Albumin-overloaded BM-MSCs per se retained their tri-lineage differentiation capacity and overexpressed hepatocyte growth factor (HGF) and TNFα-stimulating gene (TSG)-6 via P38 and NF-κB signaling. Albumin-induced tubular CCL-2, CCL-5 and TNF-α overexpression were suppressed by recombinant HGF treatment, while the upregulation of α-SMA, FN and collagen IV was attenuated by recombinant TSG-6. Neutralizing HGF and TSG-6 abolished the anti-inflammatory and anti-EMT effects of BM-MSC co-culture in albumin-induced PTECs, respectively. In vivo, albumin-overloaded mice treated with mouse BM-MSCs had markedly reduced BUN, tubular CCL-2 and CCL-5 expression, α-SMA and collagen IV accumulation independent of changes in proteinuria. These data suggest anti-inflammatory and anti-fibrotic roles of BM-MSCs on renal tubular cells under a protein overloaded condition, probably mediated via the paracrine action of HGF and TSG-6. PMID:24646687

  2. Novel Tubular Biomarkers Predict Renal Progression in Type 2 Diabetes Mellitus: A Prospective Cohort Study

    Science.gov (United States)

    Aramsaowapak, Kasemsan; Tangwonglert, Theerasak; Supasyndh, Ouppatham

    2016-01-01

    Background. Tubulointerstitial injury is both a key feature of diabetic nephropathy and an important predictor of renal dysfunction. Novel tubular biomarkers related to renal injury in diabetic nephropathy could improve risk stratification and prediction. Methods. A total of 303 type 2 diabetic patients were followed up. The baseline urine values of cystatin-C to creatinine ratio (UCCR), angiotensinogen to creatinine ratio (UANG), NGAL to creatinine ratio (UNGAL), and KIM-1 to creatinine ratio (UKIM-1) were measured. The primary outcome was a decline in estimated GFR of ≥25% yearly from baseline. Results. Urine tubular biomarkers of UCCR, UANG, UNGAL, and UKIM-1 were significantly higher according to the degree of albuminuria and all were significantly higher among patients with rapid decline in estimated GFR of ≥25% yearly from baseline. All biomarkers predicted primary outcomes with ROC for UCCR of 0.72; 95% CI 0.64–0.79, for UANG of 0.71; 95% CI 0.63–0.79, for UNGAL of 0.64; 95% CI 0.56–0.72, and for UKIM-1 of 0.71; 95% CI 0.63–0.79. Using multivariate Cox regression analysis, the number of patients with rapid renal progression was higher among those in the upper quartiles of all biomarkers than in those in the lower quartiles. Conclusions. Type 2 diabetic patients with high levels of urine tubular biomarkers had a more rapid decline in renal function. PMID:27672664

  3. 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

  4. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

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    Ryuji Morizane

    Full Text Available Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

  5. Kidney specific protein-positive cells derived from embryonic stem cells reproduce tubular structures in vitro and differentiate into renal tubular cells.

    Science.gov (United States)

    Morizane, Ryuji; Monkawa, Toshiaki; Fujii, Shizuka; Yamaguchi, Shintaro; Homma, Koichiro; Matsuzaki, Yumi; Okano, Hideyuki; Itoh, Hiroshi

    2014-01-01

    Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be induced in vitro because of the complexity of kidney structures and the diversity of kidney-component cells. Here, we describe a method of inducing renal tubular cells from mouse embryonic stem cells via the cell purification of kidney specific protein (KSP)-positive cells using an anti-KSP antibody. The global gene expression profiles of KSP-positive cells derived from ES cells exhibited characteristics similar to those of cells in the developing kidney, and KSP-positive cells had the capacity to form tubular structures resembling renal tubular cells when grown in a 3D culture in Matrigel. Moreover, our results indicated that KSP-positive cells acquired the characteristics of each segment of renal tubular cells through tubular formation when stimulated with Wnt4. This method is an important step toward kidney disease research using pluripotent stem cells, and the development of kidney regeneration therapies.

  6. Ioxaglate-induced light and electron microscopic alterations in the renal proximal tubular epithelium of rats.

    Science.gov (United States)

    Battenfeld, R; Khater A el-R; Drommer, W; Guenzel, P; Kaup, F J

    1991-01-01

    Vacuolization of the proximal tubular epithelial cells was produced in rats by the intravenous administration of the radiographic contrast medium ioxaglate at high multiples of the human diagnostic dose. Samples of the renal cortex and outer zone of the medulla were examined by light and electron microscopy. We observed enlargement, confluence, and migration of vacuoles containing pleomorphic dense material and distinct inclusion bodies. With time, vacuolization disappeared, though single vacuoles partly engaged in extruding their contents into the tubular lumen were still visible. We concluded that radiographic contrast medium at high dose levels can produce a reversible disturbance in the transport vesicular system of the proximal tubular epithelial cells without affecting the specific cell organelles. PMID:2022451

  7. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells

    OpenAIRE

    Gui, Ting; Gai, Zhibo

    2015-01-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly ...

  8. Protective mechanism of NALP3-siRNA on rat renal tubular epithelial cells from hypoxia/reoxygenation injury

    Institute of Scientific and Technical Information of China (English)

    冯娟

    2013-01-01

    Objective To explore the mechanism of protecting cells from hypoxia/reoxygenation(H/R) injury by constructing specific small interference RNA(siRNA) to inhibit NALP3 expression in rat renal tubular epithelial

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

    Directory of Open Access Journals (Sweden)

    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.

  10. 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 healthy...... and effective RPF were measured as the renal clearances of (99mTc)DTPA and (131I)hippuran, respectively. Renal tubular function was evaluated by use of the renal clearance of lithium and the urinary excretion of beta 2-microglobulin. Fish oil did not change baseline values of effective RPF, GFR, lithium...... clearance, and urinary excretion of beta 2-microglobulin in any of the groups. The infusion of amino acids induced a comparable increase in GFR, lithium clearance, and the urinary excretion rate of beta 2-microglobulin in all three groups with no additional effect of fish oil. Thus, long-term renal...

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun; ZHU Zhonghua; LIU Jianshe; YANG Xiao; FU Ling; DENG Anguo

    2007-01-01

    In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.

  13. RIPK3-Mediated Necroptosis and Apoptosis Contributes to Renal Tubular Cell Progressive Loss and Chronic Kidney Disease Progression in Rats.

    Science.gov (United States)

    Zhu, Yongjun; Cui, Hongwang; Xia, Yunfeng; Gan, Hua

    2016-01-01

    Tubulointerstitial fibrosis (TIF) is caused by the progressive loss of renal tubular cells and the consequent replacement of the extracellular matrix. The progressive depletion of renal tubular cells results from apoptosis and necroptosis; however, the relative significance of each of these cell death mechanisms at different stages during the progression of chronic kidney disease (CKD) remains unclear. We sought to explore the mechanisms of renal tubular cell death during the early and intermediate stages of chronic renal damage of subtotal nephrectomied (SNx) rats. The results of tissue histological assays indicated that the numbers of necrotic dying cells and apoptotic cells were significantly higher in kidney tissues derived from a rat model of CKD. In addition, there was a significant increase in necroptosis observed by transmission electron microscopy (TEM) and an increase in the proportion of TUNEL-positive cells in kidney tissues from SNx rats compared with control rats, and necrostatin-1 (Nec-1) could inhibit necroptosis and reduce the proportion of TUNEL-positive cells. More importantly, we observed a significant increase in the incidence of necroptosis compared with apoptosis by TEM in vivo and in vitro and a significant increase in the proportion of TUNEL-positive tubular epithelial cells that did not express caspase-3 compared with those expressing cleaved caspase-3 in vitro. Furthermore, treatment with Nec-1 and zVAD strongly reduced necroptosis- and apoptosis-mediated renal tubular cell death and decreased the levels of blood urea nitrogen and serum creatinine and tubular damage scores of SNx rats. These results suggest that necroptotic cell death plays a more significant role than apoptosis in mediating the loss of renal tubular cells in SNx rats and that effectively blocking both necroptosis and apoptosis improves renal function and tubular damage at early and intermediate stages of CKD.

  14. Intracellular calcium ions as regulators of renal tubular sodium transport.

    Science.gov (United States)

    Windhager, E; Frindt, G; Yang, J M; Lee, C O

    1986-09-15

    This review addresses the putative role of intracellular calcium ions in the regulation of sodium transport by renal tubules. Cytoplasmic calcium-ion activities in proximal tubules of Necturus are less than 10(-7) M and can be increased by lowering the electrochemical potential gradient for sodium ions across the peritubular cell membrane, or by addition of quinidine or ionomycin to peritubular fluid. Whereas lowering of the peritubular Na concentration increases cytosolic [Ca++] and [H+], ionomycin, a calcium ionophore, raises intracellular [Ca++] without decreasing pHi. The intracellular calcium-ion level is maintained by transport processes in the plasma membrane and membranes of intracellular organelles, as well as by calcium-binding proteins. Calcium ions inhibit net transport of sodium by reducing the rate of sodium entry across the luminal cell membrane. In the collecting tubule this inhibition is caused, at least in part, by an indirect reduction in the activity of the amiloride-sensitive sodium channel. PMID:2430134

  15. 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

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

    International Nuclear Information System (INIS)

    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

  17. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    International Nuclear Information System (INIS)

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  18. ApoSense: a novel technology for functional molecular imaging of cell death in models of acute renal tubular necrosis

    Energy Technology Data Exchange (ETDEWEB)

    Damianovich, Maya; Ziv, Ilan; Aloya, Tali; Grimberg, Hagit; Levin, Galit; Reshef, Ayelet; Bentolila, Alfonso; Cohen, Avi; Shirvan, Anat [NeuroSurvival Technologies (NST) Ltd., Petah Tikva (Israel); Heyman, Samuel N.; Shina, Ahuva [Mt.Scopus and the Hebrew University Medical School, Department of Medicine, Hadassah Hospital, Jerusalem (Israel); Rosen, Seymour [Beth Israel Deaconess Medical Center and Harvard Medical School, Department of Pathology, Boston, MA (United States); Kidron, Dvora [Meir Hospital, Department of Pathology, Kfar-Saba (Israel)

    2006-03-15

    Acute renal tubular necrosis (ATN), a common cause of acute renal failure, is a dynamic, rapidly evolving clinical condition associated with apoptotic and necrotic tubular cell death. Its early identification is critical, but current detection methods relying upon clinical assessment, such as kidney biopsy and functional assays, are insufficient. We have developed a family of small molecule compounds, ApoSense, that is capable, upon systemic administration, of selectively targeting and accumulating within apoptotic/necrotic cells and is suitable for attachment of different markers for clinical imaging. The purpose of this study was to test the applicability of these molecules as a diagnostic imaging agent for the detection of renal tubular cell injury following renal ischemia. Using both fluorescent and radiolabeled derivatives of one of the ApoSense compounds, didansyl cystine, we evaluated cell death in three experimental, clinically relevant animal models of ATN: renal ischemia/reperfusion, radiocontrast-induced distal tubular necrosis, and cecal ligature and perforation-induced sepsis. ApoSense showed high sensitivity and specificity in targeting injured renal tubular epithelial cells in vivo in all three models used. Uptake of ApoSense in the ischemic kidney was higher than in the non-ischemic one, and the specificity of ApoSense targeting was demonstrated by its localization to regions of apoptotic/necrotic cell death, detected morphologically and by TUNEL staining. (orig.)

  19. 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.

  20. Concurrent feline immune-complex nephritis. Tubular antigen-positive and renal amyloidosis.

    Science.gov (United States)

    Saegusa, S; Shimizu, F; Nagase, M; Kasegawa, A

    1979-08-01

    We describe tubular antigen-positive immune-complex nephritis in a case of feline renal amyloidosis. Amyloid deposition was observed in mesangial area, and thickening of capillary walls was shown in the majority of the glomeruli. This case was also characterized with typical fluorescent granular depositions of cat IgG and C3 along the glomerular capillary walls as seen in human membranous glomerulonephritis. The fluorescent pattern of tubular antigen was identical with that of IgG and C3. Electron micrograph showed the thickening and irregularity of glomerular basement membranes, fusion of foot processes, and deposits of electron-dense or sometimes translucent materials, mostly in the intramembranous location. The causal sequence of the coincidental deposition of amyloid and immune complexes is discussed. PMID:157110

  1. 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

    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...... fractional proximal reabsorption (FPR) was moderately subnormal. During the study, GFR decreased and sodium clearance was unchanged; fractional excretion of sodium therefore increased. In the group of patients randomized to treatment with enalapril (n = 34), GFR at 1 month was 83% (P ... with conventional antihypertensive drugs (n = 35), C(Li) was unchanged until severe reduction in GFR, APR and FPR decreased gradually, and potassium clearance was almost unchanged. These differences in tubular function between the two treatment regimens were significant (P

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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, p27Kip1, 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

  4. Atorvastatin ameliorates contrast medium-induced renal tubular cell apoptosis in diabetic rats via suppression of Rho-kinase pathway.

    Science.gov (United States)

    Su, Jinzi; Zou, Wenbo; Cai, Wenqin; Chen, Xiuping; Wang, Fangbing; Li, Shuizhu; Ma, Wenwen; Cao, Yangming

    2014-01-15

    Contrast medium-induced acute kidney injury (CI-AKI) remains a leading cause of iatrogenic, drug-induced acute renal failure. This study aimed to investigate the protective effects of atorvastatin against renal tubular cell apoptosis in diabetic rats and the related mechanisms. CI-AKI was induced by intravenous administration of iopromide (12ml/kg) in streptozotocin-induced diabetic rats. Atorvastatin (ATO) was administered intragastrically at the dose of 5, 10 and 30mg/kg/d in different groups, respectively, for 5 days before iopromide injection. Renal function parameters, kidney histology, renal tubular cell apoptosis, the expression of apoptosis regulatory proteins, caspase-3 and Rho-associated protein kinase 1 (ROCK-1), and the phosphorylation of myosin phosphatase target subunit -1 (MYPT-1), were determined. Atorvastatin was shown to notably ameliorate contrast medium induced medullary damage, restore renal function, and suppress renal tubular apoptosis. Meanwhile, atorvastatin up-regulated the expression of Bcl-2, down-regulated the expression of Bax, caspase-3 and ROCK-1, restored the ratio of Bcl-2/Bax, and suppressed the phosphorylation of MYPT-1 in a dose-dependent manner. Thus, atorvastatin pretreatment could dose-dependently ameliorate the development of CI-AKI, which was partly attributed to its suppression of renal tubular cell apoptosis by inhibiting the Rho/ROCK pathway.

  5. Effect of methoxychlor on Ca(2+) movement and viability in MDCK renal tubular cells.

    Science.gov (United States)

    Cheng, He-Hsiung; Lu, Yi-Chau; Lu, Ti; Cheng, Jin-Shiung; Mar, Guang-Yuan; Fang, Yi-Chien; Chai, Kuo-Liang; Jan, Chung-Ren

    2012-10-01

    The effect of the insecticide methoxychlor on the physiology of renal tubular cells is unknown. This study aimed to explore the effect of methoxychlor on cytosolic Ca(2+) concentrations ([Ca(2+) ](i) ) in MDCK renal tubular cells using the Ca(2+) -sensitive fluorescent dye fura-2. Methoxychlor at 5-20 μM increased [Ca(2+) ](i) in a concentration-dependent manner. The signal was reduced by 80% by removing extracellular Ca(2+) . Methoxychlor-induced Ca(2+) entry was not affected by nifedipine and SK&F96365 but was inhibited by econazole and protein kinase C modulators. In Ca(2+) -free medium, treatment with the endoplasmic reticulum Ca(2+) pump inhibitor thapsigargin or 2,5-di-tert-butylhydroquinone (BHQ) partly inhibited methoxychlor-induced [Ca(2+) ](i) rise. Incubation with methoxychlor also inhibited thapsigargin- or BHQ-induced [Ca(2+) ](i) rise. Inhibition of phospholipase C with U73122 nearly abolished methoxychlor-induced [Ca(2+) ](i) rise. At 5-15 μM, methoxychlor slightly increased cell viability, whereas at 20 μM, it decreased viability. The cytotoxic effect of methoxychlor was not reversed by chelating cytosolic Ca(2+) with 1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid/AM (BAPTA/AM). Annexin V-FITC data suggest that 10 μM methoxychlor inhibited apoptosis, while 20 μM methoxychlor enhanced apoptosis. Methoxychlor (10 and 20 μM) increased the production of reactive oxygen species. Together, in renal tubular cells, methoxychlor induced [Ca(2+) ](i) rise by inducing phospholipase C-dependent Ca(2+) release from multiple stores and Ca(2+) entry via protein kinase C- and econazole-sensitive channels. Methoxychlor slightly enhanced or inhibited cell viability in a concentration-dependent, Ca(2+) -independent manner. Methoxychlor induced cell death that may involve apoptosis via mitochondrial pathways.

  6. Types of transdifferentiation of renal tubular epithelial cells and its role in kidney diseases%肾小管上皮细胞转分化类型及其在肾脏疾病进展中的作用

    Institute of Scientific and Technical Information of China (English)

    王轩; 袁伟杰

    2012-01-01

    The normal shape and functions of renal tubular epithelial cells are very important for keeping renal function. Under pathological conditions, renal tubular epithelial cells transform to myofibroblast or immunocytes. The trans-differentiation of renal tubular epithelial cells acts in the progresses of many kidney diseases, such as diabetic nephropathy and lupus nephritis. In this review, we summarize the types of transdifferentiation of renal tubular epithelial cells and its roles in kidney diseases.

  7. Effects of uric acid on mitochondrial oxidative damage and apoptosis in human renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    张涛

    2014-01-01

    Objective To observe the effects of uric acid(UA)on mitochondrial oxidative damage and apoptosis in renal tubular epithelial cells(HK-2),and investigate the possible mechanism.Methods HK-2 cells were exposed to UA(480μmol/L,720μmol/L)for different time(0 h,24 h,48 h)in vitro.The mitochondrial ROS production was detected by Mito SOX staining.The mitochondrial membrane potential was measured by JC-1 staining.The expressions of prohibitin and AIF were examined by Western blotting and immunofluorescence cytochemistry.

  8. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury.

    Science.gov (United States)

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-04-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo-induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3(-/-)) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  9. Mitochondrial reactive oxygen species-mediated NLRP3 inflammasome activation contributes to aldosterone-induced renal tubular cells injury

    Science.gov (United States)

    Ding, Wei; Guo, Honglei; Xu, Chengyan; Wang, Bin; Zhang, Minmin; Ding, Feng

    2016-01-01

    Aldosterone (Aldo) is an independent risk factor for chronic kidney disease (CKD), and although Aldo directly induces renal tubular cell injury, the underlying mechanisms remain unclear. NLRP3 inflammasome and mitochondrial reactive oxygen species (ROS) have recently been implicated in various kinds of CKD. The present study hypothesized that mitochondrial ROS and NLRP3 inflammasome mediated Aldo–induced tubular cell injury. The NLRP3 inflammasome is induced by Aldo in a dose- and time-dependent manner, as evidenced by increased NLRP3, ASC, caspase-1, and downstream cytokines, such as interleukin (IL)-1β and IL-18. The activation of the NLRP3 inflammasome was significantly prevented by the selective mineralocorticoid receptor (MR) antagonist eplerenone (EPL) (P < 0.01). Mice harboring genetic knock-out of NLRP3 (NLRP3−/−) showed decreased maturation of renal IL-1β and IL-18, reduced renal tubular apoptosis, and improved renal epithelial cell phenotypic alternation, and attenuated renal function in response to Aldo-infusion. In addition, mitochondrial ROS was also increased in Aldo-stimulated HK-2 cells, as assessed by MitoSOXTM red reagent. Mito-Tempo, the mitochondria-targeted antioxidant, significantly decreased HK-2 cell apoptosis, oxidative stress, and the activation of NLRP3 inflammasome. We conclude that Aldo induces renal tubular cell injury via MR dependent, mitochondrial ROS-mediated NLRP3 inflammasome activation. PMID:27014913

  10. Prohibitin is associated with antioxidative protection in hypoxia/reoxygenation-induced renal tubular epithelial cell injury

    Science.gov (United States)

    Zhou, Tian-Biao; Qin, Yuan-Han; Lei, Feng-Ying; Huang, Wei-Fang; Drummen, Gregor P. C.

    2013-11-01

    Prohibitin is an evolutionary conserved and pleiotropic protein that has been implicated in various cellular functions, including proliferation, tumour suppression, apoptosis, transcription, and mitochondrial protein folding. We recently demonstrated that prohibitin downregulation results in increased renal interstitial fibrosis. Here we investigated the role of oxidative stress and prohibitin expression in a hypoxia/reoxygenation injury system in renal tubular epithelial cells with lentivirus-based delivery vectors to knockdown or overexpress prohibitin. Our results show that increased prohibitin expression was negatively correlated with reactive oxygen species, malon dialdehyde, transforming-growth-factor-β1, collagen-IV, fibronectin, and apoptosis (r = -0.895, -0.764, -0.798, -0.826, -0.817, -0.735 each P mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.

  11. Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing.

    Science.gov (United States)

    Yu, Wenmin; Li, Yiping; Wang, Zhi; Liu, Lei; Liu, Jing; Ding, Fengan; Zhang, Xiaoyi; Cheng, Zhengyuan; Chen, Pingsheng; Dou, Jun

    2016-09-01

    Chronic hypoxia often occurs among patients with chronic kidney disease (CKD). Renal proximal tubular cells may be the primary target of a hypoxic insult. However, the underlying transcriptional mechanisms remain undefined. In this study, we revealed the global changes in gene expression in HK‑2 human renal proximal tubular cells under hypoxic and normoxic conditions. We analyzed the transcriptome of HK‑2 cells exposed to hypoxia for 24 h using RNA sequencing. A total of 279 differentially expressed genes was examined, as these genes could potentially explain the differences in HK‑2 cells between hypoxic and normoxic conditions. Moreover, 17 genes were validated by qPCR, and the results were highly concordant with the RNA seqencing results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to better understand the functions of these differentially expressed genes. The upregulated genes appeared to be significantly enriched in the pathyway of extracellular matrix (ECM)-receptor interaction, and in paticular, the pathway of renal cell carcinoma was upregulated under hypoxic conditions. The downregulated genes were enriched in the signaling pathway related to antigen processing and presentation; however, the pathway of glutathione metabolism was downregulated. Our analysis revealed numerous novel transcripts and alternative splicing events. Simultaneously, we also identified a large number of single nucleotide polymorphisms, which will be a rich resource for future marker development. On the whole, our data indicate that transcriptome analysis provides valuable information for a more in depth understanding of the molecular mechanisms in CKD and renal cell carcinoma. PMID:27432315

  12. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells.

    Science.gov (United States)

    Gui, Ting; Gai, Zhibo

    2015-12-01

    To assess the effect of farnesoid X receptor (FXR), a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist) or DMSO (as controls) overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296). PMID:26697325

  13. Genome-wide profiling to analyze the effects of FXR activation on mouse renal proximal tubular cells

    Directory of Open Access Journals (Sweden)

    Ting Gui

    2015-12-01

    Full Text Available To assess the effect of farnesoid X receptor (FXR, a bile acid nuclear receptor, on renal proximal tubular cells, primary cultured mouse kidney proximal tubular cells were treated with GW4064 (a FXR agonist or DMSO (as controls overnight. Analysis of gene expression in the proximal tubular cells by whole genome microarrays indicated that FXR activation induced genes involved in fatty acid degradation and oxidation reduction. Among them, genes involved in glutathione metabolism were mostly induced. Here we describe in details the contents and quality controls for the gene expression and related results associated with the data uploaded to Gene Expression Omnibus (accession number GSE70296.

  14. Reduction of high-energy shock-wave-induced renal tubular injury by selenium.

    Science.gov (United States)

    Strohmaier, W L; Lahme, S; Weidenbach, P M; Bichler, K H

    1999-10-01

    In shock-wave-induced renal injury cavitation-generated free radicals play an important role. Using an in vitro model with Madin-Darby canine kidney (MDCK) cells, we investigated the influence of selenium, a free radical scavenger, in shock-wave-induced tubular cell injury. Suspensions of MDCK cells (33 x 10(6) cells/ml) were placed in small containers (volume 1.1 ml) for shock wave exposure. Two groups of 12 containers each were examined: (1) control (no medication), (2) selenium (0.4 microg/ml nutrient medium). Six containers in each group were exposed to shock waves (impulse rate 256, frequency 60 Hz, generator voltage 18 kV), while the other six containers in each group served as a control. After shock wave exposure, the concentration of cellular enzymes such as lactate dehydrogenase (LDH), N-acetyl-beta-glucosaminidase (NAG), glutamate oxaloacetate transaminase (GOT) and glutamate lactate dehydrogenase (GLDH) in the nutrient medium was examined. Following shock wave exposure there was a significant rise in LDH, NAG, GOT and GLDH concentrations. Selenium reduced this enzyme leakage significantly. Thus we conclude that selenium protects renal tubular cells against shock-wave-induced injury. Since selenium is an essential part of glutathione peroxidase, this effect seems to be mediated by a reduction in reactive oxygen species. PMID:10550528

  15. Chronic administration of AM251 improves albuminuria and renal tubular structure in obese rats.

    Science.gov (United States)

    Jenkin, Kayte A; O'Keefe, Lannie; Simcocks, Anna C; Grinfeld, Esther; Mathai, Michael L; McAinch, Andrew J; Hryciw, Deanne H

    2015-05-01

    Modulation of the endocannabinoid system as an anti-obesity therapeutic is well established; however, the direct effects of cannabinoid receptor 1 (CB1) antagonism on renal function and structure in a model of diet-induced obesity (DIO) are unknown. The aim of this study was to characterise the renal effects of the CB1 antagonist AM251 in a model of DIO. Male Sprague-Dawley rats were fed a low- or high-fat diet (HFD: 40% digestible energy from lipids) for 10 weeks to elicit DIO (n=9). In a different cohort, rats were fed a HFD for 15 weeks. After 9 weeks consuming a HFD, rats were injected daily for 6 weeks with 3 mg/kg AM251 (n=9) or saline via i.p. injection (n=9). After 10 weeks consuming a HFD, CB1 and megalin protein expression were significantly increased in the kidneys of obese rats. Antagonism of CB1 with AM251 significantly reduced weight gain, systolic blood pressure, plasma leptin, and reduced albuminuria and plasma creatinine levels in obese rats. Importantly, there was a significant reduction in tubular cross-section diameter in the obese rats treated with AM251. An improvement in albuminuria was likely due to the reduction in tubular size, reduced leptinaemia and maintenance of megalin expression levels. In obese rats, AM251 did not alter diastolic blood pressure, sodium excretion, creatinine clearance or expression of the fibrotic proteins VEGFA, TGFB1 and collagen IV in the kidney. This study demonstrates that treatment with CB1 antagonist AM251 improves renal outcomes in obese rats. PMID:25804605

  16. Renal tubular dysgenesis with hypocalvaria and ileocecal valve agenesis: an autopsy report

    Directory of Open Access Journals (Sweden)

    Ariel Barreto Nogueira

    2012-12-01

    Full Text Available Renal tubular dysgenesis (RTD is a rare, lethal, autosomal recessive disorder characterized by non-differentiation of the renal proximal convoluted tubules, resulting in oligohydramnios. It is usually diagnosed in the second trimester of pregnancy, following the oligohydramnios sequence, pulmonary hypoplasia and hypocalvaria. The prognosis is poor, and death usually occurs in utero or within the first few days of life. The pathogenesis of RTD is associated with the perinatal use of drugs, such as angiotensin- converting enzyme inhibitors, angiotensin II receptor antagonists, and anti- inflammatory drugs, as well as with fetal transfusion syndrome, genetic mutations in the pathway of the renin-angiotensin system pathway, cocaine snorting, or other pathological mechanisms that reduce renal blood flow. Here, we report the autopsy of a neonate born to consanguineous parents at 38 weeks of gestation, with RTD, decreased amniotic fluid, oligohydramnios sequence, hypocalvaria, pulmonary hypoplasia, and ileocecal valve agenesis. To our knowledge, the latter has never been reported associated with RTD.

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

    Science.gov (United States)

    Leventhal, Jeremy S; Ni, Jie; Osmond, Morgan; Lee, Kyung; Gusella, G Luca; Salem, Fadi; Ross, Michael J

    2016-01-01

    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.

  18. 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.

  19. Lactic Acidosis

    OpenAIRE

    K.Srikanth

    2012-01-01

    Abstract. Lactic acidosis is a broad-anion gap metabolic acidosis caused by lactic acid overproduction or underutilization. The quantitative dimensions of these two mechanisms commonly differ by 1 order of magnitude. Overproduction of lactic acid, also termed type A lactic acidosis, occurs when the body must regenerate ATP without oxygen (tissue hypoxia). Circulatory, pulmonary, or hemoglobin transfer disorders are commonly responsible. Overproduction of lactate also occurs with cyanide poiso...

  20. Regulation of MUTYH, a DNA Repair Enzyme, in Renal Proximal Tubular Epithelial Cells

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    Jianping Lu

    2015-01-01

    Full Text Available MUTYH is a DNA repair enzyme that initiates a base excision repair (BER by recognizing and removing 8-Oxoguanine (8-oxoG and its paired adenine. We demonstrated that both TGF-β1 and H2O2 treatment led to an increased 8-oxoG in cultured human proximal tubule epithelial (HK-2 cells, while the former induced epithelial-mesenchymal transition and the latter caused cell apoptosis. Without stimulation, HK-2 cells showed MUTYH expression in mitochondria. TGF-β1 triggered a transient upregulation of mitochondrial MUTYH and induced the expression of nuclear isoforms, while H2O2 showed no role on MUTYH expression. Ureteral obstruction (UUO mice exhibited high 8-oxoG reactivity with tubulointerstitial lesions. After obstruction, the MUTYH expression was increased only in tubules at day 3 and decreased with obvious tubular atrophy at day 10. Particularly, MUTYH was primarily located in normal tubular cytoplasm with a dominant mitochondrial form. A few cells with nuclear MUTYH expression were observed in the fibrotic interstitium. We confirmed that increased MUTYH expression was upregulated and positively correlated with the severity of kidney fibrosis. Thus, renal fibrosis caused a cell-type-specific and time-dependent response of oxidative DNA repairs, even within the same tissues. It suggests that intervention of MUTYH might be effective for therapies.

  1. 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.

  2. The small GTPase Cdc42 is necessary for primary ciliogenesis in renal tubular epithelial cells.

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H

    2011-06-24

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis.

  3. The Small GTPase Cdc42 Is Necessary for Primary Ciliogenesis in Renal Tubular Epithelial Cells*

    Science.gov (United States)

    Zuo, Xiaofeng; Fogelgren, Ben; Lipschutz, Joshua H.

    2011-01-01

    Primary cilia are found on many epithelial cell types, including renal tubular epithelial cells, where they participate in flow sensing. Disruption of cilia function has been linked to the pathogenesis of polycystic kidney disease. We demonstrated previously that the exocyst, a highly conserved eight-protein membrane trafficking complex, localizes to primary cilia of renal tubular epithelial cells, is required for ciliogenesis, biochemically and genetically interacts with polycystin-2 (the protein product of the polycystic kidney disease 2 gene), and, when disrupted, results in MAPK pathway activation both in vitro and in vivo. The small GTPase Cdc42 is a candidate for regulation of the exocyst at the primary cilium. Here, we demonstrate that Cdc42 biochemically interacts with Sec10, a crucial component of the exocyst complex, and that Cdc42 colocalizes with Sec10 at the primary cilium. Expression of dominant negative Cdc42 and shRNA-mediated knockdown of both Cdc42 and Tuba, a Cdc42 guanine nucleotide exchange factor, inhibit ciliogenesis in Madin-Darby canine kidney cells. Furthermore, exocyst Sec8 and polycystin-2 no longer localize to primary cilia or the ciliary region following Cdc42 and Tuba knockdown. We also show that Sec10 directly interacts with Par6, a member of the Par complex that itself directly interacts with Cdc42. Finally, we show that Cdc42 knockdown results in activation of the MAPK pathway, something observed in cells with dysfunctional primary cilia. These data support a model in which Cdc42 localizes the exocyst to the primary cilium, whereupon the exocyst then targets and docks vesicles carrying proteins necessary for ciliogenesis. PMID:21543338

  4. Survey on relation between Major Thalassemia and Desferiexamine with renal tubular damage.

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    H.M. Jafari, M.D.

    2007-01-01

    Full Text Available AbstractBackground and Purpose: Thalassemia is a hereditary quantitative hemoglubinopathy which is common in mediteranian area including IRAN. Homos zygotic thalassemia patients suffer from severe anemia and complication of the disease in many organs. Studies have shown different results about renal complication and disease. Thus, in this study we investigated renal function of thalassemia Major (TM patients in comparison with control group.Materials and Methods: This was a historical cohort Study. The population who TM patients was were admitted to Boalisina hospital, Sari, and control group were brothers and sisters of the patients who were matched in gender and age. Serum and urine markers of renal function were measured and demographic and therapeutic data were gathered from medical records. Analysis of the data was performed using SPSS 11 with statistical test (t, chi square.Results: the Total of 84 (42 patients and, 42 controls patients were studied. The Mean age of the patients was years. Dose of Deferral was 70±19 mg/kg. The results showed no significant statistical differences in levels of microglobulin, 24 urine protein, Excretion Fraction of Na and K between case and control group. There was significant differences in levels of serum BUN, creatinin, Potassium and urine potassium and creatinin between case and control group. Gender, level of Hb and serum Ferritin significantly affected the differences between two groups.Conclusion: In this study, evidences of renal tubular damage were not detected in TM patients. There was increase in levels of Bun, serum potassium, uric Acid, specially with sever anemia, high dose desferal and Iron over load.

  5. Stem Cell Conditioned Culture Media Attenuated Albumin-Induced Epithelial-Mesenchymal Transition in Renal Tubular Cells

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    Junping Hu

    2015-03-01

    Full Text Available Background: Proteinuria-induced epithelial-mesenchymal transition (EMT plays an important role in progressive renal tubulointerstitial fibrosis in chronic renal disease. Stem cell therapy has been used for different diseases. Stem cell conditioned culture media (SCM exhibits similar beneficial effects as stem cell therapy. The present study tested the hypothesis that SCM inhibits albumin-induced EMT in cultured renal tubular cells. Methods: Rat renal tubular cells were treated with/without albumin (20 µmg/ml plus SCM or control cell media (CCM. EMT markers and inflammatory factors were measured by Western blot and fluorescent images. Results: Albumin induced EMT as shown by significant decreases in levels of epithelial marker E-cadherin, increases in mesenchymal markers fibroblast-specific protein 1 and a-smooth muscle actin, and elevations in collagen I. SCM inhibited all these changes. Meanwhile, albumin induced NF-κB translocation from cytosol into nucleus and that SCM blocked the nuclear translocation of NF-κB. Albumin also increased the levels of pro-inflammatory factor monocyte chemoattractant protein-1 (MCP-1 by nearly 30 fold compared with control. SCM almost abolished albumin-induced increase of MCP-1. Conclusion: These results suggest that SCM attenuated albumin-induced EMT in renal tubular cells via inhibiting activation of inflammatory factors, which may serve as a new therapeutic approach for chronic kidney diseases.

  6. Expression of c-met Stimulated by High Glucose in Human Renal Tubular Epithelial Cells and Its Implication

    Institute of Scientific and Technical Information of China (English)

    LI Xing; ZHANG Muxun

    2007-01-01

    The expression of c-met stimulated by high glucose in human renal tubular epithelial cells and the role of HGF/c-met system in diabetic nephropathy were examined. The proximal tubular epithelial cells were cultured in vitro under different conditions. MTT was used for the detection of cellular proliferation and RT-PCR was employed for measurement of c-met mRNA level. Our results showed that under different conditions, there were no significant differences in the proliferation of proximal tubular epithelial cells 12 h and 24 h after the culuture (P>0.05). The proliferation of proximal tubular epithelial cells showed a significant change 96 h after the culture and the cellular proliferation induced by hepatocyte growth factor (HGF) was very active (P<0.05). Moreover, no significant difference in the expression of c-met mRNA was found 12 h after the culture under different conditions (P>0.05), while 24 and 96 h after the culture, a persistent and significantly higher expression of c-met mRNA was found in HGF-induced proliferation. It is concluded that addition of exogenous HGF could inhibit the apoptosis induced by high-level glucose, promote the proliferation of proximal tubular epithelial cells, and induce the expression of c-met. Our study suggests that local up-regulation of HGF/c-met system plays an important role in the repair of renal damage in diabetic nephropathy.

  7. Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors.

    Science.gov (United States)

    Huang, H-S; Chen, J; Chen, C-F; Ma, M-C

    2006-08-01

    We previously reported that oxidative stress and renal tubular damage occur in chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial cells after vitamin E administration and their correlations with calcium oxalate (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75% ethylene glycol (EG) for 7, 21, or 42 days to induce CaOx deposition (EG group). Another group of EG-treated rats received 200 mg kg(-1) of vitamin E intraperitoneally (EG+E group) to evaluate its effect on hyperoxaluria. Urinary electrolytes and biochemistry and levels of lipid peroxides and enzymes were examined, together with serum vitamin E levels. Levels of the tubular markers, alpha and mu glutathione S-transferase, proliferating cell nuclear antigen (PCNA), osteopontinin (OPN), and Tamm-Horsfall protein (THP) were also measured, and TUNEL staining was performed to examine the viability of the tubular epithelium. There were no significant differences between the two age-matched controls either untreated or given vitamin E. Compared to untreated controls, tubular cell death was increased at all time points in EG rats with a gradual increase in CaOx crystals, whereas the number of PCNA-positive cells was only significantly increased on day 21. In EG+E rats, tubular cell death was decreased compared to the EG group, and cell proliferation was seen at all time points, while CaOx crystal deposition was decreased, but hyperoxaluria, urinary lipid peroxides, and enzymuria were unaffected. Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine. The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP.

  8. 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.

  9. 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.

  10. Osteopathy of renal tubular acidosis: Case report%肾小管酸中毒性骨病1例

    Institute of Scientific and Technical Information of China (English)

    李欣欣

    2011-01-01

    @@ 患者男,49岁.因"腰腿疼痛3年,加重1个月"来诊.患者既往有慢性乙型肝炎病史,长期服用多种抗病毒药物.入院查体:腰椎及髋部压痛明显,直腿抬高试验及"4"字征(-).实验室检查:HLA B27(-).尿常规检查:尿蛋白(-),尿糖:(+),尿pH值7.00;电解质:TCO2 17.21 mmol/L,K+ 3.26 mmol/L,Cl- 106.00 mmol/L;肾功能检查:Cr 106.00 μmol/L,Bun 6.90 mmol/L.血钙1.92 mmol/L,血磷1.80 mmol/L.

  11. 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...... of nifedipine treatment. As compared with placebo, mean supine blood pressure decreased significantly. The glomerular filtration rate did not change but lithium clearance fell by 30%. Consequently, the absolute and the fractional proximal sodium reabsorption increased significantly. The fractional distal sodium...... reabsorption did not change. Sodium clearance, fractional sodium excretion, potassium clearance, plasma volume and extracellular fluid volume were also unchanged. 4. In conclusion, we found no changes of renal tubular sodium reabsorption during acute nifedipine treatment, whereas long-term nifedipine treatment...

  12. Acidosis and Urinary Calcium Excretion

    DEFF Research Database (Denmark)

    Alexander, R Todd; Cordat, Emmanuelle; Chambrey, Régine;

    2016-01-01

    Metabolic acidosis is associated with increased urinary calcium excretion and related sequelae, including nephrocalcinosis and nephrolithiasis. The increased urinary calcium excretion induced by metabolic acidosis predominantly results from increased mobilization of calcium out of bone...... and inhibition of calcium transport processes within the renal tubule. The mechanisms whereby acid alters the integrity and stability of bone have been examined extensively in the published literature. Here, after briefly reviewing this literature, we consider the effects of acid on calcium transport...

  13. 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 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...

  14. A simple slide-rule method for the assessment of renal tubular reaborption of phosphate in man.

    Science.gov (United States)

    Walton, R J; Bijvoet, O L

    1977-12-15

    The activity of renal tubular reabsorption of phosphate in man is best expressed as the ratio of the maximum rate or reabsorption to the glomerular filtration rate (TmP/GFR). A slide-rule method based on existing data is described for the derivation of TmP/GFR from values of phosphate and creatinine concentrations in single samples of plasma and urine. This is a simple method which is suitable both for research and for clinical purposes. PMID:923101

  15. Renal Tubular and Glomerular Function in Children with Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Mohammad Hashemi

    2009-09-01

    Full Text Available Objective:Iron deficiency anemia (IDA resulting from lack of sufficient iron for synthesis of hemoglobin is most common hematologic disease of infancy and childhood. There is little information about the renal function in iron deficiency anemia. The aim of the present study was to examine the renal function in children with iron deficiency anemia. Methods:This case-control study was performed in children with iron deficiency anemia (n=20 and healthy age matched subjects (n=20. Blood and urine samples were obtained for hematological and biochemical investigation. Statistical analysis was performed by unpaired sample t-test and Pearsons correlation coefficient. Findings: Fractional excretion of sodium (FENa+ was significantly higher in children with iron deficiency anemia than control subjects (P=0.006. There was no significant difference in the level of urine specific gravity, calcium/creatinine ratio, β2-microglobulin and creatinine clearance between case and control groups (P>0.05. There was no correlation between FENa and Hb (r=0.13, P=0.57, FENa+ and Fe+2 (r=0.079, P=0.72, FENa+ and TIBC (r=-0.083, P=0.71, FENa+ and ferritin (r=0.039, P=0.86 as well as Hb and β2-microglobulin (r=0.02, P=0.37 in IDA patients. Conclusion:The results showed that FENa+ was higher in children with iron deficiency anemia than in normal subjects. The findings revealed evidence of tubular damage in IDA; this needs confirmation by more investigation.

  16. Renal tubular injury induced by ischemia promotes the formation of calcium oxalate crystals in rats with hyperoxaluria.

    Science.gov (United States)

    Cao, Yanwei; Liu, Wanpeng; Hui, Limei; Zhao, Jianjun; Yang, Xuecheng; Wang, Yonghua; Niu, Haitao

    2016-10-01

    Hyperoxaluria and cell injury are key factors in urolithiasis. Oxalate metabolism may be altered by renal dysfunction and therefore, impact the deposition of calcium oxalate (CaOx) crystals. We investigated the relationship of renal function, oxalate metabolism and CaOx crystal deposition in renal ischemia. One hundred male Sprague-Dawley rats were randomly divided into four groups. Hyperoxaluria model (Group A and B) was established by feeding rats with 0.75 % ethylene glycol (EG). The left renal pedicle was clamped for 30 min to establish renal ischemia Groups (B and C), while Groups A and D underwent sham operation. Then, serum and urine oxalate (Ox), creatinine (Cr) and urea nitrogen (UN) levels were evaluated by liquid chromatography mass spectrometry (LCMS) and ion mass spectrum (IMS) at days 0, 2, 4, 7, and 14. CaOx crystallization was assessed by transmission electron microscope (TEM). A temporal and significant increase of serum Cr and UN levels was observed in Groups B and C compared to values obtained for Groups A and D (P renal tissue. Our results indicated that renal tubular injury induced by renal ischemia might not affect Ox levels but could promote CaOx crystal retention under hyperoxaluria.

  17. 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.

  18. 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 and...... fractional excretion of lithium (FELi) [27.0 (23.5-30.5) ml/min and 24.2 (20.3-28.2)% (means with 95% confidence interval)] were lower than exogenous values [lithium, 450 mg: 32.7 (29.9-35.4) ml/min (P <0.05) and 27.4 (25.2-29.6)% (P <0.05); lithium, 600 mg: 33.4 (29.2-37.6)ml/min (P <0.05) and 28.6 (26...

  19. 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.

  20. Renal rickets-practical approach

    Directory of Open Access Journals (Sweden)

    Manisha Sahay

    2013-01-01

    Full Text Available Rickets/osteomalacia is an important problem in a tropical country. Many cases are due to poor vitamin D intake or calcium deficient diets and can be corrected by administration of calcium and vitamin D. However, some cases are refractory to vitamin D therapy and are related to renal defects. These include rickets of renal tubular acidosis (RTA, hypophosphatemic rickets, and vitamin D dependent rickets (VDDR. The latter is due to impaired action of 1α-hydroxylase in renal tubule. These varieties need proper diagnosis and specific treatment.

  1. 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...

  2. Deficiency for the chemokine monocyte chemoattractant protein-1 aggravates tubular damage after renal ischemia/reperfusion injury.

    Directory of Open Access Journals (Sweden)

    Ingrid Stroo

    Full Text Available Temporal expression of chemokines is a crucial factor in the regulation of renal ischemia/reperfusion (I/R injury and repair. Beside their role in the migration and activation of inflammatory cells to sites of injury, chemokines are also involved in other processes such as angiogenesis, development and migration of stem cells. In the present study we investigated the role of the chemokine MCP-1 (monocyte chemoattractant protein-1 or CCL2, the main chemoattractant for monocytes, during renal I/R injury. MCP-1 expression peaks several days after inducing renal I/R injury coinciding with macrophage accumulation. However, MCP-1 deficient mice had a significant decreased survival and increased renal damage within the first two days, i.e. the acute inflammatory response, after renal I/R injury with no evidence of altered macrophage accumulation. Kidneys and primary tubular epithelial cells from MCP-1 deficient mice showed increased apoptosis after ischemia. Taken together, MCP-1 protects the kidney during the acute inflammatory response following renal I/R injury.

  3. Renal Function in Diabetic Disease Models: The Tubular System in the Pathophysiology of the Diabetic Kidney

    Science.gov (United States)

    Vallon, Volker; Thomson, Scott C.

    2013-01-01

    Diabetes mellitus affects the kidney in stages. At the onset of diabetes mellitus, in a subset of diabetic patients the kidneys grow large, and glomerular filtration rate (GFR) becomes supranormal, which are risk factors for developing diabetic nephropathy later in life. This review outlines a pathophysiological concept that focuses on the tubular system to explain these changes. The concept includes the tubular hypothesis of glomerular filtration, which states that early tubular growth and sodium-glucose cotransport enhance proximal tubule reabsorption and make the GFR supranormal through the physiology of tubuloglomerular feedback. The diabetic milieu triggers early tubular cell proliferation, but the induction of TGF-β and cyclin-dependent kinase inhibitors causes a cell cycle arrest and a switch to tubular hypertrophy and a senescence-like phenotype. Although this growth phenotype explains unusual responses like the salt paradox of the early diabetic kidney, the activated molecular pathways may set the stage for tubulointerstitial injury and diabetic nephropathy. PMID:22335797

  4. Glioma-associated oncogene homolog 1 promotes epithelial-mesenchymal transition in human renal tubular epithelial cell

    OpenAIRE

    Ding, Hong; Xu, Yanyan; Gao, Di; Wang, Lei

    2016-01-01

    Sonic hedgehog (Shh) signaling critically regulates embryogenesis and tissue homeostasis. Here, we investigated the role of Shh signaling in mediating epithelial-mesenchymal transition (EMT) in human renal tubular epithelial cells HKC-8. Our RT-PCR assays demonstrated that TGF-β1 induced time-dependent changes in the mRNA transcript levels of Shh, with a steady rise from one hour post TGF-β1 treatment and a peak at four hours post TGF-β1 treatment. Furthermore, TGF-β1 induced a time-dependent...

  5. Heat-preconditioning confers protection from Ca2+-mediated cell toxicity in renal tubular epithelial cells (BSC-1)

    OpenAIRE

    Kuhlmann, Martin K.; Betz, Regina; Hanselmann, Rainer; Köhler, Hans

    1997-01-01

    A rise in intracellular calcium may mediate ischemic damage by phospholipid hydrolysis and proteolysis Heat shock proteins have been shown to provide protection from various forms of cell stress, but not from models of Ca2+-mediated injury. The effect of heat preconditioning in a model of ionomycin-induced injury in cultured renal tubular epitheliaal cells (BSC-1) was examined. Hsp70-mRNA expression was induced by hyperthermia (HT) (42°C, 60 min). Hsp70 protein accumulation was maximal after ...

  6. Comparison of Ultrasound Corticomedullary Strain with Doppler Parameters in Assessment of Renal Allograft Interstitial Fibrosis/Tubular Atrophy.

    Science.gov (United States)

    Gao, Jing; Rubin, Jonathan M; Weitzel, William; Lee, Jun; Dadhania, Darshana; Kapur, Sandip; Min, Robert

    2015-10-01

    To compare the capability of ultrasound strain and Doppler parameters in the assessment of renal allograft interstitial fibrosis/tubular atrophy (IF/TA), we prospectively measured ultrasound corticomedullary strain (strain) and intra-renal artery Doppler end-diastolic velocity (EDV), peak systolic velocity (PSV) and resistive index (RI) in 45 renal transplant recipients before their kidney biopsies. We used 2-D speckle tracking to estimate strain, the deformation ratio of renal cortex to medulla produced by external compression using the ultrasound transducer. We also measured Doppler EDV, PSV and RI at the renal allograft inter-lobar artery. Using the Banff scoring system for renal allograft IF/TA, 45 patients were divided into the following groups: group 1 with ≤5% (n = 12) cortical IF/TA; group 2 with 6%-25% (n = 12); group 3 with 26%-50% (n = 11); and group 4 with >50% (n = 10). We performed receiver operating characteristic curve analysis to test the accuracy of these ultrasound parameters and duration of transplantation in determining >26% cortical IF/TA. In our results, strain was statistically significant in all paired groups (all p 26%, including 26%-50% and >50%) and low-grade (≤25%, including 0.05). The areas under the receiver operating characteristic curve for strain, EDV, PSV, RI and duration of transplantation in determining >26% cortical IF/TA were 0.99, 0.94, 0.88, 0.52 and 0.92, respectively. Our results suggest that corticomedullary strain seems to be superior to Doppler parameters and duration of transplantation in assessment of renal allograft cortical IF/TA.

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

    International Nuclear Information System (INIS)

    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 (·O2), 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, ·O2, 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.

  8. Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

    Science.gov (United States)

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

    2011-09-01

    Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy. PMID:21689714

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

    Directory of Open Access Journals (Sweden)

    Ana B Sanz

    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

  10. 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.

  11. 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 p......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...

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

    OpenAIRE

    Kohan Donald E; Schmid Douglas I; Hughes Alisa K

    2002-01-01

    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), h...

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

    DEFF Research Database (Denmark)

    Dimke, Henrik; Hoenderop, Joost G; Bindels, René J;

    2010-01-01

    change tubular transport of Ca2+ and Mg2+. In the distal convolutions, several proteins involved in Mg2+ transport have been identified [TRPM6 (transient receptor potential melastatin 6), proEGF (pro-epidermal growth factor) and FXYD2 (Na+/K+-ATPase gamma-subunit)]. In addition, conditions...

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

    Directory of Open Access Journals (Sweden)

    Nicolás M Kouyoumdzian

    Full Text Available 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.

  15. Dialysis Disequilibrium Syndrome: Brain death following hemodialysis for metabolic acidosis and acute renal failure – A case report

    Directory of Open Access Journals (Sweden)

    Bagshaw Sean M

    2004-08-01

    Full Text Available Abstract Background Dialysis disequilibrium syndrome (DDS is the clinical phenomenon of acute neurologic symptoms attributed to cerebral edema that occurs during or following intermittent hemodialysis (HD. We describe a case of DDS-induced cerebral edema that resulted in irreversible brain injury and death following acute HD and review the relevant literature of the association of DDS and HD. Case Presentation A 22-year-old male with obstructive uropathy presented to hospital with severe sepsis syndrome secondary to pneumonia. Laboratory investigations included a pH of 6.95, PaCO2 10 mmHg, HCO3 2 mmol/L, serum sodium 132 mmol/L, serum osmolality 330 mosmol/kg, and urea 130 mg/dL (46.7 mmol/L. Diagnostic imaging demonstrated multifocal pneumonia, bilateral hydronephrosis and bladder wall thickening. During HD the patient became progressively obtunded. Repeat laboratory investigations showed pH 7.36, HCO3 19 mmol/L, potassium 1.8 mmol/L, and urea 38.4 mg/dL (13.7 mmol/L (urea-reduction-ratio 71%. Following HD, spontaneous movements were absent with no pupillary or brainstem reflexes. Head CT-scan showed diffuse cerebral edema with effacement of basal cisterns and generalized loss of gray-white differentiation. Brain death was declared. Conclusions Death is a rare consequence of DDS in adults following HD. Several features may have predisposed this patient to DDS including: central nervous system adaptations from chronic kidney disease with efficient serum urea removal and correction of serum hyperosmolality; severe cerebral intracellular acidosis; relative hypercapnea; and post-HD hemodynamic instability with compounded cerebral ischemia.

  16. Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation

    NARCIS (Netherlands)

    Celie, Johanna W. A. M.; Katta, Kiran K.; Adepu, Saritha; Melenhorst, Wynand B. W. H.; Reijmers, Rogier M.; Slot, Edith M.; Beelen, Robert H. J.; Spaargaren, Marcel; Ploeg, Rutger J.; Navis, Gerjan; van der Heide, Jaap J. Homan; van Dijk, Marcory C. R. F.; van Goor, Harry; van den Born, Jacob

    2012-01-01

    Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft

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

    Directory of Open Access Journals (Sweden)

    K J Kelly

    Full Text Available 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.

  18. Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways.

    Science.gov (United States)

    Thongnuanjan, Penjai; Soodvilai, Sirima; Chatsudthipong, Varanuj; Soodvilai, Sunhapas

    2016-01-01

    Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment. PMID:27193727

  19. Topiramate and severe metabolic acidosis: case report Acidose metabólica grave por topiramato: relato de caso

    Directory of Open Access Journals (Sweden)

    Jayme E. Burmeister

    2005-06-01

    Full Text Available Topiramate infrequently induces anion gap metabolic acidosis through carbonic anhydrase inhibition on the distal tubule of the nephron - a type 2 renal tubular acidosis. We report on a 40 years old woman previously healthy that developed significant asymptomatic metabolic acidosis during topiramate therapy at a dosage of 100mg/day for three months. Stopping medication was followed by normalization of the acid-base status within five weeks. This infrequent side effect appears unpredictable and should be given careful attention.Topiramato pode produzir raramente uma acidose metabólica através da inibição da anidrase carbônica no túbulo distal do néfron - acidose tubular renal do tipo 2. Relatamos o caso de mulher de 40 anos previamente saudável que desenvolveu quadro de acidose metabólica assintomática grave, sem outra etiologia identificável, durante uso de topiramato na dose de 100mg/dia por três meses. Este efeito colateral, embora infrequente, parece ser imprevisível e requer atenção cuidadosa.

  20. Glioma-associated oncogene homolog 1 promotes epithelial-mesenchymal transition in human renal tubular epithelial cell.

    Science.gov (United States)

    Ding, Hong; Xu, Yanyan; Gao, Di; Wang, Lei

    2016-01-01

    Sonic hedgehog (Shh) signaling critically regulates embryogenesis and tissue homeostasis. Here, we investigated the role of Shh signaling in mediating epithelial-mesenchymal transition (EMT) in human renal tubular epithelial cells HKC-8. Our RT-PCR assays demonstrated that TGF-β1 induced time-dependent changes in the mRNA transcript levels of Shh, with a steady rise from one hour post TGF-β1 treatment and a peak at four hours post TGF-β1 treatment. Furthermore, TGF-β1 induced a time-dependent increase in the mRNA transcript levels of Gli1. Pre-treatment with 2 or 5 µM cyclopamine significantly attenuated TGF-β1-induced rise in the mRNA transcript levels of Gli1, but failed to attenuate TGF-β1-induced rise in Shh mRNA transcript levels. Additionally, immunoblotting assays and immunofluorescence staining demonstrated that inhibition of Shh signaling by cyclopamine significantly attenuated TGF-β1-induced increase in the mRNA transcript levels of α-SMA, collagen I, and fibronectin. Gli1 overexpression induced Snail1 expression. Moreover, Gli(-/-) mice that had undergone unilateral ureteral obstruction for seven days showed significant reduction in the mRNA transcript levels of Snail1 compared to the wildtype controls. In conclusion, the current study provides novel insight into the regulation of EMT by the Shh/Gli1 signaling pathway, suggesting a critical role of Shh/Gli1 signaling in EMT of human renal tubular epithelial cells. PMID:27158358

  1. Power doppler sonography in early renal transplantation: Does it differentiate acute graft rejection from acute tubular necrosis?

    Directory of Open Access Journals (Sweden)

    Haytham M Shebel

    2014-01-01

    Full Text Available To evaluate the role of power Doppler in the identification and differentiation bet-ween acute renal transplant rejection and acute tubular necrosis (ATN, we studied 67 live donor renal transplant recipients. All patients were examined by spectral and power Doppler sono-graphy. Assessment of cortical perfusion (CP by power Doppler was subjective, using our grading score system: P0 (normal CP; homogenous cortical blush extending to the capsule, P1 (reduced CP; cortical vascular cut-off at interlobular level, P2 (markedly reduced CP; scattered cortical color flow at the interlobar level. Renal biopsies were performed during acute graft dysfunction. Pathological diagnoses were based on Banff classification 1997. The Mann- Whitney test was used to test the difference between CP grades with respect to serum creatinine (SCr, and resistive index (RI. For 38 episodes of acute graft rejection grade I, power Doppler showed that CP was P1 and RI ranging from 0.78 to 0.89. For 21 episodes of acute graft rejection grade II, power Doppler showed that CP was P1, with RI ranging from 0.88 to >1. Only one case of grade III rejection had a CP of P2. Twelve biopsies of ATN had CP of P0 and RI ranging from 0.80 to 0.89 There was a statistically significant correlation between CP grading and SCr (P <0.01 as well as between CP grading and RI (P <0.05. CP grading had a higher sensitivity in the detection of early acute rejection compared with RI and cross-sectional area measurements. We conclude that power Doppler is a non-invasive sensitive technique that may help in the detection and differentiation between acute renal transplant rejection and ATN, particularly in the early post-transplantation period.

  2. Activation of SUR2B/Kir6.1-type KATP channels protects glomerular endothelial, mesangial and tubular epithelial cells against oleic acid renal damage

    Institute of Scientific and Technical Information of China (English)

    Ying ZHAO; Hai WANG

    2012-01-01

    Cumulative evidence suggests that renal vascular endothelial injury play an important role in initiating and extending tubular epithelial injury and contribute to the development of ischemic acute renal failure.Our previous studies have demonstrated that iptakalim's endothelium protection is related to activation of SUR2B/Kir6.1 subtype of ATP sensitive potassium channel (KATP) in the endothelium.It has been reported that SUR2B/Kir6.1 channels are widely distributed in the tubular epithelium,glomerular mesangium,and the endothelium and the smooth muscle of blood vessels.Herein,we hypothesized that activating renal KATP channels with iptakalim might have directly neroprotective effects.In this study,glomerular endothelial,mesangial and tubular epithelial cells which are the main cell types to form nephron were exposed to oleic acid (OA) at various concentrations for 24 h.0.25 μl/ml OA could cause cellular damage of glomerular endothelium and mesangium,while 1.25μl/ml OA could lead to the injury of three types of renal cells.It was observed that pretreatment with iptakalim at concentrations of 0.1,1,10 or 100 μmol/L prevented cellular damage of glomerular endothelium and tubular epithelium,whereas iptakalim from 1 to 100 μmol/L prevented the injury of mesangial cells.Our data showed iptakalim significantly increased survived cell rates in a concentration-dependent manner,significantly antagonized by glibenclamide,a KATP blocker.Iptakalim played a protective role in the main cell types of kidney,which was consistent with natakalim,a highly selective SUR2B/Kir6.1 channel opener.Iptakalim exerted protective effects through activating SUR2B/Kir6.1 channels,suggesting a new strategy for renal injury by its endothelial and renal cell protection.

  3. The role of AT1 and AT2 angiotensin receptors in the mechanism of apoptosis in renal tubular cells after physical exercise.

    Science.gov (United States)

    Podhorska-Okołów, M; Dziegiel, P; Gomułkiewicz, A; Dolińska-Krajewska, B; Murawska-Ciałowicz, E; Jethon, Z; Zabel, M

    2004-01-01

    Intensive physical exercise disturbs the entire homeostasis in the body and leads to changes in haemodynamic and metabolic alterations not only in skeletal muscles but also in many distant organs. In response to acute physical exercise, a decrease of the glomerular filtration may occur, followed by stimulation of the renin-angiotensin system (RAS). Recent studies have shown that both AT1 and AT2 angiotensin receptors may play a role in mediating the apoptotic process in the kidney. Our previous studies have demonstrated an occurrence of apoptosis in rat renal tubular cells after an excessive exercise. The aim of the present study was to determine the possible mechanism of exercise-induced apoptosis in rat kidney. The analysis was performed on kidneys of rats, subjected to treadmill running until exhaustion. Apoptosis was detected in paraffin sections by the TUNEL technique. The expression of AT1 and AT2 receptors in renal tubular cells was examined by immunohistochemistry and Western blot. Our results confirmed that apoptosis after physical exercise is present in renal distal tubular cells. Moreover, there was an increased expression of AT1 and AT2 receptors in distal tubular cells. These studies suggest that physical exercise may induce apoptosis by a mechanism, involving the activation of angiotensin AT1 and AT2 receptors. PMID:15638358

  4. Serum level of proximal renal tubular epithelial cell-binding immunoglobulin G in patients with lupus nephritis.

    Science.gov (United States)

    Yap, D Y H; Yung, S; Zhang, Q; Tang, C; Chan, T M

    2016-01-01

    In vitro data showed that immunoglobulin G (IgG) from lupus nephritis (LN) patients could bind to proximal renal tubular epithelial cells (PTEC), but the clinical relevance of such binding remained unclear. Binding of IgG and subclasses to PTEC was measured by cellular ELISA (expressed as OD index) in 189 serial serum samples from 23 Class III/IV ± V LN patients who had repeated renal flares (48 during renal flares, 141 during low level disease activity (LLDA)), and compared with 64 patients with non-lupus glomerular diseases (NLGD) and 23 healthy individuals. Total IgG PTEC-binding index was 0.34 ± 0.16, 0.29 ± 0.16, 0.62 ± 0.27 and 0.83 ± 0.38 in healthy controls, NLGD, LN patients during LLDA, and LN patients during nephritic flare, respectively (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). PTEC-binding index for IgG1 was 0.09 ± 0.05, 0.16 ± 0.12, 0.44 ± 0.34 and 0.71 ± 0.46 for the corresponding groups (p < 0.001, LLDA vs. renal flare; p < 0.001, healthy controls or NLGD vs. LN during LLDA or renal flare). Sixteen of 48 episodes (33.3%) of nephritic flare showed persistent PTEC-binding IgG seropositivity for more than 9.4 ± 3.1 months, despite clinical response to immunosuppressive treatment. Total IgG and IgG1 PTEC-binding correlated with anti-dsDNA level (r = 0.34 and 0.52, respectively, p < 0.001 for both), and inversely with C3 level (r = -0.26 and -0.50, respectively, p = 0.002 and<0.001). Sensitivity/specificity of PTEC-binding index in detecting renal flares was 45.8%/80.1% for total IgG (ROC AUC 0.630, p = 0.007) and 87.5%/35.5% for IgG1 (ROC AUC 0.615, p = 0.018). IgG1 PTEC-binding index correlated with tubulo-interstitial inflammation score in renal biopsy from corresponding patients. Our data suggested that total IgG and IgG1 PTEC-binding index in serum of LN patients correlate with serological activity, and in combination could predict renal flares. The correlation between IgG1

  5. Sinomenine inhibits B7-H1 and B7-DC expression on human renal tubular epithelial cells.

    Science.gov (United States)

    Chen, Yongwen; Li, Jingyi; Zhang, Jingbo; Zhao, Tingting; Zou, Liyun; Tang, Yan; Zhang, Xiaoping; Wu, Yuzhang

    2005-08-01

    Previous studies have shown that sinomenine possesses potent immunoregulatory properties. However, little is known about its exact mechanisms of action. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether sinomenine can regulate TEC activity. In this study, cultured human TECs were exposed to proinflammatory factors interferon-gamma (IFN-gamma) and tumor necrotic factor-alpha (TNF-alpha) in presence or absence of sinomenine for 72 h, followed by analysis of surface expression of costimulatory molecules. Flow cytometric analysis revealed that various costimulatory molecules were expressed on TECs and that they were significantly up-regulated by the simulation of IFN-gamma and TNF-alpha. However, sinomenine especially down-regulated B7-H1 and B7-DC expression on TECs at both mRNA and protein levels. Moreover, the significant damping effect of sinomenine on B7-H1 and B7-DC signals could promote IL-2 and IFN-gamma production by co-cultured CD4(+) T cell. Our results indicated that sinomenine could regulate TECs activity via B7-H1 and B7-DC, in addition to previously reported its effects on some pro-inflammatory factors production by macrophages and peripheral blood mononuclear cells. PMID:15953571

  6. 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.

  7. In situ lactate dehydrogenase activity - a novel renal cortical imaging biomarker of tubular injury?

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    2016-01-01

    Renal ischemia/reperfusion injury is the state of which a tissue experience injury after a phase of restrictive blood supply and recirculation. Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) in several disease states, including kidney transplantation, sepsis...... and hypovolemic shock. The most common methods to evaluate AKI are creatinine clearance, plasma creatinine, blood urea nitrogen (BUN) or renal histology. However, there is currently a lack of precise methods to directly assess renal injury state non-invasively. Hyperpolarized 13C-pyruvate magnetic resonance...... with 30 min and 60 min of ischemia followed by 24 hours of reperfusion. The pyruvate conversion was unaltered compared to sham in the 30 min I/R-I group while a significant reduced metabolic conversion was found in the post-ischemic kidney after 60 min of ischemia. This indicates that after 30 min...

  8. 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 ston

  9. Increased calcium oxalate monohydrate crystal binding to injured renal tubular epithelial cells in culture

    NARCIS (Netherlands)

    C.F. Verkoelen; B.G. van der Boom (Burt); A.B. Houtsmuller (Adriaan); F.H. Schröder (Fritz); J.C. Romijn (Johannes)

    1998-01-01

    textabstractThe retention of crystals in the kidney is considered to be a crucial step in the development of a renal stone. This study demonstrates the time-dependent alterations in the extent of calcium oxalate (CaOx) monohydrate (COM) crystal binding to Madin-Darby ca

  10. 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

    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 retinol-binding protein were unchanged in this group...

  11. In Situ lactate dehydrogenase activiy-a novel renal cortical imaging biomarker of tubular injury?

    DEFF Research Database (Denmark)

    Nielsen, Per Mose; Laustsen, Christoffer; Bertelsen, Lotte Bonde;

    Renal ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI) in several disease states, including hypovolemic shock, sepsis, surgery. Imbalance in energy metabolism and mitochondrial function is a hallmark in IRI which can be caused by mechanisms like oxidative stress...

  12. 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

    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...

  13. Effective Penetration of Cell-permeable Peptide Mimic of Tyrosine Residue 654 Domain of β-catenin into Human Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    ZENG Rui; XU Gang; HAN Min; LIU Wei; LIU Xiaocheng

    2007-01-01

    Phosphorylation of β-catenin tyrosine residue 654 plays an important role in the epithelial to myofibroblast transition (EMT). Introducing mimic peptide of tyrosine residue 654 domain of β-catenin into cells may influence phosphorylation of β-catenin tyrosine residue 654. To deliver this mimic peptide into renal epithelial cells, we used penetratin as a vector, which is a novel cell perme-able peptide, to deliver hydrophilic molecules into cells. A tyrosine 654 residue domain mimic pep-tide of β-catenin (PM) with fused penetratin was constructed, purified and then detected for the pene-tration of the mimic peptide into human renal tubular epithelial cells (HK-2). The results showed that purified fusion mimic peptide could efficiently and rapidly translocate into human renal tubular epithelial cells. It is concluded that a cell-permeable peptides mimic of tyrosine residue 654 domain of β-catenin was successfully obtained, which may provide a useful reagent for interfering the human renal tubular epithelial-mesenchymal transition.

  14. 肾小管损伤治疗的研究进展%Progress of the treatment on renal tubular injury

    Institute of Scientific and Technical Information of China (English)

    林金爱

    2013-01-01

    A variety of kidney diseases have different degree of renal tubular injury,it even occur before the kidney damage.Since renal tubular injury still lack of effective therapy,it usually recovered by renal tubular epithelial cell itself.But the self-recover process is too long.If it is unable to spend this period,renal damage may not be reversible.So effective therapy is an emergency problem to be solved in clinical.%临床上多种肾脏疾病均有不同程度的肾小管损伤,甚至在肾脏受损前已出现肾小管病变.至今肾小管损伤尚缺乏有效的治疗手段,通常等待肾小管上皮细胞的自身恢复,这一过程较漫长,若无法渡过这一时期,肾损伤可能无法逆转.因此,寻求有效的治疗手段是临床急待解决的问题.

  15. Renal proximal tubular cell fibronectin accumulation in response to glucose is polyol pathway dependent

    Science.gov (United States)

    Morrisey; Steadman; Williams; Phillips

    1999-06-01

    Thickening and reduplication of the tubular basement membrane has been reported as an early event in diabetic nephropathy. In the current study we have examined the polar requirements of proximal tubular cells for the D-glucose stimulated accumulation of fibronectin. We also examined the mechanism by which glucose led to accumulation of fibronectin, with particular emphasis on the polyol pathway. Incubation of confluent monolayers of LLC-PK1 cells grown on tissue culture inserts with 25 mM D-glucose on either their apical or basolateral aspect, led to fibronectin accumulation in the basolateral compartment. This reached statistical significance 24 h following apical addition of glucose (2.7 fold increase compared to 5 mM D-glucose, p = 0.007, n = 6), and 12 h after the basolateral addition of glucose (2.54 fold increase compared to 5 mM D-glucose, p = 0.02, n = 6). The increase in fibronectin concentration in response to glucose was inhibited by the aldose reductase inhibitor sorbinil. At a dose of 100&mgr;M sorbinil there was 59% inhibition of fibronectin accumulation in response to glucose, 48 h after the addition of the inhibitor (4.76 +/- 1.4 vs 11.53 +/- 1.41, mean +/- SD, p = 0.01, n = 3). Exposure of cells to glucose at either their apical or basolateral aspect lead to accumulation of intracellular glucose and polyol pathway activation, as assessed by sorbitol accumulation. Accumulation of intracellular glucose and hence subsequent polyol pathway activation occurred independently of transport of glucose by either apical sodium linked glucose transporter (SLGT) or basolateral GLUT 1. The data demonstrate that fibronectin generation in response to glucose was non-polar in terms application of glucose, but polar in terms of fibronectin accumulation. Furthermore modulation of fibronectin was mediated by polyol pathway activation, and more specifically related to the metabolism of sorbitol to fructose. PMID:10354307

  16. Ultrastructural study of renal tubular damage induced by captopril in adult and fetal mice

    Directory of Open Access Journals (Sweden)

    Hamdy H. Swelim and Aleya A.Sakr

    2004-12-01

    Full Text Available The present study has been designed to evaluate the possible nephrotoxicity of the angiotensin converting enzyme inhibitor, captopril on renal tubules of adult and maternally treated fetuses of CD-1 mice. The study included the effect of captopril administration for one month up to three months in adults, while in fetuses, they were exposed to the drug through their mothers in two periods. The first was from 6th-12th days of pregnancy, while the second was from 6th -18th day of pregnancy. The dose used in the present study represents the dose equivalent to the therapeutic daily dose taken by human. All the recorded tissue damage was found to be time dependent. The first remarkable feature noticed in all the treated adult animals was the presence of hyaline casts that obstructed most of the renal tubules. The second remarkable feature was the increase of the intertubular space associated with irregularity of the tubules due to the degeneration and vacuolation of the basal regions of the cells. Renal tubule cells showed large blebs, accumulaton of lipids, degeneration and necrosis. In maternally treated fetuses, the proximal convoluted tubule cells displayed moderate vacuolation and marked increase of lysosomes while some of the distal convoluted tubules revealed atrophy and their cells showed loss of mitochondria. In addition, the collecting tubules showed loss of microprojections. Worthy to mention that there was apparent increase of mesenchymal cells as well as fibroblasts in the fetuses maternally treated with captopril. The significance of these changes was discussed and it should be emphasized that captopril must be taken with caution for pregnant women and those who suffer from renal troubles. Moreover, kidney function should be monitored during therapy .

  17. Antioxidant properties of repaglinide and its protections against cyclosporine A-induced renal tubular injury

    Science.gov (United States)

    Li, Dao; Li, Jin; Li, Hui; Wu, Qiong; Li, Qi-Xiong

    2016-01-01

    Objective(s): Repaglinide (RG) is an antihyperglycemic agent used for the treatment of non-insulin-dependent diabetes mellitus. It has a good safety and efficacy profile in diabetic patients with complications in renal impairment and is an appropriate treatment choice, even for individuals with more severe degrees of renal malfunctions. The aim of the present study was to examine the protective effect of RG on cyclosporine A (CsA)-induced rat renal impairment and to evaluate the antioxidant mechanisms by which RG exerts its protective actions. Materials and Methods: Fifty male Sprague-Dawley rats weighing 250–300 g were randomly divided into five groups: administrations of olive oil (control, PO), RG (0.4 mg/kg, PO), CsA (30 mg/kg in olive oil, SC), RG (0.2 or 0.4 mg/kg, PO) plus CsA (30 mg/kg in olive oil SC) every day for 15 days. Results: SC administration of CsA (30 mg/kg) to rats produced marked elevations in the levels of renal impairment parameters such as urinary protein, N-acetyl-beta-D-glucosaminidase (NAG), serum creatinine (SCr), and blood urea nitrogen (BUN). It also caused histologic injury to the kidneys. Oral administration of RG (0.2 and 0.4 mg/kg) markedly decreased all the aforementioned changes. In addition, CsA caused increases in the levels of malondialdehyde (MDA) and decreases in superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GSR), glutathione-S-transferase (GST), and glutathione in kidney homogenate, which were reversed significantly by both doses of RG. Conclusion: The findings of our study indicate that RG may play an important role in protecting the kidney from oxidative insult.

  18. 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.

  19. HOXA13 exerts a beneficial effect in albumin-induced epithelial-mesenchymal transition via the glucocorticoid receptor signaling pathway in human renal tubular epithelial cells.

    Science.gov (United States)

    Peng, Li; He, Qingnan; Li, Xiaoyan; Shuai, Lanjun; Chen, Haixia; Li, Yongzhen; Yi, Zhuwen

    2016-07-01

    Previous studies have suggested that albumin-induced renal tubular epithelial cell injury contributes to renal interstitial fibrosis. Epithelial-mesenchymal transition (EMT) is known to be a key mechanism in the pathogenesis and progression of renal interstitial fibrosis. Homeobox protein HOX‑A13 (HOXA13) is a nuclear transcriptional factor that has been reported to be involved in renal fibrosis. However, the mechanism underlying the effect of HOXA13 in human serum albumin (HSA)‑induced EMT in HKC renal tubular epithelial cells remains to be elucidated. Thus, the aim of the present study was to investigate the role of HOXA13 in HSA‑induced EMT in HKC cells and the potential mechanism of the glucocorticoid receptor (GR) signaling pathway. The protein and mRNA expression levels of HOXA13, cytokeratin, and vimentin were determined by western blot analysis and reverse transcription‑quantitative polymerase chain reaction in HKC cells, which were co‑incubated with HSA at different concentrations or for different time periods. The results demonstrated that HOXA13 mRNA and protein expression decreased in a dose‑ and time‑dependent manner when induced by HSA in HCK cells. The liposomal transfection experiment suggested that overexpression of HOXA13 activated the GR signal, which inhibits HSA-induced EMT. HOXA13 is involved in HSA‑induced EMT in HKC cells and upregulation of HOXA13 exerts a beneficial effect in EMT, which may be associated with the GR signaling pathway. PMID:27176855

  20. 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.

  1. 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...... of the nephron. In the kidneys with intact innervation RVP elevation to 19.9 +/- 0.1 mmHg caused significant increases in both absolute (APR) and fractional (FPR) proximal reabsorption rates from 33.4 +/- 4.2 to 38.7 +/- 2.0 ml min-1 and from 0.62 +/- 0.04 to 0.71 +/- 0.04, respectively. These responses were......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...

  2. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine.

    Science.gov (United States)

    Zhang, Shiqi; Ntasis, Emmanouil; Kabtni, Sarah; van den Born, Jaap; Navis, Gerjan; Bakker, Stephan J L; Krämer, Bernhard K; Yard, Benito A; Hauske, Sibylle J

    2016-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubular epithelial cells (PTECs) more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG) or HG (30 mM), were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1), ferroportin (IREG), and transferrin receptor protein 1 (TFRC). Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity. PMID:26788523

  3. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

    Directory of Open Access Journals (Sweden)

    Shiqi Zhang

    2016-01-01

    Full Text Available Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS. Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG exposure makes cultured human umbilical vein endothelial cells (HUVECs and renal proximal tubular epithelial cells (PTECs more susceptible to metal induced toxicity and if this is ameliorated by L-carnosine. HUVECs and PTECs, cultured under normal glucose (5 mM, NG or HG (30 mM, were challenged for 24 h with FeCl3. Cell viability was not impaired under HG conditions nor did HG increase susceptibility to FeCl3. HG did not change the expression of divalent metal transporter 1 (DMT1, ferroportin (IREG, and transferrin receptor protein 1 (TFRC. Irrespective of glucose concentrations L-carnosine prevented toxicity in a dose-dependent manner, only if it was present during the FeCl3 challenge. Hence our study indicates that iron induced cytotoxicity is not enhanced under HG conditions. L-Carnosine displayed a strong protective effect, most likely by chelation of iron mediated toxicity.

  4. Intranuclear Inclusions in Renal Tubular Epithelium in Immunodeficient Mice Stain with Antibodies for Bovine Papillomavirus Type 1 L1 Protein

    Directory of Open Access Journals (Sweden)

    Elizabeth McInnes

    2015-06-01

    Full Text Available The kidneys from six immunodeficient mice examined by Cerberus Sciences and the Animal Resources Centre, displayed karyomegaly with pale eosinophilic, intranuclear inclusions upon histopathological examination. Electron microscopy performed on kidney tissue from 5/6 mice demonstrated margination of the chromatin in large nuclei. Laboratory tests were used to detect nucleic acid of papillomaviruses, polyomaviruses, circoviruses and anelloviruses (4/6 mice, a specific PCR was used to detect murine polyomavirus (1/6, and a panel of serological tests was used to detect seroconversion to major murine pathogens (1/6. All molecular and serological tests were negative. Immunohistochemistry using polyclonal anti-bovine papillomavirus type 1 (BPV-1 L1 antibody, Camvir monoclonal anti-papillomavirus antibody (directed against the seven amino acids GFGAMDF found in human papillomavirus (HPV 16 L1 protein, a commercially available mixture of two monoclonal antibodies, anti-BPV-1 L1/1H8 + Camvir antibodies, and a monoclonal anti-Hsc70 antibody revealed specific, positive staining of murine renal tubular epithelial intranuclear inclusions in 6/6 mice using the anti-BPV-1 L1 containing antibodies only. Methyl pyronin green, PAS and Feulgen histochemical reactions revealed that the intranuclear inclusions did not consist of RNA, DNA or carbohydrate. An immunohistochemical method now exists that can be used to confirm and evaluate suspected cases of murine inclusion body nephropathy.

  5. Andrographolide-induced apoptosis in human renal tubular epithelial cells: Roles of endoplasmic reticulum stress and inflammatory response.

    Science.gov (United States)

    Gu, Li-Li; Zhang, Xin-Yue; Xing, Wen-Min; Xu, Jia-Dong; Lu, Hong

    2016-07-01

    Andrographolide sodium bisulfate as a kind of soluble derivative of andrographolide (AD), is obviously known to be nephrotoxicity, but AD has not been reported clearly. Our study aimed to investigate the induction of apoptosis in human renal tubular epithelial (HK-2) cells by AD and its possible mechanism. Our results demonstrated that AD (0-250μmol/L) inhibited Hk-2 cells proliferation in a dose- and time-dependent manner and induced apoptosis, accompanied by decreased of superoxide dismutase (SOD) activity and increased of malondialdehvde (MDA) content. Simultaneously, AD regulated the expression of endoplasmic reticulum (ER) molecular chaperone glucose-regulated protein 78 (GRP78/Bip) protein, elevated the expressions of C/EBP homologous protein (CHOP) and Caspase-4, indicating activation of ER stress signaling, and induced the alterative expression of kidney injury molecule-1 (KIM-1), tumor necrosis factor-α (TNF-α) and Interleukin-6 (IL-6) proteins. It provided evidence that ER stress and inflammation would be significant mechanisms responsible for AD-induced apoptosis in addition to oxidative stress. PMID:27344125

  6. Role of connective growth factor in plasminogen activator inhibitor-1 and fibronectin expression induced by transforming growth factor β1 in renal tubular cells

    Institute of Scientific and Technical Information of China (English)

    张春; 孟宪芳; 朱忠华; 杨晓; 邓安国

    2004-01-01

    Background Connective tissue growth factor (CTGF) contributes greatly to renal tubulointerstitial fibrosis, which is the final event leading to end-stage renal failure. This study was designed to investigate the effects of CTGF antisense oligodeoxynucleotides (ODNs) on the expressions of plasminogen activator inhibitor-1 (PAI-1) and fibronectin in renal tubular cells induced by transforming growth factor β1 (TGF-β1) in addition to the role of CTGF in the accumulation and degradation of renal extracellular matrix (ECM).Methods A human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODNs were transfected into HKC cells. After HKC cells were stimulated with TGF-β1 (5 μg/L), the mRNA levels of PAI-1 and fibronectin were measured by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 and fibronectin in the medium were determined by Western blot and ELISA, respectively.Results TGF-β1 was found to induce tubular CTGF, PAI-1, and fibronectin mRNA expression. PAI-1 and fibronectin mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODNs. CTGF antisense ODNs also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 and fibronectin protein secreted into the medium.Conclusions CTGF may play a crucial role in the accumulation and degradation of excessive ECM during tubulointerstitial fibrosis, and transfecting CTGF antisense ODNs may be an effective way to prevent renal fibrosis.

  7. 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. PMID:26979714

  8. Vitamin C Attenuates Hemorrhagic Shock-induced Dendritic Cell-specific Intercellular Adhesion Molecule 3-grabbing Nonintegrin Expression in Tubular Epithelial Cells and Renal Injury in Rats

    Institute of Scientific and Technical Information of China (English)

    Li Ma; Jian Fei; Ying Chen; Bing Zhao; Zhi-Tao Yang; Lu Wang; Hui-Qiu Sheng

    2016-01-01

    Background:The expression of dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) in renal tubular epithelial cells has been thought to be highly correlated with the occurrence of several kidney diseases,but whether it takes place in renal tissues during hemorrhagic shock (HS) is unknown.The present study aimed to investigate this phenomenon and the inhibitory effect of Vitamin C (VitC).Methods:A Sprague-Dawley rat HS model was established in vivo in this study.The expression level and location of DC-SIGN were observed in kidneys.Also,the degree of histological damage,the concentrations of tumor necrosis factor-α and interleukin-6 in the renal tissues,and the serum concentration of blood urea nitrogen and creatinine at different times (2-24 h) after HS (six rats in each group),with or without VitC treatment before resuscitation,were evaluated.Results:HS induced DC-SIGN expression in rat tubular epithelial cells.The proinflammatory cytokine concentration,histological damage scores,and functional injury of kidneys had increased.All these phenomena induced by HS were relieved when the rats were treated with VitC before resuscitation.Conclusions:The results of the present study illustrated that HS could induce tubular epithelial cells expressing DC-SIGN,and the levels of proinflammatory cytokines in the kidney tissues improved correspondingly.The results also indicated that VitC could suppress the DC-SIGN expression in the tubular epithelial cells induced by HS and alleviate the inflammation and functional injury in the kidney.

  9. Proximal tubular efflux transporters involved in renal excretion of p-cresyl sulfate and p-cresyl glucuronide: Implications for chronic kidney disease pathophysiology.

    Science.gov (United States)

    Mutsaers, Henricus A M; Caetano-Pinto, Pedro; Seegers, Andries E M; Dankers, Anita C A; van den Broek, Petra H H; Wetzels, Jack F M; van den Brand, Jan A J G; van den Heuvel, Lambertus P; Hoenderop, Joost G; Wilmer, Martijn J G; Masereeuw, Rosalinde

    2015-10-01

    The uremic solutes p-cresyl sulfate (pCS) and p-cresyl glucuronide (pCG) accumulate in patients with chronic kidney disease (CKD), and might contribute to disease progression. Moreover, retention of these solutes may directly be related to renal tubular function. Here, we investigated the role of the efflux transporters Multidrug Resistance Protein 4 (MRP4) and Breast Cancer Resistance Protein (BCRP) in pCS and pCG excretion, and studied the impact of both solutes on the phenotype of human conditionally immortalized renal proximal tubule epithelial cells (ciPTEC). Our results show that p-cresol metabolites accumulate during CKD, with a shift from sulfation to glucuronidation upon progression. Moreover, pCS inhibited the activity of MRP4 by 40% and BCRP by 25%, whereas pCG only reduced MRP4 activity by 75%. Moreover, BCRP-mediated transport of both solutes was demonstrated. Exposure of ciPTEC to pCG caused epithelial-to-mesenchymal transition, indicated by increased expression of vimentin and Bcl-2, and diminished E-cadherin. This was associated with altered expression of key tubular transporters. In conclusion, BCRP is likely involved in the renal excretion of both solutes, and pCG promotes phenotypical changes in ciPTEC, supporting the notion that uremic toxins may be involved in CKD progression by negatively affecting renal tubule cell phenotype and functionality. PMID:26216510

  10. 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

  11. Hyporeninemic hypoaldosteronism in diabetic patients with chronic renal failure.

    Science.gov (United States)

    Grande Villoria, J; Macias Nunez, J F; Miralles, J M; De Castro del Pozo, S; Tabernero Romo, J M

    1988-01-01

    Plasma renin activity, plasma aldosterone levels and renal tubular capacity to excrete hydrogen ions were studied in 13 patients suffering from diabetes mellitus with a creatinine clearance of less than 40 ml/min. The results were compared with those obtained in a control group, in a group of nondiabetic subjects with chronic renal failure (CRF) and in a group of diabetic patients without CRF. Twelve of the thirteen diabetic patients with CRF had data characteristic of hyporeninemic hypoaldosteronism associated with type IV renal tubular acidosis. On comparing the results with those of the other two groups of patients, it was observed that the manifestations of the latter two groups considered separately were different from those of the problem group, although in the diabetic patients with normal glomerular filtration rate (GFR) hyporeninism but not hypoaldosteronism was present accompanied by a lower net acid excretion (p less than 0.001) due to a lower excretion of NH4 (p less than 0.05) and titratable acid (p less than 0.001) when the patients were challenged with an NH4Cl overload. We believe that a conjunction of diabetes and renal failure is necessary for the diabetic patients with a decrease in GFR to show hyporeninemic hypoaldosteronism and type IV tubular acidosis.

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

    Science.gov (United States)

    de Borst, Martin H; Nauta, Ferdau L; Vogt, Liffert; Laverman, Gozewijn D; Gansevoort, Ron T; Navis, Gerjan

    2012-01-01

    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, pglomerulo- and tubulo-protective effects as observed outweigh the possible side-effects of NSAID treatment on the long term.

  13. Study on Effect of Baoyuan Qiangshen (保元强肾) Capsule No. Ⅱ on Tubular Interstitial Injury in Chronic Renal Failure Patients

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To explore the protective effect of Baoyuan Qiangshen Capsule No. Ⅱ (BYQS) and its mechanism in treating chronic renal failure (CRF). Methods: Sixty CRF patients were divided into 2 groups randomly, the treated group used BYQS combined with Lotensin and the control group administered with essential amino acid combined with Lotensin. Changes of renal functions and tubular labelled proteins were observed. Results: The markedly effective rate and total effective rate of the treated group were 63.3% and 93.3% respectively, and those of the control group were 30.0% and 56.7% respectively, the effect of the treated group was obviously better than that of the control group (P<0.01). In the treated group after medication, blood urea nitrogen, serum creatinine and clearance rate of creatinine were improved significantly (P<0.01), while Tamm-Horfau protein increased significantly (P<0.01). Conclusion: BYQS could alleviate tubular interstitial injury significantly so as to improve the renal function and enhance the effective rate in treating CRF.

  14. Mitochondrial DNA m.3242G > A mutation, an under diagnosed cause of hypertrophic cardiomyopathy and renal tubular dysfunction?

    NARCIS (Netherlands)

    Wortmann, S.B.; Champion, M.P.; Heuvel, L.P. van den; Barth, H.; Trutnau, B.; Craig, K.; Lammens, M.M.; Schreuder, M.F.; Taylor, R.W.; Smeitink, J.A.M.; Wevers, R.A.; Rodenburg, R.J.T.; Morava, E.

    2012-01-01

    We present two new patients with the recently described mitochondrial m.3242G > A mutation. Although the mutation is situated next to the well known m.3243A > G mutation, the most common alteration associated with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode

  15. Parathyroid hormone-mitogen-activated protein kinase axis exerts fibrogenic effect of connective tissue growth factor on human renal proximal tubular cells

    Institute of Scientific and Technical Information of China (English)

    GUO Yun-shan; YUAN Wei-jie; ZHANG Ai-ping; DING Yao-hai; WANG Yan-xia

    2010-01-01

    Background Enhanced and prolonged expression of connective tissue growth factor (CTGF) is associated with kidney fibrosis. Parathyroid hormone (PTH) is involved in the genesis of disturbed calcium/phosphate metabolism and ostitis fibrosa in renal failure. PTH activated mitogen-activated protein kinase (MAPK) signaling pathway is present in renal tubular cells. The aim of this study was to identify the mechanism how the signal is transduced to result in extracellular signal-regulated protein kinase (ERK) activation, leading to upregulation of CTGF.Methods The levels of CTGF mRNA and protein in human kidney proximal tubular cells (HK-2) treated with PTH in the presence or absence of the MAPK inhibitor PD98059 were analyzed by quantitative real-time polymerase chain reaction (RT-PCR) and immunoblotting assay. The activation of the CTGF promoter in HK-2 cells was determined by the dual-luciferase assay. The effects of the protein kinase A (PKA) activator 8-Br-cAMP and protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) on MAPK phosphorylation, and the effects of the PKA inhibitor H89 and PKC inhibitor calphostin C on MAPK phosphorylation and CTGF expression were detected by immunoblotting assay.Results PD98059 inhibited the PTH stimulated expression of CTGF, which strongly suggested that the MAPK signaling pathway plays an important role in the PTH-induced CTGF upregulation in renal tubular cells. A PKA activator as well as PKC activators induced MAPK phosphorylation, and both PKA and PKC inhibitors antagonized PTH-induced MAPK phosphorylation and CTGF expression.Conclusion CTGF expression is upregulated by PTH through a PKC/PKA-ERK-dependent pathway.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Effects of 1,25-dihydroxyvitamin D3 on high glucose-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    郭汉城

    2013-01-01

    Objective To study the effects of 1,25-dihydroxyvitamin D3on high-induced expression of uncoupling protein 2 and oxidative stress in human renal tubular epithelial cells.Methods The HK-2 cells with different culture media were divided into normal glucose group (NG group,5.5 mmol/L D-glucose) ;high glucose group (HG group,30 mmol/L D-glucose) ;mannitol group (MG group,5.5 mmol/L D-glucose+24.5 mmol/L manni-

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

    Directory of Open Access Journals (Sweden)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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 10−7 M aldosterone for 1 h by chromatin immunoprecipitation with deep-sequence (ChIP-seq) and mRNA of the cell-line with treatment of 10−7 M aldosterone for 3 h by microarray. Results: 3xFLAG-hMR overexpressed in mDCT cells accumulated in the nucleus in response to 10−9 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

  1. Kidney Specific Protein-Positive Cells Derived from Embryonic Stem Cells Reproduce Tubular Structures In Vitro and Differentiate into Renal Tubular Cells

    OpenAIRE

    Ryuji Morizane; Toshiaki Monkawa; Shizuka Fujii; Shintaro Yamaguchi; Koichiro Homma; Yumi Matsuzaki; Hideyuki Okano; Hiroshi Itoh

    2013-01-01

    Embryonic stem cells and induced pluripotent stem cells have the ability to differentiate into various organs and tissues, and are regarded as new tools for the elucidation of disease mechanisms as well as sources for regenerative therapies. However, a method of inducing organ-specific cells from pluripotent stem cells is urgently needed. Although many scientists have been developing methods to induce various organ-specific cells from pluripotent stem cells, renal lineage cells have yet to be...

  2. Renal tubular SGK1 deficiency causes impaired K+ excretion via loss of regulation of NEDD4-2/WNK1 and ENaC.

    Science.gov (United States)

    Al-Qusairi, Lama; Basquin, Denis; Roy, Ankita; Stifanelli, Matteo; Rajaram, Renuga Devi; Debonneville, Anne; Nita, Izabela; Maillard, Marc; Loffing, Johannes; Subramanya, Arohan R; Staub, Olivier

    2016-08-01

    The stimulation of postprandial K(+) clearance involves aldosterone-independent and -dependent mechanisms. In this context, serum- and glucocorticoid-induced kinase (SGK)1, a ubiquitously expressed kinase, is one of the primary aldosterone-induced proteins in the aldosterone-sensitive distal nephron. Germline inactivation of SGK1 suggests that this kinase is fundamental for K(+) excretion under conditions of K(+) load, but the specific role of renal SGK1 remains elusive. To avoid compensatory mechanisms that may occur during nephrogenesis, we used inducible, nephron-specific Sgk1(Pax8/LC1) mice to assess the role of renal tubular SGK1 in K(+) regulation. Under a standard diet, these animals exhibited normal K(+) handling. When challenged by a high-K(+) diet, they developed severe hyperkalemia accompanied by a defect in K(+) excretion. Molecular analysis revealed reduced neural precursor cell expressed developmentally downregulated protein (NEDD)4-2 phosphorylation and total expression. γ-Epithelial Na(+) channel (ENaC) expression and α/γENaC proteolytic processing were also decreased in mutant mice. Moreover, with no lysine kinase (WNK)1, which displayed in control mice punctuate staining in the distal convoluted tubule and diffuse distribution in the connecting tubule/cortical colleting duct, was diffused in the distal convoluted tubule and less expressed in the connecting tubule/collecting duct of Sgk(Pax8/LC1) mice. Moreover, Ste20-related proline/alanine-rich kinase phosphorylation, and Na(+)-Cl(-) cotransporter phosphorylation/apical localization were reduced in mutant mice. Consistent with the altered WNK1 expression, increased renal outer medullary K(+) channel apical localization was observed. In conclusion, our data suggest that renal tubular SGK1 is important in the regulation of K(+) excretion via the control of NEDD4-2, WNK1, and ENaC.

  3. Severe metabolic acidosis following assault chemical burn

    Directory of Open Access Journals (Sweden)

    Sophie De Roock

    2012-01-01

    Full Text Available Assault chemical burns are uncommon in northern Europe. Besides local toxicity, systemic manifestations are possible after strong acid exposure. A 40-year-old woman was admitted 1 h after a criminal assault with sulfuric acid. The total burned surface area was 35%, third degree. Injury was due to sulfuric acid (measured pH 0.9 obtained from a car battery. Immediate complications were obstructive dyspnea and metabolic acidosis. The admission arterial pH was 6.92, with total bicarbonate 8.6 mEq/l and base deficit 23.4 mEq/l. The correction of metabolic acidosis was achieved after several hours by the administration of bicarbonate and lactate buffers. The patient developed several burns-related complications (sepsis and acute renal failure. Cutaneous projections of strong acids may cause severe metabolic acidosis, particularly when copious irrigation and clothes removal cannot be immediately performed at the scene.

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

    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.

  6. Activation of ERK accelerates repair of renal tubular epithelial cells, whereas it inhibits progression of fibrosis following ischemia/reperfusion injury.

    Science.gov (United States)

    Jang, Hee-Seong; Han, Sang Jun; Kim, Jee In; Lee, Sanggyu; Lipschutz, Joshua H; Park, Kwon Moo

    2013-12-01

    Extracellular signal-regulated kinase (ERK) signals play important roles in cell death and survival. However, the role of ERK in the repair process after injury remains to be defined in the kidney. Here, we investigated the role of ERK in proliferation and differentiation of tubular epithelial cells, and proliferation of interstitial cells following ischemia/reperfusion (I/R) injury in the mouse kidney. Mice were subjected to 30min of renal ischemia. Some mice were administered with U0126, a specific upstream inhibitor of ERK, daily during the recovery phase, beginning at 1day after ischemia until sacrifice. I/R caused severe tubular cell damage and functional loss in the kidney. Nine days after ischemia, the kidney was restored functionally with a partial restoration of damaged tubules and expansion of fibrotic lesions. ERK was activated by I/R and the activated ERK was sustained for 9days. U0126 inhibited the proliferation, basolateral relocalization of Na,K-ATPase and lengthening of primary cilia in tubular epithelial cells, whereas it enhanced the proliferation of interstitial cells and accumulation of extracellular matrix. Furthermore, U0126 elevated the expression of cell cycle arrest-related proteins, p21 and phospholylated-chk2 in the post-ischemic kidney. U0126 mitigated the post-I/R increase of Sec10 which is a crucial component of exocyst complex and an important factor in ciliogenesis and tubulogenesis. U0126 also enhanced the expression of fibrosis-related proteins, TGF-β1 and phosphorylated NF-κB after ischemia. Our findings demonstrate that activation of ERK is required for both the restoration of damaged tubular epithelial cells and the inhibition of fibrosis progression following injury.

  7. Intracellular delivery of the p38 mitogen-activated protein kinase inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)1H-imidazole] in renal tubular cells : A novel strategy to treat renal fibrosis

    NARCIS (Netherlands)

    Prakash, Jai; Sandovici, Maria; Saluja, Vinay; Lacombe, Marie; Schaapveld, Roel Q. J.; de Borst, Martin H.; van Goor, Harry; Henning, Robert H.; Proost, Johannes H.; Moolenaar, Frits; Keri, Gyorgy; Meijer, Dirk K. F.; Poelstra, Klaas; Kok, Robbert J.

    2006-01-01

    During renal injury, activation of p38 mitogen-activated protein kinase (MAPK) in proximal tubular cells plays an important role in the inflammatory events that eventually lead to renal fibrosis. We hypothesized that local inhibition of p38 within these cells may be an interesting approach for the t

  8. Renal Toxicities of Targeted Therapies.

    Science.gov (United States)

    Abbas, Anum; Mirza, Mohsin M; Ganti, Apar Kishor; Tendulkar, Ketki

    2015-12-01

    With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.

  9. Renal Toxicities of Targeted Therapies.

    Science.gov (United States)

    Abbas, Anum; Mirza, Mohsin M; Ganti, Apar Kishor; Tendulkar, Ketki

    2015-12-01

    With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease. PMID:25922090

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

    DEFF Research Database (Denmark)

    Juul, Troels; Palm, Fredrik; Nielsen, Per Mose;

    2016-01-01

    ) C MR is suitable for cells isolated from kidney tissue, without prior cell culture. METHODS: 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...

  11. Changes in Renal Function and Blood Pressure in Patients with Stone Disease

    Science.gov (United States)

    Worcester, Elaine M.

    2007-04-01

    Stone disease is a rare cause of renal failure, but a history of kidney stones is associated with an increased risk for chronic kidney disease, particularly in overweight patients. Loss of renal function seems especially notable for patients with stones associated with cystinuria, hyperoxaluria, and renal tubular acidosis, in whom the renal pathology shows deposits of mineral obstructing inner medullary collecting ducts, often diffusely. However, even idiopathic calcium oxalate stone formers have a mild but significant decrease in renal function, compared to age, sex and weight-matched normals, and appear to lose renal function with age at a slightly faster rate than non-stone formers. There is also an increased incidence of hypertension among stone formers, although women are more likely to be affected than men.

  12. 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...

  13. Some effects of ammonium salts on renal histology and function in the dog.

    Science.gov (United States)

    Orvell, B D; Wesson, L G

    1976-01-01

    NH4Cl was infused into the left renal artery of anesthetized dogs at 50-125 mum/kg/min for up to 110 min. Renal blood flow declined early then increased to supra-control levels during infusion. Kidneys perfused at 125 mum/kg/min for 90 min showed patchy to confluent mixtures of cortical necrosis and tubular necrosis. Experimental kidneys invariably showed lower urine osmolality than contralateral controls 48 h after perfusion. Kidneys with necrosis showed depressed creatinine clearance as well. Renal artery infusion of NH4 acetate or intravenous infusion of NaHCO3 during arterial infusion of NH4Cl prevented significant acidosis and caused minimal histological changes, but depression of urine osmolality was not prevented. It is concluded that renal ammonium concentrations up to 40 mum/liter for 90 min does not cause tubular necrosis but does impair urine concentration. Severe tissue damage followed renal exposure to high ammonium concentrations in the presence of metabolic or renal acidosis.

  14. Renal β-intercalated cells maintain body fluid and electrolyte balance

    OpenAIRE

    Gueutin, Victor; Vallet, Marion; Jayat, Maximilien; Peti-Peterdi, Janos; Cornière, Nicolas; Leviel, Françoise; Sohet, Fabien; Wagner, Carsten A.; Eladari, Dominique; Chambrey, Régine

    2013-01-01

    Inactivation of the B1 proton pump subunit (ATP6V1B1) in intercalated cells (ICs) leads to type I distal renal tubular acidosis (dRTA), a disease associated with salt- and potassium-losing nephropathy. Here we show that mice deficient in ATP6V1B1 (Atp6v1b1–/– mice) displayed renal loss of NaCl, K+, and water, causing hypovolemia, hypokalemia, and polyuria. We demonstrated that NaCl loss originated from the cortical collecting duct, where activity of both the epithelial sodium channel (ENaC) a...

  15. Ochratoxin A induces karyomegaly and cell cycle aberrations in renal tubular cells without relation to induction of oxidative stress responses in rats.

    Science.gov (United States)

    Taniai, Eriko; Yafune, Atsunori; Nakajima, Masahiro; Hayashi, Shim-Mo; Nakane, Fumiyuki; Itahashi, Megu; Shibutani, Makoto

    2014-01-01

    Ochratoxin A (OTA) is a renal carcinogen that induces karyomegaly in target renal tubular cells of the outer stripe of the outer medulla (OSOM). This study was performed to clarify the relationship between oxidative stress and the karyomegaly-inducing potential involving cell cycle aberration of OTA in the OSOM. Rats were treated with OTA for 28 days in combination with enzymatically modified isoquercitrin (EMIQ) or α-lipoic acid (ALA) as antioxidants. OTA increased the mRNA levels of the antioxidant enzyme-related genes Gpx1, Gpx2, Gstm1 and Nfe2l2, but did not increase the levels of Gsta5, Keap1, Nqo1, Hmox1, Aldh1a1, Por, Prdx1 and Txn1. OTA also did not change the levels of thiobarbituric acid-reactive substances, glutathione disulfide/reduced glutathione, and the immunoreactive tubular cell distribution of nuclear factor erythroid 2-related factor 2 in the OSOM. Co-treatment with EMIQ or ALA did not cause any changes in these parameters. As previously reported, OTA increased cell proliferation activity, apoptosis and immunohistochemical cellular distributions of molecules suggestive of induction of DNA damage and cell cycle aberrations involving spindle checkpoint disruption and cell cycle arrest. However, co-treatment with EMIQ or ALA did not suppress these changes, and ALA co-treatment increased the cell proliferation activity induced by OTA. These results suggest that OTA facilitates cell cycling involving cell cycle aberrations and apoptosis as a basis of the mechanism behind the development of karyomegaly and subsequent carcinogenicity targeting the OSOM, without relation to induction of oxidative stress. On the other hand, ALA may promote the OTA-induced proliferation of carcinogenic target cells.

  16. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

    Directory of Open Access Journals (Sweden)

    Kristoffer Svensson

    Full Text Available The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction.

  17. Loss of Renal Tubular PGC-1α Exacerbates Diet-Induced Renal Steatosis and Age-Related Urinary Sodium Excretion in Mice.

    Science.gov (United States)

    Svensson, Kristoffer; Schnyder, Svenia; Cardel, Bettina; Handschin, Christoph

    2016-01-01

    The kidney has a high energy demand and is dependent on oxidative metabolism for ATP production. Accordingly, the kidney is rich in mitochondria, and mitochondrial dysfunction is a common denominator for several renal diseases. While the mitochondrial master regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) is highly expressed in kidney, its role in renal physiology is so far unclear. Here we show that PGC-1α is a transcriptional regulator of mitochondrial metabolic pathways in the kidney. Moreover, we demonstrate that mice with an inducible nephron-specific inactivation of PGC-1α in the kidney display elevated urinary sodium excretion, exacerbated renal steatosis during metabolic stress but normal blood pressure regulation. Overall, PGC-1α seems largely dispensable for basal renal physiology. However, the role of PGC-1α in renal mitochondrial biogenesis indicates that activation of PGC-1α in the context of renal disorders could be a valid therapeutic strategy to ameliorate renal mitochondrial dysfunction. PMID:27463191

  18. Bidirectional signalling between EphA2 and ephrinA1 increases tubular cell attachment, laminin secretion and modulates erythropoietin expression after renal hypoxic injury.

    Science.gov (United States)

    Rodriguez, Stéphane; Rudloff, Stefan; Koenig, Katrin Franziska; Karthik, Swapna; Hoogewijs, David; Huynh-Do, Uyen

    2016-08-01

    Acute kidney injury (AKI) is common in hospitalized patients and has a poor prognosis, the severity of AKI being linked to progression to chronic kidney disease. This stresses the need to search for protective mechanisms during the acute phase. We investigated kidney repair after hypoxic injury using a rat model of renal artery branch ligation, which led to an oxygen gradient vertical to the corticomedullary axis. Three distinct zones were observed: tubular necrosis, infarction border zone and preserved normal tissue. EphA2 is a receptor tyrosine kinase with pivotal roles in cell architecture, migration and survival, upon juxtacrine contact with its membrane-bound ligand EphrinA1. Following hypoxia, EphA2 was up-regulated in cortical and medullary tubular cells, while EphrinA1 was up-regulated in interstitial cells adjacent to peritubular capillaries. Moreover, erythropoietin (EPO) messenger RNA (mRNA) was strongly expressed in the border zone of infarcted kidney within the first 6 h. To gain more insight into the biological impact of EphA2 and EphrinA1 up-regulation, we activated the signalling pathways in vitro using recombinant EphrinA1/Fc or EphA2/Fc proteins. Stimulation of EphA2 forward signalling in the proximal tubular cell line HK2 increased cell attachment and laminin secretion at the baso-lateral side. Conversely, activation of reverse signalling through EphrinA1 expressed by Hep3B cells promoted EPO production at both the transcriptional and protein level. Strikingly, in co-culture experiments, juxtacrine contact between EphA2 expressing MDCK and EphrinA1 expressing Hep3B was sufficient to induce a significant up-regulation of EPO mRNA production in the latter cells, even in the absence of hypoxic conditions. The synergistic effects of EphA2 and hypoxia led to a 15-20-fold increase of EPO expression. Collectively, our results suggest an important role of EphA2/EphrinA1 signalling in kidney repair after hypoxic injury through stimulation of (i) tubular

  19. Triptolide inhibits B7-H1 expression on proinflammatory factor activated renal tubular epithelial cells by decreasing NF-kappaB transcription.

    Science.gov (United States)

    Chen, Yongwen; Zhang, Jingbo; Li, Jingyi; Zhao, Tingting; Zou, Liyun; Tang, Yan; Zhang, Xiaoping; Wu, Yuzhang

    2006-03-01

    Triptolide has been used extensively in China for the treatment of autoimmune diseases and tumor for many centuries. Nevertheless, little is known about its exact immunosuppressive and anti-inflammatory properties. Increasing recognition of the importance of renal tubular epithelial cells (TECs) in renal diseases raises the question whether triptolide can regulate TEC activity. In this study, various cultured human and murine TECs were exposed to tumor necrotic factor-alpha (TNF-alpha) and triptolide, followed to examine the expression of B7-H1 and B7-DC. Flow cytometric analysis revealed that B7-H1 but not B7-DC constitutively expresses on TECs, and the B7-H1 protein expression was profoundly up-regulated by the stimulation of TNF-alpha with a dose-dependent manner. However, triptolide under non-cytotoxic concentration could down-regulate B7-H1 expression on activated TECs at both mRNA and protein level. This effect was transcription factor NF-kappaB dependent. Interestingly, the significant damping effect of triptolide on B7-H1 signal could promote interleukin-2 production by T cell hybridoma (C10) after antigen presentation and enhance cytokine (IFN-gamma and IL-2) secretion by anti-CD3 activated T cells. Our results indicated that triptolide could regulate TEC activity via B7-H1, in addition to previously reported it directly affects the production of some inflammatory factors by T cells, tumor cells and peripheral blood mononuclear cells. PMID:16129490

  20. 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.

  1. Generation and Characterisation of a Pax8-CreERT2 Transgenic Line and a Slc22a6-CreERT2 Knock-In Line for Inducible and Specific Genetic Manipulation of Renal Tubular Epithelial Cells.

    Science.gov (United States)

    Espana-Agusti, Judit; Zou, Xiangang; Wong, Kim; Fu, Beiyuan; Yang, Fengtang; Tuveson, David A; Adams, David J; Matakidou, Athena

    2016-01-01

    Genetically relevant mouse models need to recapitulate the hallmarks of human disease by permitting spatiotemporal gene targeting. This is especially important for replicating the biology of complex diseases like cancer, where genetic events occur in a sporadic fashion within developed somatic tissues. Though a number of renal tubule targeting mouse lines have been developed their utility for the study of renal disease is limited by lack of inducibility and specificity. In this study we describe the generation and characterisation of two novel mouse lines directing CreERT2 expression to renal tubular epithelia. The Pax8-CreERT2 transgenic line uses the mouse Pax8 promoter to direct expression of CreERT2 to all renal tubular compartments (proximal and distal tubules as well as collecting ducts) whilst the Slc22a6-CreERT2 knock-in line utilises the endogenous mouse Slc22a6 locus to specifically target the epithelium of proximal renal tubules. Both lines show high organ and tissue specificity with no extrarenal activity detected. To establish the utility of these lines for the study of renal cancer biology, Pax8-CreERT2 and Slc22a6-CreERT2 mice were crossed to conditional Vhl knockout mice to induce long-term renal tubule specific Vhl deletion. These models exhibited renal specific activation of the hypoxia inducible factor pathway (a VHL target). Our results establish Pax8-CreERT2 and Slc22a6-CreERT2 mice as valuable tools for the investigation and modelling of complex renal biology and disease. PMID:26866916

  2. Everolimus-induced epithelial to mesenchymal transition in immortalized human renal proximal tubular epithelial cells: key role of heparanase

    OpenAIRE

    Masola, Valentina; Zaza, Gianluigi; Granata, Simona; Gambaro, Giovanni; Onisto, Maurizio; Lupo, Antonio

    2013-01-01

    Background Everolimus (EVE) is a drug widely used in several renal transplant protocols. Although characterized by a relatively low nephrotoxicity, it may induce several adverse effects including severe fibro-interstitial pneumonitis. The exact molecular/biological mechanism associated to these pro-fibrotic effects is unknown, but epithelial to mesenchymal transition (EMT) may have a central role. Additionally, heparanase, an enzyme recently associated with the progression of chronic allograf...

  3. Hyperglycemia Does Not Affect Iron Mediated Toxicity of Cultured Endothelial and Renal Tubular Epithelial Cells: Influence of L-Carnosine

    OpenAIRE

    Shiqi Zhang; Emmanouil Ntasis; Sarah Kabtni; Jaap van den Born; Gerjan Navis; Stephan J L Bakker; Krämer, Bernhard K.; Benito A Yard; Hauske, Sibylle J.

    2015-01-01

    Iron has been suggested to affect the clinical course of type 2 diabetes (T2DM) as accompanying increased intracellular iron accumulation may provide an alternative source for reactive oxygen species (ROS). Although carnosine has proven its therapeutic efficacy in rodent models of T2DM, little is known about its efficacy to protect cells from iron toxicity. We sought to assess if high glucose (HG) exposure makes cultured human umbilical vein endothelial cells (HUVECs) and renal proximal tubul...

  4. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring

    Directory of Open Access Journals (Sweden)

    Sabiha S. Chowdhury

    2016-08-01

    Full Text Available Along with diabetes and obesity, chronic kidney disease (CKD is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD for 13–14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p < 0.05, n = 8 litters per group. Histological analysis of the kidney demonstrated signs of tubule damage, with significantly greater loss of brush border, and increased cell sloughing in offspring of obese compared to Control fathers. Acat1, involved in entry of fatty acid for beta-oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD.

  5. Paternal High Fat Diet in Rats Leads to Renal Accumulation of Lipid and Tubular Changes in Adult Offspring.

    Science.gov (United States)

    Chowdhury, Sabiha S; Lecomte, Virginie; Erlich, Jonathan H; Maloney, Christopher A; Morris, Margaret J

    2016-01-01

    Along with diabetes and obesity, chronic kidney disease (CKD) is increasing across the globe. Although some data support an effect of maternal obesity on offspring kidney, the impact of paternal obesity is unknown; thus, we have studied the effect of paternal obesity prior to conception. Male Sprague Dawley rats were fed chow diet or high fat diet (HFD) for 13-14 weeks before mating with chow-fed females. Male offspring were weaned onto chow and killed at 27 weeks for renal gene expression and histology. Fathers on HFD were 30% heavier than Controls at mating. At 27 weeks of age offspring of obese fathers weighed 10% less; kidney triglyceride content was significantly increased (5.35 ± 0.84 vs. 2.99 ± 0.47 μg/mg, p oxidation, was significantly upregulated, possibly to counteract increased triglyceride storage. However other genes involved in lipid metabolism, inflammation and kidney injury showed no changes. Paternal obesity was associated with renal triglyceride accumulation and histological changes in tubules, suggesting a mild renal insult in offspring, who may be at risk of developing CKD. PMID:27563922

  6. Effect of CXCR4-overexpressing bone marrow-derived mesenchymal stem cells on the repair of the co-cultured hypoxia /re-oxygenation renal tubular epithelial cells and its possible mechanism

    Institute of Scientific and Technical Information of China (English)

    刘楠梅

    2014-01-01

    Objective CXCR4-overexpressing bone marrow-derived mesenchymal stem cells(CXCR4-BMSC)were constructed and co-cultured with hypoxia/re-oxygenation pretreated renal tubular epithelial cells(HR-RTEC).Repair of HR-RTEC was detected and the possible mechanism was also discussed.Methods CXCR4-BMSC(CXCR4-BMSC/eGFP,eGFP as the tracer gene)and

  7. 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. PMID:26918530

  8. Short- and long-term follow-up of glomerular and tubular renal markers of kidney function in hyperthyroid cats after treatment with radioiodine.

    Science.gov (United States)

    van Hoek, I; Lefebvre, H P; Peremans, K; Meyer, E; Croubels, S; Vandermeulen, E; Kooistra, H; Saunders, J H; Binst, D; Daminet, S

    2009-01-01

    Hyperthyroidism can mask co-existing chronic kidney disease (CKD). Previous studies showed that post-treatment renal azotemia can be predicted by pre-treatment assessment of glomerular filtration rate (GFR). We hypothesized that treatment of hyperthyroidism may have different effects on glomerular and tubular function and these changes might be predicted by additional pre-treatment variables than GFR. Serum total T4 (TT4), creatinine and blood urea nitrogen (BUN), blood pressure (BP), body weight (BW), GFR, urine specific gravity (USG), urinary protein/creatinine ratio (UPC) and retinol binding protein/creatinine ratio (uRBP/c) were evaluated before and 1, 4, 12 and 24 weeks post-treatment with radioiodine ((131)I) in 21 non-azotemic hyperthyroid cats. Cats were divided 24 weeks post-treatment into group A (normal kidney function, n=16) and group B (impaired kidney function, n=5). Serum TT4, GFR, UPC and uRBP/c decreased significantly after treatment for the complete group and group A (P<0.05), although GFR and uRBP/c did not change in group B. Serum creatinine and BW increased significantly from 1 week after treatment (P<0.05). There was no change in BUN, USG or BP. Pre-treatment serum TT4, GFR and USG differed significantly between group A and B (P<0.05). GFR at 4 weeks after treatment and maximum decrease in GFR could be partially predicted by a formula using pre-treatment GFR, serum TT4, serum creatinine, BUN and/or USG. Significant changes in kidney function occur within 4 weeks post-treatment and none thereafter. Pre-treatment measurement of GFR, USG and serum TT4 can have possible predictive value regarding the development of post-treatment renal azotemia. PMID:19010632

  9. Tubular Secretion in CKD.

    Science.gov (United States)

    Suchy-Dicey, Astrid M; Laha, Thomas; Hoofnagle, Andrew; Newitt, Rick; Sirich, Tammy L; Meyer, Timothy W; Thummel, Ken E; Yanez, N David; Himmelfarb, Jonathan; Weiss, Noel S; Kestenbaum, Bryan R

    2016-07-01

    Renal function generally is assessed by measurement of GFR and urinary albumin excretion. Other intrinsic kidney functions, such as proximal tubular secretion, typically are not quantified. Tubular secretion of solutes is more efficient than glomerular filtration and a major mechanism for renal drug elimination, suggesting important clinical consequences of secretion dysfunction. Measuring tubular secretion as an independent marker of kidney function may provide insight into kidney disease etiology and improve prediction of adverse outcomes. We estimated secretion function by measuring secreted solute (hippurate, cinnamoylglycine, p-cresol sulfate, and indoxyl sulfate) clearance using liquid chromatography-tandem mass spectrometric assays of serum and timed urine samples in a prospective cohort study of 298 patients with kidney disease. We estimated GFR by mean clearance of creatinine and urea from the same samples and evaluated associations of renal secretion with participant characteristics, mortality, and CKD progression to dialysis. Tubular secretion rate modestly correlated with eGFR and associated with some participant characteristics, notably fractional excretion of electrolytes. Low clearance of hippurate or p-cresol sulfate associated with greater risk of death independent of eGFR (hazard ratio, 2.3; 95% confidence interval, 1.1 to 4.7; hazard ratio, 2.5; 95% confidence interval, 1.0 to 6.1, respectively). Hazards models also suggested an association between low cinnamoylglycine clearance and risk of dialysis, but statistical analyses did not exclude the null hypothesis. Therefore, estimates of proximal tubular secretion function correlate with glomerular filtration, but substantial variability in net secretion remains. The observed associations of net secretion with mortality and progression of CKD require confirmation. PMID:26614381

  10. In vitro inhibition of calcium oxalate crystallization and crystal adherence to renal tubular epithelial cells by Terminalia arjuna.

    Science.gov (United States)

    Mittal, A; Tandon, S; Singla, S K; Tandon, C

    2016-04-01

    Urolithiasis is a multifactorial disease and remains a public health problem around the world. Of all types of renal stones, calcium oxalate (CaOx) is the most common composition formed in the urinary system of the patients with urolithiasis. The present study is aimed at evaluating the antiurolithiatic properties of the Tris-Cl extract (TE) of Terminalia arjuna (T. arjuna). The antilithiatic activity of TE of T. arjuna was investigated on nucleation, aggregation, and growth of the CaOx crystals, as well as its protective potency was tested on oxalate-induced cell injury of NRK-52E renal epithelial cells. Also, in vitro antioxidant activity of TE T. arjuna bark was also determined. The TE of T. arjuna exhibited a concentration-dependent inhibition of nucleation and growth of CaOx crystals. Inhibition of aggregation of CaOx crystals remains constant. When NRK-52E cells were injured by exposure to oxalate for 48 h, the TE prevented the cells from injury and CaOx crystal adherence resulting in increased cell viability in a dose-dependent manner. The TE also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radicals with an IC50 at 51.72 µg/mL. The results indicated that T. arjuna is a potential candidate for phytotherapy against urolithiasis as it attains the ability to inhibit CaOx crystallization and scavenge DPPH free radicals in vitro along with a cytoprotective role. PMID:26424092

  11. Risk Factors for Developing Metabolic Acidosis after Radical Cystectomy and Ileal Neobladder

    Science.gov (United States)

    Yoon, Hyun Suk; Yoon, Hana; Chung, Woo Sik; Sim, Bong Suk; Ryu, Dong-Ryeol; Lee, Dong Hyeon

    2016-01-01

    Purpose To investigate the serial changes of metabolic acidosis and identify associated risk factors in patients who underwent radical cystectomy and ileal neobladder. Material and Methods From January 2010 to August 2014, 123 patients who underwent radical cystectomy and ileal neobladder reconstruction for bladder cancer were included in this study. Metabolic acidosis was defined as a serum bicarbonate level less than 22 mEq/L and impaired renal function was defined as a GFR <50ml/min. The presence of metabolic acidosis was evaluated at 1 month, 1 year, and 2 years after surgery. Multivariate logistic regression analysis was conducted to identify risk factors associated with development of metabolic acidosis. Results Metabolic acidosis was observed in 52%, 19.5%, and 7.3% of patients at 1 month, 1 year, and 2 years after surgery, respectively. At 1 month after surgery, impaired renal function was the only independent risk factor associated with metabolic acidosis (OR 3.87, P = 0.046). At 1 year after surgery, diabetes was the only independent risk factor associated with metabolic acidosis (OR 5.68, P = 0.002). At 2 years post-surgery, both age and diabetes were significant risk factors associated with metabolic acidosis. Conclusion Approximately, half of patients experienced metabolic acidosis one month after ileal neobladder reconstruction. Preoperative impaired renal function was the most significant risk factor for developing metabolic acidosis in the early postoperative period. However, the incidence of metabolic acidosis decreased to less than 20% 1 year after surgery, and diabetes was an independent risk factor during this period. PMID:27384686

  12. Citrato y litiasis renal

    Directory of Open Access Journals (Sweden)

    Elisa E. Del Valle

    2013-08-01

    Full Text Available El citrato es un potente inhibidor de la cristalización de sales de calcio. La hipocitraturia es una alteración bioquímica frecuente en la formación de cálculos de calcio en adultos y especialmente en niños. El pH ácido (sistémico, tubular e intracelular es el principal determinante de la excreción de citrato en la orina. Si bien la mayoría de los pacientes con litiasis renal presentan hipocitraturia idiopática, hay un número de causas para esta anormalidad que incluyen acidosis tubular renal distal, hipokalemia, dietas ricas en proteínas de origen animal y/o dietas bajas en álcalis y ciertas drogas, como la acetazolamida, topiramato, IECA y tiazidas. Las modificaciones dietéticas que benefician a estos pacientes incluyen: alta ingesta de líquidos y frutas, especialmente cítricos, restricción de sodio y proteínas, con consumo normal de calcio. El tratamiento con citrato de potasio es efectivo en pacientes con hipocitraturia primaria o secundaria y en aquellos desordenes en la acidificación, que provocan un pH urinario persistentemente ácido. Los efectos adversos son bajos y están referidos al tracto gastrointestinal. Si bien hay diferentes preparaciones de citrato (citrato de potasio, citrato de sodio, citrato de potasio-magnesio en nuestro país solo está disponible el citrato de potasio en polvo que es muy útil para corregir la hipocitraturia y el pH urinario bajo, y reducir marcadamente la recurrencia de la litiasis renal.

  13. Lactic acidosis induced by metformin: incidence, management and prevention.

    Science.gov (United States)

    Lalau, Jean-Daniel

    2010-09-01

    acidosis, since it provides both symptomatic and aetiological treatment (by eliminating lactate and metformin). In the third part of the review (prevention), the objective is to examine the list of contraindications to metformin (primarily related to renal and cardiovascular function). Diabetes is above all a vascular disease and metformin is a vascular drug with antidiabetic properties. Given the importance of the liver in lactate clearance, we suggest focusing on the severity of and prognosis for liver disease; renal dysfunction is only a prerequisite for metformin accumulation, which may only be dangerous per se when associated with liver failure. Lastly, in view of metformin's impressive overall effectiveness profile, it would be paradoxical to deny the majority of patients with long-established diabetes access to metformin because of the high prevalence of contraindications. The implications of these contraindications are discussed. PMID:20701406

  14. Clinical Scenarios in Chronic Kidney Disease: Cystic Renal Diseases.

    Science.gov (United States)

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria

    2016-01-01

    Cysts are frequently found in chronic kidney disease (CKD) and they have a different prognostic significance depending on the clinical context. Simple solitary parenchymal cysts and peripelvic cysts are very common and they have no clinical significance. At US, simple cyst appears as a round anechoic pouch with regular and thin profiles. On the other hand, hereditary polycystic disease is a frequent cause of CKD in children and adults. Autosomal dominant polycystic kidney disease (ADPKD) and autosomal recessive polycystic kidney disease (ARPKD) are the best known cystic hereditary diseases. ADPKD and ARPKD show a diffused cystic degeneration with cysts of different diameters derived from tubular epithelium. Medullary cystic disease may be associated with tubular defects, acidosis and lithiasis and can lead to CKD. Acquired cystic kidney disease, finally, is secondary to progressive structural end-stage kidney remodelling and may be associated with renal cell carcinoma. PMID:27169740

  15. Benchmark dose estimation for cadmium-induced renal tubular damage among environmental cadmium-exposed women aged 35-54 years in two counties of China.

    Directory of Open Access Journals (Sweden)

    Jia Hu

    Full Text Available A number of factors, including gender, age, smoking habits, and occupational exposure, affect the levels of urinary cadmium. Few studies have considered these influences when calculating the benchmark dose (BMD of cadmium. In the present study, we aimed to calculate BMDs and their 95% lower confidence bounds (BMDLs for cadmium-induced renal tubular effects in an age-specific population in south-central China.In this study, urinary cadmium, β2-microglobulin, and N-acetyl-β-D-glucosaminidase levels were measured in morning urine samples from 490 randomly selected non-smoking women aged 35-54 years. Participants were selected using stratified cluster sampling in two counties (counties A and B in China. Multiple regression and logistic regression analyses were used to investigate the dose-response relationship between urinary cadmium levels and tubular effects. BMDs/BMDLs corresponding to an additional risk (benchmark response of 5% and 10% were calculated with assumed cut-off values of the 84th and 90th percentile of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the controls.Urinary levels of β2-microglobulin and N-acetyl-β-D-glucosaminidase increased significantly with increasing levels of urinary cadmium. Age was not associated with urinary cadmium levels, possibly because of the narrow age range included in this study. Based on urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase, BMDs and BMDLs of urinary cadmium ranged from 2.08 to 3.80 (1.41-2.18 µg/g cr for subjects in county A and from 0.99 to 3.34 (0.74-1.91 µg/g cr for those in county B. The predetermined benchmark response of 0.05 and the 90th percentiles of urinary β2-microglobulin and N-acetyl-β-D-glucosaminidase levels of the subjects not exposed to cadmium (i.e., the control group served as cut-off values.The obtained BMDs of urinary cadmium were similar to the reference point of 1 µg/g cr, as suggested by the European Food Safety Authority

  16. 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...

  17. Metformin-Associated Acute Kidney Injury and Lactic Acidosis

    Directory of Open Access Journals (Sweden)

    David Arroyo

    2011-01-01

    Full Text Available Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI. Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD has no influence on the severity or outcome.

  18. Decrease in transient receptor potential melastatin 6 mRNA stability caused by rapamycin in renal tubular epithelial cells.

    Science.gov (United States)

    Ikari, Akira; Sanada, Ayumi; Sawada, Hayato; Okude, Chiaki; Tonegawa, Chie; Sugatani, Junko

    2011-06-01

    Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is used in treatments for transplantation and cancer. Rapamycin causes hypomagnesemia, although precisely how has not been examined. Here, we investigated the effect of rapamycin on the expression of transient receptor potential melastatin 6 (TRPM6), a Mg2+ channel. Rapamycin and LY-294002, an inhibitor of phosphatidilinositol-3 kinase (PI3K) located upstream of mTOR, inhibited epidermal growth factor (EGF)-induced expression of the TRPM6 protein without affecting TRPM7 expression in rat renal NRK-52E epithelial cells. Both rapamycin and LY-294002 decreased EGF-induced Mg2+ influx. U0126, a MEK inhibitor, inhibited EGF-induced increases in c-Fos, p-ERK, and TRPM6 levels. In contrast, neither rapamycin nor LY-294002 inhibited EGF-induced increases in p-ERK and c-Fos levels. EGF increased p-Akt level, an effect inhibited by LY-294002 and 1L-6-hydroxymethyl-chiro-inositol2-[(R)-2-O-methyl-3-O-octadecylcarbonate] (Akt inhibitor). Akt inhibitor decreased TRPM6 level similar to rapamycin and LY-294002. These results suggest that a PI3K/Akt/mTOR pathway is involved in the regulation of TRPM6 expression. Rapamycin inhibited the EGF-induced increase in TRPM6 mRNA but did not inhibit human TRPM6 promoter activity. In the presence of actinomycin D, a transcriptional inhibitor, rapamycin accelerated the decrease in TRPM6 mRNA. Rapamycin decreased the expression and activity of a luciferase linked with the 3'-untranslated region of human TRPM6 mRNA. These results suggest that TRPM6 expression is up-regulated by a PI3K/Akt/mTOR pathway and rapamycin reduces TRPM6 mRNA stability, resulting in a decrease in the reabsorption of Mg2+. PMID:21073857

  19. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970363 Effect on serum PTH and 1, 25(OH)2 D3levels of rapid correction of metabolic acidosis in CRFpatients with secondary hyperparathyroidism. YUANQunsheng(袁群生), et al. Renal Div, PUMC Hosp,Beijing, 100730. Chin J Nephrol 1996; 12(6): 328-331.

  20. Effects of exhaustive exercise on renal tubular apoptosis and HIF-1α expression in rats and result of total ginsenoside intervention

    Directory of Open Access Journals (Sweden)

    Hui-ling WANG

    2014-03-01

    Full Text Available Objective To investigate the effects of high strength exhaustive exercise on apoptosis of renal tubular epithelial cells (TECs and expression of hypoxia-inducible factor-1 α (HIF-1α in rats and the effect of intervention of total ginsenoside. Methods Thirty-five male Sprague-Dawley rats were randomly divided into five groups (7 each: control group (CTL, model group (divided into two subgroups: M2 and M24; total ginsenoside group (divided into two subgroups: G2 and G24. The animal model of exhaustive exercise induced acute kidney injury (AKI was reproduced by forcing the rats running on the treadmill followed by exhaustive swimming according to the protocol. Ginsenoside [100g/(kg.d] was intragastrically gavaged 5 days before exhausting exercise in rats of G2 and G24, and the same volume of water was given to rats in model and CTL groups. Apoptosis of TECs was observed under microscope after TUNEL staining. The expressions of caspase-3 and HIF-1α in TECs were analyzed by immunohistochemical staining. The protein expression of caspase-3 and HIF-1α was determined by Western blotting. Results  In model group, 11 out of 14 rats were stranded on treadmill, and the time of exhaustive swimming was significantly shorter as compared with that of CTL group; but the endurance increased significantly in total ginsenoside groups, in which only 6/14 rats were stranded on treadmill, and the swimming time was significantly longer compared with model group (P<0.05. The TUNELpositive apoptotic cells increased in M2 and M24 groups (especially in M24 group, and they were mainly distributed in thos e TECs at the corticomedullary junction in model groups; but the number of TUNEL-positive cells decreased significantly in total ginsenoside group (G2, G24 as compared with model group (P<0.05. Immunohistochemical analysis showed that caspases-3 and HIF-1α were only weakly positive in CTL group, but significantly upregulated in M2 group, and it was stronger in M

  1. Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury

    Directory of Open Access Journals (Sweden)

    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.

  2. Clinical Characteristics of Primary Renal Tubular Hypokalemic Alkalosis%原发肾小管性低钾碱中毒的临床特点

    Institute of Scientific and Technical Information of China (English)

    范树颖; 张碧丽; 王文红; 张碹; 李莉; 杜悦新

    2011-01-01

    Objective To explore the clinical characteristics of primary renal tubular hypokalemic alkalosis. Methods Eight patients with primary renal tubular hypokalemic alkalosis were selected in the Children's Hospital of Tianjin. There were 4 patients with Bartter syndrome(BS) and 4 patients with Gitelman syndrome(GS). Clinical data,biochemical tests,therapy and outcome were retrospectively analyzed.Results The onset age of BS were at infancy stage. The main symptoms included diarrhea, vomiting, dehydration and growth retardation. And the onset age of GS ranged from 10 to 15 years old with the main symptoms of weakness,paralysis and tetany. They had normal blood pressure.The biochemical tests showed hypokalemic, metabolic alkalosis, increase of urine potassium and urine chlorine in all patients. Four patients with BS had hyperreninemia and hyperaldosteronism. Angiotonin was elevated in all 4 patients with GS ,while rennin was elevated in 3 patients of them and aldosterone was obviously elevated in 2 patients. The urine Ca/Cr ratio in BS was elevated(>0.2) ,while patients with GS had hyponagnesaemia and low level of urine Ca/Ct ratio(<0.2). B - type ultrasonic wave showed that both kidneys's resonance had even reinforce in 2 patients with BS, and one of them had left pyelectasis. All symptoms resolved after treatment with potassium or combined magnesium supplementation,indomethacin,spironolactone and captopril. Conclusions Prinary renal tubular hypokalemic alkalosis is characterized by hypokalemic, metabolic alkalosis, hyperreninemic, hyperaldosteronism and normal blood pressure. Measured level of serum magnesium, urine potassium and chlorine and Ca/Ct ratio, rennin angiotonin and aldosterone can help make diagnosis. There are differences in onset mechanism,clinical manifestation,treatment and prognosis between BS and GS.%目的 探讨原发肾小管性低钾碱中毒的临床特点.方法 收集在天津市儿童医院住院治疗的原发肾

  3. [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

    Science.gov (United States)

    Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

    2015-12-01

    Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol. PMID:26654818

  4. [5-0xoproline (pyroglutamic acid) acidosis and acetaminophen- a differential diagnosis in high anion gap metabolic acidosis].

    Science.gov (United States)

    Weiler, Stefan; Bellmann, Romuald; Kullak-Ublick, Gerd A

    2015-12-01

    Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.

  5. 肾小管上皮细胞与基底膜的粘附力学特性%The adhesive mechanical properties of renal tubular epithelial cells on matrigel

    Institute of Scientific and Technical Information of China (English)

    宋关斌; 俞为群; 王东; 吴雄飞

    2000-01-01

    purpose: to investigate the adhesive properties of renal tubular epithelial cells on matrigel and compared with the following three cases: ischemia、hypoxia and ischemia & hypoxia(I/H).materials and methods: A micropipette aspiration technique was adopted to determine the adhesive mechanics of renal tubular epithelial cells on matrige. results: it showed that the adhesion of renal tubular epithelial cells on matrigel was higher than that of those three model, further more, a different factor was followed by different adhesive mechanic. conclusion: the adhesion of I/H is lower, the ischemia is higher, but all were lower compared with control. It suggested that effect of hypoxia on adhesive properties of renal tubular epithelial cells on matrigel is bigger than that of ichemia.%目的:研究模拟缺血、缺氧、缺血缺氧三种条件下肾小管上皮细胞与基底膜的粘附力学特性。材料与方法:利用微管吸吮技术测定肾小管上皮细胞与人工基底膜的粘附力。结果:模拟缺血、缺氧、缺血缺氧三种模型中肾小管上皮细胞与基底膜的粘附力均较正常情况明显降低。结论:不同模拟损伤因素对粘附力的影响不同,其中缺血缺氧组粘附力最小,单纯缺血组的影响较小。这些结果提示,在一定条件下,氧缺乏比缺血情况更能影响肾小管上皮细胞与基底膜的粘附作用。

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

    Directory of Open Access Journals (Sweden)

    Dana Galuska

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  7. Review Study of Renal Tubular Injury Markers in the Acute Kidney Injury%急性肾损伤中肾小管损伤标志物的研究进展

    Institute of Scientific and Technical Information of China (English)

    李一飞; 姚广涛

    2011-01-01

    The reports concerned with renal injury markers in recent 10 years were consulted through Science Direct database, and literature related to specific markers of renal tubular injury were compiled and analyzed. Some biomarkers have been partially verified the good sensitivity and high specificity in experimental studies and clinical observations. For example, Kidney injury molecule-1 .which would over express in the kidney injury in renal tubular epithelial cells,is sensitive to the early diagnosis of kidney cancer, ischemic and renal toxic renal injury,and detected with high stability. Liver-type fatty acid binding protein involved in local lipid metabolism of renal,with high specificity to renal proximal tubule. Its content in urine were of great value for early evaluation of various types of acute kidney injury. As a diagnostic indicator,sensitivity and specificity of Interleukin-18 were more than 90%. It could distinguish acute tubular necrosis from other types of kidney diseases, also predict the renal injury occurrence and renal function recovery. Neutrophil gelatinase-associated lipocalin was often detected as the first expressed product in the injury kidney,which changed earlier than creatinine and other markers, with obvious time advantage. All biomarkers have different characteristics and respective shortage. So joint detection were better to wider and sensitive evaluation of renal injury.%通过Science Direct数据库查阅了近10年有关肾损伤标志物的报道,对肾小管损伤特异性标志物方面的文献进行了整理和分析.一些敏感性好、特异性高的肾小管损伤标志物已在实验研究和临床观察得到了部分验证,如肾损伤分子-1,肾损伤时在肾小管上皮细胞过度表达,对肾肿瘤、缺血性和肾毒性肾损伤的早期诊断敏感性好,且检测稳定性高;肝型脂肪酸结合蛋白,参与肾局部的脂质代谢,对肾近端小管的特异性很高,其尿液含量变化在多种类型的急

  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 hypoth

  9. Metabolic evaluation in first-time renal stone formers in north India: A single center study

    Directory of Open Access Journals (Sweden)

    Akhil Joshi

    2013-01-01

    Full Text Available The risk of stone recurrence in first-time stone formers (FTSF varies from 26% to 53%. There is no consensus regarding metabolic evaluation in these individuals. We evaluated the metabolic abnormalities in first-time renal stone forming patients in North India. Thirty-nine patients, (29 males and 10 females with mean age 39.3 ± 12.9 years who presented with nephrolithiasis for the first time were evaluated. We evaluated the calcium homeostasis [serum corrected total calcium, phosphorous, creatinine, alkaline phosphatase, albumin, parathormone (iPTH, 25-hydroxy cholecalciferol (25(OHD 3 , 1-25 di-hydroxy cholecalciferol (1,25(OH 2 D 3 ] and performed the calcium load test also. Two 24-h urine collections were taken for citrate, oxalate, calcium and uric acid. Ammonium chloride loading test for diagnosis of distal renal tubular acidosis was performed in all patients. For each of the diagnostic categories, descriptive statistics were computed for all biochemical variables. A two-tailed P-value <0.05 was regarded as significant. Metabolic abnormalities were detected in 92.3% of the patients (n = 39 studied. Of them, almost 60% had two or more metabolic abnormalities. The most common metabolic abnormality was hypo-citraturia (82%, followed by hyper-oxaluria (56% and hyper-calciuria (41%. Five percent of the patients had incomplete renal tubular acidosis, signifying the importance of the ammonium chloride loading test in patients with renal stones. None of the study patients were detected to have primary hyperparathyroidism. In three patients, the etiology could not be detected. Our findings suggest that an underlying disorder is present in majority of first-time renal stone formers. Intervention with appropriate treatment can prevent recurrences. Hence, comprehensive metabolic evaluation is recommended in all FTSF.

  10. Retrospective analysis of clinical and pathological data of 104 cases of renal tubular-interstitial disease%肾小管-间质疾病104例临床病理资料回顾性分析

    Institute of Scientific and Technical Information of China (English)

    张宏岩; 孙瑶; 张磊

    2013-01-01

    目的 探讨肾小管-间质疾病的类型与疾病进展的关系,可为临床医生早期诊断及预防提供依据.方法 取自哈尔滨医科大学病理学教研室7 112例肾活检资料(1998年1月~2012年4月)中,诊断为肾小管-间质疾病104例,占1.46%(104/7 112).分析其临床资料,实验室检查和病理检查的相关性.结果 ①肾小管-间质性疾病的病理变化特点是:肾小球的球囊壁增厚、分层、纤维化,肾小球毛细血管壁增厚、缺血,严重的呈硬化改变;不同程度的肾小管萎缩,间质增生,炎细胞浸润和小动脉壁的增厚.②104例肾小管-间质性疾病中,有无蛋白尿之间有明显的差异(P<0.05);③有无炎细胞浸润和已浸润的多少之间有明显的差异(P<0.05);④而有关肾小球病变、肾小管萎缩、间质增生及临床实验室的其它几项指标间无明显的差异(P>0.05).结论 肾小管-间质性疾病的发生发展与有无炎细胞浸润及浸润的程度密切相关.临床表现为明显蛋白尿的患者,如果排除原发性或继发性肾小球肾炎时,早期诊断和预防可减轻肾小管萎缩、间质增生、纤维化及小动脉增厚、变性的发展.%Objective To investigate the relationship between the type and progression of the renal tubular-interstitial disease,and its value in the early diagnosis and prevention.Methods There were 104 cases of renal tubular-interstitial disease which accounts for 1.46% in all the 7 112 cases of renal biopsy in the Pathology Department of Harbin Medical University since January 1998 to April 2012.The clinical data,laboratory tests and pathological examination were analyzed.Results ①Pathological changes of tubular-interstital disease:glomerular capsule thickening,delamination,fibrosis,the glomerual capillary wall thickening,ischemia,and even sclerosis ; Varying degress of tubular atrophy,interstitial hyperplasia,inflammatory cell infiltration and thickening of small artery

  11. 线粒体功能障碍在尿酸损伤肾小管上皮细胞中的作用∗%The Role of Mitochondrial Dysfunction in Uric Acid Damage in Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    李文; 吴红赤; 封宝红; 赵悦; 任凤芹; 韩威

    2015-01-01

    目的::探讨线体功能在尿酸损伤肾小管上皮细胞中的作用。方法:体外培养大鼠肾小管上皮细胞,将其分为对照组(N)、尿酸0.1 mmol/L组(U1)、尿酸0.2 mmol/L组(U2)、尿酸0.4 mmol/L组(U3)、尿酸0.6 mmol/L组(U4)。观察细胞形态的改变,计算细胞凋亡率;检测细胞内活性氧( ROS)的生成情况;观察线粒体膜电位变化。结果:尿酸干预组肾小管上皮细胞形态较对照组发生明显变化。尿酸干预组肾小管上皮细胞凋亡率较对照组明显上升(P<0.05)。尿酸干预组线粒体膜电位较对照组显著下降(P<0.05),U2、U3、U4之间,随着尿酸浓度的增加线粒体膜电位逐渐下降(P<0.05)。尿酸干预组活性氧的水平较对照组明显升高(P<0.05),随尿酸浓度的增加活性氧的水平逐渐增加(P<0.05)。相关性分析显示肾小管上皮细胞凋亡率与线粒体膜电位的降低和活性氧的生成显著正相关(r=0.964,r=0.932,P<0.01)。结论:线粒体功能障碍参与了尿酸致肾小管上皮细胞损伤的过程,为尿酸性肾病的诊治提供新的靶点。%Objective:Explore the relationship between mitochondrial dysfunction and uric acid-induced tubular epithelial cell injury. Methods:Rat renal tubular epithelial cells were cultured in vitro and divided them into control group、uric acid group 0. 1 mmol/L(U1)、uric acid group 0. 2 mmol/L(U2)、uric acid group 0. 4 mmol/L(U3)、uric acid group 0. 6 mmol/L(U4), Observe The morphological changes of tubular epithelial cells were observed, Observe the cell apoptosis; Cellular reactive oxygen species ( ROS) production was determined by Fluorescent probe DCFH-DA. Mitochondrial membrane potential were measured using the JC-1 kit. Results:Compared with the control group, the morphologies of rat renal tubular epithelial cells with 0. 1 mmol/L、0. 2 mmol/L、0. 4 mmol/L、0. 6 mmol/L uric acid group have a significant change. The apoptosis rates of uric acid group were

  12. 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

    International Nuclear Information System (INIS)

    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

  13. 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.

  14. Disease: H00429 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available 4278 PMID:11045400 (gene) Rodriguez-Soriano J New insights into the pathogenesis of renal tubular acidosis--...(gene, env_factor, marker) Rodriguez Soriano J Renal tubular acidosis: the clinical entity. J Am Soc Nephrol

  15. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008463 Protective effect of recombination rat augmenter of liver regeneration on kidney in acute renal failure rats. TANG Xiaopeng(唐晓鹏), et al. Dept Nephrol, 2nd Affili Hosp Chongqing Med Univ, Chongqing 400010.Chin J Nephrol 2008;24(6):417-421. Objective To investigate the protective effects of recombination rat augmenter of liver regeneration (rrALR) on tubular cell injury and renal dysfunction

  16. C-peptide reverses TGF-beta1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy.

    Science.gov (United States)

    Hills, Claire E; Al-Rasheed, Nawal; Al-Rasheed, Nouf; Willars, Gary B; Brunskill, Nigel J

    2009-03-01

    The crucial pathology underlying progressive chronic kidney disease in diabetes is tubulointerstitial fibrosis. Central to this process is epithelial-mesenchymal transformation (EMT) of proximal tubular epithelial cells driven by maladaptive transforming growth factor-beta1 (TGF-beta1) signaling. Novel signaling roles for C-peptide have recently been discovered with evidence emerging that C-peptide may mitigate microvascular complications of diabetes. We studied the potential for C-peptide to interrupt injurious TGF-beta1 signaling pathways and thus block development of EMT in HK2 human kidney proximal tubular cells. Cells were incubated with TGF-beta1 either alone or with C-peptide in low or high glucose. Changes in cell morphology, TGF-beta1 receptor expression, vimentin, E-cadherin, and phosphorylated Smads were assessed. Luciferase reporters were used to assess Smad activity. The cytoskeleton was visualized by TRITC-phalloidin staining. The typical TGF-beta1-stimulated, EMT-associated morphological alterations of proximal tubular cells, including increased vimentin expression, decreased E-cadherin expression, and cytoskeletal rearrangements, were prevented by C-peptide treatment. C-peptide also blocked TGF-beta1-induced upregulation of expression of both type I and type II TGF-beta1 receptors and attenuated TGF-beta1-mediated Smad phosphorylation and Smad transcriptional activity. These effects of C-peptide were inhibited by pertussis toxin. The results demonstrate that C-peptide almost completely reversed the morphological changes in PT cells induced by TGF-beta1 and suggest a role or C-peptide as a renoprotective agent in diabetic nephropathy. PMID:19091788

  17. LACTIC ACIDOSIS: A RARE MANIFESTATION OF SYNTHETIC MARIJUANA INTOXICATION.

    Science.gov (United States)

    Antill, T; Jakkoju, A; Dieguez, J; Laskhmiprasad, L

    2015-01-01

    Synthetic cannabinoids are designer drugs that mimic the effect of cannabis, which has become popular with young drug users. These drugs have a similar chemical structure and pharmacologic effects as marijuana, but seem to be more potent. These substances have been banned by the US Drug Enforcement Agency in 2010. Prior to 2010, these drugs were perceived as "safer" by the general population. Synthetic cannabinoids cause effects similar to marijuana making the subjects euphoric. However, they act as full, rather than partial, agonist at the receptor sites causing more severe side effects such as severe agitation, seizures, acute renal failure, and lactic acidosis. PMID:27159480

  18. Acidosis activates complement system in vitro

    Directory of Open Access Journals (Sweden)

    Michael Emeis

    1998-01-01

    Full Text Available We investigated the in vitro effect of different form s of acidosis (pH 7.0 on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 μ mol/ml blood or lactic acid (5.5 μ mol/ml to heparin blood (N=12 caused significant activation of C3a and C5a compared to control (both p=0.002. Respiratory acidosis activated C3a (p=0.007 and C5a (p=0.003 compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5.

  19. Acidosis activates complement system in vitro.

    Science.gov (United States)

    Emeis, M; Sonntag, J; Willam, C; Strauss, E; Walka, M M; Obladen, M

    1998-01-01

    We investigated the in vitro effect of different forms of acidosis (pH 7.0) on the formation of anaphylatoxins C3a and C5a. Metabolic acidosis due to addition of hydrochloric acid (10 micromol/ml blood) or lactic acid (5.5 micromol/ml) to heparin blood (N=12) caused significant activation of C3a and C5a compared to control (both p=0.002). Respiratory acidosis activated C3a (p=0.007) and C5a (p=0.003) compared to normocapnic controls. Making blood samples with lactic acidosis hypocapnic resulted in a median pH of 7.37. In this respiratory compensated metabolic acidosis, C3a and C5a were not increased. These experiments show that acidosis itself and not lactate trigger for activation of complement components C3 and C5. PMID:9927235

  20. Mathematical Model of Ammonia Handling in the Rat Renal Medulla.

    Directory of Open Access Journals (Sweden)

    Lorette Noiret

    Full Text Available The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein release are not fully understood. We developed a mathematical model that reflects current thinking about renal ammonia handling in order to investigate the role of each tubular segment and identify some of the components which might control this balance. The model treats the movements of water, sodium chloride, urea, NH3 and [Formula: see text], and non-reabsorbable solute in an idealized renal medulla of the rat at steady state. A parameter study was performed to identify the transport parameters and microenvironmental conditions that most affect the rate of urinary ammonia excretion. Our results suggest that urinary ammonia excretion is mainly determined by those parameters that affect ammonia recycling in the loops of Henle. In particular, our results suggest a critical role for interstitial pH in the outer medulla and for luminal pH along the inner medullary collecting ducts.

  1. 二甲双胍引起乳酸性酸中毒的风险与糖尿病患者的肾功能%Risk of lactic acidosis caused by metformin and renal function of diabetic patients

    Institute of Scientific and Technical Information of China (English)

    张林; 胡茂清

    2010-01-01

    二甲双胍是治疗2型糖尿病的一线药物,其有导致乳酸性酸中毒的风险.肾小球滤过率是评估糖尿病患者是否应用二甲双胍的标准之一.然而越来越多的证据表明二甲双胍与糖尿病患者乳酸性酸中毒的发生似乎无明显的相关性,目前尚无高质量的临床证据来指导二甲双胍在糖尿病合并肾功能不全患者中的应用,但临床上尚不能仅仅依据肾小球滤过率水平来判断是否使用二甲双胍,使用之前应评估患者使用前后的效益-风险比.在糖尿病合并肾功能不全人群中应用二甲双胍的标准尚需更多的循证医学证据.%Mefformin is in the first line of treating diabetes, though it might increase the risk of lactic acidosis. Glomerular filtration rate is one of the indexs that determines whether mefformin should be used or not. However,more and more clinical studies show that the relationship between mefformin and lactic acidosis is not clear. There are few high quality clinical evidences to guide the use of mefformin in diabetic subjects with chronic kidney disease. But in clinical practice,whether mefformin is used in these diabetic subjects or not does not just depend on glomerular filtration rate, efficiency-risk ratio should be evaluated at first. The standard of using mefformin in diabetic subjects with chronic kidney disease should be provided by more evi-dences.

  2. Tubular Coupling

    Science.gov (United States)

    Rosenbaum, Bernard J. (Inventor)

    2000-01-01

    A system for coupling a vascular overflow graft or cannula to a heart pump. A pump pipe outlet is provided with an external tapered surface which receives the end of a compressible connula. An annular compression ring with a tapered internal bore surface is arranged about the cannula with the tapered internal surface in a facing relationship to the external tapered surface. The angle of inclination of the tapered surfaces is converging such that the spacing between the tapered surfaces decreases from one end of the external tapered surface to the other end thereby providing a clamping action of the tapered surface on a cannula which increases as a function of the length of cannula segment between the tapered surfaces. The annular compression ring is disposed within a tubular locking nut which threadedly couples to the pump and provides a compression force for urging the annular ring onto the cannula between the tapered surfaces. The nut has a threaded connection to the pump body. The threaded coupling to the pump body provides a compression force for the annular ring. The annular ring has an annular enclosure space in which excess cannula material from the compression between the tapered surfaces to "bunch up" in the space and serve as an enlarged annular ring segment to assist holding the cannula in place. The clamped cannula provides a seamless joint connection to the pump pipe outlet where the clamping force is uniformly applied to the cannula because of self alignment of the tapered surfaces. The nut can be easily disconnected to replace the pump if necessary.

  3. Expression of bcl-2, bax in renal proximal tubular epithelial cells of rats with arsenic poisoning%bcl-2、bax在砷中毒大鼠肾近端小管表达

    Institute of Scientific and Technical Information of China (English)

    李远慧; 金婷婷

    2011-01-01

    Objective To investigate the influence of arsenic poisoning on the expressions of bcl-2, bax apoptosis control gene in renal proximal tubular epithelial cells in rtas.Methods Forty normal SD rats were divided into high and low dose of arsenic poisoning group and control group.The body weights of the rats were 120-150g.There were 15 rats in high and low dose exposure groups,and 10 rats in the control group.The rats in high and low groups were treated with As2O3 through drinking water at the doses of 10 and 0.4 mg/kg·d.The control group was given distilled water.Four months after the treatment,the kidney tissue of the rats was collected.Two step immunohistochemistry method, cell number count, and image analyses were used in the study.Results The bcl-2 immunoractive cells decreased and the average gray value gradually increased in arsenic poisoning groups(P < 0.05).The bax immunoractive cells of renal proximal tubular epithelial were increased and the average gray value decreased ( P < 0.05 ) in arsenic poisoning groups compared to those of the control group.Conclusion The expression of bcl-2, bax apoptosis control gene are involved in the process of apoptosis of renal proximal tubular epithelial cells in arsenic poisoning rats.%目的 探讨砷中毒对大鼠肾近端小管上皮细胞凋亡调控基因bcl-2、bax影响.方法 清洁级SD大鼠40只,体重为120~150g,高、低剂量染砷组各15只,对照组10只.高、低剂量染砷组分别给予三氧化二砷(AS2O3)10、0.4 mg/kg水溶液自由饮用,对照组饮用蒸馏水.分笼喂养4个月,取肾脏标本,采用免疫组织化学二步法、细胞计数和图像分析方法测定bcl-2、bax表达.结果 高、低剂量染砷组肾近端小管上皮bcl-2阳性细胞计数分别为(1.85±1.22)与(5.47±1.62)个,明显低于对照组(8.03±2.42)个,平均灰度值逐渐增高,差异具有统计学意义(P<0.05);高、低剂量染砷组肾近端小管上皮bax阳性细胞数分别为(14.88±3.02)与(6

  4. 肾脏黏液性管状和梭形细胞癌4例报告%Clinical and pathological characteristics of renal mucinous tubular and spindle cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    王俊生; 林云华; 商建峰; 勇强; 姜永光

    2011-01-01

    目的 探讨肾脏黏液性管状和梭形细胞癌的临床病理特征.方法 回顾分析4例肾脏黏液性管状和梭形细胞癌患者的临床资料.女性3例,男性1例;年龄35~56岁,平均41岁;左肾2例,右肾2例;肾上极3例,肾下极1例;肿瘤直径3.5~6.5cm,平均5.5cm;无明显临床症状及体征,均为体检发现.B超检查提示,2例肾囊实性占位,为良性肿瘤;2例为厚壁型肾囊肿.CT检查提示,3例肾囊实性占位,为良性肿瘤;1例为厚壁型肾囊肿.2例行MRI检查提示,肾脏囊实性占位,为良性肿瘤.结果 4例患者均予手术治疗,术中发现肿块与肾组织的界限清楚,易分离;肿块呈囊实性,囊壁厚薄均匀,组织致密且内壁光滑.术后病理组织学检查示:2例为低度恶性上皮细胞肿瘤,1例为恶性肿瘤(透明细胞癌不排除),另1例为肾脏黏液性管状和梭形细胞癌.结论 肾脏黏液性管状和梭形细胞癌是一种具有良性肿瘤生长特性的低度恶性倾向的肿瘤.%Objective To explore the clinical and pathological characteristics of renal mucinous tubular and spindle cell carcinoma. Methods Clinical data of 4 patients including 3 female and 1 male aged from 35 to 56 were analyzed retrospectively. Among the 4 cases, two tumors were in the left side and two in right. Three tumors located in the upper part of kidneys, one in the lower part. The size of tumors ranged from 3.5 to 6.5 cm. There was no obvious symptom or physical sign in all cases and the tumors were detected during healthy examination. In B type untrasonography, two patients showed cystsolid tumor and two showed thick-wall cyst of kidney. In CT scan, three patients showed cystsolid tumor and one showed thick-wall cyst of kidney. In MRI scan, two patients showed cystsolid tumor. All the imaging examinations indicated the lump was benign. Results There were clear boundaries between the tumors and normal kidney tissue and the lesions were easy to be separated

  5. 促红细胞生成素防治大鼠急性肾小管坏死的实验研究%Experimental study of the prevention and treatment of acute renal tubular necrosis with erythropoietin in rats

    Institute of Scientific and Technical Information of China (English)

    余堂宏; 胡宏; 梁伟; 刘金洪

    2010-01-01

    目的 探讨促红细胞生成素对大鼠急性肾小管坏死的防治作用.方法 按10 mL·kg-1肌肉注射甘油建立大鼠急性肾小管坏死模型.30只Wistar大鼠随机(随机数字法)分为正常组、模型组、治疗组.治疗组予促红细胞生成素(1000 IU·kg-1)尾静脉注射,实验结束时检测各组大鼠血尿素氮(Bun)、血肌酐(Scr)、尿渗量、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、尿β2微球蛋白(β2-MG),肾组织匀浆丙二醇(MDA)和超氧化物歧化酶(SOD),并进行肾脏组织学观察.结果 与模型组比较,治疗组大鼠Bun、Scr、尿NAG、尿β2-MG、肾组织匀浆MDA明显下降,而尿渗量、肾组织匀浆SOD升高,肾脏病理改变好转.结论 促红细胞生成素可能通过抗氧自由基损伤,提高内源性抗氧化能力达到对急性肾小管坏死大鼠肾脏的部分保护作用.%Objective To study the preventive effects of erythropoietin (EPO) on acute tubular necrosis of kidney in rats. Method The rat models of acute renal tubular necrosis were established with injecting glycerol in dose of 10 mL/kg. Thirty Wistar rats were randomly (random number) divided into control group, model group and EPO treatment group. EPO was administered intravenously into rats of treatment group in a dose of 1000IU/kg. Levels of blood urea nitrogen (BUN) and serum creatinine (Scr), urine osmolality, urine N-acetyl-D-glucosaminidase (NAG), urine β2-microglobulin (β2-MG), tissue MDA and SOD of rats in the three groups were assayed after the experiment. Renal histological examination was also performed. Results Compared with model group, the levels of BUN and Scr, urine osmolality, NAG,β2-MG and tissue MDA in EPO treament group were significantly lower, but urine osmolality and tissue SOD of rats remarkably increased in comparison with model group. EPO also lessened the histological changes in treatment group. Conclusions EPO has some protective effects on acute renal tubular necrosis in rats, which

  6. Effect and its mechanism of FoxO3a activates FasL on renal tubular epithelial cell apoptosis induced by renal ischemia/reperfusion injury%FoxO3a 激活 FasL 介导肾缺血再灌注中肾小管上皮细胞凋亡的作用及机制

    Institute of Scientific and Technical Information of China (English)

    徐剑; 王艳; 姬怀雪; 胡书群; 董红艳; 任玲

    2014-01-01

    Objective To explore the role and mechanism of forkhead box proteinO3a activates Fas ligand on renal tubular epithelial cell ( RTC ) apoptosis induced by renal ischemia /reperfusion ( I/R ) . Methods The model by clamping renal pedicles for 45 minutes follow-ing reperfusion was established.The protein expression of forkhead box proteinO3a and Fas ligand were examined by western blotting.Apoptosis of RTC was assessed by TdT -mediated dUTP nick -end Labeling (TUNEL) method and transmission electron microscopic (TEM).Renal function was assessed by biochemical automatic analyzer .Results The protein expression level of forkhead box proteinO 3a and Fas ligand was increased significantly following renal I /R at 1 h.RTC nucleus was shrinking, crushing followed renal I /R, and a significant increase in the number of TUNEL -positive cells following renal I /R was displayed com-pared with the sham group.The level of blood urea nitrogen(BUN) and serum creatinine ( Scr) was increased significantly compared with the sham group (P <0.05,P <0.01).Conclusion FoxO3a could be acti-vated during renal I /R, and then up -regulated FasL protein expression , facilitated renal tubular epithelial cell apoptosis , in turn, aggravated renal I /R injury in rats.%目的:观察叉头框蛋白 FoxO3a 激活 Fas 配体 FasL 介导肾缺血再灌注损伤诱导肾小管上皮细胞凋亡的作用及机制。方法双侧夹闭大鼠肾蒂缺血45 min 后再灌注建立动物模型。免疫印迹分析 FoxO3a、FasL 的表达变化;原位缺口末端标记法检测大鼠肾小管上皮细胞凋亡情况;透射电镜观察肾小管上皮细胞凋亡的超微结构变化;生化全自动分析仪检测大鼠肾功能。结果大鼠肾缺血再灌注1 h 后,FoxO3a 及 FasL 蛋白表达水平明显增加;再灌注48 h,肾小管上皮细胞凋亡损伤加剧,凋亡数目明显增加,血肌酐及尿素氮水平明显升高,与假手术组相比,差异有统计学意义(P <0.05

  7. 新疆军垦细毛羊肾小管上皮细胞的原代培养及鉴定%Primary Culture and Identification of Renal Tubular Epithelial Cells of Xinjiang Fine -wool Sheep

    Institute of Scientific and Technical Information of China (English)

    潘奇; 李宏建; 潘晓亮; 张书信; 崔艳霞; 王振国; 徐亚楠

    2012-01-01

    [目的]建立一种高效、实用的新疆军垦细毛羊肾小管上皮细胞原代培养方案,为肾脏损伤引起的疾病研究奠定基础.[方法]取5~8个月大的出栏细毛羊肾脏皮质,剪成1~2 mm3大小组块,分别采用传统组织块法和改良组织块法,在含15%~ 20%新生小牛血清的DMEM的培养基中进行原代培养,无需研磨或使用酶和化学试剂,根据上皮细胞自身的生长特性,首次结合刮除法,相差消化法和差速贴壁法,分离纯化上皮细胞,再选用0.037 mm孔径网筛过滤除去肾小球上皮细胞,分离纯化培养肾小管上皮细胞,细胞免疫组化进行鉴定.[结果]改良方法与传统方法相比,细胞贴壁早,生长快,处理时间短,减少了污染机率,提高了细胞培养效率,分离培养的肾小管上皮细胞,纯度达90%以上,细胞呈多角形,鹅卵石状,折光性强,连接紧密,可传至第9代,免疫细胞化学(CK - 18)染色鉴定为阳性.[结论]改良的组织块培养与传统的组织块培养以及常用的酶消化培养相比,经济、简单、不易污染,分离培养的肾小管上皮细胞,活性高,纯度高,是一种高效、实用的细毛羊肾小管上皮细胞培养方法.%[Objective] The projected aimed to explore an effective and practical method for primary culture of Xinjiang fine - wool sheep renal tubular epithelial cells, so as to establish the basis for the study of diseases caused by kidney damage. [ Method] Renal cortex of fine - wool sheep at 5 - 8 months old were chosen and cut into pieces of 1 - 2 mm3 Traditional and modified tissue culture methods were used, and cultured in DMEM supplemented with 15% -20%newborn calf serum, without grinding or using enzymes and chemicals. All this was done based on the characteristics of epithelial cell. The renal tubular epithelial cells were separated and purified by combining scraping with the different time for cell digestion and attachment, and then filtered by 0.037 mm

  8. D-Lactic Acidosis in Humans: Review of Update

    OpenAIRE

    Kang, Kyung Pyo; Lee, Sik; Kang, Sung Kyew

    2006-01-01

    D-Lactic acidosis has been well documented in ruminants. In humans, D-lactic acidosis is very rare, but D-lactic acidosis may be more common than generally believed and should be looked for in a case of metabolic acidosis in which the cause of acidosis is not apparent. The clinical presentation of D-lactic acidosis is characterized by episodes of encephalopathy and metabolic acidosis. The entity should be considered as a diagnosis in a patient who presents with metabolic acidosis accompanied ...

  9. 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)

    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

  10. 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...

  11. Effects of halothane-nitrous oxide inhalation anesthesia and Inactin on overall renal and tubular function in Sprague-Dawley and Wistar rats

    DEFF Research Database (Denmark)

    Holstein-Rathlou, N H; Christensen, P; Leyssac, P P

    1982-01-01

    anesthesia indicating that the proximal luminal diameter was constant and independent of CIN. B. Inactin anesthesia CIN was similarly reduced but APR was more depressed (by about 35%). RPF and solute excretion rate decreased only in SPRD rats, while urine flow was significantly reduced in both strains. 1/OT......) and absolute proximal reabsorption rate (APR) was moderately decreased (by about 20%), while renal plasma flow (RPF), urine flow and solute excretion remained unchanged as compared to conscious rats. There was a linear relationship between the reciprocal of the proximal occlusion time (OT) and CIN in Halothane...... prepared rats are more severely depressed by Inactin than by Halothane-N2O anesthesia. The gas anesthesia is equally well tolerated by both strains of rats....

  12. Acidosis inhibits mineralization in human osteoblasts.

    Science.gov (United States)

    Takeuchi, Shoko; Hirukawa, Koji; Togari, Akifumi

    2013-09-01

    Osteoblasts and osteoclasts maintain bone volume. Acidosis affects the function of these cells including mineral metabolism. We examined the effect of acidosis on the expression of transcription factors and mineralization in human osteoblasts in vitro. Human osteoblasts (SaM-1 cells) derived from the ulnar periosteum were cultured with α-MEM containing 50 μg/ml ascorbic acid and 5 mM β-glycerophosphate (calcifying medium). Acidosis was induced by incubating the SaM-1 cells in 10 % CO₂ (pH approximately 7.0). Mineralization, which was augmented by the calcifying medium, was completely inhibited by acidosis. Acidosis depressed c-Jun mRNA and increased osteoprotegerin (OPG) production in a time-dependent manner. Depressing c-Jun mRNA expression using siRNA increased OPG production and inhibited mineralization. In addition, depressing OPG mRNA expression with siRNA enhanced mineralization in a dose-dependent manner. Acidosis or the OPG protein strongly inhibited mineralization in osteoblasts from neonatal mice. The present study was the first to demonstrate that acidosis inhibited mineralization, depressed c-Jun mRNA expression, and induced OPG production in human osteoblasts. These results suggest that OPG is involved in mineralization via c-Jun in human osteoblasts.

  13. Diminution of oxalate induced renal tubular epithelial cell injury and inhibition of calcium oxalate crystallization in vitro by aqueous extract of Tribulus terrestris

    Directory of Open Access Journals (Sweden)

    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.

  14. Activated extracellular signal-regulated kinases are necessary and sufficient to initiate tubulogenesis in renal tubular MDCK strain I cell cysts.

    Science.gov (United States)

    Hellman, Nathan E; Greco, Andres J; Rogers, Katherine K; Kanchagar, Chitra; Balkovetz, Daniel F; Lipschutz, Joshua H

    2005-10-01

    A classic in vitro model of renal cyst and tubule formation utilizes the Madin-Darby canine kidney (MDCK) cell line, of which two strains exist. Most cyst and tubule formation studies that utilized MDCK cells have been performed with MDCK strain II cells. MDCK strain II cells form hollow cysts in a three-dimensional collagen matrix over 10 days and tubulate in response to hepatocyte growth factor, which increases levels of active (phosphorylated) ERK1/2. In this study, we demonstrate that MDCK strain I cells also form cysts when grown in a collagen matrix; however, MDCK strain I cell cysts spontaneously initiate the primary steps in tubulogenesis. Analysis of time-lapse microscopy of both MDCK strain I and strain II cell cysts during the initial stages of tubulogenesis demonstrates a highly dynamic process with cellular extensions and retractions occurring rapidly and continuously. MDCK strain I cell cysts can spontaneously initiate tubulogenesis mainly because of relatively higher levels of active ERK in MDCK strain I, compared with strain II, cells. The presence of either of two distinct inhibitors of ERK activation (UO126 and PD09059) prevents tubulogenesis from occurring spontaneously in MDCK strain I cell cysts and, in response to hepatocyte growth factor, in strain II cell cysts. The difference between MDCK strain I and strain II cell lines is likely explained by differing embryological origins, with strain I cells being of collecting duct, and hence ureteric bud, origin. Ureteric bud cells also have high levels of active ERK and spontaneously tubulate in our in vitro collagen gel system, with tubulogenesis inhibited by UO126 and PD09059. These results suggest that a seminal event in kidney development may be the activation of ERK in the mesonephric duct/ureteric bud cells destined to form the collecting tubules.

  15. Moduretic-induced metabolic acidosis and hyperkalaemia.

    OpenAIRE

    Wan, H. H.; Lye, M. D.

    1980-01-01

    A patient who developed significant metabolic acidosis and severe hyperkalaemia while taking Moduretic (amiloride and hydrochlorothiazide) is reported. During the period of hyperkalaemia (maximum potassium 7-6 mmol/l) the patient's whole body potassium content was normal. His acid-base balance and serum potassium returned to normal some 10 days after stopping the drug. The possible mechanism of acidosis and hyperkalaemia in this patient is discussed.

  16. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    Directory of Open Access Journals (Sweden)

    Guruprasad P Bhosale

    2015-01-01

    Full Text Available Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L and severe metabolic acidosis (pH 6.65 that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurological sequelae. To the best of our knowledge, this is the first case report in adults of severe hypernatremia along with severe metabolic acidosis due to error in the preparation of dialysis fluid.

  17. Successful recovery from iatrogenic severe hypernatremia and severe metabolic acidosis resulting from accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment

    OpenAIRE

    Bhosale, Guruprasad P; Veena R Shah

    2015-01-01

    Bicarbonate dialysis is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper selection of dialysate concentrate can result in life-threatening human errors. We report a case of iatrogenic severe hypernatremia (sodium 207 mEq/L) and severe metabolic acidosis (pH 6.65) that resulted due to accidental use of inappropriate bicarbonate concentrate for hemodialysis treatment. There was successful recovery in this patient with no neurologi...

  18. The genomic analysis of lactic acidosis and acidosis response in human cancers.

    Directory of Open Access Journals (Sweden)

    Julia Ling-Yu Chen

    2008-12-01

    Full Text Available The tumor microenvironment has a significant impact on tumor development. Two important determinants in this environment are hypoxia and lactic acidosis. Although lactic acidosis has long been recognized as an important factor in cancer, relatively little is known about how cells respond to lactic acidosis and how that response relates to cancer phenotypes. We develop genome-scale gene expression studies to dissect transcriptional responses of primary human mammary epithelial cells to lactic acidosis and hypoxia in vitro and to explore how they are linked to clinical tumor phenotypes in vivo. The resulting experimental signatures of responses to lactic acidosis and hypoxia are evaluated in a heterogeneous set of breast cancer datasets. A strong lactic acidosis response signature identifies a subgroup of low-risk breast cancer patients having distinct metabolic profiles suggestive of a preference for aerobic respiration. The association of lactic acidosis response with good survival outcomes may relate to the role of lactic acidosis in directing energy generation toward aerobic respiration and utilization of other energy sources via inhibition of glycolysis. This "inhibition of glycolysis" phenotype in tumors is likely caused by the repression of glycolysis gene expression and Akt inhibition. Our study presents a genomic evaluation of the prognostic information of a lactic acidosis response independent of the hypoxic response. Our results identify causal roles of lactic acidosis in metabolic reprogramming, and the direct functional consequence of lactic acidosis pathway activity on cellular responses and tumor development. The study also demonstrates the utility of genomic analysis that maps expression-based findings from in vitro experiments to human samples to assess links to in vivo clinical phenotypes.

  19. Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Fareed B. Kamar

    2015-01-01

    Full Text Available Cholestyramine is a bile acid sequestrant that has been used in the treatment of hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due to bile acid malabsorption. This medication can rarely cause hyperchloremic nonanion gap metabolic acidosis, a complication featured in this report of an adult male with concomitant acute kidney injury. This case emphasizes the caution that must be taken in prescribing cholestyramine to patients who may also be volume depleted, in renal failure, or taking spironolactone.

  20. Hyperchloremic Metabolic Acidosis due to Cholestyramine: A Case Report and Literature Review.

    Science.gov (United States)

    Kamar, Fareed B; McQuillan, Rory F

    2015-01-01

    Cholestyramine is a bile acid sequestrant that has been used in the treatment of hypercholesterolemia, pruritus due to elevated bile acid levels, and diarrhea due to bile acid malabsorption. This medication can rarely cause hyperchloremic nonanion gap metabolic acidosis, a complication featured in this report of an adult male with concomitant acute kidney injury. This case emphasizes the caution that must be taken in prescribing cholestyramine to patients who may also be volume depleted, in renal failure, or taking spironolactone.

  1. 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...

  2. Trimethoprim/Sulfamethoxazole-Induced Severe Lactic Acidosis: A Case Report and Review of the Literature.

    Science.gov (United States)

    Bulathsinghala, Marie; Keefer, Kimberly; Van de Louw, Andry

    2016-04-01

    Propylene glycol (PG) is used as a solvent in numerous medications, including trimethoprim/sulfamethoxazole (TMP/SMX) and lorazepam, and is metabolized in the liver to lactic acid. Cases of lactic acidosis related to PG toxicity have been described and always involved large doses of benzodiazepines and PG. We present the first case of severe lactic acidosis after a 3-day course of TMP/SMX alone, involving allegedly safe amounts of PG.A 31-year-old female with neurofibromatosis and pilocytic astrocytoma, receiving temozolomide and steroids, was admitted to the intensive care unit for pneumonia and acute respiratory failure requiring intubation. Her initial hemodynamic and acid-base statuses were normal. She was treated with intravenous TMP/SMX for possible Pneumocystis jirovecii pneumonia and was successfully extubated on day 2. On day 3, she developed tachypnea and arterial blood gas analysis revealed a severe metabolic acidosis (pH 7.2, PCO2 19 mm Hg, bicarbonates 8 mEq/L) with anion gap of 25 mEq/L and lactate of 12.1 mmol/L. TMP/SMX was discontinued and the lactate decreased to 2.9 mmol/L within 24 hours while her plasma bicarbonates normalized, without additional intervention. The patient never developed hypotension or severe hypoxia, and her renal and liver functions were normal. No other cause for lactic acidosis was identified and it resolved after TMP/SMX cessation alone, suggesting PG toxicity.Although PG-related lactic acidosis is well recognized after large doses of lorazepam, clinicians should bear in mind that TMP/SMX contains PG as well and should suspect PG toxicity in patients developing unexplained metabolic acidosis while receiving TMP/SMX. PMID:27124045

  3. Radiological evaluation of renal transplantation

    International Nuclear Information System (INIS)

    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.)

  4. Metformin-associated lactic acidosis: Current perspectives on causes and risk.

    Science.gov (United States)

    DeFronzo, Ralph; Fleming, G Alexander; Chen, Kim; Bicsak, Thomas A

    2016-02-01

    Although metformin has become a drug of choice for the treatment of type 2 diabetes mellitus, some patients may not receive it owing to the risk of lactic acidosis. Metformin, along with other drugs in the biguanide class, increases plasma lactate levels in a plasma concentration-dependent manner by inhibiting mitochondrial respiration predominantly in the liver. Elevated plasma metformin concentrations (as occur in individuals with renal impairment) and a secondary event or condition that further disrupts lactate production or clearance (e.g., cirrhosis, sepsis, or hypoperfusion), are typically necessary to cause metformin-associated lactic acidosis (MALA). As these secondary events may be unpredictable and the mortality rate for MALA approaches 50%, metformin has been contraindicated in moderate and severe renal impairment since its FDA approval in patients with normal renal function or mild renal insufficiency to minimize the potential for toxic metformin levels and MALA. However, the reported incidence of lactic acidosis in clinical practice has proved to be very low (metformin are too conservative, thus depriving a substantial number of type 2 diabetes patients from the potential benefit of metformin therapy. On the other hand, the success of metformin as the first-line diabetes therapy may be a direct consequence of conservative labeling, the absence of which could have led to excess patient risk and eventual withdrawal from the market, as happened with earlier biguanide therapies. An investigational delayed-release metformin currently under development could potentially provide a treatment option for patients with renal impairment pending the results of future studies. This literature-based review provides an update on the impact of renal function and other conditions on metformin plasma levels and the risk of MALA in patients with type 2 diabetes.

  5. 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.

  6. Proximal tubule-specific glutamine synthetase deletion alters basal and acidosis-stimulated ammonia metabolism.

    Science.gov (United States)

    Lee, Hyun-Wook; Osis, Gunars; Handlogten, Mary E; Lamers, Wouter H; Chaudhry, Farrukh A; Verlander, Jill W; Weiner, I David

    2016-06-01

    Glutamine synthetase (GS) catalyzes the recycling of NH4 (+) with glutamate to form glutamine. GS is highly expressed in the renal proximal tubule (PT), suggesting ammonia recycling via GS could decrease net ammoniagenesis and thereby limit ammonia available for net acid excretion. The purpose of the present study was to determine the role of PT GS in ammonia metabolism under basal conditions and during metabolic acidosis. We generated mice with PT-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Under basal conditions, PT-GS-KO increased urinary ammonia excretion significantly. Increased ammonia excretion occurred despite decreased expression of key proteins involved in renal ammonia generation. After the induction of metabolic acidosis, the ability to increase ammonia excretion was impaired significantly by PT-GS-KO. The blunted increase in ammonia excretion occurred despite greater expression of multiple components of ammonia generation, including SN1 (Slc38a3), phosphate-dependent glutaminase, phosphoenolpyruvate carboxykinase, and Na(+)-coupled electrogenic bicarbonate cotransporter. We conclude that 1) GS-mediated ammonia recycling in the PT contributes to both basal and acidosis-stimulated ammonia metabolism and 2) adaptive changes in other proteins involved in ammonia metabolism occur in response to PT-GS-KO and cause an underestimation of the role of PT GS expression.

  7. High anion gap refractory metabolic acidosis as a critical presentation of endosulfan poisoning

    Directory of Open Access Journals (Sweden)

    Raj Kumar Sharma

    2011-01-01

    Full Text Available Organochloride insecticides are chlorinated cyclic hydrocarbons. One of such insecticides is endosulfan (6,7,8,9,10-10 hexachloro 1,5,5a,6,9,9a-hexahydro-6-methano-2,4,3-hexadithioxanthiep in 3-oxide and it has been widely used in agriculture since 1960. The uncontrolled use of these compounds in developing countries has resulted in the deaths of animals and humans. Characteristic clinical signs following acute exposure are indicative of CNS disturbances or overstimulation. Mortality and morbidity rates are high and there is no specific antidote. We present an uncommon presentation of endosulfan poisoning in a 32-year-old male with high anion gap severe refractory metabolic acidosis. The patient was treated with continuous renal replacement therapy and was salvaged. Till date, there is no case report from India for endosulfan poisoning with severe metabolic acidosis and hypotension. Through this case report, we emphasize the role of continuous renal replacement therapy as a rescue therapy for endosulfan poisoning with severe refractory metabolic acidosis and hypotension, even though it is a non dialyzable poison.

  8. Lactic Acidosis: Current Treatments and Future Directions.

    Science.gov (United States)

    Kraut, Jeffrey A; Madias, Nicolaos E

    2016-09-01

    Mortality rates associated with severe lactic acidosis (blood pHreduce mortality. This failure has been attributed to both reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification. In animal studies, hyperventilation and infusion of calcium during sodium bicarbonate administration improves cardiovascular function, suggesting that this approach could allow expression of the positive aspects of sodium bicarbonate. Other buffers, such as THAM or Carbicarb, or dialysis might also provide base with fewer untoward effects. Examination of these therapies in humans is warranted. The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na(+)/H(+) exchanger. In animal studies, selective NHE1 inhibitors improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality, supporting future research into their possible use in humans. Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis. Targeting these mechanisms could allow for more specific therapy. This Acid-Base and Electrolyte Teaching Case presents a patient with acute lactic acidosis and describes current and future approaches to treatment. PMID:27291485

  9. A supramolecular tubular nanoreactor.

    Science.gov (United States)

    Li, Zhi-Qiang; Zhang, Ying-Ming; Chen, Yong; Liu, Yu

    2014-07-01

    The extremely strong noncovalent complexation between the rigid host of phthalocyanine-bridged β-cyclodextrins and the amphiphilic guest carboxylated porphyrin is employed to construct a hollow tubular structure as a supramolecular nanoreactor. A representative coupling reaction occurs in the hydrophobic interlayers of the tubular walls in pure water at room temperature, leading to an enhancement of ten times higher reaction rate without any adverse effect on catalytic activity and conversion. PMID:24890802

  10. Starvation Ketoacidosis as a Cause of Unexplained Metabolic Acidosis in the Perioperative Period

    Science.gov (United States)

    Mostert, Monique; Bonavia, Anthony

    2016-01-01

    Patient: Female, 24 Final Diagnosis: Starvation ketoacidosis Symptoms: None Medication: — Clinical Procedure: Lumbar laminectomy Specialty: Orthopedics and Traumatology Objective: Unusual clinical course Background: Besides providing anesthesia for surgery, the anesthesiologist’s role is to optimize the patient for surgery and for post-surgical recovery. This involves timely identification and treatment of medical comorbidities and abnormal laboratory values that could complicate the patient’s perioperative course. There are several potential causes of anion and non-anion gap metabolic acidosis in surgical patients, most of which could profoundly affect a patient’s surgical outcome. Thus, the presence of an acute acid-base disturbance requires a thorough workup, the results of which will influence the patient’s anesthetic management. Case Report: An otherwise-healthy 24-year-old female presented for elective spine surgery and was found to have metabolic acidosis, hypotension, and polyuria intraoperatively. Common causes of acute metabolic acidosis were investigated and systematically ruled out, including lactic acidosis, diabetic ketoacidosis, drug-induced ketoacidosis, ingestion of toxic alcohols (e.g., methanol, ethylene glycol), uremia, and acute renal failure. Laboratory workup was remarkable only for elevated serum and urinary ketone levels, believed to be secondary to starvation ketoacidosis. Due to the patient’s unexplained acid-base disturbance, she was kept intubated postoperatively to allow for further workup and management. Conclusions: Starvation ketoacidosis is not widely recognized as a perioperative entity, and it is not well described in the medical literature. Lack of anesthesiologist awareness about this disorder may complicate the differential diagnosis for acute intraoperative metabolic acidosis and lead to a prolonged postoperative stay and an increase in hospital costs. The short- and long-term implications of perioperative

  11. Glutamatergic signaling maintains the epithelial phenotype of proximal tubular cells

    NARCIS (Netherlands)

    Bozic, M.; de Rooij, J.; Parisi, E.; Ortega, M.R.; Fernandez, E.; Valdivielso, J.M.

    2011-01-01

    Epithelial-mesenchymal transition (EMT) contributes to the progression of renal tubulointerstitial fibrosis. The N-methyl-d-aspartate receptor (NMDAR), which is present in proximal tubular epithelium, is a glutamate receptor that acts as a calcium channel. Activation of NMDAR induces actin rearrange

  12. Trauma triggering thyrotoxic crisis with lactic acidosis

    Directory of Open Access Journals (Sweden)

    Jennifer S Prosser

    2015-01-01

    Full Text Available Thyrotoxic crisis (TC is defined as a life-threatening exacerbation of the hyperthyroid state that causes multiple autonomic and metabolic disturbances. It is considered to be an endocrine emergency that must be urgently diagnosed and treated. We describe a case of TC precipitated by trauma with a resultant lactic acidosis. The patient is a 24-year-old male with a history of hyperthyroidism who presented to the emergency department following a motor vehicle accident. The patient was initially tachycardic and hypertensive, however, was afebrile. Initial laboratory analysis showed an anion gap of 26, lactic acid 7.6, free T4 5.61 and thyroid stimulating hormone < 0.015. A diagnosis of TC was made, and he was treated with intravenous fluids, propranolol, and methimazole with improvement of tachycardia and lactic acidosis. We discuss the features of this case, which reviews the presentations of TC as well as its metabolic sequelae.

  13. Trauma triggering thyrotoxic crisis with lactic acidosis.

    Science.gov (United States)

    Prosser, Jennifer S; Quan, Dan K

    2015-01-01

    Thyrotoxic crisis (TC) is defined as a life-threatening exacerbation of the hyperthyroid state that causes multiple autonomic and metabolic disturbances. It is considered to be an endocrine emergency that must be urgently diagnosed and treated. We describe a case of TC precipitated by trauma with a resultant lactic acidosis. The patient is a 24-year-old male with a history of hyperthyroidism who presented to the emergency department following a motor vehicle accident. The patient was initially tachycardic and hypertensive, however, was afebrile. Initial laboratory analysis showed an anion gap of 26, lactic acid 7.6, free T4 5.61 and thyroid stimulating hormone < 0.015. A diagnosis of TC was made, and he was treated with intravenous fluids, propranolol, and methimazole with improvement of tachycardia and lactic acidosis. We discuss the features of this case, which reviews the presentations of TC as well as its metabolic sequelae.

  14. Pathophysiology and management of progressive renal disease.

    Science.gov (United States)

    Brown, S A; Crowell, W A; Brown, C A; Barsanti, J A; Finco, D R

    1997-09-01

    Recently, the hypothesis that all renal diseases are inherently progressive and self-perpetuating has focused attention on adaptive changes in renal structure and function that occur whenever renal function is reduced. These glomerular adaptations to renal disease include increases in filtration rate, capillary pressure and size, and are referred to as glomerular hyperfiltration, glomerular hypertension and glomerular hypertrophy, respectively. Extrarenal changes, such as dietary phosphate excess, systemic hypertension, hyperlipidaemia, acidosis and hyperparathyroidism occur in animals with renal disease and may be contributors to progression of renal disease. Emphasis in the management of companion animals with renal disease has shifted to identifying, understanding and controlling those processes that play a role in the progression from early to end-stage renal failure. Advances made by veterinary nephrologists in the past 15 years permit resolution of old controversies, formulation of new hypotheses and discussion of unresolved issues about the nature of progressive renal disease in dogs and cats. PMID:9308397

  15. Hyaluronan in Tubular and Interstitial Nephrocalcinosis

    Science.gov (United States)

    Verkoelen, Carl F.

    2007-04-01

    Hyaluronan (HA) is the major glycosaminoglycan (GAG) component of the renal medullary interstitium. HA is extremely large (up to 104 kDa) and composed of thousands repeating disaccharides of glucuronic acid (GlcUA) and N-acetylglucosamine (GlcNAc). HA is synthesized by hyaluronan synthases (HASs) and degraded by hyaluronidases (Hyals). The production of HA by renomedullary interstitial cells is mediated by local osmolality. When excess water needs to be excreted, increased interstitial HA seems to antagonize water reabsorption, while the opposite occurs during water conservation. Hence, papillary interstitial HA is low and Hyal high during anti-diuresis, whereas during diuresis HA is high and Hyal low. The polyanion HA plays a role in the reabsorption of hypotonic fluid by immobilizing cations (Na+) via the carboxylate (COO-) groups of GlcUA. The binding of Ca2+ to anionic HA is probably also responsible for the fact that the papilla does not become a stone despite the extremely high interstitial phosphate and oxalate. HA is also an excellent crystal binding molecule. The expression of HA at the luminal surface of renal tubular cells leads to tubular nephrocalcinosis (tubular NC). Calcium staining methods (Von Kossa, Yasue) demonstrated that crystallization inhibitors cannot avoid the occasional precipitation of calcium phosphate in the papillary interstitium (interstitial NC). These crystals are probably immediately immobilized by the gel-like HA matrix. After ulcerating through the pelvic wall the calcified matrix becomes a Randall's plaque. The attachment of calcium oxalate crystals from the primary urine to plaque may ultimately lead to the development of clinical stones in the renal calyces (nephrolithiasis).

  16. Tubular transport and metabolism of cimetidine in chicken kidneys

    International Nuclear Information System (INIS)

    Renal tubular transport and renal metabolism of [14C]cimetidine (CIM) were investigated by unilateral infusion into the renal portal circulation in chickens (Sperber technique). [14C]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 [14C]CIM with decreasing potency: CIM, ranitidine, thiamine, procainamide, guanidine and choline. CIM inhibited the transport of [14C]thiamine, [14C]amiloride and [14C]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

  17. 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.

  18. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 冷静

    2002-01-01

    ObjectiveTo elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.MethodsA model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling (TUNEL).ResultsApoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.ConclusionTetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.``

  19. Changes of Apoptosis in Rats of Acute Ischemic Renal Injury under Treatment of Tetrandrine

    Institute of Scientific and Technical Information of China (English)

    钱玲梅; 王笑云; 等

    2002-01-01

    Objective To elucidate the effect of tetrandrine on acute ischemic renal injury and its relation with apoptosis.Methods A model for bilateral post-ischemic renal injury in rats was developed by clamping renal pedicles for 45 min.Renal tissular DNA fragmentation analysis and renal tissular HE staining were used.Also quantitative analysis of apoptosis in injured renal tubular epithelium was carried out by using TdT-mediated dUTP nick and labeling(TUNEL).Results Apoptosis of renal tubular epithelium increased in acute ischemic renal injury.Tetrandrine could remarkably decrease the level of apoptosis in injured renal tubule while protecting renal tissue against the ischemic injuries.Conclusion Tetrandrine could adjust the level of apoptosis in renal tubular epithelium and alleviate renal tissular injury.

  20. Drug-Induced Metabolic Acidosis [version 1; referees: 3 approved

    Directory of Open Access Journals (Sweden)

    Amy Quynh Trang Pham

    2015-12-01

    Full Text Available Metabolic acidosis could emerge from diseases disrupting acid-base equilibrium or from drugs that induce similar derangements. Occurrences are usually accompanied by comorbid conditions of drug-induced metabolic acidosis, and clinical outcomes may range from mild to fatal. It is imperative that clinicians not only are fully aware of the list of drugs that may lead to metabolic acidosis but also understand the underlying pathogenic mechanisms. In this review, we categorized drug-induced metabolic acidosis in terms of pathophysiological mechanisms, as well as individual drugs’ characteristics.

  1. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

    Science.gov (United States)

    Li, A; Wang, J; Zhu, D; Zhang, X; Pan, R; Wang, R

    2015-01-01

    Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work. PMID:25968940

  2. Arctigenin suppresses transforming growth factor-β1-induced expression of monocyte chemoattractant protein-1 and the subsequent epithelial-mesenchymal transition through reactive oxygen species-dependent ERK/NF-κB signaling pathway in renal tubular epithelial cells.

    Science.gov (United States)

    Li, A; Wang, J; Zhu, D; Zhang, X; Pan, R; Wang, R

    2015-01-01

    Transforming growth factor-β1 (TGF-β1) induces expression of the proinflammatory and profibrotic cytokine monocyte chemoattractant protein-1 (MCP-1) in tubular epithelial cells (TECs) and thereby contributes to the tubular epithelial-mesenchymal transition (EMT), which in turn leads to the progression of tubulointerstitial inflammation into tubulointerstitial fibrosis. Exactly how TGF-β1 causes MCP-1 overexpression and subsequent EMT is not well understood. Using human tubular epithelial cultures, we found that TGF-β1 upregulated the expression of reduced nicotinamide adenine dinucleotide phosphate oxidases 2 and 4 and their regulatory subunits, inducing the production of reactive oxygen species. These reactive species activated a signaling pathway mediated by extracellular signal-regulated kinase (ERK1/2) and nuclear factor-κB (NF-κB), which upregulated expression of MCP-1. Incubating cultures with TGF-β1 was sufficient to induce hallmarks of EMT, such as downregulation of epithelial marker proteins (E-cadherin and zonula occludens-1), induction of mesenchymal marker proteins (α-smooth muscle actin, fibronectin, and vimentin), and elevated cell migration and invasion in an EMT-like manner. Overexpressing MCP-1 in cells exposed to TGF-β1 exacerbated these EMT-like changes. Pretreating cells with the antioxidant and anti-inflammatory compound arctigenin (ATG) protected them against these TGF-β1-induced EMT-like changes; the compound worked by inhibiting the ROS/ERK1/2/NF-κB pathway to decrease MCP-1 upregulation. These findings suggest ATG as a new therapeutic candidate to inhibit or even reverse tubular EMT-like changes during progression to tubulointerstitial fibrosis, and they provide the first clues to how ATG may work.

  3. JNK在血糖波动的糖尿病大鼠肾小管上皮细胞凋亡中的作用%The role of JNK in apoptosis of renal tubular epithelial cells in diabetic rats with fluctuant high blood glucose

    Institute of Scientific and Technical Information of China (English)

    郝卯林; 戴雍月; 倪世容; 汪大望; 李素娟; 金可可

    2012-01-01

    Objective: To explore the signal transduction mechanisms of apoptosis in renal tubular epithelial cells in diabetic rate with fluctuant high blood glucose. Methods: Healthy SD rats were randomly divided into 3 groups: normal control group(A), stable high Hood glucose gnwp(B) and fluctuant high Mood glucose group(C). Diabetic rats were induced by inbaperitoneal injection of streptozotocin( SIZ, 65 mg/kg), and the fluctuant high blood glucose animal model was induced by intraperitoneal injection of ordinary insulin and glucose at different time point every day. The supenndde dismutase (SOD) activity and the content of malonaldehyde (MDA) in renal tissue homogenate were detected with colorimetry.The protein expression of Nox4 and JNK were examined by immunohistochemistry and Western bint. Apoptosis was assessed by terminal deoxynucleotidyl Iransferase-mediated dUTP nick-end labelling (TUNEL). Results: After 12 experimental weeks, significantly increased cell apoptosis, up-regulation of Nox4 and P-JNK expression in renal tubular epithelial cells were observed in B and C groups compared with those in A group. The MDA content increased and SOD activity decreased in renal tissue in B and C groups. Above effects were more obviously shown in C group. Condition: Fluctuant high blood glucose induced more apoptosis of renal tubular epithelial cell than stable high blood glucose in diabetic kidney, which might be related to the activation of JNK signal transduction pathway.%目的:探讨血糖波动的糖尿病大鼠发生肾小管上皮细胞凋亡的信号转导机制.方法:健康SD大鼠随机分为正常对照组(A)、糖尿病稳定高血糖组(B)和糖尿病波动高血糖组(C),采用链脲佐菌素(STZ)65 mg/kg腹腔注射诱发糖尿病,血糖波动组每天定时腹腔注射速效胰岛素,并错时给予葡萄糖,造成一天中血糖浓度大幅度波动模型.制模12周后,采用比色法检测肾组织匀浆中超氧化物歧化酶(SOD)活性和丙二醛(MDA

  4. Tubular toxicity of proteinuria.

    Science.gov (United States)

    Baines, Richard J; Brunskill, Nigel J

    2011-03-01

    Proteinuria is a prognostic indicator of progressive kidney disease and poor cardiovascular outcomes. Abnormally filtered bioactive macromolecules interact with proximal tubular epithelial cells (PTECs), which results in the development of proteinuric nephropathy. This condition is characterized by alterations in PTEC growth, apoptosis, gene transcription and inflammatory cytokine production as a consequence of dysregulated signaling pathways that are stimulated by proteinuric tubular fluid. The megalin-cubilin complex mediates the uptake of several proteins, including albumin, into PTECs. Megalin might also possess intrinsic signaling properties and the ability to regulate cell signaling pathways and gene transcription after processing regulated intramembrane proteolysis. Megalin could, therefore, link abnormal PTEC albumin exposure with altered growth factor receptor activation, proinflammatory and profibrotic signaling, and gene transcription. Evidence now suggests that other PTEC pathways for protein reabsorption of (patho)physiological importance might be mediated by the neonatal Fc receptor and CD36. PMID:21151210

  5. An unrecognised case of metabolic acidosis following neobladder augmentation cystoplasty

    Directory of Open Access Journals (Sweden)

    David Eldred-Evans

    2015-01-01

    Conclusion: Hyperchloremic metabolic acidosis is a well-established complication of urinary diversion. Patient with orthotopic neobladder with high residual urine and large capacity are at even higher risk of metabolic acidosis. This information should be clearly documented in the post-operative discharge documentation to ensure early recognition by non-specialists.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Jae; Choi, Chul Soon; Min, Seon Jeong; Lee, Gyung Kyu; Lee, Eil Seong; Kang, Ik Won; Bae, Sang Hoon [Hallym University College of Medicine, Chuncheon (Korea, Republic of)

    2003-12-15

    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.

  7. Classifying Virtually Special Tubular Groups

    OpenAIRE

    Woodhouse, Daniel J.

    2016-01-01

    A group is tubular if it acts on a tree with $\\mathbb{Z}^2$ vertex stabilizers and $\\mathbb{Z}$ edge stabilizers. We prove that a tubular group is virtually special if and only if it acts freely on a locally finite CAT(0) cube complex. Furthermore, we prove that if a tubular group acts freely on a finite dimensional CAT(0) cube complex, then it virtually acts freely on a three dimensional CAT(0) cube complex.

  8. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy.

    Science.gov (United States)

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  9. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Science.gov (United States)

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  10. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Temesgen Fiseha

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

  11. Tubular biomarkers to assess progression of diabetic nephropathy.

    Science.gov (United States)

    Tramonti, Gianfranco; Kanwar, Yashpal S

    2011-05-01

    Despite aggressive management, many patients with diabetic nephropathy still develop end-stage renal disease. Accompanying tubulointerstitial damage is important in the progression of diabetic nephropathy. Markers of tubular damage, such as NGAL, KIM-1, and LFABP, have been proposed for monitoring the effectiveness of therapy. However, Nielsen et al. report a lack of an independent correlation between these biomarkers and glomerular filtration rate. Therefore, these markers seem to offer no improvement in the management of diabetic nephropathy. PMID:21527942

  12. Renal arteriography

    Science.gov (United States)

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... Renal arteriography is often needed to help decide on the best treatment after other tests are done ...

  13. Tolerance of hypercapnic acidosis by the European eel, Anguilla anguilla

    DEFF Research Database (Denmark)

    McKenzie, DJ; Dalla Valle, AZ; Steffensen, JF;

    2000-01-01

    in tailbeat frequencies, aerobic scope or maximum sustainable swimming speed. The results indicate that the eel is extremely tolerant of hypercapnic acidosis. Acute, severe acidosis and hypoxaemia had no effect on CO or whole animal O2 uptake; chronic acidosis and hypoxaemia had no effect on the ability.......5 ± 2.2 vol%, significantly lower than in the control animals, where pHa was 7.89 ± 0.04 and ca,O2 11.6 ± 1.5 vol%. Exercise performance was studied in a swimming respirometer. Stepwise increases in swimming speed caused similar, exponential increases in O2 uptake in all groups, with no differences...

  14. Effects of Total Flavonoids in Xiezhuo Chubi Decoction on the Proliferation and Uric Uptake Function of Mice Renal Tubular Epithelial Cells%泄浊除痹方总黄酮对小鼠肾小管上皮细胞增殖与尿酸吸收的影响

    Institute of Scientific and Technical Information of China (English)

    吴新荣; 臧路平; 刘志刚; 孙维峰

    2012-01-01

    OBJECTIVE: To investigate the effects of total flavonoids in Xiezhuo chubi decoction on the proliferation and uric uptake function of mice renal tubular epithelial cells (RTECs) in vivo. METHODS: The RTECs were isolated from the renal tubular epithelial cells of mice by optimized primary culture method, and were cultured with total flavonoids from Xiezhuo chubi decoction of different concentrations. The activity of RTECs was assayed by MTT assay. The uric uptake medium was prepared and the uric uptake values were determined by the kit. RESULTS: The interest cells were isolated, I.e. mice renal tubular epithelial cells, and it had the function of uric uptake. The proliferation of the RTECs was inhibited by high concentrations (10, 7.5, 5.0 g·L-1) of the drug. No significant effects on the proliferation of the RTECs were observed in the low concentrations (2.5, 0,5 g·L-1); total flavonoids had no significant effect on growth activity of cells in this range of 2.5,2.0,1.5, 1.0, 0.5 g·L-1 total flavonoids inhibited uric uptake in different degree. CONCLUSION: The uric uptake function of the RETCs can be inhibited by the total flavonoids in Xiezhuo chubi decoction.%目的:研究泄浊除痹方总黄酮对小鼠肾小管上皮细胞(RTECs)增殖与尿酸吸收的影响.方法:采用优化后的小鼠RTECs原代培养方法分离该细胞,不同浓度的泄浊除痹方总黄酮孵育48 h,MTT法检测细胞活性,配制尿酸吸收培养基,进行尿酸吸收实验,采用尿酸检测试剂盒测定尿酸吸收值.结果:所分离培养的细胞为目的细胞,即小鼠RTECs,具有尿酸吸收功能;高浓度药物(10、7.5、5.0 g·L-1)对细胞增殖有不同程度的抑制作用,低浓度药物(2.5、0.5g·L-1)对细胞增殖无显著性影响;在对细胞生长活性无显著性影响的浓度梯度范围内(2.5、2.0、1.5、1.0、0.5 g·L-1),药物对尿酸吸收表现出不同程度的抑制作用.结论:泄浊除痹方总黄酮对小鼠RTECs尿酸吸收功能有一定的抑制作用.

  15. SIGNIFICANCE OF URINARY RETINOL BINDING PROTEIN IN DIAGNOSIS OF EARLY RENAL TUBULAR INJURY%尿视黄醇结合蛋白检测在糖尿病早期肾小管损伤诊断中的意义

    Institute of Scientific and Technical Information of China (English)

    樊淑珍; 刘云彪; 张彩虹

    2012-01-01

    Objective:To determine the content of Urinary Retinol Binding Protein( RBP)in urine and further,and explore the effects and significance of RBP in the diagnosis of early renal tubular injury in patients with hypertention and diabetes. Methods; 106 patients with diabetes and hypertention were divided into 6 groups,which were the group of the patients with single hypertention,hypertention complicated with kidney diseases, diabetes without kidney diseases, diabetes complicated with kidney diseases, diabetes complicated with hypertension and the patients complicated with diabetes, hypertention and kidney diseases. Meanwhile,55 healthy patients were setted as normal control group. OLYMPUS AU2700 fully automatic biochemistry analyzer was used to assay RBP in each group. Results: The RBP Value was 0.45 ±0. 16 in normal group,the RBP value were between 0. 57 ±0. 18 and 17. 22 ± 3. 11 in experience group, which implies the RBP in the hypertention patients complicated with diabetes is significantly different from group. Conclusions: Assay of RBP is important to make a diagnosis of early renal tubular injury in patients with hypertention and diabetes, which can be termed as a reference index in diagnosing early renal tubular injury in patients with hypertention and diabetes.%目的:检测尿液中视黄醇结合蛋白( Retinol - binding protein,RBP)含量水平,探讨尿液中RBP在高血压、糖尿病早期肾小管损伤中的作用及意义.方法:选取106例糖尿病及高血压病人,分为高血压无肾病组、高血压合并肾病组、糖尿病无肾病组、糖尿病合并肾病组、糖尿病高血压无肾病组和糖尿病高血压合并肾病组等6个组,同时选择55例正常体检病人做对照组.采用OLYMPUS AU2700全自动生化分析仪对各组尿液RBP进行检测,并经统计学分析处理.结果:正常对照组尿液RBP值0.45±0.16;实验组尿液RBP在0.57±0.18~17.22±3.11之间.即高血压和糖尿病病人尿液

  16. 15-脱氧-△12,14-前列腺素J2在兔肾近曲小管钠和碳酸氢根转运作用及机制%Effects and Mechanisms of 15-deoxy-△12,14-prostaglandin J2 on Na+/HCO3-Transport in Rabbit Renal Proximal Tubular

    Institute of Scientific and Technical Information of China (English)

    李月红; 王茹; 王梅

    2011-01-01

    Objective To examine the effects of 15-deoxy- Δ12,14-prostaglandin J2 (15d-PGJ2), the selective ligand of PPAR-γ, on Na+/HCO3- transport in rabbit proximal tubular and the underlying mechanisms. Methods The responses Na+/HCO3-cotransporter induced by different 15d-PGJ2 concentrations were compared in isolated rabbit renal proximal tubules, with or without MAPKK/MEK inhibitor PD98059 or PPAR-γ antagonist GW9662. The phospholipase of ERK was examined by Western blotting. Results 15d-PGJ2 stimulated the activity of Na+/HCO3- cotransporter with the concentration increase (0.1 μmol/L, 0.3 μmol/L, 1 μmol/L and 10 μmol/L). The stimulation of NBC activity induced by 0.3 μmol/1 of 15d-PGJ2 was inhibited by a MAPKK/MEK inhibitor PD98059 as well as by a PPAR-γ antagonist GW9662. In rabbit renal tubular, 0.3 μmol/L dPGJ2 and 0.3 μmol/L pioglitazone both induced the ERK phosphorylation but it was inhibited by PPAR-γ antagonist. Conclusion The PPAR-γ-dependent ERK activation was involved in PPAR-γ ligand (15-dPGJ2)-induced Na+/HCO3- cotransport stimulation in rabbit renal proximal tubular.%目的 探讨过氧化物酶体增生物活化受体-y(PPAR-y)的选择性配体15-脱氧-△12,14-前列腺素J2(15dPGJ2)在兔肾近曲小管钠和碳酸氢根的转运作用及其传导通路.方法 在15d-PGJ2(0.1、0.3、1.0、10.0 μmol/L)及PPAR-y拮抗剂(5 μmol/L GW9662)或MAPKK/ MEK抑制剂(10 μmol/L PD98059)作用下,观察兔肾近曲小管钠和碳酸氢根转运活动度的变化,Western blotting法测定细胞外信号调节激酶(extracellular signal regulated kinase,ERK)的磷酸化.结果 15d-PGJ2刺激兔肾近曲小管钠和碳酸氢根的转运,随浓度增加刺激作用增强.0.3μmol/L 15d-PGJ2引起的刺激作用被MAPKK/MEK抑制剂及PPAR-y拮抗剂阻止.PPAR-y的两种选择性配体0.3 μmol/L 15d-PGJ2和0.3 μmol/L吡格列酮刺激ERK磷酸化,并被PPAR-y拮抗剂阻滞.结论 通过PPAR-y依赖的ERK磷酸化介导15d-PGJ2在兔肾近曲小管钠和碳酸氢根的转运.

  17. IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway

    Science.gov (United States)

    Wu, Zengbin; Yu, Yang; Niu, Lei; Fei, Aihua; Pan, Shuming

    2016-01-01

    Injury of renal tubular epithelial cells can induce acute renal failure and obstructive nephropathy. Previous studies have shown that administration of insulin-like growth factor-1 (IGF-1) ameliorates the renal injury in a mouse unilateral ureteral obstruction (UUO) model, whereas the underlying mechanisms are not completely understood. Here, we addressed this question. We found that the administration of IGF-1 significantly reduced the severity of the renal fibrosis in UUO. By analyzing purified renal epithelial cells, we found that IGF-1 significantly reduced the apoptotic cell death of renal epithelial cells, seemingly through upregulation of anti-apoptotic protein Bcl-2, at protein but not mRNA level. Bioinformatics analyses and luciferase-reporter assay showed that miR-429 targeted the 3′-UTR of Bcl-2 mRNA to inhibit its protein translation in renal epithelial cells. Moreover, IGF-1 suppressed miR-429 to increase Bcl-2 in renal epithelial cells to improve survival after UUO. Furthermore, inhibition of ERK/MAPK signaling pathway in renal epithelial cells abolished the suppressive effects of IGF-1 on miR-429 activation, and then the enhanced effects on Bcl-2 in UUO. Thus, our data suggest that IGF-1 may protect renal tubular epithelial cells via activation of ERK/MAPK signaling pathway during renal injury. PMID:27301852

  18. Dopamins renale virkninger

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1990-01-01

    is closely associated with the renal treatment of water and salt but the mechanism is not yet elucidated. In low doses (1-5 micrograms/kg/min), dopamine increases renal blood flow (RBF) and the glomerular filtration rate (GFR). In addition, pronounced diuretic and natriuretic effects are observed which...... are possible not exclusively secondary to alterations in the renal haemodynamics but may also be due to specific tubular effects. Recent investigations have revealed that dopamine does not increase RBF and GFR in patients with chronic renal failure if GFR is less than 60 ml/minute. Dopamine in low doses...... dialysis unnecessary in a number of patients on account of increased diuresis and natriuresis. The effect of GFR and the significance for the prognosis are not known....

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Renal consequences of obesity.

    Science.gov (United States)

    Naumnik, Beata; Myśliwiec, Michał

    2010-08-01

    The worldwide prevalence of obesity and its associated metabolic and cardiovascular disorders has risen dramatically within the past 2 decades. Our objective is to review the mechanisms that link obesity with altered kidney function. Current evidence suggests that excess weight gain may be responsible for 65-75% of the risk for arterial hypertension. Impaired renal pressure natriuresis, initially due to increased renal tubular sodium reabsorption, is a key factor linking obesity with hypertension. Obesity increases renal sodium reabsorption by activating the renin-angiotensin and sympathetic nervous systems, and by altering intrarenal physical forces. Adipose tissue functions as an endocrine organ, secreting hormones/cytokines (e.g., leptin) which may trigger sodium retention and hypertension. Additionally, excess visceral adipose tissue may physically compress the kidneys, increasing intrarenal pressures and tubular reabsorption. Eventually, sustained obesity via hyperinsulinemia, due to resistance to insulin, causes hyperfiltration, resulting in structural changes in the kidneys--glomerular hyperthrophy and occasionally focal segmental glomerulosclerosis. The consequences of kidney injury are continuous loss of glomerular filtration rate, further increase of arterial pressure and escalation of cardiovascular morbidity and mortality. There is a growing awareness of the renal consequences of obesity, and considerable progress is being made in understanding its pathophysiology. Weight reduction results in lowered proteinuria. Aside from low sodium diet and exercises, more widespread use of renoprotective therapy (e.g., ACE inhibitors and statins) in treatment of hypertension in obese subjects should be advocated. Renal protection should result in reducing the cardiovascular complications of obesity. PMID:20671624

  1. Epithelial-to-mesenchymal transdifferentiation of renal tubular epithelial cells mediated by oxidative stress and intervention effect of probucol in diabetic nephropathy rats%氧化应激介导糖尿病大鼠肾小管上皮细胞转分化及普罗布考的干预作用

    Institute of Scientific and Technical Information of China (English)

    段绍斌; 王予慧; 刘伏友; 周巧艳; 刘芳; 李莹; 凌光辉; 李瑛; 孙林

    2011-01-01

    Objective To explore the role of oxidative stress in the epithelial-tomesenchymal transition (EMT) of tubular epithelial cells and the protective effect of probucol in rat model with diabetic nephropathy (DN). Methods Thirty SD rats were randomly divided into normal control group, DN group, probucol treatment group (supplemented 1% probucol dietary). Twentyfour hours urinary protein excretion (UTP) was measured at the 3rd, the 8th and the 12th week respectively. The biochemical indicators including blood glucose (BG), lipids [triglyceride (TG), total cholesterol (TC)], low-density lipoprotein (LDL), serum creatinine (Scr), creatinine clearance rate (Ccr),kidney tissue malondialdehyde (MDA) level and glutathione peroxidase (GSH-Px) activity were assessed at the end of the 12th week in all groups. The renal pathological changes were evaluated by hematoxylin & eosin (HE) and Masson staining. The protein expression of specificity protein 1 (Sp1), α-smooth muscle actin (α-SMA) and E-cadherin was also detected and analyzed by immunohistochemistry and Western blotting. Results Compared with the normal control group,the BG, TC, LDL, Scr, 24 h UTP and MDA level of renal tissue increased significantly and the Ccr reduced in the rats of DN group (all P<0.01). The pathological scores and the expression of Sp1 and α-SMA in renal tissue were higher in the DN animals than that in the other animals (all P<0.01), the expression of E-cadherin downregulated significantly in the DN animals (P<0.01). The MDA level of renal tissue was positively correlated to the expression of α-SMA and Sp1 protein in DN group (r=0.896, P<0.01; r=0.862, P<0.01, respectively), and negatively correlated to the expression of E-cadherin protein (r=-0.673, P<0.01). In the diabetic animals treated with probucol, the Scr, 24 h UTP, pathological scores, MDA content,expression of Sp1 and α-SMA in renal tissue were lower than those in the diabetic animals (all P<0.01). The Ccr and the

  2. Renal targeting of kinase inhibitors

    NARCIS (Netherlands)

    Dolman, M. E. M.; Fretz, M. M.; Segers, Gj. W.; Lacombe, M.; Prakash, J.; Storm, G.; Hennink, W. E.; Kok, R. J.

    2008-01-01

    Activation of proximal tubular cells by fibrotic and inflammatory mediators is an important hallmark of chronic kidney disease. We have developed a novel strategy to intervene in renal fibrosis, by means of locally delivered kinase inhibitors. Such compounds will display enhanced activity within tub

  3. Emphysema in the renal allograft

    Energy Technology Data Exchange (ETDEWEB)

    Potter, J.L.; Sullivan, B.M.; Fluornoy, J.G.; Gerza, C.

    1985-04-01

    Two diabetic patients in whom emphysematous pyelonephritis developed after renal transplantation are described. Clinical recognition of this unusual and serious infection is masked by the effects of immunosuppression. Abdominal radiographic, ultrasound, and computed tomography findings are discussed. The clinical presentation includes urinary tract infection, sepsis, and acute tubular malfunction of the allograft in insulin-dependent diabetics.

  4. Side Effects of HIV Medicines: HIV and Lactic Acidosis

    Science.gov (United States)

    ... HIV medicines. All HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class may cause lactic acidosis, but ... some HIV medicines. HIV medicines in the nucleoside reverse transcriptase inhibitor (NRTI) drug class can cause the body to ...

  5. CD36 mediates proximal tubular binding and uptake of albumin and is upregulated in proteinuric nephropathies.

    Science.gov (United States)

    Baines, Richard J; Chana, Ravinder S; Hall, Matthew; Febbraio, Maria; Kennedy, David; Brunskill, Nigel J

    2012-10-01

    Dysregulation of renal tubular protein handling in proteinuria contributes to the development of chronic kidney disease. We investigated the role of CD36 as a novel candidate mediator of albumin binding and endocytosis in the kidney proximal tubule using both in vitro and in vivo approaches, and in nephrotic patient renal biopsy samples. In CD36-transfected opossum kidney proximal tubular cells, both binding and uptake of albumin were substantially enhanced. A specific CD36 inhibitor abrogated this effect, but receptor-associated protein, which blocks megalin-mediated endocytosis of albumin, did not. Mouse proximal tubular cells expressed CD36 and this was absent in CD36 null animals, whereas expression of megalin was equal in these animals. Compared with wild-type mice, CD36 null mice demonstrated a significantly increased urinary protein-to-creatinine ratio and albumin-to-creatinine ratio. Proximal tubular cells expressed increased CD36 when exposed to elevated albumin concentrations in culture medium. Expression of CD36 was studied in renal biopsy tissue obtained from adult patients with heavy proteinuria due to minimal change disease, membranous nephropathy, or focal segmental glomerulosclerosis. Proximal tubular CD36 expression was markedly increased in proteinuric individuals. We conclude that CD36 is a novel mediator influencing binding and uptake of albumin in the proximal tubule that is upregulated in proteinuric renal diseases. CD36 may represent a potential therapeutic target in proteinuric nephropathy. PMID:22791331

  6. Metformin-induced lactic acidosis: a case series

    OpenAIRE

    Silvestre Joana; Carvalho Susana; Mendes Vitor; Coelho Luis; Tapadinhas Camila; Ferreira Pedro; Povoa Pedro; Ceia Fatima

    2007-01-01

    Abstract Introduction Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. Case presentation We present ...

  7. TCM Researches on Chronic Renal Tubulointerstitial Lesions

    Institute of Scientific and Technical Information of China (English)

    LI Hang; XIONG Jing; ZHOU Quan-rong

    2008-01-01

    @@ Researches in recent years show that progressive deterioration of the renal function caused by kidney diseases mainly relies on the severity of renal tubulointerstitial lesions (RTIL).Therefore,imp-ortance should be attached to RTIL.With its very complicated pathogenesis,RTIL is manifested as the local in flammation in renal interstitium at early stage,followed by secretion of cellular factor and then phenotype variation,apoptosis and excessive pro-liferation of renal tubular epithelial cell(RTEC),as well as increase in synthesis and decrease in degradation of extracellular matrix(ECM),causing excessive deposition of ECM and eventually-renal interstitial fibrosis(RIF).ws.

  8. Acid-base status determines the renal expression of Ca2+ and Mg2+ transport proteins.

    NARCIS (Netherlands)

    Nijenhuis, T.; Renkema, K.Y.R.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2006-01-01

    Chronic metabolic acidosis results in renal Ca2+ and Mg2+ wasting, whereas chronic metabolic alkalosis is known to exert the reverse effects. It was hypothesized that these adaptations are mediated at least in part by the renal Ca2+ and Mg2+ transport proteins. The aim of this study, therefore, was

  9. Matter transformation and research progress of diabetic nephropathy renal tubular epithelial mesenchymal%肾小管上皮间质转化与糖尿病肾病研究进展

    Institute of Scientific and Technical Information of China (English)

    张明珠; 罗卓卡; 何丽霞; 邓玉琴; 霍丹

    2015-01-01

    糖尿病肾病(diabeticnephropathy,DN)是糖尿病微血管并发症之一,为终末期肾衰的主要原因之一,严重威胁着糖尿病患者的生命及生活质量。目前几乎占所有终末期肾脏疾病的50%,因此阐明DN的发病机制,掌握其发生、发展规律显得尤为重要。%Diabetic nephropathy (diabetic nephropathy DN) is one of the diabetic microvascular complications, as a major cause of end stage renal failure, a serious threat to the life and quality of life in patients with diabetes mellitus. At present almost all end-stage renal disease 50%, therefore to clarify the pathogenesis of DN, grasp its regularity of occurrence and development is particularly important.

  10. Increased expression of intranuclear matrix metalloproteinase 9 in atrophic renal tubules is associated with renal fibrosis.

    Directory of Open Access Journals (Sweden)

    Jen-Pi Tsai

    Full Text Available BACKGROUND: Reduced turnover of extracellular matrix has a role in renal fibrosis. Matrix metalloproteinases (MMPs is associated with many glomerular diseases, but the histological association of MMPs and human renal fibrosis is unclear. METHODS: This is a retrospective study. Institutional Review Board approval was obtained for the review of patients' medical records, data analysis and pathological specimens staining with waiver of informed consents. Specimens of forty-six patients were examined by immunohistochemical stain of MMP-9 in nephrectomized kidneys, and the association of renal expression of MMP-9 and renal fibrosis was determined. MMP-9 expression in individual renal components and fibrosis was graded as high or low based on MMP-9 staining and fibrotic scores. RESULTS: Patients with high interstitial fibrosis scores (IFS and glomerular fibrosis scores (GFS had significantly higher serum creatinine, lower estimated glomerular filtration rate (eGFR, and were more likely to have chronic kidney disease (CKD and urothelial cell carcinoma. Univariate analysis showed that IFS and GFS were negatively associated with normal and atrophic tubular cytoplasmic MMP-9 expression and IFS was positively correlated with atrophic tubular nuclear MMP-9 expression. Multivariate stepwise regression indicated that MMP-9 expression in atrophic tubular nuclei (r = 0.4, p = 0.002 was an independent predictor of IFS, and that MMP-9 expression in normal tubular cytoplasm (r = -0.465, p<0.001 was an independent predictor of GFS. CONCLUSIONS: Interstitial fibrosis correlated with MMP-9 expression in the atrophic tubular nuclei. Our results indicate that renal fibrosis is associated with a decline of MMP-9 expression in the cytoplasm of normal tubular cells and increased expression of MMP-9 in the nuclei of tubular atrophic renal tubules.

  11. The relationship between the renal clearance of creatinine and the apparent renal clearance of beta-2-microglobulin in patients with normal and impaired kidney function.

    Science.gov (United States)

    Vree, T B; Guelen, P J; Jongman-Nix, B; Walenkamp, G H

    1981-07-18

    The renal clearances of creatinine and beta 2-microglobulin of patients with either normal or impaired kidney function were measured. The renal clearance of beta 2-microglobulin depends on the urinary pH and must be considered as an apparent renal clearance because after tubular reabsorption the compound is metabolized in the kidney. Impaired kidney function reduces the percentage of tubular reabsorption of beta 2-microglobulin. PMID:6166414

  12. Renal imaging in paediatrics

    International Nuclear Information System (INIS)

    The most frequent renal diseases in paediatrics include urinary tract infections, hydronephrosis, kidney anomalies and reflux. The main reason for performing DMSA scintigraphy in paediatrics is the detection of cortical abnormalities related to urinary tract infection. Because the amount of tracer retained in the tubular cells is associated with the distribution of functioning renal parenchyma in the kidney, it is possible, to evaluate the split renal function. In comparison to ultrasound and intravenous urography the sensitivity in the detection of acute as well as chronic inflammatory changes is very high, however less specific. An indication for a renography in neonates and children is beside an estimation of the total renal function and the calculation of the split renal function, the assessment of renal drainage in patients with unclear dilatation of the collecting system in ultrasound. The analysis of the time activity curve provides, especially for follow-up studies, a reproducible method to assess the urinary outflow. The diuretic scintigraphy allows the detection of urinary obstruction. Subsequently it is possible to image the micturition phase to detect vesico-ureteric reflux (indirect MCU) after drainage of tracer from the renal pelvis. An reflux in the ureters or the pelvicalyceal system is visible on the scintigraphic images and can be confirmed by time activity curves. A more invasive technique is the direct isotope cystography with bladder catheterization. The present paper should give an overview about the role of nuclear medicine in paediatric urology. (orig.)

  13. Successfully Treated Calcific Uremic Arteriolopathy: Two Cases of a High Anion Gap Metabolic Acidosis with Intravenous Sodium Thiosulfate

    Directory of Open Access Journals (Sweden)

    Joshua L. Rein

    2014-01-01

    Full Text Available Calcific uremic arteriolopathy (CUA is a rare and potentially fatal disorder of calcification involving subcutaneous small vessels and fat in patients with renal insufficiency. We describe the successful use of intravenous sodium thiosulfate (STS for the treatment of CUA in two patients. The first case was complicated by the development of a severe anion gap metabolic acidosis, which was accompanied by a seizure. Both patients had complete wound healing within five months. Although STS should be considered in the treatment of CUA, little is known about pharmacokinetics and additional studies are required to determine dosing strategies to minimize severe potential side effects.

  14. Rupture of Renal Transplant

    Directory of Open Access Journals (Sweden)

    Shona Baker

    2015-01-01

    Full Text Available Background. Rupture of renal allograft is a rare and serious complication of transplantation that is usually attributed to acute rejection, acute tubular necrosis, or renal vein thrombosis. Case Presentation. LD, a 26-year-old male with established renal failure, underwent deceased donor transplantation using kidney from a 50-year-old donor with acute kidney injury (Cr 430 mmol/L. LD had a stormy posttransplant recovery and required exploration immediately for significant bleeding. On day three after transplant, he developed pain/graft swelling and another significant haemorrhage with cardiovascular compromise which did not respond to aggressive resuscitation. At reexploration, the renal allograft was found to have a longitudinal rupture and was removed. Histology showed features of type IIa Banff 97 acute vascular rejection, moderate arteriosclerosis, and acute tubular necrosis. Conclusion. Possible ways of avoiding allograft rupture include use of well-matched, good quality kidneys; reducing or managing risk factors that would predispose to delayed graft function; ensuring a technically satisfactory transplant procedure with short cold and warm ischemia times; and avoiding large donor-recipient age gradients.

  15. General Construction of Tubular Geometry

    CERN Document Server

    Mukhopadhyay, Partha

    2016-01-01

    We consider the problem of locally describing tubular geometry around a submanifold embedded in a (pseudo)Riemannian manifold in its general form. Given the geometry of ambient space in an arbitrary coordinate system and equations determining the submanifold in the same system, we compute the tubular expansion coefficients in terms of this {\\it a priori data}. This is done by using an indirect method that crucially applies the tubular expansion theorem for vielbein previously derived. With an explicit construction involving the relevant coordinate and non-coordinate frames we verify consistency of the whole method up to quadratic order in vielbein expansion. Furthermore, we perform certain (long and tedious) higher order computation which verifies the first non-trivial spin connection term in the expansion for the first time. Earlier a similar method was used to compute tubular geometry in loop space. We explain this work in the light of our general construction.

  16. Akt2/PKBbeta-sensitive regulation of renal phosphate transport

    OpenAIRE

    Kempe, D S; Ackermann, T F; Boini, K M; Klaus, F; Umbach, A T; Dërmaku-Sopjani, M; Judenhofer, M S; Pichler, B J; Capuano, P.; Stange, G.; Wagner, C. A.; Birnbaum, M J; Pearce, D.; Föller, M; Lang, F.

    2010-01-01

    AIM: The protein kinase B (PKB)/Akt is known to stimulate the cellular uptake of glucose and amino acids. The kinase is expressed in proximal renal tubules. The present study explored the influence of Akt/PKB on renal tubular phosphate transport. METHODS: The renal phosphate transporter NaPi-IIa was expressed in Xenopus oocytes with or without PKB/Akt and Na(+) phosphate cotransport determined using dual electrode voltage clamp. Renal phosphate excretion was determined in Akt2/PKBbeta knockou...

  17. Insuficiencia renal aguda.

    Directory of Open Access Journals (Sweden)

    Carlos Hernán Mejía

    2009-10-01

    Full Text Available La insuficiencia renal aguda se diagnostica aproximadamente en 5% de los pacientes hospitalizados. Sus principales causas se relacionan con la alteración del flujo sanguíneo renal, sea por depleción de volumen, baja perfusión renal o por distribución intrarrenal inadecuada y obstrucción del árbol urinario. El diagnóstico parte de la historia clínica y un buen examen físico que corrobore el estado de volemia del paciente y se complementa con el uso adecuado de los índices urinarios (excreción de sodio y osmolaridad, el uroanálisis y la ecografía renal. Su tratamiento consiste en una adecuada recuperación del volumen, manejo de los diuréticos, soporte nutricional, conservación del equilibrio hidroelectrolítico y brindar terapia de diálisis si hay toxicidad urémica, hipercaliemia severa (>6.5 mEq/l, acidosis metabólica o sobrecarga severa de volumen.

  18. Hepatocyte growth factor prevents acute renal failure and accelerates renal regeneration in mice.

    OpenAIRE

    Kawaida, K; Matsumoto, K.; Shimazu, H.; Nakamura, T.(International Center for Elementary Particle Physics and Department of Physics, The University of Tokyo, Tokyo, Japan)

    1994-01-01

    Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppre...

  19. Mucinous tubular and spindle cell carcinoma of the kidney associated with tuberculosis

    Directory of Open Access Journals (Sweden)

    Saloua Krichen Makni

    2011-01-01

    Full Text Available Mucinous tubular and spindle cell carcinomas (MTSCC are low-grade renal epi-thelial neoplasms with approximately 100 documented cases reported in the literature. We report a case of MTSCC in a 79-year-old patient in association with a renal tuberculosis infection that has never been reported. Further investigations are needed to determine the frequency and true prognosis of these tumors.

  20. Acidosis Promotes Bcl-2 Family-mediated Evasion of Apoptosis

    Science.gov (United States)

    Ryder, Christopher; McColl, Karen; Zhong, Fei; Distelhorst, Clark W.

    2012-01-01

    Acidosis arises in solid and lymphoid malignancies secondary to altered nutrient supply and utilization. Tumor acidosis correlates with therapeutic resistance, although the mechanism behind this effect is not fully understood. Here we show that incubation of lymphoma cell lines in acidic conditions (pH 6.5) blocks apoptosis induced by multiple cytotoxic metabolic stresses, including deprivation of glucose or glutamine and treatment with dexamethasone. We sought to examine the role of the Bcl-2 family of apoptosis regulators in this process. Interestingly, we found that acidic culture causes elevation of both Bcl-2 and Bcl-xL, while also attenuating glutamine starvation-induced elevation of p53-up-regulated modulator of apoptosis (PUMA) and Bim. We confirmed with knockdown studies that these shifts direct survival decisions during starvation and acidosis. Importantly, the promotion of a high anti- to pro-apoptotic Bcl-2 family member ratio by acidosis renders cells exquisitely sensitive to the Bcl-2/Bcl-xL antagonist ABT-737, suggesting that acidosis causes Bcl-2 family dependence. This dependence appears to be mediated, in part, by the acid-sensing G protein-coupled receptor, GPR65, via a MEK/ERK pathway. PMID:22685289

  1. Metabolic Acidosis with Ophthalmic Dorzolamide in a Neonate.

    Science.gov (United States)

    Capino, Amanda C; Dannaway, Douglas C; Miller, Jamie L

    2016-01-01

    Carbonic anhydrase inhibitors are a common cause of normal anion gap metabolic acidosis; however, development is less commonly associated with ophthalmic administration of these agents. We report a case of a premature neonate who was being treated at our institution with betaxolol, dorzolamide, and latanoprost ophthalmic products for suspected bilateral congenital glaucoma. In addition, the patient was also receiving caffeine, ursodiol, and acidified liquid human milk fortifier. The patient developed a normal anion gap metabolic acidosis, and both dorzolamide ophthalmic solution and the acidified human milk fortifier were considered potential causes. Upon discontinuation of the dorzolamide ophthalmic solution and the switching of liquid human milk fortifiers, the normal anion gap metabolic acidosis gradually resolved. As a result of the pH and acidity, the acidified liquid human milk fortifier is thought to be associated with an anion gap acidosis; therefore, dorzolamide is suspected to be the primary cause of a normal gap acidosis. This case demonstrates that systemic effects can occur with ophthalmic administration of dorzolamide in a premature neonate. Ophthalmic agents should not be overlooked as a potential cause of systemic toxicity. PMID:27453705

  2. Growth Hormone Therapy in Children with Chronic Renal Failure

    OpenAIRE

    Cayir, Atilla; Kosan, Celalettin

    2014-01-01

    Growth is impaired in a chronic renal failure. Anemia, acidosis, reduced intake of calories and protein, decreased synthesis of vitamin D and increased parathyroid hormone levels, hyperphosphatemia, renal osteodystrophy and changes in growth hormone-insulin-like growth factor and the gonadotropin-gonadal axis are implicated in this study. Growth is adversely affected by immunosuppressives and corticosteroids after kidney transplantation. Treating metabolic disorders using the recombinant huma...

  3. Mathematical Model of Ammonia Handling in the Rat Renal Medulla

    OpenAIRE

    Noiret, Lorette; Baigent, Stephen; Jalan, Rajiv; Thomas, S. Randall

    2015-01-01

    The kidney is one of the main organs that produces ammonia and release it into the circulation. Under normal conditions, between 30 and 50% of the ammonia produced in the kidney is excreted in the urine, the rest being absorbed into the systemic circulation via the renal vein. In acidosis and in some pathological conditions, the proportion of urinary excretion can increase to 70% of the ammonia produced in the kidney. Mechanisms regulating the balance between urinary excretion and renal vein ...

  4. Etiopathology of chronic tubular, glomerular and renovascular nephropathies: Clinical implications

    Directory of Open Access Journals (Sweden)

    Ortiz Alberto

    2011-01-01

    Full Text Available Abstract Chronic kidney disease (CKD comprises a group of pathologies in which the renal excretory function is chronically compromised. Most, but not all, forms of CKD are progressive and irreversible, pathological syndromes that start silently (i.e. no functional alterations are evident, continue through renal dysfunction and ends up in renal failure. At this point, kidney transplant or dialysis (renal replacement therapy, RRT becomes necessary to prevent death derived from the inability of the kidneys to cleanse the blood and achieve hydroelectrolytic balance. Worldwide, nearly 1.5 million people need RRT, and the incidence of CKD has increased significantly over the last decades. Diabetes and hypertension are among the leading causes of end stage renal disease, although autoimmunity, renal atherosclerosis, certain infections, drugs and toxins, obstruction of the urinary tract, genetic alterations, and other insults may initiate the disease by damaging the glomerular, tubular, vascular or interstitial compartments of the kidneys. In all cases, CKD eventually compromises all these structures and gives rise to a similar phenotype regardless of etiology. This review describes with an integrative approach the pathophysiological process of tubulointerstitial, glomerular and renovascular diseases, and makes emphasis on the key cellular and molecular events involved. It further analyses the key mechanisms leading to a merging phenotype and pathophysiological scenario as etiologically distinct diseases progress. Finally clinical implications and future experimental and therapeutic perspectives are discussed.

  5. Lipopolysaccharide-induced acute renal failure in conscious rats

    DEFF Research Database (Denmark)

    Jonassen, Thomas E N; Graebe, Martin; Promeneur, Dominique;

    2002-01-01

    In conscious, chronically instrumented rats we examined 1) renal tubular functional changes involved in lipopolysaccharide (LPS)-induced acute renal failure; 2) the effects of LPS on the expression of selected renal tubular water and sodium transporters; and 3) effects of milrinone......, a phosphodiesterase type 3 (PDE3) inhibitor, and Ro-20-1724, a PDE4 inhibitor, on LPS-induced changes in renal function. Intravenous infusion of LPS (4 mg/kg b.wt. over 1 h) caused an immediate decrease in glomerular filtration rate (GFR) and proximal tubular outflow without changes in mean arterial pressure (MAP......-alpha and lactate, inhibited the LPS-induced tachycardia, and exacerbated the acute LPS-induced fall in GFR. Furthermore, Ro-20-1724-treated rats were unable to maintain MAP. We conclude 1) PDE3 or PDE4 inhibition exacerbates LPS-induced renal failure in conscious rats; and 2) LPS treated rats develop an escape...

  6. Renal alterations in feline immunodeficiency virus (FIV)-infected cats: a natural model of lentivirus-induced renal disease changes.

    Science.gov (United States)

    Poli, Alessandro; Tozon, Natasa; Guidi, Grazia; Pistello, Mauro

    2012-09-01

    Human immunodeficiency virus (HIV) is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV) share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy. PMID:23170163

  7. Renal Alterations in Feline Immunodeficiency Virus (FIV-Infected Cats: A Natural Model of Lentivirus-Induced Renal Disease Changes

    Directory of Open Access Journals (Sweden)

    Mauro Pistello

    2012-08-01

    Full Text Available Human immunodeficiency virus (HIV is associated with several renal syndromes including acute and chronic renal failures, but the underlying pathogenic mechanisms are unclear. HIV and feline immunodeficiency virus (FIV share numerous biological and pathological features, including renal alterations. We investigated and compared the morphological changes of renal tissue of 51 experimentally and 21 naturally infected cats. Compared to the latter, the experimentally infected cats exhibited some mesangial widening and glomerulonephritis, milder proteinuria, and lower tubular and interstitial alterations. The numbers of giant protein tubular casts and tubular microcysts were also lower. In contrast, diffuse interstitial infiltrates and glomerular and interstitial amyloidosis were detected only in naturally infected cats. Similar alterations are found in HIV infected patients, thus supporting the idea of a causative role of FIV infection in renal disease, and underlining the relevance of the FIV and its natural host as an animal model for investigating lentivirus-associated nephropathy.

  8. Tubular engraftment and myofibroblast differentiation of recipient-derived cells after experimental kidney transplantation

    NARCIS (Netherlands)

    Broekema, Martine; Harmsen, Martin C.; Koerts, Jasper A.; Van Kooten, Theo G.; Navis, Gerjan; Van Luyn, Marja J. A.; Popa, Eliane R.

    2007-01-01

    Background. In human renal allografts, recipient-derived cells engrafted in various kidney substructures, have been detected in the long term after transplantation. Here we investigated tubular engraftment and myofibroblast differentiation of recipient-derived cells at short term after experimental

  9. Type B Lactic Acidosis Associated With Venlafaxine Overdose.

    Science.gov (United States)

    Iragavarapu, Chaitanya; Gupta, Tanush; Chugh, Savneek S; Aronow, Wilbert S; Frishman, William H

    2016-01-01

    Lactic acidosis that is not secondary to tissue hypoperfusion or hypoxemia (type B lactic acidosis) is a rare but potentially fatal condition that has been associated with drugs like metformin, linezolid, and nucleoside reverse-transcriptase inhibitors in patients with HIV. We report the first case of type B lactic acidosis caused by overdose of the serotonin-norepinephrine reuptake inhibitor, venlafaxine. A 55-year-old man with no significant medical history was brought to the emergency department after intentional ingestion of around 80 capsules of venlafaxine (a total dose of over 6000 mg) in an attempt to commit suicide. Complete blood count and comprehensive metabolic panel were unremarkable except for a bicarbonate level of 13 mEq/L and an anion gap of 22 mEq/L. An arterial blood gas revealed a pH of 7.39, partial pressure of CO2 of 19 mm Hg, calculated bicarbonate of 11.5 mEq/L, and a lactate level of 8.6 mmol/L. The patient was started on aggressive intravenous hydration with normal saline along with oral activated charcoal with sorbitol. Repeat laboratory work after 4 hours showed an improvement in anion gap (15 mEq/L) and serum lactate (5.6 mmol/L). The patient remained stable throughout the hospital stay and lactic acidosis resolved in 24 hours. In the absence of hypotension, hypoxemia, kidney or liver dysfunction, myopathy, malignancy, or use of other medications, venlafaxine was the most likely cause of lactic acidosis in our case. Rapid improvement of acidosis was probably related to clearance of the drug. PMID:25405896

  10. Ventilatory response in metabolic acidosis and cerebral blood volume in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Sluijs, M.C. van der; Oeseburg, B.; Folgering, H.T.M.

    2001-01-01

    The relationship between alterations in cerebral blood volume (CBV) and central chemosensitivity regulation was studied under neutral metabolic conditions and during metabolic acidosis. Fifteen healthy subjects (5610 years) were investigated. To induce metabolic acidosis, ammonium chloride (NH(4)Cl)

  11. Litiasis renal: Modificaciones bioquímicas durante el seguimiento Renal lithiasis: Biochemical changes in the follow-up

    Directory of Open Access Journals (Sweden)

    Francisco R. Spivacow

    2006-06-01

    Full Text Available Con el objeto de evaluar si se producen modificaciones bioquímicas durante el seguimiento de pacientes nefrolitiásicos, se estudiaron 237 pacientes (115 mujeres y 122 hombres con una edad promedio de 39 ± 8 y 42 ± 7 años respectivamente controlados durante 23.7 ± 19.3 meses. A todos se les realizó un estudio metabólico de litiasis renal inicial y como mínimo uno o más posteriormente con las mismas características que el basal. No fueron incluidos pacientes con los diagnósticos de riñón en esponja, acidosis renotubular, hiperparatiroidismo primario, malformaciones renales o infecciones urinarias. Del total de pacientes, 139 (Grupo I presentaron en el seguimiento una modificación metabólica no evidenciada en el estudio inicial, mientras que 98 (Grupo II no. El tiempo de seguimiento de los primeros, no fue significativamente diferente de aquellos que no modificaron el diagnóstico basal. Las alteraciones bioquímicas agregadas más frecuentes fueron, hipocitraturia en el 43.1%, hipercalciuria idiopática en 20.8% y alteraciones del ácido úrico en 16.5%. De 110 pacientes seguidos más de 3 años, 37 (33% recurrieron. De éstos, 25 (23% modificaron el diagnóstico metabólico basal vs. 12 (11% que mantuvieron el mismo diagnóstico (p With the aim of assessing if biochemical changes occur in the follow up of patients with renal lithiasis, 237 patients were studied (115 women and 122 men, mean age 39 ± 8 and 42 ± 7 years, respectively and controlled during 27.3 ± 19.3 months. All of them had previously undergone metabolic evaluations at baseline and one or more than one control studies afterwards. Patients with a diagnosis of sponge kidney, renal tubular acidosis, primary hyperparathyroidism, anatomical malformations of the urinary tract, or urinary infections were not included. Two populations were identified: those who presented changes in the baseline diagnosis (139 patients, Group I and those who presented no changes (98

  12. The Effects of Shenhua Tablet Compound on the Location of NaDC1 in Renal Tubular Epithelial Cells with Anoxia/reoxygenation%复方肾华片对缺氧/复氧肾小管上皮细胞NaDC1转运蛋白定位的影响

    Institute of Scientific and Technical Information of China (English)

    魏日胞; 杨悦; 张雪光; 方谦; 张玉强

    2013-01-01

    Objective:To observe the effect of the Shenhua-containing serum on the location of Sodium-dependent dicarboxylate transporter 1 (NaDC1) in the renal tubular epithelial cells of rats.Methods:After 3 days of continuous intragastric drug administration,male Wistar rats were sacrificed and Shenhua-containing serum has been prepared and separated.Renal tubular epithelial cells (RTECs) were divided into a normal serum-GFP-empty plasmid group,a normal serum-GFP-NaDC1 plasmid group,a Shenhua-containing serum-GFP-empty plasmid group and a Shenhua-containing serum-GFP-NaDC1 plasmid group.After anoxia/reoxygenation,immunofluorescence and immunoblot were performed.Results:Immunofluorescence examinations revealed a widened distribution of NaDC1 in normal serum-GFP-empty plasmid group,normal serum-GFP-NaDC1 plasmid group and Shenhua-containing serum-GFP-empty plasmid group,in Shenhua-containing serum-GFP-NaDC1 plasmid group,NaDC1 was distributed at membrane.Immunoblot show that approximately 90% of the NaDC1 was expressed at the basolateral membrane of RTECs in Shenhua-containing serum-GFP-NaDC1 plasmid group,whereas other three groups were expressed on the apical and basolateral surfaces at the nearly equal level.Conclusion:The Shenhua-containing serum effectively promoted the recovery of the polarity of RTECs caused by anoxia/reoxygenation.%目的:观察复方肾华含药血清对缺氧/复氧模型肾小管上皮细胞钠/二羧酸协同转运蛋白1(NaDC1)的定位影响.方法:雄性wistar大鼠,灌胃给药3d后处死,分离含药血清备用.分离培养大鼠肾小管上皮细胞,随机分4组:正常血清GFP空质粒组、正常血清GFP-NaDC1质粒组、肾华含药血清GFP空质粒组和肾华含药血清GFP-NaDC1质粒组,分别进行质粒转染后,在正常培养基或肾华含药血清培养基中培养,进行缺氧/复氧处理后应用免疫荧光和生物素化免疫印迹技术观察肾小管上皮细胞NaDC1的分布变化及表达.结果:免疫荧光结

  13. Influence of fasudil on the epithelial-mesenchymal transdifferentiation of renal tubular epithelial cells in diabetic rats%法舒地尔对糖尿病大鼠肾小管上皮细胞转分化的影响

    Institute of Scientific and Technical Information of China (English)

    吴甘霖; 贾汝汉; 涂亚芳; 丁国华

    2009-01-01

    目的 观察法舒地尔对糖尿病大鼠肾小管上皮细胞转分化的影响并探讨其机制.方法 将实验性Wistar大鼠随机分为正常对照组、糖尿病组、法舒地尔治疗组.3个月后处死动物,PAS染色法观察肾小球病理变化,Mason染色法观察肾间质病理变化;免疫组化观察肾脏皮质ROCK Ⅰ、α平滑肌肌动蛋广1(α-SMA)、E钙黏蛋白(E-cadherin)的变化和β连环蛋白(β-catenin)的细胞定位改变;Western印迹法观察肾脏皮质p-MYPT1、β-SMA、E-cadherin、胞膜β-catenin蛋白的变化;实时定量PCR法观察ROCK Ⅰ、E-cadherin和总β-catenin的mRNA变化.结果 法舒地尔治疗可改善肾间质纤维化状况.与正常对照组相比,糖尿病组大鼠肾皮质内p-MYPT1、α-SMA蛋门表达增强(均P<0.01);E-cadherin、胞膜β-catenin的蛋白表达减弱(均P<0.01);ROCK1、总β-catenin mRNA表达增强(均P<0.01);E-cadherin mRNA表达减弱(P<0.01).与糖尿病组相比,治疗组p-MYPT1、α-SMA蛋白表达减弱(均P<0.01);E-cadherin、胞膜β-catenin的蛋白表达增强(均P<0.05);ROCK1、β-catenin mRNA表达减弱(均P<0.01);E-cadherin mRNA表达增强(P<0.01).结论 法舒地尔可能通过抑制Rho激酶活性减轻糖尿病大鼠肾小管上皮细胞转分化和肾间质纤维化,作用可能与法舒地尔恢复肾小管上皮细胞的黏附特性与紧密连接复合体有关.%Objective To investigate the influence of fasudil on the epithelialmesenchymal transdifferentiation of renal tubular epithelial cells in diabetic rats and to explore the mechanism. Methods Wistar mts were randomly divided into three groups:control,diabetes and fasudil-treatment.All the rots were sacrificed after three months of feeding with or without fasudil.Pathological changes of the glomeruli and renal interstitium were studied by periodic acidSchiff'S staining and Masson staining,respectively.Expression of ROCKI,α-SMA,E-cadherin and the distribution of β-catenin was examined by

  14. 半胱氨酸蛋白酶-8和P53在慢性砷中毒大鼠肾近端小管表达的研究%Expression of cysteine caspase-8 and P53 in renal proximal tubular epithelial cell of chronic arsenic poisoning rats

    Institute of Scientific and Technical Information of China (English)

    钱立全; 李远慧; 孔祥照; 金婷婷; 李娜

    2012-01-01

    Objective To study the molecular mechanism of renal injury of chronic arsenic poisoning rats induced by the expression of cysteine caspase-8 and P53 in renal proximal tubular epithelial cells.Methods Sixty healthy SD rats were divided into three groups,high-,low-dose group,and control group,n =20 in each group.The rats in high and low dose groups were treated with As203 through drinking water,10.0 and 0.4 mg/kg,respectively.The control rats were given distilled water.Four months later,serum and urinary arsenic level was determined,and kidney specimens were taken.The expression of cysteine caspase-8 and P53 in renal proximal tubular epithelial cells was detected by histological technique-HE staining and SABC immunohistochemistry.In addition,cell number counting and image analyses were used in the study.Results The number of caspase-8 positive cells of renal proximal tubule in control group,low-and high-dose group was 3.33±1.32,31.14±8.02 and 46.50±7.20 cell number/visual fields,respectively,which was increased with dose increasing(all P <0.05);the average gray value was 151.34±6.40,133.58±4.63 and 128.34±16.28,respectively,decreased with dose increasing(all P <0.05).The number of P53 positive cells was 3.17±1.59,26.29±4.23 and 47.00±6.22 cell number/visual fields,respectively,increased with dose increasing (all P < 0.05) ; the average gray value was 142.54±8.06,121.48±5.68 and 101.89±6.35,respectively,decreased with dose increasing (all P < 0.05).Conclusion The increase of caspase-8 and P53 positive cells is one of the molecular mechanisms of renal injury induced by arsenic poisoning.%目的 探讨慢性砷中毒大鼠肾近端小管细胞半胱氨酸蛋白酶-8(caspase-8)和P53表达致肾脏损伤的分子机制.方法 60只SD大鼠分为对照组,低、高剂量组,每组20只,高、低剂量组分别给予三氧化二砷(As2O3) 10.0、0.4 mg/kg水溶液自由饮用,对照组自由饮用蒸馏水.分笼4个月,测定血砷、尿砷,取肾脏

  15. 肾脏黏液性管状和梭形细胞癌的临床病理特点分析%Clinical and pathologic features of renal mucinous tubular and spindle cell carcinoma

    Institute of Scientific and Technical Information of China (English)

    宋志刚; 于国; 宋欣; 高杰; 韦立新

    2011-01-01

    目的 探讨肾脏黏液性管状和梭形细胞癌的临床病理学特点.方法 分析3例肾脏黏液性管状和梭形细胞癌的临床特点、组织形态及免疫表型(CD10、CK7、EMA、P504S、Vimentin),并复习相关文献.结果 3例黏液性管状和梭形细胞癌中,男1例,女2例,年龄39~57岁,平均48岁,肿瘤最大直径4.2~9.0cm,平均5.9cm,术后随访18~44个月,均无复发及转移.肿瘤大体切面为实性、灰白色,无包膜,但与周围肾组织分界清晰.镜下观察肿瘤组织包括由立方细胞紧密排列构成的狭长小管结构及梭形细胞两种成分,且两种成分交错分布,可以见到过渡区域,其中1例缺乏梭形细胞区域,2例背景中可见黏液样基质,1例可见透明细胞、乳头状结构及泡沫细胞.免疫组化染色显示3例肿瘤CK7、EMA、P504S均呈阳性表达,1例CD10呈阳性表达,2例Vimentin呈弱阳性表达.结论 肾脏黏液性管状和梭形细胞癌是一种低度恶性的多形性肿瘤,组织形态学谱系较宽,由小管状结构和梭形细胞两种成分以不同比例构成,可以缺乏其中一种成分,也可缺乏黏液样基质,有些病例可见灶状透明细胞、乳头状结构.免疫表型上对于近端肾单位及远端肾单位的标记均可表达.%Objective To explore the clinical and pathologic features of the mucinous tubular and spindle cell carcinoma (MTSCC) of kidney. Methods The clinical features, tissue morphology and immunophenotypes (including CD10, CK7, EMA, P5O4S and Vimentin) of 3 cases of MTSCC were analyzed, and the related literature was reviewed. Results Among the 3 MTSCC patients, 1 was male and 2 were females, aged from 39 to 57 years with a mean age of 48. The diameter of tumors ranged from 4. 2cm to 9. Ocm with a mean of 5. 9cm. The 3 patients were followed-up for 18 to 44 months, and no recurrence or metastasis was found. Under general observation, the tumor was well-circumscribed, without capsule, and the cut surface

  16. 尿蛋白及晚期糖基化终产物对肾小管上皮细胞溶酶体的影响%Effect of urinary proteins and advanced glycosylation end products on ly-sosomes in renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    邓健锟; 王淑君; 吴洪銮; 罗勉娜; 许碧华; 梁东; 潘庆军; 刘华锋; 刘伟敬

    2015-01-01

    目的:探讨慢性肾脏病( CKD)病程中所产生的病理产物尿蛋白及晚期糖基化终产物( AGE)对肾小管上皮细胞( tubular epithelial cells,TECs)溶酶体结构与功能的影响,为阻止或延缓CKD病情进展探索新思路。方法:临床上选取未经特殊治疗的微小病变肾病综合征(MCNS)患者(n=11)、糖尿病肾病(DN)患者(n=11)及活检基本正常(n=6)的肾组织标本,以溶酶体相关膜蛋白1(lysosomal-associated membrane protein 1,LAMP1)和组织蛋白酶B( cathepsin B,CB)行间接免疫荧光染色;体外以8 g/LJ尿蛋白或100 mg/L晚期糖基化终产物刺激人肾小管上皮细胞系( HK-2细胞),以LAMP1和CB行间接免疫荧光染色,检测 CB及组织蛋白酶L ( cathepsin L,CL)活性,并观察DQ-卵清蛋白降解情况。结果: MCNS及DN患者TECs存在溶酶体膜透化( lysosomal membrane per-meabilization,LMP)现象。与正常对照组相比,尿蛋白及AGE-BSA均可致HK-2细胞LMP发生率上升,CB及CL活性降低,溶酶体对DQ-卵清蛋白的降解能力降低( P<0.05)。结论: CKD病理产物尿蛋白和晚期糖基化终产物均可致TECs出现LMP现象,并使溶酶体消化功能下降,这可能是CKD肾小管间质纤维化进展的重要机制之一。%[ ABSTRACT] AIM:To investigate the effects of pathological products, urinary proteins and advanced glycosyla-tion end products ( AGE) produced in the progression of chronic kidney disease ( CKD) , on the structure and function of lysosomes in renal tubular epithelial cells ( TECs ) , and try to find a novel approach for preventing or delaying CKD. METHODS:The renal specimens of the untreated patients with minimal change nephrotic syndrome (MCNS), diabetic nephropathy (DN) or normal kidney were collected.The expression of lysosomal-associated membrane protein 1 (LAMP1) and cathepsin B ( CB) was studied in TECs by indirect

  17. STUDY OF RENAL FAILURE IN MALARIA

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    Girish Pamappa

    2016-01-01

    Full Text Available Renal failure is a serious complication of malaria, with a mortality of 14 to 33%. In view of the significant morbidity and mortality due to acute renal failure in malaria, there is need to identify patients at an early stage and to intensify care given to reduce morbidity and mortality. AIMS  To evaluate the clinical profile of Acute Renal Failure (ARF in malaria.  To evaluate the factors associated with adverse outcome, relation of severity of renal impairment on final outcome in patients with ARF due to malaria. MATERIAL AND METHODS This study was conducted at a tertiary care hospital over a period of 12 months. STUDY DESIGN  Type of study: Prospective Analytical, Observational Study.  Sample Size: 50 patients admitted to ICU, Kidney Unit, and the Medicine Wards with Malaria and ARF. Inclusion Criteria Clinically screened patients with evidence of malarial parasites in the blood smears or by antigen detection with clinical features or biochemical evidence of acute renal failure. Exclusion Criteria  Presence of any disease or condition leading to ARF or affecting the outcome of malarial ARF.  Other causes of Fever, Jaundice and Oliguria, like Leptospirosis, Dengue. METHODOLOGY Fifty patients who fulfilled the inclusion criteria were interrogated with regards to the complaints, clinical signs. Blood tests were sent on admission. Details were recorded as per the clinical proforma. The patients were followed until their discharge/death. RESULTS Oliguria was present in only 30% of patients. 30% of patients received haemodialysis. The mortality was 12% for severe renal failure. On Univariate analysis, Acidosis and Cerebral malaria were highly significant predictors of mortality. Other significant predictors were Renal failure, Oliguria, Shock, DIC, Hyperparasitemia, Leukocytosis (TLC. On Multivariate analysis, Oliguria, Cerebral malaria, Acidosis, Shock and two or more complications were the independent predictors of mortality

  18. BIOPSY PROVEN ACUTE TUBULAR NECROSIS DUE TO RHABDOMYOLYSIS IN A DENGUE FEVER PATIENT: A CASE REPORT AND REVIEW OF LITERATURE

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    Liliany P. Repizo

    2014-01-01

    Full Text Available Renal histology results are very scarce in dengue-associated rhabdomyolysis patients developing acute kidney injury (AKI. We report a case of dengue fever-induced AKI associated to rhabdomyolysis with a renal biopsy showing acute tubular necrosis (ATN and renal deposition of myoglobin. A 28-year-old patient who presented dengue fever (DF complicated by severe AKI and rhabdomyolysis is described. The patient required hemodialysis for three weeks. A renal biopsy revealed ATN with positive staining for myoglobin in the renal tubuli. The patient was discharged with recovered renal function. In conclusion, this case report described a biopsy proven ATN associated to DF-induced rhabdomyolysis, in which renal deposition of myoglobin was demonstrated. We suggest that serum creatine phosphokinase should be monitored in DF patients to allow for an early diagnosis of rhabdomyolysis and the institution of renal protective measures.

  19. Efeitos da correção da acidose metabólica com bicarbonato de sódio sobre o catabolismo protéico na insuficiência renal crônica The effects of the correction of metabolic acidosis with sodium bicarbonate on protein catabolism in chronic kidney failure

    OpenAIRE

    Mafra, Denise; Burini, Roberto Carlos

    2001-01-01

    A desnutrição protéico-energética constitui problema comum aos pacientes com insuficiência renal crônica, influenciando diretamente na sua morbi-mortalidade. A acidose metabólica tem papel no catabolismo protéico, ativando a via proteolítica proteasoma-ubiquitina, dependente de adenosina trifosfato, e conjuntamente com glicocorticóides induz uma maior atividade na desidrogenase que degrada os aminoácidos de cadeia ramificada. Esta revisão teve como objetivo descrever o mecanismo pelo qual a a...

  20. Phenylbutyrate Therapy for Pyruvate Dehydrogenase Complex Deficiency and Lactic Acidosis

    Science.gov (United States)

    Ferriero, Rosa; Manco, Giuseppe; Lamantea, Eleonora; Nusco, Edoardo; Ferrante, Mariella I.; Sordino, Paolo; Stacpoole, Peter W.; Lee, Brendan; Zeviani, Massimo; Brunetti-Pierri, Nicola

    2014-01-01

    Lactic acidosis is a build-up of lactic acid in the blood and tissues, which can be due to several inborn errors of metabolism as well as nongenetic conditions. Deficiency of pyruvate dehydrogenase complex (PDHC) is the most common genetic disorder leading to lactic acidosis. Phosphorylation of specific serine residues of the E1α subunit of PDHC by pyruvate dehydrogenase kinase (PDK) inactivates the enzyme, whereas dephosphorylation restores PDHC activity. We found that phenylbutyrate enhances PDHC enzymatic activity in vitro and in vivo by increasing the proportion of unphosphorylated enzyme through inhibition of PDK. Phenylbutyrate given to C57B6/L wild-type mice results in a significant increase in PDHC enzyme activity and a reduction of phosphorylated E1α in brain, muscle, and liver compared to saline-treated mice. By means of recombinant enzymes, we showed that phenylbutyrate prevents phosphorylation of E1α through binding and inhibition of PDK, providing a molecular explanation for the effect of phenylbutyrate on PDHC activity. Phenylbutyrate increases PDHC activity in fibroblasts from PDHC-deficient patients harboring various molecular defects and corrects the morphological, locomotor, and biochemical abnormalities in the noam631 zebrafish model of PDHC deficiency. In mice, phenylbutyrate prevents systemic lactic acidosis induced by partial hepatectomy. Because phenylbutyrate is already approved for human use in other diseases, the findings of this study have the potential to be rapidly translated for treatment of patients with PDHC deficiency and other forms of primary and secondary lactic acidosis. PMID:23467562

  1. Cerebrovascular response to acute metabolic acidosis in humans.

    NARCIS (Netherlands)

    Ven, M.T.P. van de; Colier, W.N.J.M.; Kersten, B.T.P.; Oeseburg, B.; Folgering, H.T.M.

    2003-01-01

    OBJECTIVES: Evaluation of the cerebrovascular response (delta CBV/delta PaCO2) during baseline metabolic conditions and acute metabolic acidosis. METHODS: 15 healthy subjects, 5 m, 10 f, 56 +/- 10 yrs were investigated. For acidification, NH4Cl was given orally. CBV was measured using Near Infrared

  2. Metformin-induced lactic acidosis: a case series

    Directory of Open Access Journals (Sweden)

    Silvestre Joana

    2007-10-01

    Full Text Available Abstract Introduction Unlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin. Case presentation We present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day, perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day, glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A

  3. Tubular cystourethroneostomy after total prostatectomy.

    Science.gov (United States)

    Melchior, H

    1975-01-01

    After radical prostatectomy cystourethroneostomy is done as a tubular cystourethroplasty. In the last 13 months 14 patients have been operated on in this manner. In 12 patients continence was achieved; 2 patients had a temporary stress incontinence. The stress incontinence could be treated successfully by temporary electrostimulation of the pelvic floor by an anal plug stimulator.

  4. Excitons in tubular molecular aggregates

    NARCIS (Netherlands)

    Didraga, C; Knoester, J

    2004-01-01

    We present a brief overview of recent work on the optical properties of molecular aggregates with a tubular (cylindrical) shape. The exciton states responsible for these properties can be distinguished with regard to a transverse wave number, which directly relates to optical selection rules and pol

  5. Renal ammonia excretion in response to hypokalemia: effect of collecting duct-specific Rh C glycoprotein deletion

    OpenAIRE

    Lee, Hyun-Wook; Verlander, Jill W.; Bishop, Jesse M.; Handlogten, Mary E.; Han, Ki-Hwan; Weiner, I. David

    2012-01-01

    The Rhesus factor protein, Rh C glycoprotein (Rhcg), is an ammonia transporter whose expression in the collecting duct is necessary for normal ammonia excretion both in basal conditions and in response to metabolic acidosis. Hypokalemia is a common clinical condition associated with increased renal ammonia excretion. In contrast to basal conditions and metabolic acidosis, increased ammonia excretion during hypokalemia can lead to an acid-base disorder, metabolic alkalosis, rather than mainten...

  6. Two Cases of Hypophosphatemia with Increased Renal Phosphate Excretion in Legionella Pneumonia

    Science.gov (United States)

    Watanabe, Shuhei; Kono, Keiji; Fujii, Hideki; Nakai, Kentaro; Goto, Shunsuke; Nishi, Shinichi

    2016-01-01

    We encountered 2 cases of hypophosphatemia due to Legionella pneumonia. Both cases showed increased urinary phosphate excretion and renal tubular dysfunction, which ameliorated with recovery from Legionella pneumonia. Serum fibroblast growth factor-23 level was suppressed, whereas serum 1,25(OH)2 vitamin D and parathyroid hormone levels were normal. Delayed elevation of serum 1,25(OH)2 vitamin D levels was observed with improvement in renal tubular function. These findings suggested hypophosphatemia might be mediated by renal tubular dysfunction. PMID:27066493

  7. Development of diabetes-induced acidosis in the rat retina.

    Science.gov (United States)

    Dmitriev, Andrey V; Henderson, Desmond; Linsenmeier, Robert A

    2016-08-01

    We hypothesized that the retina of diabetic animals would be unusually acidic due to increased glycolytic metabolism. Acidosis in tumors and isolated retina has been shown to lead to increased VEGF. To test the hypothesis we have measured the transretinal distribution of extracellular H(+) concentration (H(+)-profiles) in retinae of control and diabetic dark-adapted intact Long-Evans rats with ion-selective electrodes. Diabetes was induced by intraperitoneal injection of streptozotocin. Intact rat retinae are normally more acidic than blood with a peak of [H(+)]o in the outer nuclear layer (ONL) that averages 30 nM higher than H(+) in the choroid. Profiles in diabetic animals were similar in shape, but diabetic retinae began to be considerably more acidic after 5 weeks of diabetes. In retinae of 1-3 month diabetics the difference between the ONL and choroid was almost twice as great as in controls. At later times, up to 6 months, some diabetics still demonstrated abnormally high levels of [H(+)]o, but others were even less acidic than controls, so that the average level of acidosis was not different. Greater variability in H(+)-profiles (both between animals and between profiles recorded in one animal) distinguished the diabetic retinae from controls. Within animals, this variability was not random, but exhibited regions of higher and lower H(+). We conclude that retinal acidosis begins to develop at an early stage of diabetes (1-3 months) in rats. However, it does not progress, and the acidity of diabetic rat retina was diminished at later stages (3-6 months). Also the diabetes-induced acidosis has a strongly expressed local character. As result, the diabetic retinas show much wider variability in [H(+)] distribution than controls. pH influences metabolic and neural processes, and these results suggest that local acidosis could play a role in the pathogenesis of diabetic retinopathy. PMID:27262608

  8. Comparison of end-tidal carbon dioxide and arterial blood bicarbonate levels in patients with metabolic acidosis referred to emergency medicine

    Science.gov (United States)

    Taghizadieh, Ali; Pouraghaei, Mahboub; Moharamzadeh, Payman; Ala, Alireza; Rahmani, Farzad; Basiri Sofiani, Karim

    2016-01-01

    Introduction: The routine and gold standard method to diagnose of acid – base disturbance is arterial blood gas (ABG) sampling. Capnography could be used to measure the end-tidal carbon dioxide (ETCO2) levels and ETco2 has a close correlation with the PaCo2. The aim of this study was comparison the ETco2 and arterial blood bicarbonate levels in patients with metabolic acidosis. Methods: In a descriptive-analytical study that performed in Emergency Department of Emam Reza Medical Research and Training Hospital of Tabriz on patients with metabolic acidosis, ETco2 level and blood bicarbonate levels in 262 patients were evaluated. Results: Mean of ETco2 and Hco3 levels in patients with metabolic acidosis were 22.29 ± 4.15 and 12.78 ± 3.83, respectively. In all patients, the significant direct linear relationship was found between ETco2 with Hco3 (r = 0.553, P < 0.001). We had 4 groups of patients with metabolic acidosis, also there is a significant direct linear relationship between the ETCo2 and the Hco3 level of arterial blood in patients with renal failure (P < 0.001 and r = 0.551), sepsis (P < 0.001 and r = 0.431), drug toxicity (P < 0.001 and r = 0.856), and ketoacidosis (DKA) (P < 0.001 and r = 0.559). Conclusion: According to the results of this study, capnography can be used for primary diagnosis of metabolic acidosis in spontaneously breathing patients who referred to the emergency wards, however, the ABG must be considered as the gold standard tool for diagnosis and guiding the treatment. PMID:27777693

  9. Renal manifestations of genetic mitochondrial disease

    OpenAIRE

    O’Toole JF

    2014-01-01

    John F O'Toole Department of Internal Medicine, Division of Nephrology, MetroHealth Medical System, Case Western Reserve University School of Medicine, Cleveland, OH, USA Abstract: Mitochondrial diseases can be related to mutations in either the nuclear or mitochondrial genome. Childhood presentations are commonly associated with renal tubular dysfunction, but renal involvement is less commonly reported outside of this age-group. Mitochondrial diseases are notable for the significant...

  10. Diagnostic Challenge in a Patient with Severe Anion Gap Metabolic Acidosis

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    Eugene M. Tan

    2015-01-01

    Full Text Available The approach to the patient with acute renal failure and elevated anion and osmolal gap is difficult. Differential diagnoses include toxic alcohol ingestion, diabetic or starvation ketoacidosis, or 5-oxoproline acidosis. We present a 76-year-old female with type 2 diabetes mellitus, who was found at home in a confused state. Laboratory analysis revealed serum pH 6.84, bicarbonate 5.8 mmol/L, pCO2 29 mmHg, anion gap 22.2 mmol/L, osmolal gap 17.4 mOsm/kg, elevated beta-hydroxybutyrate (4.2 mmol/L, random blood sugar 213 mg/dL, creatinine 2.1 mg/dL, and potassium 7.5 mmol/L with no electrocardiogram (EKG changes. Fomepizole and hemodialysis were initiated for presumed ethylene glycol or methanol ingestion. Drug screens returned negative for ethylene glycol, alcohols, and acetaminophen, but there were elevated urine levels of acetone (11 mg/dL. The acetaminophen level was negative, and 5-oxoproline was not analyzed. After 5 days in the intensive care unit (ICU, her mental status improved with supportive care. She was discharged to a nursing facility. Though a diagnosis was not established, our patient’s presentation was likely due to starvation ketosis combined with chronic acetaminophen ingestion. Acetone ingestion is less likely. Overall, our case illustrates the importance of systematically approaching an elevated osmolal and anion gap metabolic acidosis.

  11. Markers of renal function tests

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    Shivaraj Gowda

    2010-04-01

    Full Text Available Background: The markers of renal function test assess the normal functioning of kidneys. These markers may be radioactive and non radioactive. They indicate the glomerular filtration rate, concentrating and diluting capacity of kidneys (tubular function. If there is an increase or decrease in the valves of these markers it indicates dysfunction of kidney. Aim: The aim of this review is to compare and analyze the present and newer markers of renal function tests which help in diagnosis of clinical disorders. Material & Methods: An extensive literature survey was done aiming to compare and compile renal function tests makers required in diagnosis of diseases. Results: Creatinine, urea, uric acid and electrolytes are makers for routine analysis whereas several studies have confirmed and consolidated the usefulness of markers such as cystatin C and β-Trace Protein. Conclusion: We conclude that further investigation is necessary to define these biomarkers in terms of usefulness in assessing renal function.

  12. Influence of albumin-activated renal proximal tubular epithelial cells on peritubular capillaries and its potential mechanism%白蛋白活化肾小管上皮细胞对肾小管周微血管的影响及机制研究

    Institute of Scientific and Technical Information of China (English)

    林静; 何娅妮; 王惠明; 李开龙; 丁涵露; 申海鹰; 杨聚荣

    2008-01-01

    Objective To explore the influence of albumin-activated renal tubular epithelial cells (RTECs)on peritubular capillaries in co-culture system and its potential mechanism. Methods Endocytosis of TRITC labeled bovine scrum albumin (TRITC-BSA) by HKC was detected by laser scanning confocal fluorescence microscope. HKC or HKC transfected with cubilin (endocytic receptor of albumin) siRNA or pre-treated with rotenone was incubated with albumin(20 g/L) for 24 h respectively. Fluorescence probe technique and spectrometry were applied for determination of intracellular superoxide anion O2-and H2O2 in supematant. Then, the albumin-aetivated-HKC, pretreated-HKC with cubilin siRNA or rotenone, was cultured with HUVEC for 24 h in co-culture system respectively. HUVEC proliferation was determined by MTT and cellular apoptosis was analyzed by flow cytometry. Tabular morphogenesis of endothelial cells was examinedby microscopy. Results TRITC-BSA uptake was obviously lower in HKC transfected with cubilin siRNA. Intracellular generation of O2-and H2O2 in culture supernatant was increased in dose-and time-dependent manner after stimulating with albumin. The levels of O2-and H2O2 were suppressed by cubilin siRNA and rotenone. In co-culture system, albumin-activated-HKC induced endothelial cells apoptosis and inhibited their capillary tubular morphogenesis. Pretreatment of HKC with cubilin siRNA or rotenone could suppress endothelial cells apoptosis and promote capillary tubular morphogenesis. Conclusions There may be a crosstalk between RTECs and peritubular microvascular endothelial cells in renal proteinurie diseases. The generation of ROS by albumin-activated RTECs may play an important role in this process.%目的 探讨人类血清白蛋白(HSA)超负荷损伤肾小管上皮细胞后对肾间质微血管损伤的影响及可能机制.方法 激光共聚焦显微镜观察肾小管上皮细胞(HKC)吞饮罗丹明标记白蛋白(TRITC-BSA)以及吞饮受体cubilin siRNA对其的

  13. Hepatocyte Growth Factor Prevents Acute Renal Failure of Accelerates Renal Regeneration in mice

    Science.gov (United States)

    Kawaida, Kouichi; Matsumoto, Kunio; Shimazu, Hisaaki; Nakamura, Toshikazu

    1994-05-01

    Although acute renal failure is encountered with administration of nephrotoxic drugs, ischemia, or unilateral nephrectomy, there has been no effective drug which can be used in case of acute renal failure. Hepatocyte growth factor (HGF) is a potent hepatotropic factor for liver regeneration and is known to have mitogenic, motogenic, and morphogenic activities for various epithelial cells, including renal tubular cells. Intravenous injection of recombinant human HGF into mice remarkably suppressed increases in blood urea nitrogen and serum creatinine caused by administration of cisplatin, a widely used antitumor drug, or HgCl_2, thereby indicating that HGF strongly prevented the onset of acute renal dysfunction. Moreover, exogenous HGF stimulated DNA synthesis of renal tubular cells after renal injuries caused by HgCl_2 administration and unilateral nephrectomy and induced reconstruction of the normal renal tissue structure in vivo. Taken together with our previous finding that expression of HGF was rapidly induced after renal injuries, these results allow us to conclude that HGF may be the long-sought renotropic factor for renal regeneration and may prove to be effective treatment for patients with renal dysfunction, especially that caused by cisplatin.

  14. α1B-Adrenoceptors mediate adrenergically-induced renal vasoconstrictions in rats with renal impairment

    Institute of Scientific and Technical Information of China (English)

    Md Abdul Hye KHAN; Munavvar Abdul SATTAR; Nor Azizan ABDULLAH; Edward James JOHNS

    2008-01-01

    Aim: This study examined whether α1B-adrenoceptors are involved in mediating adrenergically-induced renal vasoconstrictor responses in rats with pathophysi-ological and normal physiological states. Methods: Male Wistar Kyoto and spon-taneously hypertensive rats were induced with acute renal failure or experimental early diabetic nephropathy by cisplatin or streptozotocin, respectively. Cisplatin-induced renal failure was confirmed by impaired renal function and pronounced tubular damage. Experimental early diabetic nephropathy was confirmed by hyperglycemia, changes in physiological parameters, and renal function. The hemodynamic study was conducted on anesthetized rats after 7 d of cisplatin (renal failure) and 4 weeks of streptozotocin (experimental early diabetic nephropathy). Results: In the rats with renal failure and experimental early dia-betic nephropathy, there were marked reductions in their baseline renal blood flow (P0.05) in the renal failure and experimental early diabetic nephropathy rats, respectively, as compared to their non-renal failure and non-diabetic nephropathy controls. In the rats with renal impairment, chloroethylclonidine caused either accentuation or attenuation (all P0.05). Conclusion: This study demonstrated the presence of functional α1B-adrenoceptors that mediated the adrenergically-induced renal vaso-constrictions in rats with renal impairment, but not in rats with normal renal function.

  15. Novel approaches to assessing renal function in cirrhotic liver disease.

    Science.gov (United States)

    Portal, Andrew J; Austin, Mark; Heneghan, Michael A

    2007-09-01

    Renal dysfunction is common in patients with end-stage liver disease. Etiological factors include conditions as diverse as acute tubular necrosis, immunoglobulin A nephropathy and hepatorenal syndrome. Current standard tests of renal function, such as measurement of serum urea and creatinine levels, are inaccurate as the synthesis of these markers is affected by the native liver pathology. This article reviews novel markers of renal function and their potential use in patients with liver disease.

  16. Trauma renal Renal trauma

    Directory of Open Access Journals (Sweden)

    Gerson Alves Pereira Júnior

    1999-02-01

    Full Text Available Apresentamos uma revisão sobre trauma renal, com ênfase na avaliação radiológica, particularmente com o uso da tomografia computadorizada, que tem se tornado o exame de eleição, ao invés da urografia excretora e arteriografia. O sucesso no tratamento conservador dos pacientes com trauma renal depende de um acurado estadiamento da extensão da lesão, classificado de acordo com a Organ Injury Scaling do Colégio Americano de Cirurgiões. O tratamento conservador não-operatório é seguro e consiste de observação contínua, repouso no leito, hidratação endovenosa adequada e antibioti- coterapia profilática, evitando-se uma exploração cirúrgica desnecessária e possível perda renal. As indicações para exploração cirúrgica imediata são abdome agudo, rápida queda do hematócrito ou lesões associadas determinadas na avaliação radiológica. Quando indicada, a exploração renal após controle vascular prévio é segura, permitindo cuidadosa inspeção do rim e sua reconstrução com sucesso, reduzindo a probabilidade de nefrectomia.We present a revision of the renal trauma with emphasis in the radiographic evaluation, particularly CT scan that it has largely replaced the excretory urogram and arteriogram in the diagnostic worh-up and management of the patient with renal trauma. The successful management of renal injuries depends upon the accurate assessment of their extent in agreement with Organ Injury Scaling classification. The conservative therapy managed by careful continuous observation, bed rest, appropriate fluid ressuscitation and prophylactic antibiotic coverage after radiographic staging for severely injured kidneys can yield favorable results and save patients from unnecessary exploration and possible renal loss. The indications for immediate exploratory laparotomy were acute abdomen, rapidly dropping hematocrit or associated injuries as determinated from radiologic evaluation. When indicated, renal exploration

  17. Acidosis ruminal en bovinos lecheros: implicaciones sobre la producción y la salud animal - Ruminal acidosis in dairy cattle: implications for animal health and production

    Directory of Open Access Journals (Sweden)

    Granja Salcedo, Yury Tatiana

    2012-04-01

    Full Text Available ResumenLa acidosis ruminal es un importante problema en la producción de bovinos alimentados con dietas ricas en concentrados, especialmente en vacas de alta producción lechera.AbstractRuminal acidosis is a major problem in the production of cattle fed diets rich in concentrates, especially in cows of high milk production.

  18. Metabolic acidosis may be as protective as hypercapnic acidosis in an ex-vivo model of severe ventilator-induced lung injury: a pilot study

    Directory of Open Access Journals (Sweden)

    Patsouris Efstratios

    2011-04-01

    Full Text Available Abstract Background There is mounting experimental evidence that hypercapnic acidosis protects against lung injury. However, it is unclear if acidosis per se rather than hypercapnia is responsible for this beneficial effect. Therefore, we sought to evaluate the effects of hypercapnic (respiratory versus normocapnic (metabolic acidosis in an ex vivo model of ventilator-induced lung injury (VILI. Methods Sixty New Zealand white rabbit ventilated and perfused heart-lung preparations were used. Six study groups were evaluated. Respiratory acidosis (RA, metabolic acidosis (MA and normocapnic-normoxic (Control - C groups were randomized into high and low peak inspiratory pressures, respectively. Each preparation was ventilated for 1 hour according to a standardized ventilation protocol. Lung injury was evaluated by means of pulmonary edema formation (weight gain, changes in ultrafiltration coefficient, mean pulmonary artery pressure changes as well as histological alterations. Results HPC group gained significantly greater weight than HPMA, HPRA and all three LP groups (P = 0.024, while no difference was observed between HPMA and HPRA groups regarding weight gain. Neither group differ on ultrafiltration coefficient. HPMA group experienced greater increase in the mean pulmonary artery pressure at 20 min (P = 0.0276 and 40 min (P = 0.0012 compared with all other groups. Histology scores were significantly greater in HP vs. LP groups (p Conclusions In our experimental VILI model both metabolic acidosis and hypercapnic acidosis attenuated VILI-induced pulmonary edema implying a mechanism other than possible synergistic effects of acidosis with CO2 for VILI attenuation.

  19. Lipasuria in acute pancreatitis: result of tubular dysfunction?

    Science.gov (United States)

    Muench, R; Buehler, H; Kehl, O; Ammann, R

    1987-01-01

    Lipase, in contrast to amylase, is completely reabsorbed by the proximal tubules after glomerular filtration. Therefore, no lipase is detectable in the unconcentrated urine according to the current opinion. The handling of lipase (detected with an enzyme-immunoassay) by the kidney was investigated in comparison with creatinine, amylase, and beta-2-microglobulin by clearance studies in acute pancreatitis (n = 10), burn injury (n = 4), glomerular proteinuria (n = 8), and controls without evidence of pancreatic or renal diseases (n = 5). In initial stages of acute pancreatitis a measurable clearance of lipase (mean: 49.6 microliters/min, range: 0.5-234) was found in association with corresponding increased clearances of beta-2-microglobulin (mean: 10.5 ml/min, range: 0.02-58.9) and of amylase (mean: 8.9 ml/min, range: 2.4-22.6) in nine of ten patients. This finding is consistent with a defect of tubular function. However, regression analysis failed to show a significant correlation between lipase and beta-2-microglobulin clearance. Repeated measurements during the course of pancreatitis in seven patients showed reversibility of tubular dysfunction. In patients with burn injury a similar elevation of clearances of beta-2-microglobulin and of amylase was found, but tubular dysfunction in this condition was not associated with lipasuria. In glomerular proteinuria a lipase clearance was found in two of five cases with moderate, and in the other three cases with severe impairment of creatinine clearance. beta-2-microglobulin clearance was normal in the former and only slightly elevated in the latter group. In conclusion lipase is measurable in the urine of most patients with acute pancreatitis as a result of a reversible tubular dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

  20. Evaluation and treatment of chronic renal failure.

    Science.gov (United States)

    Moudgil, A; Bagga, A

    1999-01-01

    Chronic renal failure (CRF) is the irreversible deterioration of renal function that gradually progresses to end stage renal disease (ESRD). The chief causes of CRF include obstructive uropathy, primary glomerular diseases, reflux nephropathy and hypoplastic or dysplastic kidneys. Progressive hyperperfusion and hyperfiltration causes increasing glomerular injury and further renal damage. Symptoms of CRF are usually seen when GFR is between 10-25% of normal. Children with severe CRF often suffer from failure to thrive, growth retardation, acidosis, anemia and renal osteodystrophy. Management of CRF aims at retarding progression of renal damage and treatment of complications related to renal dysfunction. Measures suggested to retard progression include protein restriction, strict control of hypertension, use of angiotensin converting enzyme inhibitors and control of hyperlipidemia. Appropriate amounts of protein and calories are recommended to prevent growth failure. Nutritional supplements are often required. The availability of recombinant erythropoietin, calcitriol and human growth hormone has significantly improved the management of these patients. Once ESRD supervenes, renal replacement therapy in the form of chronic peritoneal or hemodialysis and transplantation is necessary.

  1. Blood Parameters Modification at Different Ruminal Acidosis Conditions

    Directory of Open Access Journals (Sweden)

    Roberta De Nardi

    2013-09-01

    Full Text Available This study evaluated the reliability of various blood parameters to assess the ruminal acidosis in cattle. Six whole heifers were fed three experimental rations in a 3 x 3 Latin square design. The diets had different starch levels: high (HS, medium (MS or low (CT. Ruminal pH values were continuously measured using wireless sensors. To evaluate the severity of ruminal acidosis, the amount of time per day that the pH was below 5.8, 5.5 and 5.0 was recorded. Blood samples were analyzed for complete blood count, venous blood gas and biochemical profile at 8:00 and 12:00 h. The data were analyzed according to a mixed model. Feeding on CT, MS and HS led to significant differences in DMI (7.7 vs. 6.9 vs. 5.1 kg/d; P < 0.01 which modified the amount of time per day that the pH was below 5.0 (0 vs. 12 vs. 92 min; P < 0.10. Feeding MS and HS diets led to inflammation as indicated by the significant increment of white blood cells when compared to the CT ones and to blood concentration due to the osmotic pressure at ruminal level. Furthermore a significant decrease of bicarbonate level, CO2 partial pressure and oxyhemoglobin was observed as consequence of the activation of metabolic processes aimed to prevent metabolic acidosis. No differences were observed on blood sampling time, suggesting that one daily blood sample was enough to evaluate the metabolic variations related to ruminal acidosis.

  2. Complement and contact activation in term neonates after fetal acidosis

    Science.gov (United States)

    Sonntag, J.; Wagner, M.; Strauss, E.; Obladen, M.

    1998-01-01

    AIMS—To evaluate complement and contact activation after fetal acidosis.
METHODS—Fifteen term neonates with hypoxic-ischaemic encephalopathy after umbilical arterial pH 7.20. Determinations of the complement function and C1-inhibitor activity were performed as kinetic tests 22-28 hours after birth. C1q, C1-inhibitor, and factor B concentrations were determined by radial immunodiffusion and those of C3a, C5a, and factor XIIa by enzyme immunoabsorbent assay.
RESULTS—Median complement function (46 vs 73 %), C1q (4.3 vs 9.1 mg/dl), and factor B (5.2 vs 7.7 mg/dl) decreased after fetal acidosis. The activated split products C3a (260 vs 185 µg/l), C5a (5.0 vs 0.6 µg/l), and factor XIIa (3.2 vs 1.3 µg/l) increased in the neonates after fetal acidosis. No differences were found in the concentration and activity of C1-inhibitor.
CONCLUSIONS—Complement and contact activation occurred in the newborns with hypoxic-ischaemic encephalopathy. Activation of these systems generates mediators which can trigger inflammation and tissue injury.

 PMID:9577283

  3. Role of ATP-dependent K channels in the effects of erythropoietin in renal ischaemia injury

    Directory of Open Access Journals (Sweden)

    Tonguç Utku Yilmaz

    2015-01-01

    Interpretation & conclusions: Our results showed that the cell proliferative, cytoprotective and anti-apoptotic effects of EPO were associated with KATP channels in the renal tubular cell culture model under hypoxic/normal conditions.

  4. Renal function in tyrosinaemia type I after liver transplantation : A long-term follow-up

    NARCIS (Netherlands)

    Pierik, LJWM; van Spronsen, FJ; Bijleveld, CMA; van Dael, CML

    2005-01-01

    Hereditary tyrosinaemia type I is an autosomal recessive inborn error of tyrosine catabolism caused by a deficiency of the enzyme fumarylacetoacetase that results in liver failure, hepatocellular carcinoma, renal tubular dysfunction and acute intermittent porphyria. When treated with liver transplan

  5. Effects of hyperventilation and hypocapnic/normocapnic hypoxemia on renal function and lithium clearance in humans

    DEFF Research Database (Denmark)

    Christensen, H; Klausen, T; Fogh-Andersen, N;

    1998-01-01

    Using the renal clearance of lithium as an index of proximal tubular outflow, this study tested the hypothesis that acute hypocapnic hypoxemia decreases proximal tubular reabsorption to the same extent as hypocapnic normoxemia (hyperventilation) and that this response is blunted during normocapnic...

  6. Protection Effect of Berberine Ischemia-Reperfusion for Renal Tubular Epithelial Cell of Rats%盐酸小檗碱对大鼠肾小管上皮细胞缺血再灌注损伤的保护作用

    Institute of Scientific and Technical Information of China (English)

    张日东; 白瑞苗; 魏敬

    2011-01-01

    Objective: To observe the effect of the berberine (BBR) on ischemia-reperfusion for renal tubular epithelial cells (NRK-52E) of rat.Method: Using chemical hypoxia cobalt chloride ( CoCl2 ) to stimulate NRK52E cells to develop a chemical model of hypoxia-reoxygenation injury.Then, the cells were treated with different concentrations ( 1 × 10 -6,1 × 10 -5, 1 × 10 -4 mol· L -1 ) of BBR.Methylthiazolyldiphenyl-tetrazolium bromide (MTT)was used to test the activity of the cells.Malondialdehyde (MDA) and superoxide dismutase (SOD)content of each group were determined; Hoechst33258 staining was used to detect the morphological changes of apoptotic cells of each group; Annexin V-FITC/PI staining was applied to detect the rate of apoptosis cell in each group.Result:MTT results showed that 1 × 10-4 mol· L-l BBR was toxic to the cells,but 1 × 10-6 mol·L-1and 1 × 10-5 mol· L-1 BBR could increase the ischemia-reperfusion group cell survival,especially in 1 × 10-5 mol·L-1 for the high; Hoechst33258 showed almost no apoptotic cells in the normal group,in the model group there were mostly nuclear staining of apoptotic cells,while BBR (1 × 10 -5 mol·L-1) pretreatment significantly reduced apoptosis cells; With the normal control groups, the MDA of ischemia-reperfusion group content was significantly higher ( P < 0.05 ), but the SOD was significantly lower ( P < 0.05 ).The pretreatment with BBR group, MDA was significantly lower than that of before treatment (P < 0.05), SOD was higher than the ischemia- reperfusion group ( P < 0.05 ), the role of BBR depends on the concentration between 1 × 10-6 mol·L-i and 1 × 10-5 mol· L-1.The Flow Cytometry showed that the apoptosis rate of 1 × 10-5 ,1 × 10-6 mol· L-1 BBR group and ischemia-reperfusion group were 11.1% ,32.2% and 56.2%, and the differences were significantly (P < 0.05).Conclusion: The pretreatment with BBR on the ischemia-reperfusion cell has protective effects on renal tubular epithelial

  7. Effects of heme oxygenase-1 on rat renal tubular epithelial cell apoptosis induced by albumin%血红素加氧酶1对白蛋白诱导肾小管上皮细胞凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    马瑨; 刘章锁; 王沛; 骆红

    2009-01-01

    目的 探讨血红素加氧酶1(HO-1)对白蛋白诱导肾小管上皮细胞凋亡的影响及其可能机制.方法 体外培养大鼠肾小管上皮细胞(NRK-52E)为正常对照.白蛋白对照组加去脂的小牛血清白蛋白(BSA)30 g/L共同培养.干预组先加钴卟啉(Cobalt protoporphyrinIX,CoPP,血红素加氧酶1诱导剂)5 μmol/L,0.5 h后再加入BSA 30 g/L,作用24 h.四甲基偶氮唑盐(MTT)比色法检测CoPP对BSA抑制NRK-52E细胞增殖的影响.细胞免疫荧光染色检测细胞凋亡率.RT-PCR法检测凋亡相关蛋白Bcl-2、Bax mRNA表达情况.结果 与正常对照组比较,BSA对细胞增殖具有抑制作用并诱导细胞凋亡,差异有统计学意义(P<0.05),而CoPP对BSA引起的细胞毒性作用具有保护作用(P<0.05);BSA对照组HO-1 mRNA表达增加(0.44±0.06比0.39±0.05,P<0.05),差异有统计学意义(P<0.05).CoPP预处理后,HO-1mRNA表达(0.50±0.06)较BSA对照组增加(P<0.05).BSA可上调Bax mRNA表达(0.87±0.04比0.67±0.03,P<0.05)及下调Bcl-2 mRNA的表达(0.25±0.04比0.42±0.02,P<0.05),当加入CoPP预处理后可抑制上述改变(Bax mRNA:0.75±0.07,Bcl-2 mRNA:0.36±0.03,均P<0.05).结论 BSA可显著增加细胞的凋亡率并直接调控凋亡相关蛋白mRNA的表达,CoPP可抑制上述BSA的作用.HO-1对BSA所致肾小管上皮细胞凋亡具有保护作用,可以抑制细胞凋亡.%Objective To investigate the influence of heme oxygenase-1 (HO-1) on rat renal tubular epithelial cell apoptosis induced by albumin and the possible mechanism. Methods The renal tubular epithelial cells (NRK-52E) were cultured in DMEM/F12 1:1 medium as normal control group; NRK-52E cells were cultured with 30 g/L fat-free bovine serum albumin (BSA) as the BSA control group; NRK-52E cells were cultured with CoPP (Cobalt pretoporphyrin Ⅸ) 5 μ mol/L for 24 hours as the treatment group. MTT assay was used to observe the effects of CoPP on growth inhibition induced by BSA in NRK-52E cells. The effect of CoPP was

  8. Expression of Omi/HtrA2 in Human Renal Proximal Tubular Epithelial Cells with Hypoxia/Reoxygenation and Effect of Erythropoietin on It%Omi/HtrA2在缺氧复氧后人近曲肾小管上皮细胞中的表达及促红细胞生成素对其表达的影响

    Institute of Scientific and Technical Information of China (English)

    邹礼乐; 徐富翠; 梅欣明; 雷小平; 董文斌

    2012-01-01

    目的 探讨缺氧复氧(H/R)后人近曲肾小管上皮细胞内Omi/HtrA2的表达变化及促红细胞生成素(EPO)干预的影响.方法 以人近曲肾小管上皮细胞株(HK-2细胞)为研究对象,将其分为对照组、H/R组及EPO干预组.对照组常规培养;H/R组缺氧24h后复氧6 h;EPO干预组在H/R前加入5 000 U·L-1EPO预处理.倒置显微镜观察细胞形态,四甲基偶氮唑蓝(MTT)法检测细胞活力,流式细胞仪检测细胞凋亡,免疫组织化学检测细胞内Omi/HtrA2表达变化.结果 与对照组比较,H/R组细胞数量减少,细胞形态发生改变,细胞活力下降,细胞凋亡率显著增加,细胞内Omi/HtrA2表达增强,差异均有统计学意义(Pa<0.05);而与H/R组相比,EPO干预组细胞数量增多,细胞形态明显改善,细胞活力增加,细胞凋亡率下降,Omi/HtrA2表达减弱,差异均有统计学意义(Pa<0.05).但各指标均未恢复至对照组水平.结论.H/R可通过上调Omi/HtrA2表达而促进肾小管上皮细胞凋亡,EPO对H/R肾小管上皮细胞具有保护作用,其机制可能与抑制Omi/HtrA2表达、减少细胞凋亡有关.%Objective To investigate the expression of Omi/HtrA2 in renal tubular epithelial cells with hypoxia /reoxygenation( H/R) and to evaluate the effect of erythropoietin ( EPO) on it. Methods Human renal proximal tubular epithelial cell line HK - 2 cell was used as target cell. The cultural cells in orifice were divided into the following groups: control group, H/R group and EPO group. The cells of control group were cultivated with normal nutritive medium; the cells of the H/R group were exposed to hypoxia for 24 h.then to normoxia for 6 h;and the cells of EPO group were added 5 000 U · L-1 EPO before H/R. The change of morphology was observed under inverted microscope,the cell viability was measured by 3 - (4,5 ) - dimethylthiahiazo ( -z-yl) -3,5 - di - phenytetrazoliumromide ( MTT) method. The rate of apoptosis cells was detected by flow cytometry

  9. Intervene of Hedgehog signal on expression of proliferating cell nuclear antigen in renal tubular epithelial cells%干预Hedgehog信号对肾小管上皮细胞增殖细胞核抗原表达的影响

    Institute of Scientific and Technical Information of China (English)

    陆红; 吴莲凤; 林成成; 王斯璐; 梁勇; 白永恒

    2015-01-01

    目的:探讨Hedgehog(HH)信号通路的活化和抑制对肾小管上皮细胞中增殖细胞核抗原(PCNA)表达的影响。方法:根据干预措施将体外培养的大鼠肾小管上皮细胞NRK-52E分为对照组、活化组(10μg/L Shh)和干预组(10μg/L Shh加5μmol/L环杷明)。细胞培养24 h后,细胞免疫荧光染色检测HH信号关键分子Ptch1、Smo和Gli1,以及细胞增殖标志物PCNA的表达,real-time RT-PCR检测Ptch1和Smo mRNA的表达。结果:免疫荧光染色显示,对照组细胞维持一定的增殖状态,HH信号活性较低,PCNA表达水平较低;当外源性重组蛋白Shh活化NRK-52E细胞24 h后,Smo和Gli1 mRNA和蛋白表达显著升高,Ptch1的表达显著下调,这提示Shh可激活HH信号(P<0.05)。在此过程中,PCNA表达水平显著升高,NRK-52E细胞数量增加,同时伴随细胞形态的改变;在Shh的基础上加入环杷明干预后,HH信号被抑制(P<0.05),PCNA表达下降,NRK-52E细胞增殖被抑制,出现凋亡或坏死。结论:HH信号与肾小管上皮细胞的增殖密切相关。通过药物调控HH信号的活化,可影响PCNA的表达,进而影响细胞增殖效应。%Objective: To explore and investigate the activation and inhibition of Hedgehog signal regulated on expression of proliferating cell nuclear antigen (PCNA) in renal tubular epithelial cells (NRK-52E).Methods:NRK-52E cells were randomly divided into control group (treated with solvent only), activated group (treated with Shh at the concentrations with 10 μg/L) and treatment group (treated with Shh at the concentration of 10 μg/L plus cyclopamine at the concentrations with 5 μmol/L). After cultured for 24 h, immunolfuorescence staining was used to evaluate the expressions of Ptch1, Smo, Gli1, and PCNA. The expression levels of Ptch1 and Smo mRNA were quantiifed by real-time RT-PCR.Results: NRK-52E cells without drug treatment maintain slowed proliferation

  10. Renal Type A Intercalated Cells Contain Albumin in Organelles with Aldosterone-Regulated Abundance

    OpenAIRE

    Jensen, Thomas Buus; Cheema, Muhammad Umar; Szymiczek, Agata; Damkier, Helle Hasager; Praetorius, Jeppe

    2015-01-01

    Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells i...

  11. Species diversity regarding the presence of proximal tubular progenitor cells of the kidney

    Directory of Open Access Journals (Sweden)

    J. Hansson

    2016-02-01

    Full Text Available The cellular source for tubular regeneration following kidney injury is a matter of dispute, with reports suggesting a stem or progenitor cells as the regeneration source while linage tracing studies in mice seemingly favor the classical theory, where regeneration is performed by randomly surviving cells. We, and others have previously described a scattered cell population localized to the tubules of human kidney, which increases in number following injury. Here we have characterized the species distribution of these proximal tubular progenitor cells (PTPCs in kidney tissue from chimpanzee, pig, rat and mouse using a set of human PTPC markers. We detected PTPCs in chimpanzee and pig kidneys, but not in mouse tissue. Also, subjecting mice to the unilateral urethral obstruction model, caused clear signs of tubular injury, but failed to induce the PTPC phenotype in renal tubules.

  12. In-vitro activation of complement system by lactic acidosis in newborn and adults

    Directory of Open Access Journals (Sweden)

    Friederike Hecke

    2001-01-01

    Full Text Available Introduction: Complement activation occurs secondary to a variety of external stimuli. Lactic acidosis has been previously shown to activate the complement factors C3a and C5a. In the present investigation we examined the differential effect of lactic acidosis on anaphylatoxin levels in cord and adult blood. Furthermore we aimed to determine if the entire complement cascade could be activated by lactic acidosis.

  13. Blockade of Death Ligand TRAIL Inhibits Renal Ischemia Reperfusion Injury

    International Nuclear Information System (INIS)

    Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI). Many investigators have reported that cell death via apoptosis significantly contributed to the pathophysiology of renal IRI. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor superfamily, and induces apoptosis and inflammation. However, the role of TRAIL in renal IRI is unclear. Here, we investigated whether TRAIL contributes to renal IRI and whether TRAIL blockade could attenuate renal IRI. AKI was induced by unilateral clamping of the renal pedicle for 60 min in male FVB/N mice. We found that the expression of TRAIL and its receptors were highly upregulated in renal tubular cells in renal IRI. Neutralizing anti-TRAIL antibody or its control IgG was given 24 hr before ischemia and a half-dose booster injection was administered into the peritoneal cavity immediately after reperfusion. We found that TRAIL blockade inhibited tubular apoptosis and reduced the accumulation of neutrophils and macrophages. Furthermore, TRAIL blockade attenuated renal fibrosis and atrophy after IRI. In conclusion, our study suggests that TRAIL is a critical pathogenic factor in renal IRI, and that TRAIL could be a new therapeutic target for the prevention of renal IRI

  14. Renal hemodynamics, function, and oxygenation during cardiac surgery performed on cardiopulmonary bypass: a modeling study

    OpenAIRE

    Sgouralis, Ioannis; Evans, Roger G.; Gardiner, Bruce S; Smith, Julian A.; Fry, Brendan C.; Layton, Anita T.

    2015-01-01

    Abstract Acute kidney injury, a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB), is thought to be driven partly by hypoxic damage in the renal medulla. To determine the causes of medullary hypoxia during CPB, we modeled its impact on renal hemodynamics and function, and thus oxygen delivery and consumption in the renal medulla. The model incorporates autoregulation of renal blood flow and glomerular filtration rate and the utilization of oxygen for tubular ...

  15. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia

    NARCIS (Netherlands)

    S. Kroening; E. Neubauer; B. Wullich; J. Aten; M. Goppelt-Struebe

    2010-01-01

    Kroening S, Neubauer E, Wullich B, Aten J, Goppelt-Struebe M. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia. Am J Physiol Renal Physiol 298:F796-F806, 2010. First published December 23, 2009; doi:10.1152/aj

  16. Acute renal failure following binge drinking and nonsteroidal antiinflammatory drugs.

    Science.gov (United States)

    Wen, S F; Parthasarathy, R; Iliopoulos, O; Oberley, T D

    1992-09-01

    Two college students who developed reversible acute deterioration in renal function following binge drinking of beer and the use of nonsteroidal antiinflammatory drugs (NSAIDs) are reported. Both patients presented with back and flank pain with muscle tenderness, but showed no evidence of overt rhabdomyolysis. The first case had marked renal failure, with a peak serum creatinine reaching 575 mumol/L (6.5 mg/dL), and acute tubular necrosis was documented by renal biopsy. The second case had only modest elevation in serum creatinine, and renal function rapidly improved on rehydration. The contribution of the potential muscle damage associated with alcohol ingestion to the changes in renal function in these two cases is not clear. However, the major mechanism for the acute renal failure was thought to be related to inhibition of renal prostaglandin synthesis in the face of compromised renal hemodynamics secondary to alcohol-induced volume depletion. PMID:1519610

  17. [Acetaminophen (paracetamol) causing renal failure: report on 3 pediatric cases].

    Science.gov (United States)

    Le Vaillant, J; Pellerin, L; Brouard, J; Eckart, P

    2013-06-01

    Renal failure secondary to acetaminophen poisoning is rare and occurs in approximately 1-2 % of patients with acetaminophen overdose. The pathophysiology is still being debated, and renal acetaminophen toxicity consists of acute tubular necrosis, without complication if treated promptly. Renal involvement can sometimes occur without prior liver disease, and early renal manifestations usually occur between the 2nd and 7th day after the acute acetaminophen poisoning. While therapy is exclusively symptomatic, sometimes serious metabolic complications can be observed. The monitoring of renal function should therefore be considered as an integral part of the management of children with acute, severe acetaminophen intoxication. We report 3 cases of adolescents who presented with acute renal failure as a result of voluntary drug intoxication with acetaminophen. One of these 3 girls developed severe renal injury without elevated hepatic transaminases. None of the 3 girls' renal function required hemodialysis, but one of the 3 patients had metabolic complications after her acetaminophen poisoning. PMID:23628119

  18. Disease: H00428 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available ne, env_factor, marker) Rodriguez Soriano J Renal tubular acidosis: the clinical ...) PMID:11045400 (gene) Rodriguez-Soriano J New insights into the pathogenesis of ...a DM, Oliveira EA, Silva AC Molecular pathophysiology of renal tubular acidosis. Curr Genomics 10:51-9 (2009...1 (gene) Fry AC, Karet FE Inherited renal acidoses. Physiology (Bethesda) 22:202-11 (2007) PMID:12138150 (ge

  19. Bone Disease in Medullary Sponge Kidney and Effect of Potassium Citrate Treatment

    OpenAIRE

    Fabris, Antonia; Bernich, Patrizia; Abaterusso, Cataldo; Marchionna, Nicola; Canciani, Chiara; Nouvenne, Antonio; Zamboni, Mauro; Lupo, Antonio; Gambaro, Giovanni

    2009-01-01

    Background and objectives: In medullary sponge kidney (MSK)—a common malformative renal condition in patients with calcium nephrolithiasis—hypercalciuria, incomplete distal renal tubular acidosis, and hypocitraturia are common. Clinical conditions with concomitant hypercalciuria and/or incomplete distal renal tubular acidosis are almost invariably associated with bone disease, making osteopathy highly likely in MSK, too. Patients with MSK have never been investigated for osteopathy; neither h...

  20. Pathogenic role of glomerulo-tubular junction stenosis in glomerulocystic disease.

    Science.gov (United States)

    Hotta, O; Sato, M; Furuta, T; Taguma, Y

    1999-03-01

    Glomerulocystic disease is an uncommon cystic renal condition characterized by cystic dilatation forming a glomerular cyst. The pathogenesis of this familial disease is unknown. We performed a serial section study using a biopsy specimen of a 16-year old female patient with glomerular cystic disease who had a family history of end stage renal failure. A total of 14 different glomeruli were analyzed, four of which exhibited a cystic appearance. Five glomerulotubular junctions were observed by serial sections, two of which had a stenotic appearance where glomerular cystic changes and periglomerular fibrosis were observed concomitantly. There were no such cystic glomerular changes in the other three glomeruli with non-stenotic glomerulo-tubular junctions. These findings suggest that the glomerular cystic lesion develops as a consequence of glomerulo-tubular junctional stenosis probably caused by periglomerular fibrosis.

  1. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984).

    Science.gov (United States)

    DiBartola, S P; Rutgers, H C; Zack, P M; Tarr, M J

    1987-05-01

    The historic, physical, laboratory, and histologic findings for 74 cats with chronic renal disease were reviewed. Most cats were older, and no breed or sex predilection was detected. This most common clinical signs detected by owners were lethargy, anorexia, and weight loss. Dehydration and emaciation were common physical examination findings. Common laboratory findings were nonregenerative anemia, lymphopenia, azotemia, hypercholesterolemia, metabolic acidosis, hyperphosphatemia, and isosthenuria. The most common morphologic diagnosis was chronic tubulointerstitial nephritis of unknown cause. The other pathologic diagnoses were renal lymphosarcoma, renal amyloidosis, chronic pyelonephritis, chronic glomerulonephritis, polycystic renal disease, and pyogranulomatous nephritis secondary to feline infectious peritonitis. PMID:3583899

  2. Lipid peroxidation and renal injury in renal ischemia/reperfusion: Effect of Benincasa cerifera

    Directory of Open Access Journals (Sweden)

    Bhalodia Y

    2009-01-01

    Full Text Available To investigate the role of the methanolic fruit extract of Benincasa cerifera on lipid peroxidation (LPO and renal pathology in ischemia/reperfusion (I/R.In experimental methodology, both renal pedicles were occluded for 60 min followed by 24 h of reperfusion. B. cerifera (500 mg/kg/day was administered orally for 5 days prior to induction of renal ischemia and was continued for 1 day after ischemia. At the end of the reperfusion period, rats were sacrificed. Sham-operated rats followed same procedure except renal arteries occlusion. LPO and histopathological analysis were done in renal tissue. Serum creatinine and urea levels were measured for the evaluation of renal function. In ischemia/reperfusion (I/R rats, malondialdehyde (MDA levels were increased significantly when compared with sham-control rats. Histological changes showed tubular cell swelling, interstitial oedema, tubular dilation and moderate-to-severe necrosis in epithelium of I/R rat as compared to sham control. The methanolic fruit extract of B. cerifera could attenuate the heightened MDA levels. I/R-induced renal injury was markedly diminished by administration of B. cerifera These results indicate that the methanolic fruit extract of B. cerifera attenuate renal damage after I/R injury of the kidney by potent antioxidant or free radical scavenging activity.

  3. The role of dietary acid load and mild metabolic acidosis in insulin resistance in humans.

    Science.gov (United States)

    Williams, Rebecca S; Kozan, Pinar; Samocha-Bonet, Dorit

    2016-05-01

    Type 2 diabetes is increasingly being recognised as a global health crisis (World Health Organisation). Insulin resistance is closely associated with obesity and precedes the development of type 2 diabetes. However, there is now increasing evidence to suggest that diet itself may independently be associated with type 2 diabetes risk. A diet with a high acid load (or high potential renal net acid load, PRAL) can result in a decrease in pH towards the lower end of the normal physiological range, which may in turn lead to the development of insulin resistance. Conversely, reducing dietary acid load (the so called 'alkaline diet') may be protective and prevent the onset of type 2 diabetes. Here, we explore the influence of dietary acid load on the development of mild metabolic acidosis and induction of insulin resistance. Whilst large prospective cohort studies link high dietary acid load or low serum bicarbonate with the development of type 2 diabetes, the effect of a diet with a low acid (or high alkaline) load remains unclear. Further interventional studies are required to investigate the influence of dietary composition on the body's acid/base balance, insulin resistance and incidence of type 2 diabetes. PMID:26363101

  4. PGI2 synthesis and excretion in dog kidney: evidence for renal PG compartmentalization

    Energy Technology Data Exchange (ETDEWEB)

    Boyd, R.M.; Nasjletti, A.; Heerdt, P.M.; Baer, P.G.

    1986-01-01

    To assess the concept of compartmentalization of renal prostaglandins (PG), we compared entry of PGE2 and the PGI2 metabolite 6-keto-PGF1 alpha into the renal vascular and tubular compartments, in sodium pentobarbital-anesthetized dogs. Renal arterial 6-keto-PGF1 alpha infusion increased both renal venous and urinary 6-keto-PGF1 alpha outflow. In contrast, renal arterial infusion of arachidonic acid (AA) or bradykinin (BK) increased renal venous 6-keto-PGF1 alpha outflow but had no effect on its urinary outflow. Both urinary and renal venous PGE2 outflows increased during AA or BK infusion. Ureteral stopped-flow studies revealed no postglomerular 6-keto-PGF1 alpha entry into tubular fluid. During renal arterial infusion of (3H)PGI2 and inulin, first-pass 3H clearance was 40% of inulin clearance; 35% of urinary 3H was 6-keto-PGF1 alpha, and two other urinary metabolites were found. During renal arterial infusion of (3H)6-keto-PGF1 alpha and inulin, first-pass 3H clearance was 150% of inulin clearance; 75% of urinary 3H was 6-keto-PGF1 alpha, and only one other metabolite was found. We conclude that in the dog PGE2 synthesized in the kidney enters directly into both the renal vascular and tubular compartments, but 6-keto-PGF1 alpha of renal origin enters directly into only the renal vascular compartment.

  5. Renal failure in Yemen.

    Science.gov (United States)

    Al-Rohani, M

    2004-01-01

    Renal failure remains a serious cause of mortality in Yemen. Our region has 1.25 million population and our hospital is the central hospital, which has a nephrology department and performs dialysis for the region. Between January 1998 and December 2002, we admitted 547 patients; including children, with acute renal failure (ARF) and chronic renal failure (CRF). CRF was observed in 400 patients, an incidence of 64 per million per year and a prevalence of 320 per million. ARF occurred in 147 persons with an incidence of 23.5 per million per year and a prevalence of 117.5 patients per million. Of all patients, 72% were adults (age range, 20-60 years) with a male preponderance. As a tropical country, malaria (27.9%), diarrhea (13.6%), and other infectious diseases were the main causes. Next most common were obstructive diseases causing CRF and ARF (26.8% and 12.9%, respectively), mainly urolithiasis, Schistosomiasis, and prostatic enlargement. However the cause of CRF in 57.5% of patients was unknown as most persons presented late with end-stage disease (64.7%), requiring immediate intervention. Other causes, such as hepatorenal syndrome, snake bite, diabetes mellitus, and hypertension, showed low occurrence rates. Patients presented to the hospital mostly in severe uremia and without a clear history of prior medications. The major findings were vomiting, acidosis, and hypertension with serum creatinine values ranging between 2.8-45 mg/dL (mean value, 13.4 mg/dL). Anemia was observed in 80.4% of CRF versus 62.6% of ARF patients. Hypertension prevalence was 65.5% among CRF patients, of whom 25% were in hypertensive crisis, whereas among ARF the prevalence was only 26.5%. PMID:15350475

  6. Renal biomarkers in domestic species.

    Science.gov (United States)

    Hokamp, Jessica A; Nabity, Mary B

    2016-03-01

    Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies. PMID:26918420

  7. Modified tubularized incised plate urethroplasty

    Directory of Open Access Journals (Sweden)

    Shivaji Mane

    2013-01-01

    Full Text Available Aim: To share our experience of doing tubularized incised plate urethroplasty with modifications. Materials and Methods: This is a single surgeon personal series from 2004 to 2009. One hundred patients of distal hypospadias were subjected for Snodgrass urethroplasty with preputioplasty. The age range was 1 to 5 year with mean age of 2.7 years. Selection criteria were good urethral plate, without chordee and torsion needing complete degloving. Main technical modification from original Snodgrass procedure was spongioplasty, preputioplasty, and dorsal slit when inability to retract prepuce during surgery. Results: Average follow-up period is 23 months. Seven (7% patients developed fistula and one patient had complete preputial dehiscence. Phimosis developed in three (3% patients and required circumcision. Dorsal slit was required in seven patients. One patient developed meatal stenosis in postoperative period. All other patients are passing single urinary stream and have cosmesis that is acceptable. Conclusions: Modified tubularized incised plate urethroplasty with preputioplasty effectively gives cosmetically normal looking penis with low complications.

  8. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    Energy Technology Data Exchange (ETDEWEB)

    Van der Hauwaert, Cynthia; Savary, Grégoire [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Buob, David [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Leroy, Xavier; Aubert, Sébastien [Institut de Pathologie, Centre de Biologie Pathologie Génétique, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); Flamand, Vincent [Service d' Urologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Hennino, Marie-Flore [EA4483, Université de Lille 2, Faculté de Médecine de Lille, Pôle Recherche, 59045 Lille (France); Service de Néphrologie, Hôpital Huriez, Centre Hospitalier Régional Universitaire de Lille, 59037 Lille (France); Perrais, Michaël [Institut National de la Santé et de la Recherche Médicale, UMR837, Centre de Recherche Jean-Pierre Aubert, Equipe 5, 59045 Lille (France); and others

    2014-09-15

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue.

  9. Expression profiles of genes involved in xenobiotic metabolism and disposition in human renal tissues and renal cell models

    International Nuclear Information System (INIS)

    Numerous xenobiotics have been shown to be harmful for the kidney. Thus, to improve our knowledge of the cellular processing of these nephrotoxic compounds, we evaluated, by real-time PCR, the mRNA expression level of 377 genes encoding xenobiotic-metabolizing enzymes (XMEs), transporters, as well as nuclear receptors and transcription factors that coordinate their expression in eight normal human renal cortical tissues. Additionally, since several renal in vitro models are commonly used in pharmacological and toxicological studies, we investigated their metabolic capacities and compared them with those of renal tissues. The same set of genes was thus investigated in HEK293 and HK2 immortalized cell lines in commercial primary cultures of epithelial renal cells and in proximal tubular cell primary cultures. Altogether, our data offers a comprehensive description of kidney ability to process xenobiotics. Moreover, by hierarchical clustering, we observed large variations in gene expression profiles between renal cell lines and renal tissues. Primary cultures of proximal tubular epithelial cells exhibited the highest similarities with renal tissue in terms of transcript profiling. Moreover, compared to other renal cell models, Tacrolimus dose dependent toxic effects were lower in proximal tubular cell primary cultures that display the highest metabolism and disposition capacity. Therefore, primary cultures appear to be the most relevant in vitro model for investigating the metabolism and bioactivation of nephrotoxic compounds and for toxicological and pharmacological studies. - Highlights: • Renal proximal tubular (PT) cells are highly sensitive to xenobiotics. • Expression of genes involved in xenobiotic disposition was measured. • PT cells exhibited the highest similarities with renal tissue

  10. Ileal bladder substitute: antireflux nipple or afferent tubular segment?

    Science.gov (United States)

    Studer, U E; Spiegel, T; Casanova, G A; Springer, J; Gerber, E; Ackermann, D K; Gurtner, F; Zingg, E J

    1991-01-01

    Spheroidal bladder substitutes made from double-folded ileal segments, similar to Goodwin's cup-patch technique, are devoid of major coordinated wall contractions. This, together with the reservoir's direct anastomosis to the membranous urethra, prevents major intraluminal pressure peaks and assures a residue-free voiding of sterile urine. In order to determine whether, under these conditions, an afferent tubular isoperistaltic ileal segment of 20-cm length protects the upper urinary tract as efficiently as an antireflux nipple, 60 male patients who were subjected to radical cystectomy were prospectively randomised to groups in which a bladder substitute was formed together with either of these 2 antireflux devices. An analysis of the results obtained in 20 patients from each group who could be followed for more than 1 year (median observation time 30 and 36 months) showed no differences between the groups in metabolic disturbances, kidney size, reservoir capacity, diurnal and nocturnal urinary continence, the incidence of urinary tract infection or episodes of acute pyelonephritis. Later than 1 year postoperatively, intravenous urograms of the renoureteral units of 25% of the patients with antireflux nipples showed persistent but generally slight dilatation of the upper urinary tracts. This observation was significantly more frequent than it was in patients with afferent tubular segments. Urodynamic and radiographic studies showed that the competence of the antireflux nipples was secured by the raised surrounding intravesical pressure. This, however, also resulted in a transient functional obstruction, and a gradual rise of the basal pressure in the upper urinary tracts was recorded. In patients with afferent ileal tubular segments, contrast medium could be forced upwards into the renal pelvis when the bladder substitutes were overfilled. However, despite raised intravesical pressures, peristalsis in the isoperistaltic afferent tubular segment gradually returned

  11. Acidosis slows electrical conduction through the atrio-ventricular node

    Directory of Open Access Journals (Sweden)

    Ashley Muir Nisbet

    2014-06-01

    Full Text Available Acidosis affects the mechanical and electrical activity of mammalian hearts but comparatively little is known about its effects on the function of the atrio-ventricular node (AVN. In this study, the electrical activity of the epicardial surface of the left ventricle of isolated Langendorff-perfused rabbit hearts was examined using optical methods. Perfusion with hypercapnic Tyrode’s solution (20% CO2, pH 6.7 increased the time of earliest activation (Tact from 100.5+7.9 to 166.1+7.2ms (n=8 at a pacing cycle length (PCL of 300ms (37oC. Tact increased at shorter PCL, and the hypercapnic solution prolonged Tact further: at 150ms PCL, Tact was prolonged from 131.0+5.2 to 174.9+16.3ms. 2:1 AVN block was common at shorter cycle lengths. Atrial and ventricular conduction times were not significantly affected by the hypercapnic solution suggesting that the increased delay originated in the AVN. Isolated right atrial preparations were superfused with Tyrode’s solutions at pH 7.4 (control, 6.8 and 6.3. Low pH prolonged the atrial-Hisian (AH interval, the effective and functional refractory periods and Wenckebach cycle length significantly. Complete AVN block occurred in 6 out of 9 preparations. Optical imaging of conduction at the AV junction revealed increased conduction delay in the region of the AVN, with less marked effects in atrial and ventricular tissue. Thus acidosis can dramatically prolong the AVN delay, and in combination with short cycle lengths, this can cause partial or complete AVN block and is therefore implicated in the development of brady-arrhythmias in conditions of local or systemic acidosis.

  12. Postoperative metabolic acidosis following the minimally invasive radiofrequency maze procedure

    Directory of Open Access Journals (Sweden)

    Raymond Patrick Hom

    2016-01-01

    Full Text Available Purpose: Atrial fibrillation (AF is the most common arrhythmia treated in the world. While medical treatment with antiarrhythmic drugs remains the primary treatment modality, symptomatic refractory AF often requires treatment with a catheter or surgical ablation. One minimally invasive therapy is the Mini-Maze procedure, which utilizes epicardial radiofrequency ablation via a subxiphoid approach to rid the heart of arrhythmogenic atrial foci without a median sternotomy or cardiopulmonary bypass. The goal of this retrospective cohort study was to identify clinical factors associated with metabolic acidosis following the Mini-Maze procedure. Materials and Methods: After Institutional Review Board approval, we studied patients undergoing the Mini-Maze procedure, off-pump coronary artery bypass grafting or patients conventional Cox-Maze on cardiopulmonary bypass. The first base deficit value obtained in the Intensive Care Unit was used as a measure of metabolic acidosis. Using logistic regression with Akaike information criteria, we analyzed preoperative, intraoperative, and postoperative data to determine the factors associated with changes in base deficit. Results: A multivariable model using stepwise selection demonstrated that diabetes mellitus and weight were associated with a decrease in the base deficit by 2.87 mEq/L (95% CI: −5.55-−0.19 and 0.04 mEq/L (95%CI: −0.08, 0.004, respectively. Furthermore, creatinine was associated with a 1.57 mEq/L (95% CI: 0.14, 2.99 increase in the base deficit. Conclusion: The Mini-Maze procedure was not associated with postoperative metabolic acidosis. Instead, nondiabetic patients and patients with higher creatinine were associated with greater base deficits after undergoing cardiac surgery.

  13. A Fatal Case of Metformin-associated Lactic Acidosis.

    Science.gov (United States)

    Ozeki, Toshikazu; Kawato, Rui; Watanabe, Mitsuru; Minatoguchi, Shun; Murai, Yukari; Ryuge, Akihiro; Takasugi, Koji; Hamada, Takuya; Oyama, Yukako; Nomura, Atsushi; Tomino, Tatsuhito; Shimizu, Hideaki; Fujita, Yoshiro

    2016-01-01

    A 72-year-old woman with a history of type 2 diabetes mellitus was brought to the ER with metformin-associated lactic acidosis. She received continuous hemofiltration and hemodialysis, but the laboratory analyses showed no improvement. She died 11 hours after admission. Metformin is minimally bound to proteins and is readily dialyzable, but a prolonged period of dialysis is required, because metformin has a very large distribution volume and is distributed to multiple compartments. The peak blood metformin level was 432 mg/L in this case, which is one of the highest metformin concentrations ever reported, and eight hours of hemodialysis were not sufficient to reduce the serum level.

  14. Long-term observations on tubular and glomerular function in cadmium-exposed persons

    Energy Technology Data Exchange (ETDEWEB)

    Piscator, M.

    1984-03-01

    Four groups of cadmium-exposed persons, from different workplaces and with different types of exposure, have been followed for periods of 9-20 years. In one group the total observation time is over 30 years, since they were included in Friberg's original study. The studies include determination of inulin or creatinine clearance, protein excretion and specific indicators of renal tubular dysfunction. The results indicate that once tubular dysfunction is established, it is irreversible, even when it is minor. In some persons it was noted that the development of renal dysfunction seemed to be a multistage process. The initial stage is characterized by an increased excretion of low molecular weight proteins like ..beta../sub 2/-microglobulin and ribonuclease. After a period of several years with no or low exposure, there was a relatively sharp increase in excretion of total proteins and albumin and a decrease in glomerular filtration rate. This is interpreted as being the result of further increases in renal concentration of cadmium and in spread of cadmium along the tubules. Metallothionein absorption in the tubules, its catabolism and synthesis must play an important role for the development and progress of the tubular dysfunction. It was not possible to show that a decrease in glomerular filtration rate occurs before low molecular weight proteinuria. 15 references, 2 figures, 2 tables.

  15. Tubular stabilizer bars – calculations and construction

    Directory of Open Access Journals (Sweden)

    Adam-Markus WITTEK

    2011-01-01

    Full Text Available The article outlines the calculation methods for tubular stabilizer bars. Modern technological and structural solutions in contemporary cars are reflected also in the construction, selection and manufacturing of tubular stabilizer bars. A proper construction and the selection of parameters influence the strength properties, the weight, durability and reliability as well as the selection of an appropriate production method.

  16. Tubular lining material for pipelines having bends

    Energy Technology Data Exchange (ETDEWEB)

    Moringa, A.; Sakaguchi, Y.; Hyodo, M.; Yagi, I.

    1987-03-24

    A tubular lining material for pipelines having bends or curved portions comprises a tubular textile jacket made of warps and wefts woven in a tubular form overlaid with a coating of a flexible synthetic resin. It is applicable onto the inner surface of a pipeline having bends or curved portions in such manner that the tubular lining material with a binder onto the inner surface thereof is inserted into the pipeline and allowed to advance within the pipeline, with or without the aid of a leading rope-like elongated element, while turning the tubular lining material inside out under fluid pressure. In this manner the tubular lining material is applied onto the inner surface of the pipeline with the binder being interposed between the pipeline and the tubular lining material. The lining material is characterized in that a part of all of the warps are comprised of an elastic yarn around which, over the full length thereof, a synthetic fiber yarn or yarns have been left-and/or right-handedly coiled. This tubular lining material is particularly suitable for lining a pipeline having an inner diameter of 25-200 mm and a plurality of bends, such as gas service pipelines or house pipelines, without occurrence of wrinkles in the lining material in a bend.

  17. 大黄素诱导人肾上皮HK-2细胞凋亡及内质网应激的介导作用%Induction of apoptosis in human renal tubular epithelial HK-2 cells by emodin and mediation of endoplasmic reticulum stress

    Institute of Scientific and Technical Information of China (English)

    关翠雯; 金晶; 朱少华; 王奕菲; 黄芝瑛

    2013-01-01

    Objective To investigate the induetion of apoptosis in human renal tubular epithelial HK-2 cells by emodin and whether endoplasmic reticulum (ER) stress is involved in its mechanism.Methods HK-2 cells were cultured and treated with various concentration of emodin at different time points.The cell viability was determined by MTT assay.The gene expression of glucose-regulated protein 78 (GRP78),CCAAT/enhancer-binding protein-homologous protein (CHOP),activating transcription factor 3 (ATF3),and X-box binding protein 1 splicing (XBP1s) was evaluated by quantitative real-time PCR.The protein expression of caspase-3,GRP78,CHOP,and eukaryotic initiation factor 2 alpha (eIF2α) was detected by Western blotting.Results The viability of HK-2 cells was decreased by emodin in a dose-dependent manner,and the apoptosis of the cells was associated with caspase-3 shear activation.The treatment with emodin in HK-2 cells caused the increase in eIF2α phosphorylation,XBP1 mRNA splicing,the gene expression of GRP78,CHOP,and ATF3,and the protein expression of GRP78 and CHOP.The pretreatment with 4-phenylbutyric acid and salubrinal significantly increased the viability of HK-2 cells,indicating the role of ER stress in emodin-induced apoptosis.Conclusion Emodin induces the apoptosis in HK-2 cells and ER stress is involved in emodin-induced apoptosis.%目的 研究大黄素诱导人肾小管上皮HK-2细胞凋亡的作用及其机制是否与内质网应激有关.方法 不同浓度大黄素处理HK-2细胞不同时间.MTT法检测细胞存活率,实时荧光定量PCR (RT-PCR)检测葡萄糖调节蛋白78 (GRP78)、CCAAT/增强子结合蛋白同源蛋白(CHOP)、转录激活因子3(ATF3)和X盒结合蛋白1(XBP1)的基因表达,Western blotting 法检测caspase-3、GRP78、CHOP、真核生物启动因子2α (eIF2α)的蛋白表达.结果 大黄素以浓度相关方式降低HK-2细胞存活率,诱导caspase-3剪切.RT-PCR检测表明,大黄素能诱导内质网相关基因GRP78

  18. Tubular inverse opal scaffolds for biomimetic vessels

    Science.gov (United States)

    Zhao, Ze; Wang, Jie; Lu, Jie; Yu, Yunru; Fu, Fanfan; Wang, Huan; Liu, Yuxiao; Zhao, Yuanjin; Gu, Zhongze

    2016-07-01

    There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially oriented elliptical pattern microstructures on their surfaces. It is demonstrated that these tailored tubular scaffolds can effectively make endothelial cells to form an integrated hollow tubular structure on their inner surface and induce smooth muscle cells to form a circumferential orientation on their outer surface. These features of our tubular scaffolds make them highly promising for the construction of biomimetic blood vessels.There is a clinical need for tissue-engineered blood vessels that can be used to replace or bypass damaged arteries. The success of such grafts depends strongly on their ability to mimic native arteries; however, currently available artificial vessels are restricted by their complex processing, controversial integrity, or uncontrollable cell location and orientation. Here, we present new tubular scaffolds with specific surface microstructures for structural vessel mimicry. The tubular scaffolds are fabricated by rotationally expanding three-dimensional tubular inverse opals that are replicated from colloidal crystal templates in capillaries. Because of the ordered porous structure of the inverse opals, the expanded tubular scaffolds are imparted with circumferentially

  19. Effects of 1, 25 ( OH ) 2D3 on parathyroid hormone induced transdifferentiation and TGF-β1 expression in cultured human renal tubular epithelial cells%1,25(OH)2D3对甲状旁腺素诱导的肾小管上皮细胞转分化和TGF-β1的表达的影响

    Institute of Scientific and Technical Information of China (English)

    李晓东; 李英; 丁新国; 高山林; 郭志军

    2012-01-01

    AIM: To explore the effects of 1, 25 (OH)2D3 on parathyroid hormone (PTH) induced transdif-ferentiation and TGF-p, expression in cultured human renal tubular epithelial cells. METHODS: HK-2 cells were cultured in DMEM/F12 medium supplemented with 50 mL/L FBS. Cells were divided into three groups. (1) Control group: without PTH or 1, 25(OH)2D3; (2) PTH group: 10-10mol/LPTH; (3) PTH and 1, 25(OH)2D3 group: 10-10 mol/L PTH and different concentrations of 1, 25(OH)2D3 (10-10, 10-9, 10-8 and 10-7 mol/L). The gene expressions of a-SMA and TGF-p, were detected by semi-quantitative RT-PCR. The protein expressions of a-SMA and TGF-p, were detected by Western blot. Immunocytochemisty (ICC) was used to measure the expression of a-SMA in HK-2. ELISA was used to assay the level of TGF-p, in the supernatant. RESULTS: The gene expressions of a-SMA and TGF-p, in PTH group were significantly higher than those in control group (P<0.05). In contrast, they were significantly lower in PTH and 1, 25(OH)2D3 group than those in PTH group ( P < 0. 05). Western blot results showed α-SMA could not be detected in normal HK-2 cells, which could be detected in PTH group. TGF-p, protein expression in PTH group was higher than that in control group. In PTH and 1, 25(OH)2D3 group, a-SMA and TGF-p, protein expressions were significantly lower than those in PTH group ( P <0.05). ICC results showed that a-SMA was hardly expressed in cells of control group. However, positive expression of a-SMA could be seen in many cells in PTH group. In PTH and 1, 25(OH)2D3 group, the cells of a-SMA positive expressed were significantly less than those in PTH group (P<0.05). ELISA results showed that the level of TGF-p, in the supernatant of PTH group was higher than that in control group, which was also higher than that in PTH and 1, 25 (OH)2D3 group (P<0. 05). CONCLUSION; 1, 25(OH)2D3 can attenuate PTH-induced transdifferentiation and TGF-p, expression in cultured human renal tubular epithelial cells

  20. Renal histology in polycystic kidney disease with incipient and advanced renal failure.

    Science.gov (United States)

    Zeier, M; Fehrenbach, P; Geberth, S; Möhring, K; Waldherr, R; Ritz, E

    1992-11-01

    Renal specimens were obtained at surgery or postmortem from patients with autosomal dominant polycystic kidney disease (ADPKD). Patients had either serum creatinine (SCr) below 350 mumol/liter (N = 12) or terminal renal failure (N = 50). Specimens were examined by two independent observers using a carefully validated score system. Mean glomerular diameters were similar in ADPKD patients with early renal failure (176 +/- 38 microns) and in victims of traffic accidents (177 +/- 23 microns), while they were significantly greater in diabetics with comparable renal function (205 +/- 16 microns). Glomerular diameters in ADPKD patients with terminal renal failure (191 +/- 45 microns) and with early renal failure were not significantly different. On average, 29% of glomeruli (17 to 62) were globally sclerosed in early renal failure, and 49% (19 to 93) in terminal renal failure. The proportion of glomeruli with segmental sclerosis was less than 4% in both groups. Marked vascular sclerosis, interstitial fibrosis, and tubular atrophy were present in early renal failure, and even more so in terminal renal failure. Interstitial infiltrates were scarce and consisted mainly of CD4 positive lymphocytes and CD68 positive macrophages. Immunestaining with monoclonal renin antibodies showed an increased juxtaglomerular index and expression of renin by arterioles adjacent to cysts, as well as by cyst wall epithelia. The data show more severe vascular and interstitial, but not glomerular, changes in ADPKD with advanced as compared to early renal failure.

  1. A perspective on Serum Lactic acid, Lactic Acidosis in a Critical Care Unit

    Directory of Open Access Journals (Sweden)

    Agela A.Elbadri

    2013-06-01

    Full Text Available Breast cancer is one of the major surgical problems encountered in Libya. Lactic acidosis is a universal complication in breast cancer patients and can be considered a possible prognostic marker. Therefore, it will be beneficial to correctly understand and review the biochemistry underlying lactic acidosis and its possible significance as a prognostic marker in critical care patients, including breast cancer.

  2. Metformin and lactic acidosis : cause or coincidence? A review of case reports

    NARCIS (Netherlands)

    Stades, AME; Heikens, JT; Erkelens, DW; Holleman, F; Hoekstra, JBL

    2004-01-01

    Objective. Metformin has been associated with the serious side-effect lactic acidosis. However, it remains unclear whether the use of metformin was a cause or a coincidence in lactic acidosis. Design. A literature search of the Index Medicus (1959-66) and of the databases Embase, Medline, Medline Ex

  3. Ruminal Acidosis in Feedlot: From Aetiology to Prevention

    Directory of Open Access Journals (Sweden)

    Joaquín Hernández

    2014-01-01

    Full Text Available Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored.

  4. Ruminal acidosis in feedlot: from aetiology to prevention.

    Science.gov (United States)

    Hernández, Joaquín; Benedito, José Luis; Abuelo, Angel; Castillo, Cristina

    2014-01-01

    Acute ruminal acidosis is a metabolic status defined by decreased blood pH and bicarbonate, caused by overproduction of ruminal D-lactate. It will appear when animals ingest excessive amount of nonstructural carbohydrates with low neutral detergent fiber. Animals will show ruminal hypotony/atony with hydrorumen and a typical parakeratosis-rumenitis liver abscess complex, associated with a plethora of systemic manifestations such as diarrhea and dehydration, liver abscesses, infections of the lung, the heart, and/or the kidney, and laminitis, as well as neurologic symptoms due to both cerebrocortical necrosis and the direct effect of D-lactate on neurons. In feedlots, warning signs include decrease in chewing activity, weight, and dry matter intake and increase in laminitis and diarrhea prevalence. The prognosis is quite variable. Treatment will be based on the control of systemic acidosis and dehydration. Prevention is the most important tool and will require normalization of ruminal pH and microbiota. Appropriate feeding strategies are essential and involve changing the dietary composition to increase neutral detergent fiber content and greater particle size and length. Appropriate grain processing can control the fermentation rate while additives such as prebiotics or probiotics can help to stabilize the ruminal environment. Immunization against producers of D-lactate is being explored.

  5. Rumen microbial and fermentation characteristics are affected differently by bacterial probiotic supplementation during induced lactic and subacute acidosis in sheep

    OpenAIRE

    Lettat Abderzak; Nozière Pierre; Silberberg Mathieu; Morgavi Diego P; Berger Claudette; Martin Cécile

    2012-01-01

    Abstract Background Ruminal disbiosis induced by feeding is the cause of ruminal acidosis, a digestive disorder prevalent in high-producing ruminants. Because probiotic microorganisms can modulate the gastrointestinal microbiota, propionibacteria- and lactobacilli-based probiotics were tested for their effectiveness in preventing different forms of acidosis. Results Lactic acidosis, butyric and propionic subacute ruminal acidosis (SARA) were induced by feed chalenges in three groups of four w...

  6. Acidosis láctica grave asociada a intoxicación por metformina Severe lactic acidosis associated to metformin intoxication

    Directory of Open Access Journals (Sweden)

    M. S. Holanda Peña

    2007-02-01

    Full Text Available La metformina es una biguanida ampliamente utilizada en el tratamiento de la diabetes mellitus tipo II. Entre los efectos secundarios derivados de su empleo destaca por su baja frecuencia de presentación pero potencial gravedad la acidosis láctica. El diagnóstico de la misma se basa generalmente en la coexistencia de la acidosis láctica en un paciente en tratamiento con metformina con uno o mas factores de riesgo para la presentación de la misma. El desarrollo de acidosis láctica en relación con el tratamiento con metformina conlleva una mortalidad que oscila entre 50-80%.Metformin is a biguanide extensively used in the treatment of type II diabetes mellitus. Between the nocive effects of the metformin emphasizes tha lactic acidosis because of its low frecuency but potential severity. The diagnosis of the poisoning due to metformin is based on the coexistence of lactic acidosis and one or more of the risk factors. The development of lactic acidosis in metformin poisoning is associated to a range of 50-80% of mortality.

  7. Diagnosing vascular causes of renal failure.

    Science.gov (United States)

    Abuelo, J G

    1995-10-15

    The incidence of renal failure due to vascular diseases is increasing. Two reasons for this are the epidemic of atherosclerotic vascular disease in the aging population and the widespread use of vasoactive drugs that can adversely affect renal function. These vascular causes of renal failure include vasomotor disorders such as that associated with nonsteroidal antiinflammatory drugs, small-vessel diseases such as cholesterol crystal embolization, and large-vessel diseases such as renal artery stenosis. These causes of azotemia are less familiar to physicians than more classic causes, such as acute tubular necrosis, and are less likely to be recognized in their early stages. This article describes the various vascular diseases that impair renal function and outlines the steps necessary to identify them. Although some of these conditions, such as renal artery stenosis, can gradually impair function, the vascular causes of acute renal failure are emphasized in this article. Because the vasculitides primarily cause renal failure through secondary glomerulonephritis, they are mentioned only briefly. Extensive testing is rarely necessary because the cause is usually suspected through syndrome recognition. The diagnosis can then be confirmed by the results of one or two additional tests or by improved renal function after treatment.

  8. Purinergic Signalling in Inflammatory Renal Disease

    Directory of Open Access Journals (Sweden)

    Nishkantha eArulkumaran

    2013-07-01

    Full Text Available Extracellular purines have a role in renal physiology and adaption to inflammation. However, inflammatory renal disease may be mediated by extracellular purines, resulting in renal injury. The role of purinergic signalling is dependent on the concentrations of extracellular purines. Low basal levels of purines are important in normal homeostasis and growth. Concentrations of extracellular purines are significantly elevated during inflammation and mediate either an adaptive role or propagate local inflammation. Adenosine signalling mediates alterations in regional renal blood flow by regulation of the renal microcirculation, tubulo-glomerular feedback, and tubular transport of sodium and water. Increased extracellular ATP and renal P2 receptor-mediated inflammation are associated with various renal diseases, including hypertension, diabetic nephropathy, and glomerulonephritis. Experimental data suggests P2 receptor deficiency or receptor antagonism is associated with amelioration of antibody-mediated nephritis, suggesting a pathogenic (rather than adaptive role of purinergic signalling. We discuss the role of extracellular nucleotides in adaptation to ischaemic renal injury and in the pathogenesis of inflammatory renal disease.

  9. Renal perfusion scintiscan

    Science.gov (United States)

    Renal perfusion scintigraphy; Radionuclide renal perfusion scan; Perfusion scintiscan - renal; Scintiscan - renal perfusion ... supply the kidneys. This is a condition called renal artery stenosis. Significant renal artery stenosis may be ...

  10. Tubular bioreactor and its application; Tubular bioreactor to sono tekiyo

    Energy Technology Data Exchange (ETDEWEB)

    Endo, I.; Nagamune, T. [The University of Tokyo, Tokyo (Japan). Faculty of Engineering; Yuki, K. [Nikka Whisky Distilling Co. Ltd. Tokyo (Japan); Inaba, H. [Sumitomo Heavy Industries, Ltd., Tokyo (Japan)

    1994-09-05

    The loop type tubular bioreactor (TBR) was developed where biocatalysts are trapped in the reactor by membrane module. A UF membrane or MF membrane and crossflow filtration were adopted for the membrane module, and the reactor loop was composed of four membrane modules. The reactor was operated at 2-4 m/s in membrane surface velocity and 300-400 kPa in filtration pressure. As the result of the high-density culture of lactic acid bacteria and yeast, a biomass concentration was more than 10 times that in batch culture, suggesting the remarkable enhancement of a production efficiency. As the result of the continuous fermentation of cider, the fast fermentation more than 60 times that in conventional ones was obtained together with the same quality as conventional ones. Such a fast fermentation was probably achieved by yeast suspended in the fermenter of TBR, by yeast hardly affected physico-chemically as compared with immobilized reactors, and by small effect of mass transfer on reaction systems. 4 refs., 6 figs.

  11. Evaluation of allograft perfusion by radionuclide first-pass study in renal failure following renal transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Baillet, G.; Ballarin, J.; Urdaneta, N.; Campos, H.; Vernejoul, P. de; Fermanian, J.; Kellershohn, C.; Kreis, H.

    1986-04-01

    To assess the diagnostic value of indices measured on a first-pass curve, we performed 72 radionuclide renal first-pass studies (RFP) in 21 patients during the early weeks following renal allograft transplantation. The diagnosis was based on standard clinical and biochemical data and on fine needle aspiration biopsy (FNAB) of the transplant. Aortic and renal first-pass curves were filtered using a true low-pass filter and five different indices of renal perfusion were computed, using formulae from the literature. Statistical analysis performed on the aortic and renal indices indicated excellent reproducibility of the isotopic study. Although renal indices presented a rather large scatter, they all discriminated well between normal and rejection. Three indices have a particularly good diagnostic value. In the discrimination between rejection and Acute Tubular Necrosis (ATN), only one index gave satisfying results. The indices, however, indicate that there are probably ATN with an alternation of renal perfusion and rejection episodes where perfusion is almost intact. We conclude that radionuclide first-pass study allows accurate and reproducible quantitation of renal allograft perfusion. The measured parameters are helpful to follow up the course of a post-transplantation renal failure episode and to gain more insight into renal ischemia following transplantation.

  12. Protocol biopsies for renal transplantation

    Directory of Open Access Journals (Sweden)

    Rush David

    2010-01-01

    Full Text Available Protocol biopsies in renal transplantation are those that are procured at predetermined times post renal transplantation, regardless of renal function. These biopsies have been useful to study the natural history of the transplanted kidney as they have detected unexpected - i.e. "subclinical" pathology. The most significant subclinical pathologies that have been detected with protocol biopsies have been acute lesions, such as cellular and antibody mediated rejection, and chronic lesions, such as interstitial fibrosis and tubular atrophy, and transplant glomerulopathy. The potential benefit of early recognition of the above lesions is that their early treatment may result in improved long-term outcomes. Conversely, the identification of normal histology on a protocol biopsy, may inform us about the safety of reduction in overall immunosuppression. Our centre, as well as others, is attempting to develop non-invasive methods of immune monitoring of renal transplant patients. However, we believe that until such methods have been developed and validated, the protocol biopsy will remain an indispensable tool for the complete care of renal transplant patients.

  13. Marble brain syndrome: osteopetrosis, renal acidosis and calcification of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Jacquemin, C.; Mullaney, P.; Svedberg, E. [King Khaled Eye Specialist Hospital, Riyadh (Saudi Arabia)

    1998-10-01

    Cerebral calcification in children is frequently associated with systemic metabolic disease. We present a case of ``marble brain syntrome``, which showed this abnormality. (orig.) (orig.) With 2 figs.

  14. Iatrogenic Digital Compromise with Tubular Dressings

    Directory of Open Access Journals (Sweden)

    Corre, Kenneth A

    2009-08-01

    Full Text Available Objective: This case report describes a digit amputation resulting from an improperly applied tubular dressing. The safe application of digital tubular dressings, and the rationale behind it, is detailed to raise emergency physician (EP awareness.Methods: We present a case report of a recent iatrogenic-induced digit ischemia caused by improperly applied tube gauze. We review the literature on the subject and the likely sources of poor outcomes presented. The proper application of tubular gauze dressings is then outlined.Conclusion: EPs and emergency department personnel must be educated on the safe application of tubular gauze dressings to avoid dire outcomes associated with improper applications.[WestJEM. 2009;10:190-192.

  15. Acute starvation in pregnancy: a cause of severe metabolic acidosis.

    Science.gov (United States)

    Patel, A; Felstead, D; Doraiswami, M; Stocks, G M; Waheed, U

    2011-07-01

    We report a case of starvation-induced metabolic ketoacidosis in a previously healthy 29-year-old, nulliparous woman at 32 weeks of gestation. She was admitted to hospital with mild preeclampsia associated with persistent nausea and vomiting that progressed to severe preeclampsia requiring urgent control of hypertension before caesarean delivery. Prolonged and severe vomiting limited oral caloric intake and led to starvation ketoacidosis, characterised by ketonuria and a raised anion gap metabolic acidosis that required intensive care support. Despite significant metabolic derangement the patient appeared clinically well. Intravascular volume was replenished. Fluid restriction used as part of our preeclampsia treatment regimen delayed the therapeutic administration of sufficient dextrose, which rapidly corrected her metabolic derangement when commenced after delivery. Electrolyte supplementation was given to prevent re-feeding syndrome. Both mother and baby were discharged without sequelae.

  16. Thermal CFD Analysis of Tubular Light Guides

    OpenAIRE

    Ondřej Šikula; Jitka Mohelníková; Josef Plášek

    2013-01-01

    Tubular light guides are applicable for daylighting of windowless areas in buildings. Despite their many positive indoor climate aspects they can also present some problems with heat losses and condensation. A computer CFD model focused on the evaluation of temperature distribution and air flow inside tubular light guides of different dimensions was studied. The physical model of the tested light guides of lengths more than 0.60 m proves shows that Rayleigh numbers are adequate for a turbulen...

  17. Tubular localization and expressional dynamics of aquaporins in the kidney of seawater-challenged Atlantic salmon

    DEFF Research Database (Denmark)

    Engelund, Morten Buch; Madsen, Steffen S

    2015-01-01

    in renal function from filtration towards secretion. We localized aquaporins (Aqp) in Atlantic salmon renal tubular segments by immunohistochemistry and monitored their expressional dynamics using RT-PCR and immunoblotting. Three aquaporins: Aqpa1aa, Aqp1ab and Aqp8b and two aquaglyceroporins Aqp3a and Aqp....... Aqp10b was expressed apically and along the lateral membrane. Aqp8b was mainly basolateral and Aqp1ab was located in sub-apical intracellular compartments. mRNAs of aqp8b and aqp10b were higher in FW smolts compared to FW parr, whereas the opposite was true for aqp1aa. Aqp mRNA levels changed...... in response to both SW and sham transfer. Protein levels, however, were stable for most paralogs. In conclusion, aquaporins are abundant in salmon proximal renal tubules and may participate in water secretion and thus urine modification as suggested for other vertebrates. Further studies should seek to couple...

  18. 78 FR 37584 - U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United...

    Science.gov (United States)

    2013-06-21

    ... Employment and Training Administration U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United States Steel Corporation, Mckeesport, Pennsylvania; Notice of Amended... workers of U.S. Steel Tubular Products, McKeesport Tubular Operations Division, a subsidiary of...

  19. Risk factors for mortality in children with diabetic keto acidosis from developing countries

    Institute of Scientific and Technical Information of China (English)

    Varadarajan; Poovazhagi

    2014-01-01

    Diabetic keto acidosis(DKA) is the major cause for mortality in children with Diabetes mellitus(DM). With increasing incidence of type 1 DM worldwide, there is an absolute increase of DM among children between 0-14 year age group and overall incidence among less than 30 years remain the same. This shift towards younger age group is more of concern especially in developing countries where mortality in DKA is alarmingly high. Prior to the era of insulin, DKA was associated with 100% mortality and subsequently mortality rates have come down and is now, 0.15%-0.31% in developed countries. However the scenario in developing countries like India, Pakistan, and Bangladesh are very different and mortality is still high in children with DKA. Prospective studies on DKA in children are lacking in developing countries. Literature on DKA related mortality are based on retrospective studies and are very recent from countries like India, Pakistan and Bangladesh. There exists an urgent need to understand the differences between developed and developing countries with respect to mortality rates and factors associated with increased mortality in children with DKA. Higher mortality rates, increased incidence of cerebral edema, sepsis, shock and renal failure have been identified among DKA in children from developing countries.Root cause for all these complications and increased mortality in DKA could be delayed diagnosis in children from developing countries. This necessitates creating awareness among parents, public and physicians by health education to identify symptoms of DM/DKA in children, in order to decrease mortality in DKA. Based on past experience in Parma, Italy it is possible to prevent occurrence of DKA both in new onset DM and in children with established DM, by simple interventions to increase awareness among public and physicians.

  20. Markers of acidosis and stress in a sprint versus a conducted electrical weapon.

    Science.gov (United States)

    Ho, Jeffrey D; Dawes, Donald M; Nystrom, Paul C; Collins, Donal P; Nelson, Rebecca S; Moore, Johanna C; Miner, James R

    2013-12-10

    Both profound acidosis and catecholamine excess have been proposed as underlying physiologic derangements in subjects at high risk for arrest related death (ARD). In this study, the objective was to determine a level of physical exertion that is "equivalent" in terms of levels of acidosis and catecholamines to a "standard" TASER X26 exposure. Data were collected on subjects who underwent a 5-s TASER X26 exposure or a sprint of variable distances during a law enforcement training exercise. Our results show that levels of acidosis and catecholamines are less among subjects exposed to the TASER X26 than among subjects who sprinted 20 yards or more. PMID:24314505

  1. Mixed organic solvents induce renal injury in rats.

    Directory of Open Access Journals (Sweden)

    Weisong Qin

    Full Text Available To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF in the ratio of 2:2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5-6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16 and 25% (4/16, respectively. Urinary N-Acetyl-β-(D-Glucosaminidase (NAG activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM. Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli.

  2. The use of lithium clearance measurements as an estimate of glomerulo-tubular function.

    Science.gov (United States)

    Whiting, P H

    1999-01-01

    Lithium clearance measurements are based on the observation that lithium undergoes isoosmotic reabsorption in the proximal renal tubule to the same extent as salt and water, but undergoes neither reabsorption nor secretion elsewhere in the nephron. Consequently, lithium clearance values estimate the delivery of isoosmotic fluid to the loop of Henle and hence provide an assessment of proximal tubular reabsorption of isoosmotic fluid. If sodium clearance and urinary flow rate are also measured, then this allows the derivation of a number of parameters relating to both the absolute and relative renal handling of isoosmotic fluid in the proximal and distal regions of the kidney. Consequently, lithium clearance techniques can be used in both experimental and clinical studies to evaluate glomerulo-tubular function and provide information regarding the handling of sodium and water by the proximal and distal nephron in both health and disease. The use of lithium clearance measurements in the assessment of glomerulo-tubular function in patients treated with rIL2 for colorectal cancer is described and its application to both drug-induced toxicity and other disease states discussed.

  3. The swan-neck lesion: proximal tubular adaptation to oxidative stress in nephropathic cystinosis.

    Science.gov (United States)

    Galarreta, Carolina I; Forbes, Michael S; Thornhill, Barbara A; Antignac, Corinne; Gubler, Marie-Claire; Nevo, Nathalie; Murphy, Michael P; Chevalier, Robert L

    2015-05-15

    Cystinosis is an inherited disorder resulting from a mutation in the CTNS gene, causing progressive proximal tubular cell flattening, the so-called swan-neck lesion (SNL), and eventual renal failure. To determine the role of oxidative stress in cystinosis, histologic sections of kidneys from C57BL/6 Ctns(-/-) and wild-type mice were examined by immunohistochemistry and morphometry from 1 wk to 20 mo of age. Additional mice were treated from 1 to 6 mo with vehicle or mitoquinone (MitoQ), an antioxidant targeted to mitochondria. The leading edge of the SNL lost mitochondria and superoxide production, and became surrounded by a thickened tubular basement membrane. Progression of the SNL as determined by staining with lectin from Lotus tetragonolobus accelerated after 3 mo, but was delayed by treatment with MitoQ (38 ± 4% vs. 28 ± 1%, P injury molecule-1 (KIM-1) nor cell death was observed. After 9 mo, clusters of proximal tubules exhibited localized oxidative stress (4-hydroxynonenal binding), expressed KIM-1, and underwent apoptosis, leading to the formation of atubular glomeruli and accumulation of interstitial collagen. We conclude that nephron integrity is initially maintained in the Ctns(-/-) mouse by adaptive flattening of cells of the SNL through loss of mitochondria, upregulation of transgelin, and thickened basement membrane. This adaptation ultimately fails in adulthood, with proximal tubular disruption, formation of atubular glomeruli, and renal failure. Antioxidant treatment targeted to mitochondria delays initiation of the SNL, and may provide therapeutic benefit in children with cystinosis. PMID:25694483

  4. NLRP3炎性小体在高糖诱导大鼠肾小管上皮细胞炎性反应中的变化%The changes of NLRP3 inflammasome in the high glucose-induced inflammatory response of rat renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    赵宏宇; 李荣山; 于为民; 乔玉峰; 王卫; 冯娟; 郝洁芦; 邵珊

    2013-01-01

    Objective To investigate the expressions of NLRP3 inflammasome and inflammatory factor protein in the high glucose-induced rat renal tubular epithelial cells (NRK-52E) and to make clear its effect on inflammatory damage through transfection of small interfering RNA (siRNA).Methods (1)The NRK-52E cells were divided into control group and high glucose (HG) 6,12,24 and 48 h groups.Western blotting was adopted to detect the protein expressions of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1.(2) NRK-52E cells were divided into the control group,high glucose group,HG+NLRP3-siRNA group,and HG+irrespective siRNA group on the basis of the result of above-mentioned tests.After 48 h fostering,the expression of NLRP3 mRNA was detected by RT-PCR,and the expressions of NLRP3,ASC,IL-1β,IL-6,and TNF-a proteins were determined by Western blotting.Results (1) The expressions of NLRP3 and ASC were gradually increased,and the highest expression was in the 48 h group after stimulation by high glucose (P<0.05) ; the expression of caspase-1 was significantly higher than that in the control group (P<0.05).(2) Compared with the control group,the expressions of NLRP3,ASC,IL-1β,IL-6,and TNF-a proteins were significandy increased in the HG group (P < 0.05); these expressions in the HG + NLRP3-siRNA group were significantly decreased than those in the HG groups (P<0.05).Conclusion High glucose induces the activation of NLRP3 inflammasome in the NRK-52E cells,leading to the expression and release of its downstream inflammatory factors.It is assumed that the NLRP3 inflammasome may be involved in the high glucose-induced inflammatory damage in NRK-52E cells.%目的 观察高糖诱导大鼠肾小管上皮细胞(NRK-52E) NLRP3炎性小体及炎症因子蛋白的表达,并通过转染NLRP3特异性小干扰质粒(siRNA)明确NLRP3炎性小体是否参与其炎症损伤. 方法 (1)将NRK-52E细胞分为对照(NC)组及高糖(HG)6、12、24、48 h

  5. Effect of FUT8 on megalin and albumin over load - induced MCP expression in renal tubular epithelial cell%FUT8对megalin功能及白蛋白负荷致肾小管上皮细胞单核细胞趋化蛋白1表达的影响

    Institute of Scientific and Technical Information of China (English)

    王大鹏; 林洪丽; 郑美洁; 谢华; 沈楠; 孙艳玲

    2011-01-01

    [目的]探讨α1-6-岩藻糖基转移酶(α1-6-fucosyltransferase,FUT8)所催化的核心岩藻糖基化对低密度脂蛋白受体相关蛋白-2(LRP-2,meglain)内吞白蛋白功能和对白蛋白超负荷诱导的肾小管上皮细胞炎症的影响.[方法]用10 mg/mL的牛血清白蛋白(BSA)孵育HK-2细胞4 h建立白蛋白超负荷细胞模型,分别用FUT8siRNA或FUT8过表达载体转染,用流式细胞仪测定白蛋白的绑定和内吞以及megalin的核心岩藻糖基化水平.用免疫印迹、免疫沉淀和凝集素印迹方法测定单核细胞趋化蛋白-1(MCP-1)及megalin的蛋白表达,用单因素方差检验方法进行统计学处理.[结果]BSA的绑定和内吞有时间和浓度依赖性.BSA诱导后HK-2细胞FUT8、MCP-1明显升高.白蛋白超负荷条件下,FUT8过表达组细胞MCP-1表达水平明显高于BSA组.此外,FUT8的过表达显著提高megalin的核心岩藻糖基化水平及绑定和内吞白蛋白能力.沉默FUT8基因降低megalin的核心岩藻糖基化及绑定、内吞白蛋白能力,同时抑制MCP-1的升高,使其保持在正常表达水平.[结论]核心岩藻糖基化是megalin发挥白蛋白绑定和内吞功能的必需过程,抑制megalin蛋白合成后的核心岩藻糖基化修饰能够减轻蛋白超负荷诱导的肾小管上皮细胞炎症介质表达.%[Objective] To investigate the role of core fucosylation in megalin- mediated binding and endocytosis as well as its effect on albumin overload - induced renal tubular epithelia. [ Methods ] An albumin overload cell model of HK - 2 cell was constructed with 10 mg/mL BSA,and then FUT8siRNA or FUT8 over- expression vector was transfected into the cells. The binding and endocytosis of BSA and the core fucose on megalin were determined by flow - cytometry. The expression of MCP - 1 and megalin were detected with western blot, immunoprecipitation and lectin blot. Data were assessed by ANOVA analysis. [Results] Both of binding and endocytosis for BSA were time

  6. Parathyroid hormone-induced connective tissue growth factor expression in human renal proximal tubular epithelial cells requires NF-κB signaling pathway%甲状旁腺激素通过NF-κB诱导人近曲小管上皮细胞结缔组织生长因子表达

    Institute of Scientific and Technical Information of China (English)

    郭云珊; 袁伟杰; 张爱平; 丁尧海; 王艳侠

    2009-01-01

    目的 观察甲状旁腺激素(PTH)对人肾小管上皮细胞分泌结缔组织生长因子(CTGF)的影响,并探讨其信号传导通路及NF-κB在此过程中的作用.方法 应用荧光实时定量PCR、Western印迹技术,观察PTH诱导人近端肾小管上皮细胞系HK-2细胞CTGFmRNA和蛋白合成情况;从转录水平探讨PTH对CTGF基因启动子活性的调控作用.采用凝胶迁移实验(EMSA)技术检测PTH刺激HK-2细胞后NF-κB的DNA结合能力;NF-κB抑制剂PDTC阻断信号通路以明确PTH发挥作用的信号途径.结果 HK-2细胞有基础量的CTGFmRNA表达和蛋白合成,PTH刺激后其表达及合成量显著增加.PTH最佳刺激浓度是10-10 mol/L,最佳刺激时间是72 h.10-10 mol/L PTH作用HK-2细胞12 h后,荧光素酶活性显著高于未刺激组(1.8884±0.0780比0.9891±0.0300,P<0.01).正常情况下,胞核内NF-κB处于无活性状态,PTH刺激HK-2细胞后,NF-κB的DNA结合能力明显增强,10-10 mol/L PTH作用30 min时NF-κB活性达到高峰;而后随FTH浓度和作用时间增加,NF-κB活性有所下降.PDTC预处理HK-2细胞后,PTH诱导细胞CTGF mRNA表达显著低于PTH组(0.33±0.05比3.84±0.68,P<0.05),CTGF蛋白表达亦显著低于PTH组(0.56±0.23比3.76±0.54,P<0.01);PDTC亦显著抑制CTGF基因启动子活性,其萤火虫荧光素酶相对活性显著低于PTH组(1.1942±0.0107比1.8884±0.0780,P<0.01).结论 PTH可诱导HK-2细胞高表达CTGF,且在一定范围内呈时间、剂量依赖,其作用可能是通过NF-κB信号通路来实现的.%Objective To investigate the effect of PTH on the expression of CTGF in human renal proximal tubular epithelial cell line HK-2 and the role of nuclear factor kappa-B (NF-κB)signaling pathway.Methods The expression of CTGF mRNA and protein in HK-2 cells was measured by real time PCR and Western blot,respectively.The activity of NF-κB in HK-2 cells was measured by EMSA to investigate the mechanism by which PTH induced CTGF expression.The signaling

  7. Role of Wnt signaling pathway on the epithelial to mesenchymal transition induced by parathyroid hormone in renal tubular epithelial cells%甲状旁腺激素通过介导Wnt信号通路诱导人近曲小管上皮细胞转分化

    Institute of Scientific and Technical Information of China (English)

    郭云珊; 丁尧海; 杨炳琴; 张颖玮; 张磊; 李宏栋; 张峥梅; 徐红; 张晓苹

    2015-01-01

    目的 观察甲状旁腺激素(PTH)对人肾小管上皮细胞(HK-2)间充质转分化的影响,探讨Wnt信号通路在其中的作用.方法 细胞被分为对照组和PTH处理组.实时定量-聚合酶链反应(RT-PCR)和Western印迹法检测α平滑肌肌动蛋白(α-SMA)及钙黏素E(E-cadherin) mRNA及蛋白的表达;10-10mol/L PTH作用细胞48 h后,采用实时定量PCR芯片技术检测Wnt通路相关基因表达.不同浓度PTH作用后和10-10 mol/L PTH作用不同时间后,用RT-PCR、Western印迹法检测Wnt4 mRNA及蛋白的表达.构建Wnt4过表达及敲除Wnt4的细胞模型,用RT-PCR、Western印迹法检测α-SMA、E-cadherin、Wnt4 mRNA及蛋白质表达.结果 与PTH处理组相比,PTH+DKK1组α-SMA mRNA和蛋白表达量明显降低;E-cadherinmRNA及蛋白表达量明显升高(均P<0.01).PTH处理组细胞有18个Wnt信号通路基因显著上调和9个基因下调;与对照组相比,PTH处理组细胞Wnt4 mRNA和蛋白表达量明显增加(均P<0.01);与PTH处理组相比,PTH+Wnt4过表达组α-SMA mRNA和蛋白表达量明显上调,E-cadherin mRNA和蛋白表达量明显下调(均P<0.05).与PTH处理组相比,PTH+Wnt4 siRNA组α-SMA mRNA和蛋白表达量降低,E-cadherin mRNA和蛋白相对表达量升高(均P<0.05).结论 甲状旁腺激素诱导HK-2细胞间充质转分化.其机制可能与PTH激活Wnt信号通路,尤其Wnt4信号通路有关.%Objective To observe the effect of parathyroid hormone on transdifferentiation of human renal proximal tubular epithelial cell (HK-2),and to investigate the role of Wnt signaling pathway in this process.Methods The expression of α-SMA,E-cadherin mRNA and protein was detected by real-time PCR and Western blotting.After the induction of 10-10 mol/L PTH for 48 h,the Wnt pathway associated gene expression profiling was detected by quantitative PCR-microarray.The expression of Wnt4 mRNA and protein under various concentrations of PTH or after exposed to 10-10 mol/L PTH for different time

  8. Influence of focal adhesion kinase on epithelial-mesenchymal transition of human renal proximal tubular epithelial cells induced by transforming growth factor β1%黏着斑激酶在转化生长因子β1诱导的人肾小管上皮细胞转分化中的作用

    Institute of Scientific and Technical Information of China (English)

    邓冰清; 朱忠华; 张春; 杨晓; 刘建社

    2009-01-01

    Western blot.Results The expression of E-cadherin mRNA and protein was markedly decreased in HK-2 cells induced by TGF-β1,and the expression of α-SMA mRNA and protein was dramatically increased.Western blot analysis demonstrated that then protein levels of FAK and p-FAK(Tyr397)were progressively increased in a time-dependent manner in response to TGF-β1 treatment in HK-2 cells.When transfected with FAK-siRNA,the FAK mRNA and protein expression was markedly inhibited with 50% and 41%.Knockdown expression of FAK led to a severe blockage of TGF-β1-induced E-cadherin suppression and α-SMA induction.Conclusions The expression of FAK is up-regulated in HK-2 cells stimulated by TGF-β1.But the EMT induced by TGF-β1 in HK-2 cells is inhibited by FAK knockdown,which suggests that FAK plays an important role in TGF-β1-induced tubular EMT and renal fibrosis.

  9. Renal catabolism of albumin – current views and controversies

    Directory of Open Access Journals (Sweden)

    Jakub Gburek

    2011-10-01

    Full Text Available Albumin is the main protein of blood plasma, lymph, cerebrospinal fluid and interstitial fluid. The protein assists in many important body functions, including maintenance of proper colloidal osmotic pressure, transport of important metabolites and antioxidant action. Synthesis of albumin takes place mainly in the liver, and its catabolism occurs mostly in vascular endothelium of muscle, skin and liver as well as in the kidney tubular epithelium. Renal catabolism of albumin consists of glomerular filtration and tubular reabsorption. The tubular processes include endocytosis via the multiligand scavenger receptor tandem megalin and cubilin-amnionless complex. Possible ways of further catabolism of this protein are lysosomal proteolysis to amino acids and short peptides, recycling of degradation products into the bloodstream and tubular lumen or transcytosis of whole molecules. The article discusses the molecular aspects of these processes and presents the controversies arising in the light of the last decade of research.

  10. Renal angiomyolipoma

    DEFF Research Database (Denmark)

    Holm-Nielsen, P; Sørensen, Flemming Brandt

    1988-01-01

    Renal angiomyolipoma is a rare lesion composed of smooth muscle cells, adipose tissue and abnormal vessels. It is currently classified as a benign, non-epithelial renal tumor. It has a high incidence in patients suffering from tuberous sclerosis but is more frequently found as an isolated renal...... features. However, a smaller number of smooth muscle cells also contained lipid, thus simulating an intermediate cell stage between adipose- and smooth muscle cells. The abnormal thickening of the subendothelial spaces contained collagen fibrils in a homogeneous matrix, fibroblast-like cells and non......-specific vesicular structures. These findings suggest a secondary vascular damage, i.e. the thickened vessels may not be a primary, integral part of renal angiomyolipoma. Evidence of a common precursor cell of renal angiomyolipoma was not disclosed. It is concluded that renal angiomyolipoma is a hamartoma composed...

  11. APOPTOSIS INDUCED BY CYCLOSPORINE A IN RENAL TUBULAR AND INTERSTITIAL CELLS AND THE PROTECTIVE EFFECTS OF ENALAPRIL AND LOSARTAN ON IT%环孢菌素A致大鼠肾小管间质细胞凋亡及Losartan、Enalapril的保护作用

    Institute of Scientific and Technical Information of China (English)

    张国华; 张训; 侯凡凡; 王力; 易朝辉

    2001-01-01

    以低盐饮食(钠含量0.05%)饲养大鼠7天后随机分成①对照组,②CsA 处理组,③CsA+盐酸维拉帕米处理组,④CsA+Losartan处理组,⑤CsA+Enalapril处理组。CsA皮下注射剂量为15mg/(kg*d),连续4周。用TUNEL法检测凋亡细胞,免疫组化方法观察增殖细胞核抗原(PCNA)、Fas抗原表达。结果发现CsA处理后大鼠肾小管间质凋亡细胞较对照组明显增加,增殖细胞也有代偿性增加,肾小管上皮细胞Fas抗原表达增多。与CsA处理组相比,Losartan、Enalapril处理组肾小管间质细胞凋亡和Fas抗原表达明显减少。结果提示CsA可促进肾小管间质细胞凋亡,导致肾小管间质纤维化,Fas可能是介导肾小管细胞凋亡的重要介质。Losartan、Enalapril对CsA所致的肾小管间质细胞凋亡有保护作用。%The rats were fed on low salt diet for seven days,and then were randomly divided into five groups: control (n=7), CsA treated (n=7), CsA+Verapamil (n=7), CsA+Enalapril (n=7) and CsA+Losartan (n=7).CsA was given by subcutaneous injection (15mg*kg-1*d-1) for four weeks. The apoptosis of tubular and interstitial cells was detected by TUNEL assay. The proliferating cell nuclear antigen and Fas antigen expression were examined by immunohistochemical staining. Apoptosis of tubular and interstitial cells increased in CsA treated rats. CsA+Losartan and CsA+Enalapril treated rats had a statistically significant decrease in apoptosis when compared to CsA treated rats (7.3±1.1 and 6.6±0.8 vs 13.9±1.2 respectively, P<0.01 in all),and the tubular Fas antigen expression in CsA + Losartan or CsA+ Enalapril group was significantly lower than in CsA treated group(19.8±2.4 and 18.2±1.8 vs 37.8±5.7 respectively, P<0.01 in all).The results showed that CsA nephropathy was associated with marked increase in apoptosis of tubular and interstitial cells. Fas may be an important mediator of tubular apoptosis induced by CsA. Enalapril and

  12. The effect of surgery on the renal excretion of beta 2-microglobulin.

    Science.gov (United States)

    Walenkamp, G H; Vree, T B; Guelen, P J; Jongman-Nix, B

    1983-03-28

    Surgical trauma causes an increase in the renal excretion rate of beta 2-microglobulin whilst creatinine excretion is not influenced. The increase in the renal excretion rate of beta 2-microglobulin is probably the result of an increased release of beta 2-microglobulin by the cells which exceeds a maximum in the active tubular reabsorption of the compound by the proximal tubule cell. The renal excretion of beta 2-microglobulin is proportional to the relative clinical trauma score. PMID:6189646

  13. Nitric oxide differentially regulates renal ATP-binding cassette transporters during endotoxemia

    OpenAIRE

    Heemskerk, Suzanne; van Koppen, Arianne; van den Broek, Luc; Poelen, Geert J. M.; Wouterse, Alfons C; Dijkman, Henry B. P. M.; Russel, Frans G. M.; Masereeuw, Rosalinde

    2007-01-01

    Nitric oxide (NO) is an important regulator of renal transport processes. In the present study, we investigated the role of NO, produced by inducible NO synthase (iNOS), in the regulation of renal ATP-binding cassette (ABC) transporters in vivo during endotoxemia. Wistar–Hannover rats were injected with lipopolysaccharide (LPS+) alone or in combination with the iNOS inhibitor, aminoguanidine. Controls received detoxified LPS (LPS−). After LPS+, proximal tubular damage and a reduction in renal...

  14. Extensive Thrombosis of the Inferior Vena Cava and Left Renal Vein in a Neonate.

    Science.gov (United States)

    Kdous, Moez; Khlifi, Oussema; Brahem, Marwene; Khrouf, Mohamed; Amari, Sarah; Ferchiou, Monia; Zhioua, Fethi

    2015-01-01

    Antenatal renal vein thrombosis is a rarely described diagnostic finding, with variable consequences on kidney function. We present the case of an affected fetus, born at 35-week gestation, with intrauterine oligohydramnios and two small kidneys. A renal ultrasound carried out after birth confirmed the presence of prenatal abnormalities. Renal vein thrombosis was not diagnosed at the time. The baby died 20 days later of kidney failure, metabolic acidosis, and polypnea with severe hypotrophy. Autopsy revealed atrophied kidneys and adrenal glands. The vena cava had thrombosis occupying most of its length. The right renal vein was normal, while the left renal vein was threadlike and not permeable. Histologically, there was necrosis of the left adrenal gland with asymmetrical bilateral renal impairment and signs of ischemic and hemorrhagic lesions. A review of thrombophilia was carried out and a heterozygous mutation in Factor V was found in both the mother and the child.

  15. Renal liposarcoma

    Directory of Open Access Journals (Sweden)

    Diogo A.L. Bader

    2004-06-01

    Full Text Available INTRODUCTION: Liposarcoma is a malignant mesenchymal tumor frequently located in retroperitoneum, and rarely presenting an isolated lesion in kidney. CASE REPORT: Female, Caucasian, 49-year old patient, with family history of renal polycystic disease, was selected for organ donation. During preoperative examinations a renal pleomorphic liposarcoma was detected. She was treated with radical nephrectomy and remains asymptomatic, without evidences of recurrence in control ecographic examinations after a 4-year follow-up. COMMENTS: Renal liposarcoma is a rare tumor. We report one case incidentally diagnosed during a routine pre-transplantation assessment in renal donor.

  16. RENAL CRYOABLATION

    Directory of Open Access Journals (Sweden)

    A. V. Govorov

    2012-01-01

    Full Text Available Renal cryoablation is an alternative minimally-invasive method of treatment for localized renal cell carcinoma. The main advantages of this methodology include visualization of the tumor and the forming of "ice ball" in real time, fewer complications compared with other methods of treatment of renal cell carcinoma, as well as the possibility of conducting cryotherapy in patients with concomitant pathology. Compared with other ablative technologies cryoablation has a low rate of repeat sessions and good intermediate oncological results. The studies of long-term oncological and functional results of renal cryoablation are presently under way.

  17. Disease: H00243 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available iology of renal tubular acidosis. Curr Genomics 10:51-9 (2009) PMID:11045400 (gene) Rodriguez-Soriano J New ...rol 14:1121-36 (2000) PMID:12138150 (gene, env_factor, marker, drug) Rodriguez Soriano J Renal tubular acido

  18. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009221 Nephroprotective effects of subcapsular transplantation of metanephric mesenchymal cells on acute tubular necrosis rats.CHEN DAN(陈丹),et al.Div of Pediatr Nephrol,Dept Pediatr,2nd Xiangya Hosp Central South Univ,Changsha 410011,Chin J Nephrol,2009;25(3):191-197.

  19. Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists

    OpenAIRE

    Lucia, A.; Hoyos, J; Santalla, A; Perez, M; Carvajal, A.; Chicharro, J.

    2002-01-01

    Objective: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists.

  20. Improving the welfare of dairy goats: Feeding behaviour identifies goats at risk of subacute rumen acidosis

    OpenAIRE

    Giger-Reverdin, Sylvie; Sauvant, Daniel; Duvaux-Ponter, Christine

    2013-01-01

    Main messages: Feeding behaviour is highly variable between animals. Feeding behaviour modifies rumen pH pattern and occurrence of subacute ruminal acidosis (SARA). Avoiding SARA increases animal welfare, milk production and therefore farm profit - ability.

  1. Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac contractility

    Institute of Scientific and Technical Information of China (English)

    Ming ZHENG; Rong HOU; Rui-ping XIAO

    2004-01-01

    AIM: To determine the possible role of pH in mediating activation of p38 mitogen-activated protein kinase (MAPK) and the consequent function of activated p38 MAPK in regulating cardiac contractility. METHODS: Adult rat cardiomyocytes were isolated and cultured. Low pH media was used to induce intracellular acidosis and contraction of single cardiomyocyte was measured. RESULTS: Phosphorylation of p38 MAPK was increased during ischemia, and pHi was decreased. Intracellular acidosis activated p38 MAPK to a similar level as ischemia. Inhibition of p38 MAPK activation by SB203580, a specific inhibitor of p38 MAPK, reversed acidosis-mediated reduction of myocyte contractility. CONCLUSION: In adult rat cardiomyocytes, intracellular acidification activated p38 MAPK and decreased cardiac contractility. Pretreatment of cardiomyocytes with SB203580 completely blocked p38 MAPK activation and partially reversed acidosis-mediated decline of cardiac contractility.

  2. Thermal CFD Analysis of Tubular Light Guides

    Directory of Open Access Journals (Sweden)

    Ondřej Šikula

    2013-12-01

    Full Text Available Tubular light guides are applicable for daylighting of windowless areas in buildings. Despite their many positive indoor climate aspects they can also present some problems with heat losses and condensation. A computer CFD model focused on the evaluation of temperature distribution and air flow inside tubular light guides of different dimensions was studied. The physical model of the tested light guides of lengths more than 0.60 m proves shows that Rayleigh numbers are adequate for a turbulent air flow. The turbulent model was applied despite the small heat flux differences between the turbulent and laminar model. The CFD simulations resulted into conclusions that the growing ratio of length/diameter increases the heat transmission loss/linear transmittance as much as by 50 percent. Tubular light guides of smaller diameters have lower heat transmission losses compared to the wider ones of the same lengths with the same outdoor temperature being taken into account. The simulation results confirmed the thermal bridge effect of the tubular light guide tube inside the insulated flat roof details. The thermal transmittance of the studied light guides in the whole roof area was substituted with the point thermal bridges. This substitution gives possibility for simple thermal evaluation of the tubular light pipes in roof constructions.

  3. Progressive renal failure due to renal infiltration by BK polyomavirus and leukaemic cells: which is the culprit?

    Science.gov (United States)

    Sangala, Nicholas; Dewdney, Alex; Marley, Nicholas; Cranfield, Tanya; Venkat-Raman, Gopalakrishnan

    2011-02-01

    Renal infiltration with leukaemic cells is a common finding in patients suffering with chronic lymphocytic leukaemia (CLL) but rarely does it lead to significant renal dysfunction. Similarly, BK nephropathy is a recognized cause of graft failure in renal transplant recipients but rarely causes significant disease in native kidneys. In the few reports where leukaemic infiltration of the kidney has led to significant renal impairment, the pathological process causing renal dysfunction is not identified on biopsy. In these cases, it is unclear whether BK polyomavirus (BKV) nephropathy has been excluded. We describe a case of dual pathologies in a patient with Binet stage C CLL and deteriorating renal function where renal biopsy reveals leukaemic infiltration of the kidney occurring alongside BKV nephropathy. The relative importance of each pathology in relation to the rapid decline to end-stage renal failure remains unclear, but the presence of both pathologies appears to impart a poor prognosis. Additionally, we describe the novel histological finding of loss of tubular integrity resulting in tubular infiltration and occlusion by leukaemic cells. It is possible that the patient with advanced CLL is at particular risk of BK activation, and the presence of BK nephropathy may compromise tubular integrity allowing leukaemic cell infiltration and obstruction of tubules. This case bares remarkable resemblance to the first and only other report of its kind in the literature. It is not clear how available immunocytochemistry for polyoma infection is outside transplant centres, and it is possible that BK nephropathy is being under-diagnosed in patients with CLL in the context of declining renal function. At present, the combination of BKV nephropathy and leukaemic infiltration represents a management conundrum and the prognosis is poor. Further research is required in order to better understand the pathological process and therefore develop management strategies.

  4. Renal involvement in dogs with babesiosis

    Directory of Open Access Journals (Sweden)

    R.G. Lobetti

    2001-07-01

    Full Text Available Proteinuria, and renal tubular casts and epithelial cells in urine sediment, are commonly observed in both complicated and uncomplicated babesiosis, but do not necessarily reflect or predict renal failure. This study investigated the presence and degree of renal damage in canine babesiosis. Renal function and integrity were evaluated using serum urea and creatinine, serum electrolytes (sodium and potassium, fractional clearance of sodium (FcNa and potassium (FcK, urine enzyme activity of gamma-glutamyl transpeptidase and alkaline phosphatase, urine protein:creatinine ratio, and urinalysis. One control group (n =10 and 3 groups of babesiosis cases were studied: mild uncomplicated (n =10, severe uncomplicated (n = 11, and complicated (n = 9. All babesiosis groups showed well-concentrated urine. Mean serum urea was elevated in the severe and complicated groups, and was significantly different from the control group. There was no statistically significant difference between the groups for creatinine, although the complicated group had a mean value above the normal reference range. Hypokalaemia was uncommon in all the groups. Hyperkalaemia was present in only 2 dogs in the complicated group. Marginal hyponatraemia was present in a minority of dogs in all groups. The serumelectrolytes were not significantly different between groups. There was no overall elevation, nor any statistically significant difference in both the FcNa and FcK between the groups. Only 1 dog, in the complicated group, showed marked enzymuria. Proteinuria was a common finding and was significantly different between the severe and complicated groups and the control group. Some dogs in all groups had renal tubular epithelial cells in the urinary sediment, which increased in severity from the mild to the complicated groups and was significantly different from the control group. This study demonstrated that minimal renal damage occurs more often in canine babesiosis than significant

  5. Renal fallure

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920705 Endothelin and acute renal failure:study on their relationship and possiblemechanisms. LIN Shanyan(林善锬), et al.Renal Res Lab, Huashan Hosp, Shanghai MedUniv, Shanghai, 200040. Natl Med J China 1992;72(4): 201-205. In order to investigate the role of endothelin

  6. Pyruvate carboxylase deficiency: An underestimated cause of lactic acidosis

    Directory of Open Access Journals (Sweden)

    F. Habarou

    2015-03-01

    Full Text Available Pyruvate carboxylase (PC is a biotin-containing mitochondrial enzyme that catalyzes the conversion of pyruvate to oxaloacetate, thereby being involved in gluconeogenesis and in energy production through replenishment of the tricarboxylic acid (TCA cycle with oxaloacetate. PC deficiency is a very rare metabolic disorder. We report on a new patient affected by the moderate form (the American type A. Diagnosis was nearly fortuitous, resulting from the revision of an initial diagnosis of mitochondrial complex IV (C IV defect. The patient presented with severe lactic acidosis and pronounced ketonuria, associated with lethargy at age 23 months. Intellectual disability was noted at this time. Amino acids in plasma and organic acids in urine did not show patterns of interest for the diagnostic work-up. In skin fibroblasts PC showed no detectable activity whereas biotinidase activity was normal. We had previously reported another patient with the severe form of PC deficiency and we show that she also had secondary C IV deficiency in fibroblasts. Different anaplerotic treatments in vivo and in vitro were tested using fibroblasts of both patients with 2 different types of PC deficiency, type A (patient 1 and type B (patient 2. Neither clinical nor biological effects in vivo and in vitro were observed using citrate, aspartate, oxoglutarate and bezafibrate. In conclusion, this case report suggests that the moderate form of PC deficiency may be underdiagnosed and illustrates the challenges raised by energetic disorders in terms of diagnostic work-up and therapeutical strategy even in a moderate form.

  7. Nebulized Pentamidine-Induced Acute Renal Allograft Dysfunction

    Directory of Open Access Journals (Sweden)

    Siddhesh Prabhavalkar

    2013-01-01

    Full Text Available Acute kidney injury (AKI is a recognised complication of intravenous pentamidine therapy. A direct nephrotoxic effect leading to acute tubular necrosis has been postulated. We report a case of severe renal allograft dysfunction due to nebulised pentamidine. The patient presented with repeated episodes of AKI without obvious cause and acute tubular necrosis only on renal histology. Nebulised pentamidine was used monthly as prophylaxis for Pneumocystis jirovecii pneumonia, and administration preceded the creatinine rise on each occasion. Graft function stabilised following discontinuation of the drug. This is the first report of nebulized pentamidine-induced reversible nephrotoxicity in a kidney allograft. This diagnosis should be considered in a case of unexplained acute renal allograft dysfunction.

  8. Renal control of calcium, phosphate, and magnesium homeostasis.

    Science.gov (United States)

    Blaine, Judith; Chonchol, Michel; Levi, Moshe

    2015-07-01

    Calcium, phosphate, and magnesium are multivalent cations that are important for many biologic and cellular functions. The kidneys play a central role in the homeostasis of these ions. Gastrointestinal absorption is balanced by renal excretion. When body stores of these ions decline significantly, gastrointestinal absorption, bone resorption, and renal tubular reabsorption increase to normalize their levels. Renal regulation of these ions occurs through glomerular filtration and tubular reabsorption and/or secretion and is therefore an important determinant of plasma ion concentration. Under physiologic conditions, the whole body balance of calcium, phosphate, and magnesium is maintained by fine adjustments of urinary excretion to equal the net intake. This review discusses how calcium, phosphate, and magnesium are handled by the kidneys.

  9. Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Hommel, Eva; Friberg, Lars; Mølvig, Jens;

    2010-01-01

    Increased urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients...... with type 2 diabetes and normal or increased UOER....

  10. Tubular membrane bioreactors for biotechnological processes.

    Science.gov (United States)

    Wolff, Christoph; Beutel, Sascha; Scheper, Thomas

    2013-02-01

    This article is an overview of bioreactors using tubular membranes such as hollow fibers or ceramic capillaries for cultivation processes. This diverse group of bioreactor is described here in regard to the membrane materials used, operational modes, and configurations. The typical advantages of this kind of system such as environments with low shear stress together with high cell densities and also disadvantages like poor oxygen supply are summed up. As the usage of tubular membrane bioreactors is not restricted to a certain organism, a brief overview of various applications covering nearly all types of cells from prokaryotic to eukaryotic cells is also given here. PMID:23224587

  11. Tubular solid oxide fuel cell current collector

    Science.gov (United States)

    Bischoff, Brian L.; Sutton, Theodore G.; Armstrong, Timothy R.

    2010-07-20

    An internal current collector for use inside a tubular solid oxide fuel cell (TSOFC) electrode comprises a tubular coil spring disposed concentrically within a TSOFC electrode and in firm uniform tangential electrical contact with the electrode inner surface. The current collector maximizes the contact area between the current collector and the electrode. The current collector is made of a metal that is electrically conductive and able to survive under the operational conditions of the fuel cell, i.e., the cathode in air, and the anode in fuel such as hydrogen, CO, CO.sub.2, H.sub.2O or H.sub.2S.

  12. Renal effects of amino acids and dopamine in renal transplant recipients treated with or without cyclosporin A

    DEFF Research Database (Denmark)

    Hansen, J M; Olsen, Niels Vidiendal; Leyssac, P P

    1996-01-01

    proximal and distal tubular handling of sodium (and water) were comparable between the two groups of patients. Dopamine caused significant natriuresis in both groups. 5. In conclusion, low-dose cyclosporin A seems not to attenuate the renal haemodynamic and tubular response to infusions of amino acids......1. The nephrotoxic effects of cyclosporin A may diminish the ability of the transplanted kidney to increase the glomerular filtration rate and effective renal plasma flow during infusion of dopamine or amino acids. 2. The present study included 16 renal transplant recipients transplanted for more...... than 6 months. Eight of the patients were on immunosuppressive treatment including cyclosporin A [cyclosporin A group; cyclosporin A dose, 2.7 +/- 0.4 mg/kg; S-creatinine, 105 +/- 12 mumol/l (means +/- SEM)], whereas eight patients had never received cyclosporin A (non-cyclosporin A group; S...

  13. Acidosis environment promotes osteoclast formation by acting on the last phase of preosteoclast differentiation: a study to elucidate the action points of acidosis and search for putative target molecules.

    Science.gov (United States)

    Kato, Kohtaro; Morita, Ikuo

    2011-08-01

    Acidosis promoted tartaric acid-resistant acid phosphatase-positive multinuclear cell (TRAP+MNC) or osteoclast formation. Large osteoclast or TRAP+LMNC formation was observed far more in an acidosis environment than in a physiologically neutral environment. One of the major action points of acidosis was determined to be located in the last phase of preosteoclast differentiation using a co-culture system and a soluble RANKL-dependent bone marrow cell culture system. On-going osteoclast formation in an acidosis environment markedly deteriorated when the medium was replaced with physiologically neutral medium within the first 6h; however, bone marrow cells previously stimulated in an acidosis environment for 9h differentiated into TRAP+LMNC in pH 7.4 medium. Messenger RNA (mRNA) expression levels of DC-STAMP, a key molecule in cell fusion, and NFATc1 did not increase in the acidosis environment compared with those under physiologically neutral conditions. Ruthenium red, a general TRP antagonist, deteriorated acidosis-promoted TRAP+LMNC formation. 4-Alpha-PDD, a TRPV4-specific agonist, added in the last 21 h of preosteoclast differentiation, potentiated TRAP+LMNC formation in a mild acidosis environment, showing synergism between TRPV4 activation and acidosis. RN1734, a TRPV4-specific antagonist, partly inhibited acidosis-promoted TRAP+LMNC formation. We thus narrowed down the major action points of acidosis in osteoclast formation and elucidated the characteristics of this system in detail. Our results show that acidosis effectively uses TRPV4 to drive large-scale cell fusion and also utilizes systems independently of TRPV4. PMID:21575626

  14. [Renal elastography].

    Science.gov (United States)

    Correas, Jean-Michel; Anglicheau, Dany; Gennisson, Jean-Luc; Tanter, Mickael

    2016-04-01

    Renal elastography has become available with the development of noninvasive quantitative techniques (including shear-wave elastography), following the rapidly growing field of diagnosis and quantification of liver fibrosis, which has a demonstrated major clinical impact. Ultrasound or even magnetic resonance techniques are leaving the pure research area to reach the routine clinical use. With the increased incidence of chronic kidney disease and its specific morbidity and mortality, the noninvasive diagnosis of renal fibrosis can be of critical value. However, it is difficult to simply extend the application from one organ to the other due to a large number of anatomical and technical issues. Indeed, the kidney exhibits various features that make stiffness assessment more complex, such as the presence of various tissue types (cortex, medulla), high spatial orientation (anisotropy), local blood flow, fatty sinus with variable volume and echotexture, perirenal space with variable fatty content, and the variable depth of the organ. Furthermore, the stiffness changes of the renal parenchyma are not exclusively related to fibrosis, as renal perfusion or hydronephrosis will impact the local elasticity. Renal elastography might be able to diagnose acute or chronic obstruction, or to renal tumor or pseudotumor characterization. Today, renal elastography appears as a promising application that still requires optimization and validation, which is the contrary for liver stiffness assessment. PMID:26976058

  15. Kidney injury molecule-1 expression is closely associated with renal allograft damage.

    Science.gov (United States)

    Song, Lianlian; Xue, Lijuan; Yu, Jinyu; Zhao, Jun; Zhang, Wenlan; Fu, Yaowen

    2013-08-01

    The aim of our study was to investigate the expression of kidney injury molecule-1 (KIM-1) in renal allograft biopsy samples and assess the clinical significance of its use as a biomarker for tissue damage. A total of 69 renal allograft biopsy samples from 17 patients with normal serum creatinine and 52 cases of increased serum creatinine were collected. They were divided into different groups according to the Banff 2007 diagnostic criteria. KIM-1 expression was detected by immunohistochemical methods and the association of KIM-1 and blood biochemical indexes was analyzed. KIM-1 expression increased as Banff 2007 classification grade increased and was positively correlated with tubular inflammation severity in the acute T-cell rejection group. Moreover, KIM-1 expression was strongly positive in the chronic active antibody-mediated rejection group. Interestingly, KIM-1 was weakly positive in the normal group without obvious acute rejection and injury of immunosuppressant toxicity. In this group, 27.3% (3/11) of the cases with normal serum creatinine level showed weakly positive KIM-1 expression in their renal tissues. KIM-1 expression level is positively correlated with renal allograft damage and tubular cell injury. KIM-1 is expressed in tubular epithelial cells before blood biochemical indexes become elevated and morphological changes occur. KIM-1 expression is an early, sensitive, and specific biomarker to determine renal tubular epithelial cell injury in renal allograft tissue.

  16. Nlrp3 prevents early renal interstitial edema and vascular permeability in unilateral ureteral obstruction.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Progressive renal disease is characterized by tubulo-interstitial injury with ongoing inflammation and fibrosis. The Nlrp3 inflammasome contributes to these pathophysiological processes through its canonical effects in cytokine maturation. Nlrp3 may additionally exert inflammasome-independent effects following tissue injury. Hence, in this study we investigated potential non-canonical effects of Nlrp3 following progressive renal injury by subjecting WT and Nlrp3-deficient (-/- mice to unilateral ureter obstruction (UUO. Our results revealed a progressive increase of renal Nlrp3 mRNA in WT mice following UUO. The absence of Nlrp3 resulted in enhanced tubular injury and dilatation and an elevated expression of injury biomarker NGAL after UUO. Moreover, interstitial edema was significantly elevated in Nlrp3-/- mice. This could be explained by increased intratubular pressure and an enhanced tubular and vascular permeability. In accordance, renal vascular leakage was elevated in Nlrp3-/- mice that associated with reduced mRNA expression of intercellular junction components. The decreased epithelial barrier function in Nlrp3-/- mice was not associated with increased apoptosis and/or proliferation of renal epithelial cells. Nlrp3 deficiency did not affect renal fibrosis or inflammation. Together, our data reveal a novel non-canonical effect of Nlrp3 in preserving renal integrity and protection against early tubular injury and interstitial edema following progressive renal injury.

  17. Early segmental changes in ischemic acute tubular necrosis of the rat kidney

    DEFF Research Database (Denmark)

    Faarup, Poul; Nørgaard, Tove; Hegedüs, Viktor;

    2004-01-01

    pentothal-anesthetized Wistar rats (body weight 200-250 g) ischemia of the right kidney was obtained by clamping (clamp diameter 0.15 mm) the ipsilateral renal artery for varying periods of time (10 min to 6 h) followed by removal and instant freezing of the kidney in isopentane at -165 degrees C...... and subsequent freeze-substitution in alcohol. The microscopic slides from the kidneys were silver methenamine-PAS stained. In the segments of the proximal convoluted tubules of the nephrons, presence of nuclear pyknosis, places of denuded basement membranes and presence of exfoliated tubular cells were counted...

  18. Renal effects of methoxyverapamil in anesthetized rats.

    Science.gov (United States)

    Brown, B; Churchill, P

    1983-05-01

    The purpose of these experiments was to determine the renal effects of methoxyverapamil (D-600). Three groups of rats were anesthetized with sodium pentobarbital and given 0, 0.85 or 1.69 nmol/min of methoxyverapamil i.v. Increases in urine flow and Na, K and Ca excretory rates occurred, in an apparently dose-dependent manner. Plasma Na and arterial renin concentration decreased at both doses and, at the higher dose, mean arterial blood pressure and effective renal plasma flow decreased while plasma K increased. Plasma Ca, glomerular filtration rate, filtration fraction and total renal plasma flow were not affected. The findings that methoxyverapamil increased urine flow and electrolyte excretion without changing glomerular filtration rate are consistent with the hypothesis that methoxyverapamil acts directly on tubular reabsorptive mechanisms. These effects, and the effect on plasma renin concentration, could contribute to the beneficial effects of this and other Ca entry antagonists in the treatment of hypertension.

  19. Cellular distribution of cell cycle-related molecules in the renal tubules of rats treated with renal carcinogens for 28 days: relationship between cell cycle aberration and carcinogenesis.

    Science.gov (United States)

    Taniai, Eriko; Hayashi, Hitomi; Yafune, Atsunori; Watanabe, Maiko; Akane, Hirotoshi; Suzuki, Kazuhiko; Mitsumori, Kunitoshi; Shibutani, Makoto

    2012-09-01

    Some renal carcinogens can induce karyomegaly, which reflects aberrant cell division in the renal tubules, from the early stages of exposure. To clarify the cell cycle-related changes during the early stages of renal carcinogenesis, we performed immunohistochemical analysis of tubular cells in male F344 rats treated with carcinogenic doses of representative renal carcinogens for 28 days. For this purpose, the karyomegaly-inducing carcinogens ochratoxin A (OTA), ferric nitrilotriacetic acid, and monuron, and the non-karyomegaly-inducing carcinogens tris(2-chloroethyl) phosphate and potassium bromate were examined. For comparison, a karyomegaly-inducing non-carcinogen, p-nitrobenzoic acid, and a non-carcinogenic non-karyomegaly-inducing renal toxicant, acetaminophen, were also examined. The outer stripe of the outer medulla (OSOM) and the cortex + OSOM were subjected to morphometric analysis of immunoreactive proximal tubular cells. Renal carcinogens, irrespective of their karyomegaly-inducing potential, increased proximal tubular cell proliferation accompanied by an increase in topoisomerase IIα-immunoreactive cells, suggesting a reflection of cell proliferation. Karyomegaly-inducing carcinogens increased nuclear Cdc2-, γH2AX-, and phosphorylated Chk2-immunoreactive cells in both areas, the former two acting in response to DNA damage and the latter one suggestive of sustained G₂. OTA, an OSOM-targeting carcinogen, could easily be distinguished from untreated controls and non-carcinogens by evaluation of molecules responding to DNA damage and G₂/M transition in the OSOM. Thus, all renal carcinogens examined facilitated proximal tubular proliferation by repeated short-term treatment. Among these, karyomegaly-inducing carcinogens may cause DNA damage and G₂ arrest in the target tubular cells.

  20. Drill pipes and casings utilizing multi-conduit tubulars

    Energy Technology Data Exchange (ETDEWEB)

    Curlett, H.B.

    1989-01-24

    A seal adapted for use with a multi-conduit well tubular, or the like, is described which consists of: a plate with fluid passages, each passage corresponding to an opening of a conduit of the multiconduit tubular, and a groove on the plate around each passage; and elastomer means partially embeddable into each groove for sealing each conduit of a tubular to a corresponding conduit of another similar tubular.

  1. Work tool in a tubular element

    International Nuclear Information System (INIS)

    The stand, which is positioned in relation with the tubular element, has clutch disengagement means for a working rod in rotation, with at least two positioning regions on the rod. Application for laser welding a sleeve into PWR steam generator tubes

  2. Tubular Membrane Plant-Growth Unit

    Science.gov (United States)

    Dreschel, Thomas W.

    1992-01-01

    Hydroponic system controls nutrient solution for growing crops in space. Pump draws nutrient solution along inside of tubular membrane in pipe from reservoir, maintaining negative pressure in pipe. Roots of plants in slot extract nutrient through membrane within pipe. Crop plants such as wheat, rice, lettuce, tomatoes, soybeans, and beans grown successfully with system.

  3. Osteodistrofia renal

    OpenAIRE

    Teles, Tobias José Freitas Trindade

    2014-01-01

    A doença renal crónica é um problema de saúde mundial, com incidência e prevalência crescentes. Apesar dos avanços científicos na compreensão da patogénese e o desenvolvimento de terapêuticas mais eficazes, a osteodistrofia renal continua a ser uma complicação importante nos doentes renais crónicos. A osteodistrofia renal abrange um espectro diverso de alterações ósseas nos doentes com doença renal crónica, classificada histologicamente por lesões de elevada ou baixa taxa de remodelação ó...

  4. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930150 Epidermal growth factor and its recep-tor in the renal tissue of patients with acute re-nal failure and normal persons.LIU Zhihong(刘志红),et al.Jinling Hosp,Nanjing,210002.Natl Med J China 1992;72(10):593-595.Epidermal growth factor(EGF)and its receptor(EGF-R)were identified by immunohis-tochemical method(4 layer PAP)in the renaltissue specimens obtained from 11 normal kid-neys and 17 cases of acute renal failure(ARF).The quantitative EGF and EGF-R in the tissuewere expressed as positive tubules per mm~2.The amount of EGF and EGF-R in renal tissue

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950351 Serum erythropoietin levels in chronic renalinsufficiency.ZHAI Depei(翟德佩),et al.DeptNephrol.General Hosp,Tianjin Med Univ,Tianjin,300000.Tianjin Med J 1995;23(1):19-21.Patients with chronic renal insufficiency(CRI) areoften associated with anemia.The deficiency of EPOproduction in the kidney is thought to be a key factorin the pathogenesis of renal anemia.Serum erythropoi-

  6. Renal liposarcoma

    OpenAIRE

    Diogo A.L. Bader; Luis A.B. Peres; Sérgio L. Bader

    2004-01-01

    INTRODUCTION: Liposarcoma is a malignant mesenchymal tumor frequently located in retroperitoneum, and rarely presenting an isolated lesion in kidney. CASE REPORT: Female, Caucasian, 49-year old patient, with family history of renal polycystic disease, was selected for organ donation. During preoperative examinations a renal pleomorphic liposarcoma was detected. She was treated with radical nephrectomy and remains asymptomatic, without evidences of recurrence in control ecographic examinations...

  7. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    2005234 Association between serum fetuin-A and clinical outcome in end-stage renal disease patients. WANG Kai(王开), Dept Renal Dis, Renji Hosp Shanghai, 2nd Med Univ, Shanghai 200001. Chin J Nephrol, 2005;21(2):72-75. Objective: To investigate the change of serum fetuin-A level before and after dialysis, and the association of serum fetuin-A level with clinical parameters

  8. Reliability Analysis of Tubular Joints in Offshore Structures

    DEFF Research Database (Denmark)

    Thoft-Christensen, Palle; Sørensen, John Dalsgaard

    1987-01-01

    Reliability analysis of single tubular joints and offshore platforms with tubular joints is" presented. The failure modes considered are yielding, punching, buckling and fatigue failure. Element reliability as well as systems reliability approaches are used and illustrated by several examples....... Finally, optimal design of tubular.joints with reliability constraints is discussed and illustrated by an example....

  9. Vibration analysis of ultrasonic tubular resonators

    Institute of Scientific and Technical Information of China (English)

    LIANG Zhaofeng; MO Xiping; ZHOU Guangping

    2012-01-01

    The frequency equation of the axisymmetric coupled vibration of a ultrasonic tubular resonator with both ends free is derived by an exact solution method, based on classical Fliigge thin shell theory. The dependence of the dimensionless frequency Ω on the ratio of length to radius 1/a, the ratio of radius to thickness a/h and Poisson's ratio v is investigated, and the axisymmetric coupled vibration of the ultrasonic tubular resonator with both ends shear diaphragm is compared with that with both ends free. The accuracy of two-dimensional and three-dimensional apparent elasticity method is also assessed by the comparison with the exact solution method. Finally, the mode shapes of the ultrasonic tubular resonator are calculated by the exact solution method, and its transform efficient is analyzed. The results show that as for two boundary conditions of both ends free and both ends shear diaphragm, the difference of the effect of the boundary conditions on the dimensionless frequency of the axisymmetric coupled vibration of the ultrasonic tubular resonator becomes smaller as l/a increases, and the larger a/h, the smaller the difference. Moreover, for free-free boundary conditions, the change of a/h has nearly no effect on the dimensionless frequency of the thin tubular resonator usually considered to mean a/h 〉 10. Purthermore, the dimensionless frequency Ω decreases as v in- creases for a given l/a, and the impact of v on Ω is different for different l/a, and the maximum impact will appear when l/a = π. Finally, the study also shows the three-dimensional apparent elasticity method has very high accuracy.

  10. Effects of Sodium Citrate on Salt Sensitivity and Kidney Injury in Chronic Renal Failure

    OpenAIRE

    Kim, Sejoong; Yang, Jin Young; Jung, Eun Sook; Lee, Jeonghwan; Heo, Nam Ju; Lee, Jae Wook; Na, Ki Young; Han, Jin Suk

    2014-01-01

    Metabolic acidosis, which is observed in salt-sensitive hypertension, is also associated with kidney injury. Alkali therapy in chronic renal failure (CRF) may ameliorate the progression of kidney disease; however, few studies have examined the effects of alkali therapy on salt sensitivity and kidney injury in CRF. We randomly administered standard diet (SD), sodium chloride with 20% casein diet (NACL), or sodium citrate with 20% casein diet (NACT) to Sprague-Dawley rats after a CRF or a sham ...

  11. Effect of sodium bicarbonate administration on mortality in patients with lactic acidosis: a retrospective analysis.

    Directory of Open Access Journals (Sweden)

    Hyun Jeong Kim

    Full Text Available BACKGROUND: Lactic acidosis is a common cause of high anion gap metabolic acidosis. Sodium bicarbonate may be considered for an arterial pH <7.15 but paradoxically depresses cardiac performance and exacerbates acidosis by enhancing lactate production. This study aimed to evaluate the cause and mortality rate of lactic acidosis and to investigate the effect of factors, including sodium bicarbonate use, on death. METHODS: We conducted a single center analysis from May 2011 through April 2012. We retrospectively analyzed 103 patients with lactic acidosis among 207 patients with metabolic acidosis. We used SOFA and APACHE II as severity scores to estimate illness severity. Multivariate logistic regression analysis and Cox regression analysis models were used to identify factors that affect mortality. RESULTS: Of the 103 patients with a mean age of 66.1±11.4 years, eighty-three patients (80.6% died from sepsis (61.4%, hepatic failure, cardiogenic shock and other causes. The percentage of sodium bicarbonate administration (p = 0.006, catecholamine use, ventilator care and male gender were higher in the non-survival group than the survival group. The non-survival group had significantly higher initial and follow-up lactic acid levels, lower initial albumin, higher SOFA scores and APACHE II scores than the survival group. The mortality rate was significantly higher in patients who received sodium bicarbonate. Sodium bicarbonate administration (p = 0.016 was associated with higher mortality. Independent factors that affected mortality were SOFA score (Exp (B = 1.72, 95% CI = 1.12-2.63, p = 0.013 and sodium bicarbonate administration (Exp (B = 6.27, 95% CI = 1.10-35.78, p = 0.039. CONCLUSIONS: Lactic acidosis, which has a high mortality rate, should be evaluated in patients with metabolic acidosis. In addition, sodium bicarbonate should be prescribed with caution in the case of lactic acidosis because sodium bicarbonate

  12. Renal neurohormonal regulation in heart failure decompensation.

    Science.gov (United States)

    Jönsson, Sofia; Agic, Mediha Becirovic; Narfström, Fredrik; Melville, Jacqueline M; Hultström, Michael

    2014-09-01

    Decompensation in heart failure occurs when the heart fails to balance venous return with cardiac output, leading to fluid congestion and contributing to mortality. Decompensated heart failure can cause acute kidney injury (AKI), which further increases mortality. Heart failure activates signaling systems that are deleterious to kidneys such as renal sympathetic nerve activity (RSNA), renin-angiotensin-aldosterone system, and vasopressin secretion. All three reduce renal blood flow (RBF) and increase tubular sodium reabsorption, which may increase renal oxygen consumption causing AKI through renal tissue hypoxia. Vasopressin contributes to venous congestion through aquaporin-mediated water retention. Additional water retention may be mediated through vasopressin-induced medullary urea transport and hyaluronan but needs further study. In addition, there are several systems that could protect the kidneys and reduce fluid retention such as natriuretic peptides, prostaglandins, and nitric oxide. However, the effect of natriuretic peptides and nitric oxide are blunted in decompensation, partly due to oxidative stress. This review considers how neurohormonal signaling in heart failure drives fluid retention by the kidneys and thus exacerbates decompensation. It further identifies areas where there is limited data, such as signaling systems 20-HETE, purines, endothelin, the role of renal water retention mechanisms for congestion, and renal hypoxia in AKI during heart failure.

  13. Haptoglobin and serum amyloid a in subacute ruminal acidosis in goats

    Directory of Open Access Journals (Sweden)

    F.H.D. González

    2010-12-01

    Full Text Available Ruminal acidosis is a frequent disorder that occurs in goats as a consequence of feedingmistakes in animals not adapted to a diet of easily fermentable carbohydrates. The subacuteform of the disease is difficult to diagnose because no apparent signs are shownand the acid-base parameters may remain within the normal range. The present studyaimed at testing the hypothesis that haptoglobin (Hp and serum amyloid A (SAA,the two major acute phase proteins in ruminants, may be useful as markers of subacuteacidosis in goats.A subacute acidosis was induced in six Murciano-Granadina goats through a diet of60% mixed feed-40% alfalfa hay offered during 5 days to goats not adapted to eatmixed feed. Two goats were rumen-fistulated to investigate the effect of feeding onruminal pH. Sampling of blood and urine of all animals was done before the inductionof the acidosis, during 5 days after the onset of induction and for 18 days after theinduction (recovery period.Ruminal pH in the fistulated goats dropped to less than 5.5 during the inductionperiod, and half of the goats had diarrhea on the third day after the induction of acidosis.Acid-base parameters showed that the acid-base compensatory mechanisms wereefficient in maintaining the equilibrium. Serum Hp had a moderate increase duringthe induction period, while SAA did not change. These results suggest that Hp mightbe a potential marker for ruminal acidosis in goats.

  14. Flozins, inhibitors of type 2 renal sodium-glucose co-transporter – not only antihyperglycemic drugs

    OpenAIRE

    Mizerski Grzegorz; Kicinski Pawel; Jaroszynski Andrzej

    2015-01-01

    The kidneys play a crucial role in the regulation of the carbohydrate metabolism. In normal physiological conditions, the glucose that filters through the renal glomeruli is subsequently nearly totally reabsorbed in the proximal renal tubules. Two transporters are engaged in this process: sodium-glucose co-transporter type 1 (SGLT1), and sodium-glucose co-transporter type type 2 (SGLT2) - this being located in the luminal membrane of the renal tubular epithelial cells. It was found that the a...

  15. 78 FR 14361 - U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United...

    Science.gov (United States)

    2013-03-05

    ... Employment and Training Administration U.S. Steel Tubular Products, Inc., Mckeesport Tubular Operations Division, Subsidiary of United States Steel Corporation, Mckeesport, PA; Notice of Initiation of...) filed on December 20, 2012 on behalf of workers of U.S. Steel Tubular Products, McKeesport...

  16. Statins and progressive renal disease.

    Science.gov (United States)

    Buemi, Michele; Senatore, Massimino; Corica, Francesco; Aloisi, Carmela; Romeo, Adolfo; Cavallaro, Emanuela; Floccari, Fulvio; Tramontana, Domenico; Frisina, Nicola

    2002-01-01

    Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.

  17. Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells

    International Nuclear Information System (INIS)

    The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood. We have now studied molecular pathways leading to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both CsA and tacrolimus elicited a proinflammatory response in tubular cells as evidenced by a transcriptomics approach. Transcriptomics also suggested several potential pathways leading to expression of proinflammatory genes. Validation and functional studies disclosed that in tubular cells, CNIs activated protein kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK signaling and the Unfolded Protein Response (UPR) to promote NF-κB activation and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK activation and inflammation. A murine model of CsA nephrotoxicity corroborated activation of the proinflammatory pathways identified in cell cultures. Human CNIs nephrotoxicity was also associated with NF-κB, STAT3 and IRE1α activation. In conclusion, CNIs recruit several intracellular pathways leading to previously non-described proinflammatory actions in renal tubular cells. Identification of these pathways provides novel clues for therapeutic intervention to limit CNIs nephrotoxicity. - Highlights: • Molecular mechanisms modulating CNI renal inflammation were investigated. • Kinases, immune receptors and ER stress mediate the inflammatory response to CNIs. • Several intracellular pathways activate NF-κB in CNIs-treated tubular cells. • A NF-κB-dependent cytokine profile characterizes CNIs-induced inflammation. • CNI nephrotoxicity was associated to inflammatory

  18. Cisplatin nephrotoxicity involves mitochondrial injury with impaired tubular mitochondrial enzyme activity.

    Science.gov (United States)

    Zsengellér, Zsuzsanna K; Ellezian, Lena; Brown, Dan; Horváth, Béla; Mukhopadhyay, Partha; Kalyanaraman, Balaraman; Parikh, Samir M; Karumanchi, S Ananth; Stillman, Isaac E; Pacher, Pál

    2012-07-01

    Cisplatin is a widely used antineoplastic agent. However, its major limitation is dose-dependent nephrotoxicity whose precise mechanism is poorly understood. Recent studies have suggested that mitochondrial dysfunction in tubular epithelium contributes to cisplatin-induced nephrotoxicity. Here the authors extend those findings by describing the role of an important electron transport chain enzyme, cytochrome c oxidase (COX). Immunohistochemistry for COX 1 protein demonstrated that, in response to cisplatin, expression was mostly maintained in focally damaged tubular epithelium. In contrast, COX enzyme activity in proximal tubules (by light microscopy) was decreased. Ultrastructural analysis of the cortex and outer stripe of the outer medulla showed decreased mitochondrial mass, disruption of cristae, and extensive mitochondrial swelling in proximal tubular epithelium. Functional electron microscopy showed that COX enzyme activity was decreased in the remaining mitochondria in the proximal tubules but maintained in distal tubules. In summary, cisplatin-induced nephrotoxicity is associated with structural and functional damage to the mitochondria. More broadly, using functional electron microscopy to measure mitochondrial enzyme activity may generate mechanistic insights across a spectrum of renal disorders. PMID:22511597

  19. Renal allograft rejection: sonography and scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Singh, A.; Cohen, W.N.

    1980-07-01

    A total of 30 renal allograft patients who had sonographic B scanning and radionuclide studies of the transplant was studied as to whether: (1) the allograft rejection was associated with any consistent and reliable sonographic features and (2) the sonograms complemented the radionuclide studies. Focal areas of decreased parenchymal echogenicity were the most striking and consistent sonographic finding in chymal echogenicity were the most striking and consistens sonographic finding in allograft rejection. This was observed in most of the patients exhibiting moderate or severe rejection, but was frequently absent with mild rejection. Areas of decreased parenchymal echogenicity were not seen during episodes of acute tubular necrosis. Therefore, sonography showing zones of decreased parenchymal echogenicity was complementary to radionuclide studies in the diagnosis of allograft rejection versus acute tubular necrosis. Corticomedullary demarcation was difficult to interpret because of technical variables, and was inconsistently related to rejection in this series.

  20. In vivo and in vitro analysis of age-associated changes and somatic cellular senescence in renal epithelial cells.

    Directory of Open Access Journals (Sweden)

    Birgit Berkenkamp

    Full Text Available Acute kidney injury is a major clinical problem and advanced age is associated with ineffective renal regeneration and poor functional outcome. Data from kidney injury models suggest that a loss of tubular epithelial proliferation contributes to a decrease in renal repair capacity with aging, but aging can also lead to a higher severity of inflammation and damage which may influence repair. In this study we tested intrinsic age-dependent changes in tubular epithelial proliferation in young and old mice, by injecting low-dose lead acetate as a non-injurious mitogen. In parallel, we explored in vitro techniques of studying cellular senescence in primary tubular epithelial cells (PTEC. Lead acetate induced tubular epithelial proliferation at a significantly higher rate in young as compared to old mice. Old kidneys showed significantly more senescence as demonstrated by increased p16 (INK4a, senescence associated β-galactosidase, and γH2AX(+/Ki-67(- cells. This was paralleled in old kidneys by a higher number of Cyclin D1 positive tubular cells. This finding was corroborated by a positive correlation between Cyclin D1 positivity and age in human renal biopsies. When tubular cells were isolated from mouse kidneys they rapidly lost their age-associated differences under culture conditions. However, senescence was readily induced in PTEC by γ-irradiation representing a future model for study of cellular senescence in the renal epithelium. Together, our data indicate that the tubular epithelium of aged kidney has an intrinsically reduced proliferative capacity probably due to a higher load of senescent cells. Moreover, stress induced models of cellular senescence are preferable for study of the renal epithelium in vitro. Finally, the positive correlation of Cyclin D1 with age and cellular senescence in PTEC needs further evaluation as to a functional role of renal epithelial aging.