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Sample records for renal tubular handling

  1. Distal renal tubular acidosis

    Science.gov (United States)

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

  2. Proximal renal tubular acidosis

    Science.gov (United States)

    Renal tubular acidosis - proximal; Type II RTA; RTA - proximal; Renal tubular acidosis type II ... by alkaline substances, mainly bicarbonate. Proximal renal tubular acidosis (Type II RTA) occurs when bicarbonate is not ...

  3. Hypercalcaemia of malignancy: evidence for a nonparathyroid humoral agent with an effect on renal tubular handling of calcium.

    Science.gov (United States)

    Ralston, S H; Fogelman, I; Gardner, M D; Dryburgh, F J; Cowan, R A; Boyle, I T

    1984-02-01

    The renal handling of calcium was examined in 31 patients with hypercalcaemia of malignancy. Results were compared with those from patients with primary hyperparathyroidism, and normal controls rendered hypercalcaemic by calcium infusion. On relating the urinary calcium excretion indices to serum calcium values, inappropriately low rates of urinary calcium excretion were generally found in patients with malignancy associated hypercalcaemia. Further, the pattern of urinary calcium excretion in these subjects was similar to that found in patients with primary hyperparathyroidism. These observations suggest that, in many solid tumours, the development of hypercalcaemia may be attributable to a humoral mediator with a parathyroid hormone-like effect on renal tubular calcium reabsorption. The relatively frequent occurrence of hypercalcaemia in malignant disease thus may be partially explained by the presence of this humoral agent, which may impair the renal excretion of an increase in filtered calcium load, whether due to bone metastases, or humorally mediated osteolysis.

  4. 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

    The kidney plays an important role in maintaining the systemic Ca2+ and Mg2+ balance. Thus the renal reabsorptive capacity of these cations can be amended to adapt to disturbances in plasma Ca2+ and Mg2+ concentrations. The reabsorption of Ca2+ and Mg2+ is driven by transport of other electrolytes......, sometimes through selective channels and often supported by hormonal stimuli. It is, therefore, not surprising that monogenic disorders affecting such renal processes may impose a shift in, or even completely blunt, the reabsorptive capacity of these divalent cations within the kidney. Accordingly, in Dent......'s disease, a disorder with defective proximal tubular transport, hypercalciuria is frequently observed. Dysfunctional thick ascending limb transport in Bartter's syndrome, familial hypomagnesaemia with hypercalciuria and nephrocalcinosis, and diseases associated with Ca2+-sensing receptor defects, markedly...

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

    Directory of Open Access Journals (Sweden)

    Menegon L.F.

    1998-01-01

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

  6. Effect of felodipine on renal haemodynamics and tubular sodium handling after single-dose cyclosporin infusion in renal transplant recipients treated with azathioprine and prednisolone.

    Science.gov (United States)

    Madsen, J K; Kornerup, H J; Pedersen, E B

    1995-11-01

    A total of 25 renal transplant recipients, treated solely with prednisolone and azathioprine, were investigated in a randomized, double-blind, placebo-controlled, cross-over study. The effect of a single oral dose of felodipine 5 mg or placebo on: glomerular filtration rate (GFR); renal plasma flow (RPF); renal vascular resistance (RVR); renal tubular sodium and water handling, measured by the lithium clearance technique; plasma levels of angiotensin II (AngII), aldosterone (Aldo), atrial natriuretic factor (ANF) and arginine vasopressin (AVP); blood pressure (BP), and heart rate (HR) was studied before, during, and after an intravenous infusion of cyclosporin (CyA). Three consecutive clearance periods were performed, each lasting 1 h. During the second period, CyA (0.75 mg kg-1 body weight) was infused. Before infusion of CyA, felodipine caused a significant rise (6.7%) in RPF and lowered RVR, but did not change GFR significantly. The rise in RPF was abolished by infusion of CyA. After infusion, both GFR (7.8%) and RPF (9.4%) were significantly higher and RVR lower after felodipine than after placebo. Proximal tubular output and total sodium excretion were higher on the felodipine day before and after, but not during CyA infusion. In all three periods felodipine reduced both systolic and diastolic BP. In conclusion, a single dose of felodipine increases RPF and decreases blood pressure in renal transplant recipients not treated with CyA. Although some of these changes are abolished by an acute intravenous infusion of CyA, the effects of felodipine are present again also during the 1st hour after the infusion and thereby indicate at least in part some renal protective effect of felodipine. It is suggested that a higher dose of felodipine might also have been preventive against CyA renal side-effects during the acute infusion.

  7. 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...... 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...

  8. Effects of supplemental recombinant bovine somatotropin and mist-fan cooling on the renal tubular handling of sodium in different stages of lactation in crossbred Holstein cattle.

    Science.gov (United States)

    Boonsanit, Dolrudee; Chanpongsang, Somchai; Chaiyabutr, Narongsak

    2012-08-01

    The effect of supplementary administration of recombinant bovine somatotrophin (rbST) on the renal tubular handling of sodium in crossbred 87.5% Holstein cattle housed in normal shade (NS) or mist-fan cooled (MF) barns was evaluated. The cows were injected with 500 mg rbST at three different stages of lactation. The MF barn housed cows showed a slightly decreased ambient temperature and temperature humidity index, but an increased relative humidity. Rectal temperature and respiration rates were significantly lower in cooled cows. The rbST treated cows, housed in NS or MF barns, showed markedly increased milk yields, total body water, extracellular fluid and plasma volume levels, along with a reduced rate of urine flow and urinary excretion of sodium, potassium and chloride ions and osmolar clearance, in all three stages of lactation. Renal tubular sodium and water reabsorption were increased after rbST administration without any alteration in the renal hemodynamics. Lithium clearance data suggested that the site of response is in the proximal nephron segment, which may be mediated via increases in the plasma levels of aldosterone and IGF-1, but not vasopressin, during rbST administration.

  9. Renal tubular acidosis.

    Science.gov (United States)

    Rothstein, M; Obialo, C; Hruska, K A

    1990-12-01

    Renal tubular acidosis refers to a group of disorders that result from pure tubular damage without concomitant glomerular damage. They could be hereditary (primary) or acquired (secondary to various disease states like sickle cell disease, obstructive uropathy, postrenal transplant, autoimmune disease, or drugs). The hallmark of the disorder is the presence of hyperchloremic metabolic acidosis with, or without, associated defects in potassium homeostasis, a UpH greater than 5.5 in the presence of systemic acidemia, and absence of an easily identifiable cause of the acidemia. There are three physiologic types whose basic defects are impairment of or a decrease in acid excretion, i.e., type 1 (dRTA); a failure in bicarbonate reabsorption, i.e., type 2 (pRTA); and deficiency of buffer or impaired generation of NH4+, i.e., type 4 RTA. Several pathophysiologic mechanisms have been postulated for these various types. pRTA is the least common of all in the adult population. It rarely occurs as an isolated defect. It is frequently accompanied by diffuse proximal tubule transport defects with aminoaciduria, glycosuria, hyperphosphaturia, and so forth (Fanconi syndrome). dRTA is associated with a high incidence of nephrolithiasis, nephrocalcinosis, osteodystrophy, and growth retardation (in children). Osteodystrophy also occurs in pRTA to a lesser degree and is believed to be secondary to hypophosphatemia. Patients with type 4 RTA usually have mild renal insufficiency from either diabetes mellitus or interstitial nephritis. Acute bicarbonate loading will result in a high fractional excretion of bicarbonate greater than 15% (FEHCO3- greater than 15%) in patients with pRTA, but FEHCO3- less than 3% in patients with dRTA. Type I patients will also have a low (U - B) PCO2 with bicarbonate loading. They are also unable to lower their urine pH to less than 5.5 with NH4Cl loading. The treatment of these patients involves avoidance of precipitating factors when possible, treatment

  10. 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

    (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...

  11. 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. 2016 BMJ Publishing Group Ltd.

  12. Genetics Home Reference: renal tubular dysgenesis

    Science.gov (United States)

    ... groups? Genetic Changes Mutations in the ACE , AGT , AGTR1 , or REN gene can cause renal tubular dysgenesis . ... receptor type 1 (AT1 receptor; produced from the AGTR1 gene), stimulating chemical signaling. By binding to the ...

  13. 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...

  14. 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.

  15. 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.

  16. Distal renal tubular acidosis with hereditary spherocytosis.

    Science.gov (United States)

    Sinha, Rajiv; Agarwal, Indira; Bawazir, Waleed M; Bruce, Lesley J

    2013-07-01

    Hereditary spherocytosis (HS) and distal renal tubular acidosis (dRTA), although distinct entities, share the same protein i.e. the anion exchanger1 (AE1) protein. Despite this, their coexistence has been rarely reported. We hereby describe the largest family to date with co-existence of dRTA and HS and discuss the molecular basis for the co-inheritance of these conditions.

  17. Mechanisms in hyperkalemic renal tubular acidosis.

    Science.gov (United States)

    Karet, Fiona E

    2009-02-01

    The form of renal tubular acidosis associated with hyperkalemia is usually attributable to real or apparent hypoaldosteronism. It is therefore a common feature in diabetes and a number of other conditions associated with underproduction of renin or aldosterone. In addition, the close relationship between potassium levels and ammonia production dictates that hyperkalemia per se can lead to acidosis. Here I describe the modern relationship between molecular function of the distal portion of the nephron, pathways of ammoniagenesis, and hyperkalemia.

  18. The syndrome of renal tubular acidosis with nerve deafness.

    Science.gov (United States)

    Donckerwolcke, R A; Van Biervliet, J P; Koorevaar, G; Kuijten, R H; Van Stekelenburg, G J

    1976-01-01

    Two brothers with renal tubular acidosis and nerve deafness are described. Studies of the physiopathological characteristics of the renal acidification defect show that the defect is limited to the distal tubule. Renal tubular acidosis with nerve deafness is a distinct nosologic entity that is determined by an autosomal recessive trait.

  19. Relationships between the renal handling of DMPS and DMSA and the renal handling of mercury.

    Science.gov (United States)

    Zalups, Rudolfs K; Bridges, Christy C

    2012-09-17

    Within the body of this review, we provide updates on the mechanisms involved in the renal handling mercury (Hg) and the vicinal dithiol complexing/chelating agents, 2,3-bis(sulfanyl)propane-1-sulfonate (known formerly as 2,3-dimercaptopropane-1-sulfonate, DMPS) and meso-2,3-bis(sulfanyl)succinate (known formerly as meso-2,3-dimercaptosuccinate, DMSA), with a focus on the therapeutic effects of these dithiols following exposure to different chemical forms of Hg. We begin by reviewing briefly some of the chemical properties of Hg, with an emphasis on the high bonding affinity between mercuric ions and reduced sulfur atoms, principally those contained in protein and nonprotein thiols. A discussion is provided on the current body of knowledge pertaining to the handling of various mercuric species within the kidneys, focusing on the primary cellular targets that take up and are affected adversely by these species of Hg, namely, proximal tubular epithelial cells. Subsequently, we provide a brief update on the current knowledge on the handling of DMPS and DMSA in the kidneys. In particular, parallels are drawn between the mechanisms participating in the uptake of various thiol S-conjugates of Hg in proximal tubular cells and mechanisms by which DMPS and DMSA gain entry into these target epithelial cells. Finally, we discuss factors that permit DMPS and DMSA to bind intracellular mercuric ions and mechanisms transporting DMPS and DMSA S-conjugates of Hg out of proximal tubular epithelial cells into the luminal compartment of the nephron, and promoting urinary excretion.

  20. 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...... tubular absorption via P2 receptors. The apical P2Y2 receptor plays a crucial role in this process. ATP is released continuously into the tubular lumen. The release is augmented in response to an increase of tubular flow and after stimulation of G-protein-coupled receptors. The primary cilium appears...

  1. 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.

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

    DEFF Research Database (Denmark)

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

    1990-01-01

    1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during...... infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...... tubular outflow) increased by 38% (P less than 0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P less than 0.001). Calculated absolute distal sodium reabsorption [(CLi-CNa) x PNa, where PNa is plasma...

  3. 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

    1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity. 2. Glomerular function and the renal tubular handling of sodium during...... infusion of amino acids was studied in 12 normal volunteers. 3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P less than 0.05). GFR was increased by 13% (P less than 0.001). Clearance of lithium (CLi) (used as an index of proximal...... tubular outflow) increased by 38% (P less than 0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P less than 0.001). Calculated absolute distal sodium reabsorption [(CLi-CNa) x PNa, where PNa is plasma...

  4. 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...... the elements necessary for agonist-mediated intercellular communication. ATP is released from epithelial cells, which activates P2 receptors in the apical and basolateral membrane and thereby modulates tubular transport. Termination of the signal is conducted via the breakdown of ATP to adenosine. Recent far......-reaching advances indicate that ATP is often used as a local transmitter for classical sensory transduction. This transmission apparently also applies to sensory functions in the kidney. Locally released ATP is involved in sensing of renal tubular flow or in detecting the distal tubular load of NaCl at the macula...

  5. 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 ...

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

    DEFF Research Database (Denmark)

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

    1996-01-01

    The influence of angiotensin-converting enzyme (ACE) inhibition on renal tubular function in progressive chronic nephropathy was investigated in 69 patients by the lithium clearance (C(Li)) method. Studies were done repeatedly for up to 2 years during a controlled trial on the effect of enalapril....... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  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. Klinefelter's syndrome with renal tubular acidosis: impact on height.

    Science.gov (United States)

    Jebasingh, F; Paul, T V; Spurgeon, R; Abraham, S; Jacob, J J

    2010-02-01

    A 19-year-old Indian man presented with a history of proximal muscle weakness, knock knees and gynaecomastia. On examination he had features of rickets and bilateral small testes. Karyotyping revealed a chromosomal pattern of 47,XXX, confirming the diagnosis of Klinefelter's syndrome. He was also found to have hyperchloraemic metabolic acidosis with hypokalaemia, hypophosphataemia, phosphaturia and glycosuria, which favoured a diagnosis of proximal renal tubular acidosis. Patients with Klinefelter's syndrome typically have a tall stature due to androgen deficiency, resulting in unfused epiphyses and an additional X chromosome. However, this patient had a short stature due to associated proximal renal tubular acidosis. To the best of our knowledge, this is the second case of Klinefelter's syndrome with short stature due to associated renal tubular acidosis reported in the literature. This report highlights the need to consider other causes when patients with Klinefelter's syndrome present with a short stature.

  10. How renal cells handle urea.

    Science.gov (United States)

    Bagnasco, S M

    2000-01-01

    The urine concentration process requires an osmolality gradient along the renal cortico-medullary axis, with highest values in the renal papilla. NaCl and urea are the major solutes in the renal inner medulla, concentrations of urea up to 500-600 mM are found in the rat renal papilla. Urea can diffuse across cell membranes and contributes to balance intracellular and extracellular osmotic equilibrium. However, urea has perturbing effects on enzyme activity, and in concentrations above 300 mM is toxic for renal cultured cells. There is increasing evidence that urea can induce cellular responses distinct from those due to NaCl and other non-permeable solutes, including upregulation of immediate-early genes (IEGs). Urea transport by epithelial and endothelial cells is important for intra-medullary urea recycling and preservation of high urea concentration in the inner medulla. Trans-cellular movement of urea in cells expressing urea transporters may influence intracellular levels of this solute and modulate urea-induced signaling pathways. Regulation of urea transporters expression and activity can therefore be viewed as one aspect of cellular adaptation to urea. We have identified tonicity-responsive transcription as one mechanism regulating expression of the urea transporter UT-A. The short-term and long-term effects of variable extracellular urea concentration on the function of renal cells remain still unclear.

  11. sup 99m Tc renal tubular function agents: Current status

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    Eshima, D.; Fritzberg, A.R.; Taylor, A. Jr. (Emory Univ. School of Medicine, Atlanta, GA (USA))

    1990-01-01

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

  12. THE RENAL HANDLING OF HEMOGLOBIN

    Science.gov (United States)

    Bunn, H. Franklin; Esham, William T.; Bull, Robert W.

    1969-01-01

    The glomerular filtration of hemoglobin (α2β2) was studied under conditions in which its dissociation into αβ dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of 59Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose. PMID:5778789

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    Alejandra Droguett

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

  15. Distal renal tubular acidosis with multiorgan autoimmunity: A case report

    NARCIS (Netherlands)

    M.J. Van Den Wildenberg (Maria J.); E.J. Hoorn (Ewout); N. Mohebbi (Nilufar); C.A. Wagner (Carsten); A.J.J. Woittiez; P.A.M. de Vries; P. Laverman (Peter)

    2015-01-01

    textabstractA 61-year-old woman with a history of pernicious anemia presented with progressive muscle weakness and dysarthria. Hypokalemic paralysis (serum potassium, 1.4 mEq/L) due to distal renal tubular acidosis (dRTA) was diagnosed. After excluding several possible causes, dRTA was considered au

  16. Renal tubular leakage complicating microcephalic osteodysplastic primordial dwarfism.

    Science.gov (United States)

    Eason, J; Hall, C M; Trounce, J Q

    1995-01-01

    We describe a male infant with phenotypic and radiological features of microcephalic osteodysplastic primordial dwarfism type I/III. He showed severe osteoporosis and biochemical derangement owing to renal tubular leakage, which has not previously been reported in this condition. He died aged 5 months. Images PMID:7783178

  17. Renal sodium handling and sodium sensitivity

    Directory of Open Access Journals (Sweden)

    Alissa A. Frame

    2017-06-01

    Full Text Available The pathophysiology of hypertension, which affects over 1 billion individuals worldwide, involves the integration of the actions of multiple organ systems, including the kidney. The kidney, which governs sodium excretion via several mechanisms including pressure natriuresis and the actions of renal sodium transporters, is central to long term blood pressure regulation and the salt sensitivity of blood pressure. The impact of renal sodium handling and the salt sensitivity of blood pressure in health and hypertension is a critical public health issue owing to the excess of dietary salt consumed globally and the significant percentage of the global population exhibiting salt sensitivity. This review highlights recent advances that have provided new insight into the renal handling of sodium and the salt sensitivity of blood pressure, with a focus on genetic, inflammatory, dietary, sympathetic nervous system and oxidative stress mechanisms that influence renal sodium excretion. Increased understanding of the multiple integrated mechanisms that regulate the renal handling of sodium and the salt sensitivity of blood pressure has the potential to identify novel therapeutic targets and refine dietary guidelines designed to treat and prevent hypertension.

  18. Distal renal tubular acidosis without renal impairment after use of tenofovir: a case report

    OpenAIRE

    2016-01-01

    Background Tenofovir, one of antiretroviral medication to treat human immunodeficiency virus (HIV) infection, is known to cause proximal renal tubular acidosis such as Fanconi syndrome, but cases of distal renal tubular acidosis had never been reported. Case presentation A 20-year-old man with HIV infection developed nausea and vomiting without diarrhea after starting antiretroviral therapy. Arterial blood gas revealed non-anion-gap metabolic acidosis and urine test showed positive urine anio...

  19. 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

  20. Tubular Peroxiredoxin 3 as a Predictor of Renal Recovery from Acute Tubular Necrosis in Patients with Chronic Kidney Disease.

    Science.gov (United States)

    Wu, Chia-Lin; Su, Tzu-Cheng; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Chung-Ho; Yang, Tao-Hsiang; Chiu, Ping-Fang; Tarng, Der-Cherng

    2017-02-27

    Peroxiredoxin 3 (PRX3) is a mitochondrial antioxidant that regulates apoptosis in various cancers. However, whether tubular PRX3 predicts recovery of renal function following acute kidney injury (AKI) remains unknown. This retrospective cohort study included 54 hospitalized patients who had AKI with biopsy-proven acute tubular necrosis (ATN). The study endpoint was renal function recovery within 6 months. Of the 54 enrolled patients, 25 (46.3%) had pre-existing chronic kidney disease (CKD) and 33 (61%) recovered renal function. Tubular PRX3 expression was higher in patients with ATN than in those without renal function recovery. The level of tubular but not glomerular PRX3 expression predicted renal function recovery from AKI (AUROC = 0.76). In multivariate Cox regression analysis, high PRX3 expression was independently associated with a higher probability of renal function recovery (adjusted hazard ratio = 8.99; 95% CI 1.13-71.52, P = 0.04). Furthermore, the discriminative ability of the clinical model for AKI recovery was improved by adding tubular PRX3. High tubular PRX3 expression was associated with a higher probability of renal function recovery from ATN. Therefore, tubular PRX3 in combination with conventional predictors can further improve recovery prediction and may help with risk stratification in AKI patients with pre-existing CKD.

  1. Renal tubular function in children with beta-thalassemia minor.

    Science.gov (United States)

    Kalman, Süleyman; Atay, A Avni; Sakallioglu, Onur; Ozgürtaş, Taner; Gök, Faysal; Kurt, Ismail; Kürekçi, A Emin; Ozcan, Okan; Gökçay, Erdal

    2005-10-01

    beta-thalassemia minor is a common heterozygous haemoglobinopathy that is characterized by both microcytosis and hypochromia. It requires no treatment. It has been postulated that low-grade haemolysis, tubular iron deposition and toxins derived from erythrocytes might cause renal tubular damage in adult patients with beta-thalassemia minor. Our aim was to investigate the renal tubular functions in children with beta-thalassemia minor and to determine its possible harmful effects. The study was conducted on 32 children (14 female and 18 male) at the age of 5.8 +/- 3.1 years (range 2-14 years) with beta-thalassemia minor. The patients were classified as anaemic (haemoglobin (Hb) 11 g/dL) (Group 2, n = 18). A control group was formed with 18 healthy children whose ages and sexes match those in other groups (Group 3, n = 18). Fractional excretion of sodium (FE(Na), %), fractional excretion of magnesium (FE(Mg), %), fractional excretion of uric acid (FE(UA), %) and tubular phosphorus reabsorption (TPR,%) were calculated with standard formulas. Urinary calcium excretion (mg/kg per 24 h), zinc (Zn) (microg/dL), glucosuria (mg/dL), beta-2 microglobulin (mg/dL) and N-acetyl-beta-D-glycosaminidase (NAG, U/mmol creatinine) levels were measured through biochemical methods. There was no statistically significant difference among the three groups in terms of the results of FE(Na) (%), FE(Mg) (%), FE(UA) (%), TPR (%), calciuria (mg/kg per 24 h), NAG, urine Zn, proteinuria, glucosuria or urine beta- 2 microglobulin levels (P > 0.05). On the contrary of children with beta-thalassemia major, renal tubular dysfunction has not been determined in children with beta-thalassemia minor in the present study.

  2. 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.

  3. 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.

  4. Hypokalemic periodic paralysis and distal renal tubular acidosis associated with renal morphological changes.

    Science.gov (United States)

    Gupta, Ratan; Saurabh, Kumar; Sharma, Shobha; Gupta, Riyanka

    2013-03-01

    We report an unusual case of 5-yrs-old girl presenting with recurrent episodic weakness with documented hypokalemia, polyuria and failure to thrive. The child was finally diagnosed as having distal renal tubular acidosis. Imaging studies revealed associated hypoechoic spaces in renal medulla. Long term treatment with alkali and maintenance of normokalemia lead to regression of these morphological changes.

  5. Everything you need to know about distal renal tubular acidosis in autoimmune disease

    NARCIS (Netherlands)

    T. Both (Tim); R. Zietse (Bob); E.J. Hoorn (Ewout); P.M. van Hagen (Martin); V.A.S.H. Dalm (Virgil); J.A.M. van Laar (Jan); P.L.A. van Daele (Paul)

    2014-01-01

    textabstractRenal acid-base homeostasis is a complex process, effectuated by bicarbonate reabsorption and acid secretion. Impairment of urinary acidification is called renal tubular acidosis (RTA). Distal renal tubular acidosis (dRTA) is the most common form of the RTA syndromes. Multiple pathophysi

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

    DEFF Research Database (Denmark)

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

    1985-01-01

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

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

    Directory of Open Access Journals (Sweden)

    P Ravi

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Manjunath Kulkarni

    2016-02-01

    Full Text Available 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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    R A Misgar

    2017-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  13. Reduction of metformin renal tubular secretion by cimetidine in man.

    OpenAIRE

    Somogyi, A.; Stockley, C; Keal, J; Rolan, P; Bochner, F

    1987-01-01

    To determine whether cimetidine altered the renal handling of metformin, seven subjects took 0.25 g metformin daily with and without cimetidine 0.4 g twice daily. Blood and urine samples were collected and assayed for metformin, cimetidine and creatinine by h.p.l.c. Cimetidine significantly increased the area under the plasma metformin concentration-time curve by an average of 50% and reduced its renal clearance over 24 h by 27% (P less than 0.008). There was no alteration in the total urinar...

  14. 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.

  15. 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.

  16. 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.

  17. 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....

  18. 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.

  19. Tenofovir is associated with increased tubular proteinuria and asymptomatic renal tubular dysfunction in Ghana.

    Science.gov (United States)

    Chadwick, David R; Sarfo, Fred S; Kirk, Elaine S M; Owusu, Dorcas; Bedu-Addo, George; Parris, Victoria; Owusu, Ann Lorraine; Phillips, Richard

    2015-12-01

    HIV infection is associated with increased risk of renal dysfunction, including tubular dysfunction (TD) related to antiretroviral therapy (ART). Tenofovir disoproxil fumarate (TDF) is becoming available for ART in sub-Saharan Africa, although data on its long-term safety there is limited. We aimed to study the prevalence of HIV-associated renal dysfunction in Ghana and explore associations between proteinuria or TD and potential risk factors, including TDF use. A single-centre cross-sectional observational study of patients taking ART was undertaken. Creatinine clearance (CrCl) was calculated and proteinuria detected with dipsticks. Spot urinary albumin and protein:creatinine ratios (uACR/uPCR) were measured and further evidence of TD (defined as having two or more characteristic features) sought. Logistic regression analysis identified factors associated with proteinuria or TD. In 330 patients, of whom 101 were taking TDF (median 20 months), the prevalence of CrCl proteinuria and TD was 7 %, 37 % and 15 %. Factors associated with proteinuria were baseline CD4-count [aOR 0.86/100 cell increment (95 % CI, 0.74-0.99)] and TDF use [aOR 2.74 (95 % CI, 1.38-5.43)]. The only factor associated with TD was TDF use [aOR 3.43 (95 % CI, 1.10-10.69)]. In a subset with uPCR measurements, uPCRs were significantly higher in patients taking TDF than those on other drugs (10.8 vs. 5.7 mg/mmol, p proteinuria and TD are common and associated with TDF use in Ghana. Further longitudinal studies to determine whether proteinuria, TD or TDF use are linked to progressive decline in renal function or other adverse outcomes are needed in Africa.

  20. 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

    rHuEPO elevates hemoglobin concentration both by increasing red blood cell volume and by a decrease in plasma volume. This study delineates the association of rHuEPO-induced changes in blood volumes with changes in the renin-aldosterone system and renal function. 16 healthy males were given rHuEPO...... tubular outflow and to assess segmental renal tubular handling of sodium and water. rHuEPO-induced increases in hematocrit occurred from day 10 onwards and was caused by both an increase in red cell volume and a fall in plasma volume. Well before that (from day 2 and throughout the treatment time), rHuEPO...... decreased plasma levels of renin and aldosterone (N = 8) by 21 - 33 % (P EPO values returned to baseline. On days 11 and 29 C(Li) increased (P

  1. Tubular kidney injury molecule-1 (KIM-1) in human renal disease

    NARCIS (Netherlands)

    van Timmeren, M. M.; van den Heuvel, M. C.; Bailly, V.; Bakker, S. J. L.; van Goor, H.; Stegeman, C. A.

    2007-01-01

    KIM-1, a transmembrane tubular protein with unknown function, is undetectable in normal kidneys, but is markedly induced in experimental renal injury. The KIM-1 ectodomain is cleaved, detectable in urine, and reflects renal damage. KIM-1 expression in human renal biopsies and its correlation with ur

  2. 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.

  3. 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.)

  4. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

    Directory of Open Access Journals (Sweden)

    Ana M Blázquez-Medela

    Full Text Available Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD eventually leading to end stage renal disease (ESRD and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR or L-NAME induced hypertension rendered hyperglycemic (or not as controls.Combination of hypertension and hyperglycemia (but not each of these factors independently causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors.Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  7. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria.

    Science.gov (United States)

    Chen, Jun-Feng; Wu, Qi-Shun; Xie, Yu-Xian; Si, Bo-Lin; Yang, Ping-Ping; Wang, Wen-Yan; Hua, Qin; He, Qing

    2017-10-01

    Mitochondrial dysfunction causes renal tubular epithelial cell injury and promotes cell apoptosis and renal tubulointerstitial fibrosis (TIF) progression. TNF receptor-associated protein 1 (TRAP1) is a molecular chaperone protein that is localized in mitochondria. It plays an important role in cell apoptosis; however, its functional mechanism in TIF remains unclear. In this study, we observed the effects of TRAP1 in renal tubular epithelial cell mitochondria in mice with unilateral ureteral obstruction and its function in cell apoptosis and TIF. Results show that TRAP1 could protect the mitochondrial structure in renal tubular epithelial cells; maintain the levels of mitochondrial membrane potential, ATP, and mitochondrial DNA copy number; inhibit reactive oxygen species production; stabilize the expression of the mitochondrial inner membrane protein mitofilin; reduce renal tubular epithelial cell apoptosis; and inhibit TIF. These results provide new theoretical foundations for additional understanding of the antifibrotic mechanism of TRAP1 in the kidney.-Chen, J.-F., Wu, Q.-S., Xie, Y.-X., Si, B.-L., Yang, P.-P., Wang, W.-Y., Hua, Q., He, Q. TRAP1 ameliorates renal tubulointerstitial fibrosis in mice with unilateral ureteral obstruction by protecting renal tubular epithelial cell mitochondria. © FASEB.

  8. Effect of nitrendipine on renal function and on hormonal parameters after intravascular iopromide

    DEFF Research Database (Denmark)

    Madsen, J K; Jensen, J W; Sandermann, J

    1998-01-01

    . Renal tubular function was estimated from the clearance of lithium. Hormones were measured by radioimmunoassays. RESULTS: Arteriography with iopromide did not change renal function. No differences between the nitrendipine and placebo groups were found in renal hemodynamics, tubular sodium handling...

  9. 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.)

  10. Expression of cleaved caspase-3 in renal tubular cells in Plasmodium falciparum malaria patients.

    Science.gov (United States)

    Wichapoon, Benjamas; Punsawad, Chuchard; Viriyavejakul, Parnpen

    2017-01-01

    In Plasmodium falciparum malaria, the clinical manifestation of acute kidney injury (AKI) is commonly associated with acute tubular necrosis (ATN) in the kidney tissues. Renal tubular cells often exhibit various degrees of cloudy swelling, cell degeneration, and frank necrosis. To study individual cell death, this study evaluates the degree of renal tubular necrosis in association with apoptosis in malarial kidneys. Kidney tissues from P. falciparum malaria with AKI (10 cases), and without AKI (10 cases) were evaluated for tubular pathology. Normal kidney tissues from 10 cases served as controls. Tubular necrosis was assessed quantitatively in kidney tissues infected with P. falciparum malaria, based on histopathological evaluation. In addition, the occurrence of apoptosis was investigated using cleaved caspase-3 marker. Correlation between tubular necrosis and apoptosis was analyzed. Tubular necrosis was found to be highest in P. falciparum malaria patients with AKI (36.44% ± 3.21), compared to non-AKI (15.88% ± 1.63) and control groups (2.58% ± 0.39) (all p < 0.001). In the AKI group, the distal tubules showed a significantly higher degree of tubular necrosis than the proximal tubules (p = 0.021) and collecting tubules (p = 0.033). Tubular necrosis was significantly correlated with the level of serum creatinine (r = 0.596, p = 0.006), and the occurrence of apoptosis (r = 0.681, p = 0.001). In malarial AKI, the process of apoptosis occurs in ATN. © 2016 Asian Pacific Society of Nephrology.

  11. Altered renal sodium handling and risk of incident hypertension: Results of the Olivetti Heart Study

    Science.gov (United States)

    D’Elia, Lanfranco; Cappuccio, Francesco P.; Iacone, Roberto; Russo, Ornella; Galletti, Ferruccio; Strazzullo, Pasquale

    2017-01-01

    Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study). The study included 294 untreated normotensive non-diabetic men with normal renal function examined twice (1994–95 and 2002–04). Renal tubular Na handling was estimated by exogenous lithium clearance. Fractional reabsorption of Na in proximal and distal tubules was calculated and included in the analysis. At baseline, there was no association between BP and either proximal or distal fractional reabsorption of Na. At the end of the 8-year follow-up, direct associations were observed between baseline proximal (but not distal) Na fractional reabsorption and the changes occurred in systolic and diastolic BP over time (+2.79 and +1.53 mmHg, respectively, per 1SD difference in proximal Na-FR; phypertension, independently of potential confounders (OR: 1.34, 95%CI:1.06–1.70). The results of this prospective investigation strongly suggest a causal relationship between an enhanced rate of Na reabsorption in the proximal tubule and the risk of incident hypertension in initially normotensive men. PMID:28196131

  12. Renal handling of beta-2-microglobulin, amylase and albumin in acute pancreatitis.

    Science.gov (United States)

    Karlsson, F A; Jacobson, G

    1979-01-01

    The renal handling of beta-2-microglobulin, amylase and albumin was studied in patients with acute pancreatitis. The data were compared with results obtained from patients with glomerular proteinuria and from patients with tubular proteinuria. Initially during acute pancreatitis, the clearance ratio (clearance protein/clearance creatinine) for beta-2-microglobulin was increased dramatically (77-fold) compared to normals. After four to seven days this ratio had fallen and was elevated only 7-fold. The corresponding figures for amylase were 3.3 and 1.8 times and for albumin 9 and 5 times respectively. In glomerular disease, the clearance ratios for beta-2-microglobulin, amylase and albumin were increased 6, 1.1, and 154 times and in tubular disease 448, 1.1, and 28 times, respectively. The electrophoretic pattern of the urinary proteins during pancreatitis was mostly normal. In a few cases, slight tubular proteinuria was noticed. Amylase activity in serum and urine from patients with pancreatitis was found to sediment, (S20,W = 4.6) in a sucrose gradient, identical to amylase from normal serum and urine. The marked increase in the excretion of beta-2-microglobulin probably reflects interference of the kidney function at the proximal tubular level. Determinations of this protein in urine may be of value in studies of kidney dysfunction that can accompany pancreatitis.

  13. mTORC1 maintains renal tubular homeostasis and is essential in response to ischemic stress.

    Science.gov (United States)

    Grahammer, Florian; Haenisch, Nora; Steinhardt, Frederic; Sandner, Lukas; Sander, Lukas; Roerden, Malte; Arnold, Frederic; Cordts, Tomke; Wanner, Nicola; Reichardt, Wilfried; Kerjaschki, Dontscho; Ruegg, Markus A; Hall, Michael N; Moulin, Pierre; Busch, Hauke; Boerries, Melanie; Walz, Gerd; Artunc, Ferruh; Huber, Tobias B

    2014-07-08

    Mammalian target of rapamycin complex 1 (mTORC1) is a key regulator of cell metabolism and autophagy. Despite widespread clinical use of mTORC1 inhibitors, the role of mTORC1 in renal tubular function and kidney homeostasis remains elusive. By using constitutive and inducible deletion of conditional Raptor alleles in renal tubular epithelial cells, we discovered that mTORC1 deficiency caused a marked concentrating defect, loss of tubular cells, and slowly progressive renal fibrosis. Transcriptional profiling revealed that mTORC1 maintains renal tubular homeostasis by controlling mitochondrial metabolism and biogenesis as well as transcellular transport processes involved in countercurrent multiplication and urine concentration. Although mTORC2 partially compensated for the loss of mTORC1, exposure to ischemia and reperfusion injury exaggerated the tubular damage in mTORC1-deficient mice and caused pronounced apoptosis, diminished proliferation rates, and delayed recovery. These findings identify mTORC1 as an important regulator of tubular energy metabolism and as a crucial component of ischemic stress responses.

  14. Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor

    Directory of Open Access Journals (Sweden)

    Prabahar Murugesan

    2008-01-01

    Full Text Available Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with renal magnesium wasting, decreased tubular absorption of phosphorus, hypo-uricemia with renal uric acid wasting, renal glycosuria and tubular proteinuria have been described even in patients with beta thalassemia minor. We here in report a 24-year old female patient who was found to have thalassemia minor and nephrocalcinosis with evidence of renal tubular dysfunction. Investigations revealed normal renal function, hypercalciuria, reduced tubular reabsorption of phos-phorus, hypomagnesemia and renal magnesium wasting. Screening for aminoaciduria was found to be negative. An acid loading test revealed normal urinary acidification. Ultrasonogram of the abdomen revealed nephrocalcinosis and splenomegaly. Detailed work up for anemia showed normal white cell and platelet count while peripheral smear showed microcytic hypochromic anemia with few target cells. Hemoglobin electrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% and hemo-globin F of 1.8% consistent with beta thalassemia minor. Her parental screening was normal. A diag-nosis of beta thalassemia minor with renal tubular dysfunction was made and the patient was started on thiazide diuretics to reduce hypercalciuria and advised regular follow-up.

  15. Prolactin and dopamine 1-like receptor interaction in renal proximal tubular cells.

    Science.gov (United States)

    Crambert, Susanne; Sjöberg, Agneta; Eklöf, Ann-Christine; Ibarra, Fernando; Holtbäck, Ulla

    2010-07-01

    Prolactin is a natriuretic hormone and acts by inhibiting the activity of renal tubular Na(+)-K(+)-ATPase activity. These effects require an intact renal dopamine system. Here, we have studied by which mechanism prolactin and dopamine interact in Sprague-Dawley rat renal tissue. Na(+)-K(+)-ATPase activity was measured as ouabain-sensitive ATP hydrolysis in microdissected renal proximal tubular segments. Intracellular signaling pathways were studied by a variety of different techniques, including Western blotting using phosphospecific antibodies, immunoprecipitation, and biotinylation assays. We found that dopamine and prolactin regulated Na(+)-K(+)-ATPase activity via similar signaling pathways, including protein kinase A, protein kinase C, and phosphoinositide 3-kinase activation. The cross talk between prolactin and dopamine 1-like receptors was explained by a heterologous recruitment of dopamine 1-like receptors to the plasma membrane in renal proximal tubular cells. Prolactin had no effect on Na(+)-K(+)-ATPase activity in spontaneously hypertensive rats, a rat strain with a blunted response to dopamine. These results further emphasize the central role of the renal dopamine system in the interactive regulation of renal tubular salt balance.

  16. Tubulointerstitial Nephritis Complicated by Fanconi Syndrome and Renal Tubular Acidosis Associated with three autoimmune diseases

    OpenAIRE

    Io, Kumiko; Obata, Yoko; Nishino, Tomoya; Hirose, Misaki; Yamashita, Hiroshi; Uramatsu, Tadashi; Ichikawa, Tatsuki; Hayashi, Tomayoshi; Kawakami, Atsushi; Taguchi, Takashi; Kohno, Shigeru

    2013-01-01

    A 45-year-old woman experiencing back pain showed signs of metabolic acidosis and electrolyte imbalances. The results of blood and urine tests indicated Fanconi syndrome and renal tubular acidosis. An x-ray showed vertebral fractures, which were thought to responsible for the back pain. In addition, the patient had proteinuria and renal dysfunction; therefore, renal biopsy was performed, and tubulointerstitial nephritis (TIN) was diagnosed. While investigating TIN, primary biliary cirrhosis a...

  17. 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;

    , apoptosis and inflammation. Lactate dehydrogenase (LDH) activity has previously been suggested as a renal tubular injury marker, but has a major limitation in the sense that it can only be measured in terminal kidneys. By the use of a hyperpolarized [1-13C]pyruvate magnetic resonance imaging (MRI) approach...... to monitor metabolic changes, we here investigate LDH activity and renal metabolism after IRI. This procedure gives a novel non-invasive method for investigation renal tissue injury in concern with IRI....

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Role of claudins in renal calcium handling

    Directory of Open Access Journals (Sweden)

    Armando Luis Negri

    2015-07-01

    Full Text Available Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR, which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline.

  20. 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),

  1. Renal tubular epithelial cell prorenin receptor regulates blood pressure and sodium transport.

    Science.gov (United States)

    Ramkumar, Nirupama; Stuart, Deborah; Mironova, Elena; Bugay, Vladislav; Wang, Shuping; Abraham, Nikita; Ichihara, Atsuhiro; Stockand, James D; Kohan, Donald E

    2016-07-01

    The physiological significance of the renal tubular prorenin receptor (PRR) has been difficult to elucidate due to developmental abnormalities associated with global or renal-specific PRR knockout (KO). We recently developed an inducible renal tubule-wide PRR KO using the Pax8/LC1 transgenes and demonstrated that disruption of renal tubular PRR at 1 mo of age caused no renal histological abnormalities. Here, we examined the role of renal tubular PRR in blood pressure (BP) regulation and Na(+) excretion and investigated the signaling mechanisms by which PRR regulates Na(+) balance. No detectable differences in BP were observed between control and PRR KO mice fed normal- or low-Na(+) diets. However, compared with controls, PRR KO mice had elevated plasma renin concentration and lower cumulative Na(+) balance with normal- and low-Na(+) intake. PRR KO mice had an attenuated hypertensive response and reduced Na(+) retention following angiotensin II (ANG II) infusion. Furthermore, PRR KO mice had significantly lower epithelial Na(+) channel (ENaC-α) expression. Treatment with mouse prorenin increased, while PRR antagonism decreased, ENaC activity in isolated split-open collecting ducts (CD). The prorenin effect was prevented by protein kinase A and Akt inhibition, but unaffected by blockade of AT1, ERK1/2, or p38 MAPK pathways. Taken together, these data indicate that renal tubular PRR, likely via direct prorenin/renin stimulation of PKA/Akt-dependent pathways, stimulates CD ENaC activity. Absence of renal tubular PRR promotes Na(+) wasting and reduces the hypertensive response to ANG II.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Ishida, Tokiko; Kotani, Hirokazu; Miyao, Masashi; Kawai, Chihiro; Jemail, Leila; Abiru, Hitoshi; Tamaki, Keiji

    2016-01-01

    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 pathophysiological mechanisms of

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

    Directory of Open Access Journals (Sweden)

    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

  5. Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

    Science.gov (United States)

    Nielsen, A H; Knudsen, F; Danielsen, H; Pedersen, E B; Fjeldborg, P; Madsen, M; Brøchner-Mortensen, J; Kornerup, H J

    1987-02-01

    In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

  6. 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

  7. Biotransformation, transport and toxicity studies in rat renal proximal tubular cells.

    NARCIS (Netherlands)

    Haenen, H.E.M.G.

    1996-01-01

    SummaryRenal proximal tubular (RPT) cells can be exposed apically to glomerulary filtrated and basolaterally to non-filtrated nephrotoxic compounds. To excrete these compounds via the urine, RPT cells are equipped with transport systems able to transport nephrotoxicants from the basolateral to the a

  8. 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.

  9. Renal phenotypic investigations of megalin-deficient patients: novel insights into tubular proteinuria and albumin filtration.

    Science.gov (United States)

    Storm, Tina; Tranebjærg, Lisbeth; Frykholm, Carina; Birn, Henrik; Verroust, Pierre J; Nevéus, Tryggve; Sundelin, Birgitta; Hertz, Jens Michael; Holmström, Gerd; Ericson, Katharina; Christensen, Erik I; Nielsen, Rikke

    2013-03-01

    The reabsorption of filtered plasma proteins, hormones and vitamins by the renal proximal tubules is vital for body homeostasis. Studies of megalin-deficient mice suggest that the large multi-ligand endocytic receptor megalin plays an essential role in this process. In humans, dysfunctional megalin causes the extremely rare Donnai-Barrow/Facio-Oculo-Acustico-Renal (DB/FOAR) syndrome characterized by a characteristic and multifaceted phenotype including low-molecular-weight proteinuria. In this study, we examined the role of megalin for tubular protein reabsorption in humans through analysis of proximal tubular function in megalin-deficient patients. Direct sequencing of the megalin-encoding gene (LRP2) was performed in a family in which three children presented with classical DB/FOAR manifestations. Renal consequences of megalin deficiency were investigated through immunohistochemical analyses of renal biopsy material and immunoblotting of urine samples. In the patients, a characteristic urinary protein profile with increased urinary excretion of vitamin D-binding protein, retinol-binding protein and albumin was associated with absence of, or reduced, proximal tubular endocytic uptake as shown by renal immunohistochemistry. In the absence of tubular uptake, urinary albumin excretion was in the micro-albuminuric range suggesting that limited amounts of albumin are filtered in human glomeruli. This study demonstrated that megalin plays an essential role for human proximal tubular protein reabsorption and suggests that only limited amounts of albumin is normally filtered in the human glomeruli. Finally, we propose that the characteristic urinary protein profile of DB/FOAR patients may be utilized as a diagnostic marker of megalin dysfunction.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis.

    Science.gov (United States)

    Yılmaz, Hakkı; Kaya, Mustafa; Özbek, Mustafa; ÜUreten, Kemal; Safa Yıldırım, İ

    2013-07-01

    We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia.

  13. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  15. 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.

  16. Influence of urinary sodium excretion on the clinical assessment of renal tubular calcium reabsorption in hypercalcaemic man.

    Science.gov (United States)

    Ralston, S H; Gardner, M D; Dryburgh, F J; Cowan, R A; Boyle, I T

    1986-06-01

    The relation between urinary sodium excretion (NaE) and renal tubular calcium reabsorption (TmCa/GFR) was assessed in patients with hypercalcaemia associated with malignancy and primary hyperparathyroidism. On acute saline loading of seven normally hydrated patients with primary hyperparathyroidism and five patients with malignancy, raised values of TmCa/GFR were reduced to normal in most cases, in association with increases in NaE. The reduction in TmCa/GFR, which occurred, may have been due to a reduction in proximal tubular calcium reabsorption associated with sodium: this would have obscured the effect of humorally mediated increases in distal tubular calcium reabsorption, which are stimulated either by parathyroid hormone or by a putative humoral mediator in hypercalcaemia of malignancy. In patients who were normally hydrated NaE and TmCa/GFR were not significantly correlated. When data were included from patients who were dehydrated and from those undergoing acute saline loading, significant inverse correlations between NaE and TmCa/GFR were observed both in primary hyperparathyroidism (r = -0.49; p less than 0.02) and malignancy (r = -0.60; p less than 0.001). In clinical practice changes in TmCa/GFR associated with sodium seem to be of minor importance under normal circumstances, but they become evident at the upper and lower extremes of urinary sodium excretion. In clinical studies of renal calcium handling urinary sodium excretion must also be assessed, as interpreting TmCa/GFR data is difficult in states of excessive sodium loading or depletion.

  17. Renal tubular acidosis type IV as a complication of lupus nephritis.

    Science.gov (United States)

    Sánchez-Marcos, C; Hoffman, V; Prieto-González, S; Hernández-Rodríguez, J; Espinosa, G

    2016-03-01

    Renal tubular acidosis (RTA) is a rare complication of renal involvement of systemic lupus erythematosus (SLE). We describe a 24-year-old male with type IV lupus nephropathy as a presenting manifestation of SLE. He presented with improvement of renal function following induction therapy with three pulses of methylprednisolone and 500 mg biweekly pulses of cyclophosphamide. However, a week after the first pulse of cyclophosphamide, the patient presented with a significant increase in legs edema and severe hyperkalemia. Type IV RTA associated with hyporeninemic hypoaldosteronism was suspected in the presence of metabolic acidosis with a normal anion gap, severe hyperkalemia without worsening renal function, and urinary pH of 5. RTA was confirmed with a transtubular potassium concentration gradient of 2 and low levels of plasma aldosterone, renin, angiotensin II, and cortisol. Intravenous bicarbonate, high-dose furosemide, and fludrocortisone were administered with normalization of potassium levels and renal function.

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

    Directory of Open Access Journals (Sweden)

    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

  19. HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells.

    Science.gov (United States)

    Ross, Michael J; Fan, Cheng; Ross, Michael D; Chu, Te-Huatearina; Shi, Yueyue; Kaufman, Lewis; Zhang, Weijia; Klotman, Mary E; Klotman, Paul E

    2006-05-01

    HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of renal epithelial cells, but the cellular response to this infection remains poorly defined. In these studies, we used oligonucleotide microarrays to identify differentially expressed genes in renal tubular epithelial cells from a patient with HIVAN at three time points after infection with vesicular stomatitis virus-pseudotyped gag/pol-deleted HIV-1. Very few genes were differentially expressed 12 and 24 hours after infection. Three days after infection, however, 47 genes were upregulated by at least 1.8-fold. The most prominent response of these cells to HIV-1 expression was production of proinflammatory mediators, including chemokines, cytokines, and adhesion molecules. Many of the upregulated genes are targets of interleukin 6 and nuclear factor kappa B regulation, suggesting a central role for these proteins in the response of tubular epithelial cells to HIV-1 infection. Analysis of kidneys from HIV-1 transgenic mice revealed upregulation of many of the proinflammatory genes identified in the microarray studies. These studies provide novel insights into the mechanisms by which HIV-1 infection of tubular epithelial cells leads to tubulointerstitial inflammation and progressive renal injury.

  20. 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.

  1. Renal Differentiation of Mesenchymal Stem Cells Seeded on Nanofibrous Scaffolds Improved by Human Renal Tubular Cell Lines-Conditioned Medium.

    Science.gov (United States)

    Ardeshirylajimi, Abdolreza; Vakilian, Saeid; Salehi, Mohammad; Mossahebi-Mohammadi, Majid

    Kidney injuries and renal dysfunctions are one of the most important clinical problems, and tissue engineering could be a valuable method for solving it. The objective of this study was to investigate the synergistic effect of renal cell line-conditioned medium and Polycaprolactone (PCL) nanofibers on renal differentiation of human mesenchymal stem cells (MSCs). In the current study, after stem cells isolation and characterization, PCL nanofibrous scaffold was fabricated using electrospinning methods and characterized morphologically, mechanically, and for biocompatibility. The renal differentiation of seeded MSCs on the surface of PCL nanofibers with and without human renal tubular cell lines-conditioned medium was investigated by evaluation of eight important renal-related genes expression by real-time reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. Fabricated nanofibrous scaffolds were good in all characterized items. Almost highest expression of all genes was detected in stem cells seeded on PCL under conditioned media in comparison with the stem cells seeded on PCL, tissue culture polystyrene (TCPS) under renal induction medium, and TCPS under conditioned medium. According to the results, PCL nanofibers in contribution with conditioned medium can provide the optimal conditions for renal differentiation of MSCs and could be a promising candidate for renal tissue engineering application.

  2. An experimental renal acidification defect in patients with hereditary fructose intolerance. I. Its resemblance to renal tubular acidosis.

    Science.gov (United States)

    Morris, R C

    1968-06-01

    In three unrelated patients with hereditary fructose intolerance (HFI), but in none of five normal subjects, the experimental administration of fructose invariably induced a reversible dysfunction of the renal tubule with biochemical and physiological characteristics of renal tubular acidosis. During a state of ammonium chloride-induced acidosis, (a) urinary pH was greater than six and the rate of excretion of net acid (titratable acid plus ammonium minus bicarbonate) was inappropriately low, (b) the glomerular filtration rate remained unchanged or decreased modestly, and (c) urinary excretion of titratable acid increased briskly with diuresis of infused phosphate, although urinary pH changed little. The tubular dysfunction, which also includes impaired tubular reabsorption of alpha amino nitrogen and phosphate, persisted throughout administration of fructose and disappeared afterward. The tubular dysfunction was not causally dependent on hypoglucosemia, ammonium chloride-induced acidosis or osmotic diuresis. Rather, it appeared causally related to the fructose-induced metabolic abnormality of patients with HFI. The causal enzymatic defect, the virtual absence of fructose-1-phosphate aldolase, occurs in the kidney as well as in the liver of patients with HFI.

  3. Inhibition of tubular cell proliferation by neutralizing endogenous HGF leads to renal hypoxia and bone marrow-derived cell engraftment in acute renal failure.

    Science.gov (United States)

    Ohnishi, Hiroyuki; Mizuno, Shinya; Nakamura, Toshikazu

    2008-02-01

    During the progression of acute renal failure (ARF), the renal tubular S3 segment is sensitive to ischemic stresses. For reversing tubular damage, resident tubular cells proliferate, and bone marrow-derived cells (BMDC) can be engrafted into injured tubules. However, how resident epithelium or BMDC are involved in tubular repair remains unknown. Using a mouse model of ARF, we examined whether hepatocyte growth factor (HGF) regulates a balance of resident cell proliferation and BMDC recruitment. Within 48 h post-renal ischemia, tubular destruction became evident, followed by two-waved regenerative events: 1) tubular cell proliferation between 2 and 4 days, along with an increase in blood HGF; and 2) appearance of BMDC in the tubules from 6 days postischemia. When anti-HGF IgG was injected in the earlier stage, tubular cell proliferation was inhibited, leading to an increase in BMDC in renal tubules. Under the HGF-neutralized state, stromal cell-derived factor-1 (SDF1) levels increased in renal tubules, associated with the enhanced hypoxia. Administrations of anti-SDF1 receptor IgG into ARF mice reduced the number of BMDC in interstitium and tubules. Thus possible cascades include 1) inhibition of tubular cell proliferation by neutralizing HGF leads to renal hypoxia and SDF1 upregulation; and 2) BMDC are eventually engrafted in tubules through SDF1-mediated chemotaxis. Inversely, administration of recombinant HGF suppressed the renal hypoxia, SDF1 upregulation, and BMDC engraftment in ARF mice by enhancing resident tubular cell proliferation. Thus we conclude that HGF is a positive regulator for eliciting resident tubular cell proliferation, and SDF1 for BMDC engraftment during the repair process of ARF.

  4. DNA damage response in renal ischemia-reperfusion and ATP-depletion injury of renal tubular cells.

    Science.gov (United States)

    Ma, Zhengwei; Wei, Qingqing; Dong, Guie; Huo, Yuqing; Dong, Zheng

    2014-07-01

    Renal ischemia-reperfusion leads to acute kidney injury (AKI) that is characterized pathologically by tubular damage and cell death, followed by tubular repair, atrophy and interstitial fibrosis. Recent work suggested the possible presence of DNA damage response (DDR) in AKI. However, the evidence is sketchy and the role and regulation of DDR in ischemic AKI remain elusive. In this study, we demonstrated the induction of phosphorylation of ATM, H2AX, Chk2 and p53 during renal ischemia-reperfusion in mice, suggesting DDR in kidney tissues. DDR was also induced in vitro during the recovery or "reperfusion" of renal proximal tubular cells (RPTCs) after ATP depletion. DDR in RPTCs was abrogated by supplying glucose to maintain ATP via glycolysis, indicating that the DDR depends on ATP depletion. The DDR was also suppressed by the general caspase inhibitor z-VAD and the overexpression of Bcl-2, supporting a role of apoptosis-associated DNA damage in the DDR. N-acetylcysteine (NAC), an antioxidant, suppressed the phosphorylation of ATM and p53 and, to a less extent, Chk2, but NAC increased the phosphorylation and nuclear foci formation of H2AX. Interestingly, NAC increased apoptosis, which may account for the observed H2AX activation. Ku55933, an ATM inhibitor, blocked ATM phosphorylation and ameliorated the phosphorylation of Chk2 and p53, but it increased H2AX phosphorylation and nuclear foci formation. Ku55933 also increased apoptosis in RPTCs following ATP depletion. The results suggest that DDR occurs during renal ischemia-reperfusion in vivo and ATP-depletion injury in vitro. The DDR is partially induced by apoptosis and oxidative stress-related DNA damage. ATM, as a sensor in the DDR, may play a cytoprotective role against tubular cell injury and death.

  5. 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....

  6. 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.

  7. 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

  8. Acute effect of cisplatin on renal hemodynamics and tubular function in dog kidneys

    DEFF Research Database (Denmark)

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

    1986-01-01

    The present study was designed to investigate the early hemodynamic and tubular effects of cisplatin administration on dogs. To localize the nephrotoxic actions of cisplatin, we have taken advantage of the lithium clearance method. After infusion of 5 mg of cisplatin per kg, an immediate and sign.......56 +/- 0.04 and from 4.76 +/- 0.32 mmol/min to 3.92 +/- 0.23 mmol/min, respectively. The results show that administration of cisplatin causes an acute, mainly proximal tubular impairment in dogs without alterations in renal hemodynamics......./min) and fractional lithium clearance (from 0.31 +/- 0.03 to 0.44 +/- 0.04) was seen. This occurred without measurable changes in glomerular filtration rate and renal blood flow. The calculated fractional as well as absolute rates of proximal reabsorption of sodium decreased significantly from 0.68 +/- 0.03 to 0...

  9. Erythrophagocytosis of Lead-Exposed Erythrocytes by Renal Tubular Cells: Possible Role in Lead-Induced Nephrotoxicity

    OpenAIRE

    Kwon, So-Youn; Bae, Ok-Nam; Noh, Ji-Yoon; Kim, Keunyoung; Kang, Seojin; Shin, Young-Jun; Lim, Kyung-Min; Chung, Jin-Ho

    2014-01-01

    Background: Nephrotoxicity associated with lead poisoning has been frequently reported in epidemiological studies, but the underlying mechanisms have not been fully described. Objectives: We examined the role of erythrocytes, one of the major lead reservoirs, in lead-associated nephrotoxicity. Methods and results: Co-incubation of lead-exposed human erythrocytes with HK-2 human renal proximal tubular cells resulted in renal tubular cytotoxicity, suggesting a role of erythrocytes in lead-induc...

  10. Renal sodium handling in children with nephrotic relapse: relation to hypovolaemic symptoms.

    Science.gov (United States)

    Van de Walle, J G; Donckerwolcke, R A; Greidanus, T B; Joles, J A; Koomans, H A

    1996-11-01

    We studied renal sodium handling during water diuresis in children in the early phase of relapse of minimal lesion nephrotic syndrome (MLNS). Findings were related to presence or absence of symptoms suggestive of hypovolaemia, and to neurohumoral factors, and were compared to results of similar studies in the same children in remission. Nine children (aged 7.8 +/- 3.1 years) presented with hypovolaemic symptoms, and 10 (7.4 +/- 4.3 years) without such symptoms. Both groups displayed severe proteinuria, hypoproteinaemia and oedema. Symptomatic patients showed tendency for a low glomerular filtration rate, and significantly impaired urine dilution, decreased fractional sodium and lithium excretions, and elevated diluting segment reabsorption [CH2O/(CH2O + CNa)] and sodium/potassium exchange [UK/(UK + UNa)]. In the non-symptomatic patients these parameters were normal. Plasma renin and aldosterone were significantly elevated in the symptomatic children, and strongly correlated with all parameters of tubule sodium reabsorption. Weaker associations were found for plasma noradrenaline and atrial natriuretic peptide. Vasopressin was also relatively high in the symptomatic group, but showed no association with impaired urine dilution. The diffusely stimulated tubular sodium reabsorption in the symptomatic children, in association with stimulated neurohumoral factors, indicates that secondary sodium retention contributes to oedema formation in at least a subset of children developing a nephrotic relapse. This may be limited to the early stage, and be more pronounced in some patients than in others. The tubular defect responsible for maintenance of oedema in stabilized MLNS remains unclear.

  11. [Sjögren syndrome associated with renal tubular acidosis type I].

    Science.gov (United States)

    Górriz, L; Molino, R; Arjona, D; Estripeaut, D

    2000-01-01

    Primary Sjögren's Syndrome complicated with a renal tubular acidosis type 1 and hypocalcemic paralysis, as the principal clinical manifestation, is uncommon. Although the initial manifestations of the nephropathy are not well understood, it is believed that the invasion of mononuclear cells and the high level of circulating antibodies, play an important role in the pathogenesis of the disease. We present a patient with hypocalcemic paralysis as an initial manifestation of a latent Sjögren's disease. The glandular biopsy was normal, suggesting a mayor participation of an immunological humoral factor in the renal lesion.

  12. 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.

  13. Tauroursodeoxycholic Acid Attenuates Renal Tubular Injury in a Mouse Model of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Jing Zhang

    2016-09-01

    Full Text Available Renal tubular injury is a critical factor in the pathogenesis of diabetic nephropathy (DN. Endoplasmic reticulum (ER stress is involved in diabetic nephropathy. Tauroursodeoxycholic acid (TUDCA is an effective inhibitor of ER stress. Here, we investigated the role of TUDCA in the progression of tubular injury in DN. For eight weeks, being treated with TUDCA at 250 mg/kg intraperitoneal injection (i.p. twice a day, diabetic db/db mice had significantly reduced blood glucose, albuminuria and attenuated renal histopathology. These changes were associated with a significant decreased expression of ER stress markers. At the same time, diabetic db/db mice had more TUNEL-positive nuclei in the renal tubule, which were attenuated by TUDCA treatment, along with decreases in ER stress–associated apoptotic markers in the kidneys. In summary, the effect of TUDCA on tubular injury, in part, is associated with inhibition of ER stress in the kidneys of diabetic db/db mice. TUDCA shows potential as a therapeutic target for the prevention and treatment of DN.

  14. Dental Aspect of Distal Tubular Renal Acidosis with Genu Valgum Secondary to Rickets: A Case Report

    Directory of Open Access Journals (Sweden)

    Rakesh N. Bahadure

    2012-01-01

    Full Text Available Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis. Distal renal tubular acidosis (type I RTA is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic, pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year.

  15. Dental aspect of distal tubular renal acidosis with genu valgum secondary to rickets: a case report.

    Science.gov (United States)

    Bahadure, Rakesh N; Thosar, Nilima; Kriplani, Ritika; Baliga, Sudhindra; Fulzele, Punit

    2012-01-01

    Distal renal tubular acidosis is a disease that occurs when the kidneys do not remove acid properly into the urine, leaving the blood too acidic (called acidosis). Distal renal tubular acidosis (type I RTA) is caused by a defect in the kidney tubes that causes acid to build up in the bloodstream. It ultimately results rickets which include chronic skeletal pain, in skeletal deformities, skeletal fractures. Rickets is among the most frequent childhood diseases in many developing countries. Dental problems in rickets include delayed eruption of permanent teeth, premature fall of deciduous teeth, defects in structure of teeth, enamel defects in permanent teeth (hypoplastic), pulp defects, intraglobular dentine, and caries tooth. Herewith, reported a case of distal tubular renal acidosis with genu valgum secondary to rickets, with pain and extraoral swelling associated with right and left mandibular 1st permanent molars. Teeth were infected with pulp without being involved with caries. Radiographically cracks in enamel and dentin were observed. Pulp revascularization with 46 and root canal treatment was done for 36 with followup of 1 year.

  16. 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.

  17. [Itai-itai disease: cadmium-induced renal tubular osteomalacia].

    Science.gov (United States)

    Aoshima, Keiko

    2012-01-01

    Cadmium (Cd) is one of the most toxic elements to which humans could be exposed at work or in the environment. The outbreak of itai-itai disease, which is the most severe stage of chronic Cd poisoning, occurred in the Cd-polluted Jinzu River basin in Toyama. In this area, the river was contaminated by slag from a mine upstream; as a consequence, the soil in rice paddies was polluted with heavy metals including Cd through irrigation water from around 1910 to the 1960s. The government of Toyama prefecture carried out an extensive survey on Cd concentration in rice and soil of the paddy fields and declared that the upper layer of a total of 1500 ha of paddy fields should be replaced by nonpolluted soil. Then, an intervention program of soil replacement in the polluted paddy fields was continually carried out from 1980 to 2011. As a result, Cd concentration in rice markedly decreased. The kidney is the organ critically affected after long-term exposure to Cd. Proximal tubular dysfunction (RTD) has been found among the inhabitants of the Jinzu River basin. The very recent report by the Environmental Agency in Japan in 2009 has disclosed that b2-microglobulinuria with RTD is still found at a high prevalence among the inhabitants of the Jinzu River basin of both sexes. Twenty patients with itai-itai disease (1 male and 19 females), who attended our hospital and received medical examination during 2000 to 2008, had applied for recognition as itai-itai disease patients to the government of Toyama prefecture. In this paper, the recent epidemiological and clinical features of itai-itai disease are discussed on the basis of a review of the cases of these 19 female patients.

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

    Science.gov (United States)

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

    2011-01-01

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

  19. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Changes in renal tri-iodothyronine and thyroxine handling during fasting

    NARCIS (Netherlands)

    E.J. Rolleman; G. Hennemann; H. van Toor (Hans); C.H.H. Schoenmakers (Christian); E.P. Krenning (Eric); M. de Jong (Marion)

    2000-01-01

    textabstractOBJECTIVE: Liver handling of thyroid hormones (TH) has been known to alter significantly during fasting. This study investigates whether renal handling of TH is also changed during fasting. METHODS: We measured urinary excretion rates and clearances of free

  2. Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method

    DEFF Research Database (Denmark)

    Abildgaard, U; Holstein-Rathlou, N H; Leyssac, P P

    1986-01-01

    The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 +/- 7%), sodium...... reabsorption of sodium and water increased significantly by 9 +/- 2% and 8 +/- 2%. Low-frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 +/- 6%), sodium clearance (31 +/- 4%), lithium clearance (17 +/- 5%) and in fractional...... lithium clearance (18 +/- 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 +/- 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 +/- 5% and 16 +/- 5%. These changes in tubular sodium and water reabsorption during...

  3. 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

  4. 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.)

  5. 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.

  6. Hypokalemic periodic paralysis due to proximal renal tubular acidosis in a case with membranoproliferative glomerulonephritis.

    Science.gov (United States)

    Santra, Gouranga; De, Dibyendu; Sinha, Pradip Kumar

    2011-11-01

    Proximal renal tubular acidosis (pRTA) is a rare disorder. Hypokalemia may be associated with it; occasionally leading to features like hypokalemic periodic paralysis. Though pRTA is a tubulointerstitial kidney disease, glomerulonephritis may occasionally lead to pRTA by tubular damage through leaking proteins, cytokines or by inflammatory infiltrates. In our reported case a 27 year old male had recurrent episodes of hypokalemic quadriparesis. Investigations revealed features of pRTA including hypokalemia and non-anion-gap hyperchloremic metabolic acidosis. His urine pH dropped to 5 with NH4Cl loading test. Kidney biopsy showed membranoproliferative glomerulonephritis with tubulointerstitial damage. Hypokalemic periodic paralysis and pRTA are uncommon associations of membranoproliferative glomerulonephritis.

  7. Role of Stat3 Signaling in Control of EMT of Tubular Epithelial Cells During Renal Fibrosis

    Directory of Open Access Journals (Sweden)

    Jingsong Liu

    2017-08-01

    Full Text Available Background/Aims: Transforming growth factor β 1 (TGFβ1 plays a critical role in the epithelial-to-mesenchymal transition (EMT of renal tubular epithelial cells (TECs during renal injury, a major cause of acute renal failure, renal fibrosis and obstructive nephropathy. However, the underlying molecular mechanisms remain ill-defined. Here, we addressed this question. Methods: Expression of TGFβ1, Snail, and phosphorylated Stat3 was examined by immunohistochemistry in the kidney after induction of unilateral ureteral obstruction (UUO in mice. In vitro, primary TECs were purified by flow cytometry, and then challenged with TGFβ1 with/without presence of specific inhibitors for phosphorylation of SMAD3 or Stat3. Protein levels were determined by Western blotting. Results: We detected significant increases in Snail and phosphorylated Stat3, an activated form for Stat3, in the kidney after induction of UUO in mice. In vitro, TGFβ1-challenged primary TECs upregulated Snail, in a SMAD3/Stat3 dependent manner. Conclusion: Our study sheds light on the mechanism underlying the EMT of TECs after renal injury, and suggests Stat3 signaling as a promising innovative therapeutic target for prevention of renal fibrosis.

  8. 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.

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

    Science.gov (United States)

    Agarwal, Amit; Kumar, Pradeep; Gupta, Nomeeta

    2015-11-01

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

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

    DEFF Research Database (Denmark)

    Alexander, R Todd; Dimke, Henrik

    2017-01-01

    of clinical conditions, but most commonly for the management of blood pressure and fluid balance. The pharmacological targets of diuretics generally directly facilitate sodium (Na+) transport, but also indirectly affect renal Ca2+ and Mg2+ handling, i.e. by establishing a prerequisite electrochemical gradient...

  11. 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.

  12. Effects of "in vivo" administration of baclofen on rat renal tubular function.

    Science.gov (United States)

    Donato, Verónica; Pisani, Gerardo Bruno; Trumper, Laura; Monasterolo, Liliana Alicia

    2013-09-05

    The effects of the in vivo administration of baclofen on renal tubular transport and aquaporin-2 (AQP2) expression were evaluated. In conscious animals kept in metabolic cages, baclofen (0.01-1mg/kg, s.c.) induced a dose-dependent increment in the urine flow rate (UFR) and in sodium and potassium excretion, associated with an increased osmolal clearance (Closm), a diminished urine to plasma osmolality ratio (Uosm/Posm) and a decrease in AQP2 expression. The above mentioned baclofen effects on functional parameters were corroborated by using conventional renal clearance techniques. Additionally, this model allowed the detection of a diminution in glucose reabsorption. Some experiments were performed with water-deprived or desmopressin-treated rats kept in metabolic cages. Either water deprivation or desmopressin treatment decreased the UFR and increased the Uosm/Posm. Baclofen did not change the Uosm/Posm or AQP2 expression in desmopressin-treated rats; but it increased the UFR and diminished the Uosm/Posm and AQP2 expression in water-deprived animals. These results indicate that in vivo administration of baclofen promotes alterations in proximal tubular transport, since glucose reabsorption was decreased. The distal tubular function was also affected. The increased Closm indicates an alteration in solute reabsorption at the ascending limb of the Henle's loop. The decreased Uosm/Posm and AQP2 expression in controls and in water-deprived, but not in desmopressin-treated rats, lead us to speculate that some effect of baclofen on endogenous vasopressin availability could be responsible for the impaired urine concentrating ability, more than any disturbance in the responsiveness of the renal cells to the hormone.

  13. 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.

  14. Calcium oxalate monohydrate crystals internalized into renal tubular cells are degraded and dissolved by endolysosomes.

    Science.gov (United States)

    Chaiyarit, Sakdithep; Singhto, Nilubon; Thongboonkerd, Visith

    2016-02-25

    Interaction between calcium oxalate crystals and renal tubular cells has been recognized as one of the key mechanisms for kidney stone formation. While crystal adhesion and internalization have been extensively investigated, subsequent phenomena (i.e. crystal degradation and dissolution) remained poorly understood. To explore these mechanisms, we used fluorescein isothiocyanate (FITC)-labelled calcium oxalate monohydrate (COM) crystals (1000 μg/ml of crystals/culture medium) to confirm crystal internalization into MDCK (Type II) renal tubular cells after exposure to the crystals for 1 h and to trace the internalized crystals. Crystal size, intracellular and extracellular fluorescence levels were measured using a spectrofluorometer for up to 48 h after crystal internalization. Moreover, markers for early endosome (Rab5), late endosome (Rab7) and lysosome (LAMP-2) were examined by laser-scanning confocal microscopy. Fluorescence imaging and flow cytometry confirmed that FITC-labelled COM crystals were internalized into MDCK cells (14.83 ± 0.85%). The data also revealed a reduction of crystal size in a time-dependent manner. In concordance, intracellular and extracellular fluorescence levels were decreased and increased, respectively, indicating crystal degradation/dissolution inside the cells and the degraded products were eliminated extracellularly. Moreover, Rab5 and Rab7 were both up-regulated and were also associated with the up-regulated LAMP-2 to form large endolysosomes in the COM-treated cells at 16-h after crystal internalization. We demonstrate herein, for the first time, that COM crystals could be degraded/dissolved by endolysosomes inside renal tubular cells. These findings will be helpful to better understand the crystal fate and protective mechanism against kidney stone formation.

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

    Science.gov (United States)

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

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

  16. 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.

  17. Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.

    Science.gov (United States)

    Bando, Hironori; Hashimoto, Naoko; Hirota, Yushi; Sakaguchi, Kazuhiko; Hisa, Itoko; Inoue, Yoshifumi; Imanishi, Yasuo; Seino, Susumu; Kaji, Hiroshi

    2009-01-01

    A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D(3) with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

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

    DEFF Research Database (Denmark)

    Andersen, NN; Ladefoged, NN

    1991-01-01

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

  19. Renal tubular acidosis presenting as respiratory paralysis: Report of a case and review of literature

    Directory of Open Access Journals (Sweden)

    Kalita J

    2010-01-01

    Full Text Available Respiratory paralysis due to renal tubular acidosis (RTA is rare. We report a 22-year-old lady who developed severe bulbar, respiratory and limb paralysis following respiratory infection. She had hypokalemia (1.6 meq/L and hyperchloremic (110 meq/l acidosis (pH 7.1. She was diagnosed as distal RTA by ammonium chloride test. She improved following sodium bicarbonate and potassium supplementation. RTA should be differentiated from familial periodic paralysis (FPP because acetazolamide used in FPP aggravates RTA and sodium bicarbonate used in RTA aggravates hypokalemic periodic paralysis.

  20. Functional coupling of renal K+ and Na+ handling causes high blood pressure in Na+ replete mice.

    Science.gov (United States)

    Vitzthum, Helga; Seniuk, Anika; Schulte, Laura Helene; Müller, Maxie Luise; Hetz, Hannah; Ehmke, Heimo

    2014-03-01

    A network of kinases, including WNKs, SPAK and Sgk1, is critical for the independent regulation of K+ and Na+ transport in the distal nephron. Angiotensin II is thought to act as a key hormone in orchestrating these kinases to switch from K+ secretion during hyperkalaemia to Na+ reabsorption during intravascular volume depletion, thus keeping disturbances in electrolyte and blood pressure homeostasis at a minimum. It remains unclear, however, how K+ and Na+ transport are regulated during a high Na+ intake, which is associated with suppressed angiotensin II levels and a high distal tubular Na+ load. We therefore investigated the integrated blood pressure, renal, hormonal and gene and protein expression responses to large changes of K+ intake in Na+ replete mice. Both low and high K+ intake increased blood pressure and caused Na+ retention. Low K+ intake was accompanied by an upregulation of the sodium-chloride cotransporter (NCC) and its activating kinase SPAK, and inhibition of NCC normalized blood pressure. Renal responses were unaffected by angiotensin AT1 receptor antagonism, indicating that low K+ intake activates the distal nephron by an angiotensin-independent mode of action. High K+ intake was associated with elevated plasma aldosterone concentrations and an upregulation of the epithelial sodium channel (ENaC) and its activating kinase Sgk1. Surprisingly, high K+ intake increased blood pressure even during ENaC or mineralocorticoid receptor antagonism, suggesting the contribution of aldosterone-independent mechanisms. These findings show that in a Na+ replete state, changes in K+ intake induce specific molecular and functional adaptations in the distal nephron that cause a functional coupling of renal K+ and Na+ handling, resulting in Na+ retention and high blood pressure when K+ intake is either restricted or excessively increased.

  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

    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 .... In the conventional group, the fractional clearances of these three plasma proteins all increased. It is concluded that in progressive chronic nephropathy ACE-inhibitor treatment was associated with different adaptive tubular changes in the handling of sodium, water, and protein compared with conventional...

  2. Cubilin is an albumin binding protein important for renal tubular albumin reabsorption.

    Science.gov (United States)

    Birn, H; Fyfe, J C; Jacobsen, C; Mounier, F; Verroust, P J; Orskov, H; Willnow, T E; Moestrup, S K; Christensen, E I

    2000-05-01

    Using affinity chromatography and surface plasmon resonance analysis, we have identified cubilin, a 460-kDa receptor heavily expressed in kidney proximal tubule epithelial cells, as an albumin binding protein. Dogs with a functional defect in cubilin excrete large amounts of albumin in combination with virtually abolished proximal tubule reabsorption, showing the critical role for cubilin in the uptake of albumin by the proximal tubule. Also, by immunoblotting and immunocytochemistry we show that previously identified low-molecular-weight renal albumin binding proteins are fragments of cubilin. In addition, we find that mice lacking the endocytic receptor megalin show altered urinary excretion, and reduced tubular reabsorption, of albumin. Because cubilin has been shown to colocalize and interact with megalin, we propose a mechanism of albumin reabsorption mediated by both of these proteins. This process may prove important for understanding interstitial renal inflammation and fibrosis caused by proximal tubule uptake of an increased load of filtered albumin.

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

    Directory of Open Access Journals (Sweden)

    Arundhati G Diwan

    2014-01-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

  5. Hyperkalemic distal renal tubular acidosis caused by immunosuppressant treatment with tacrolimus in a liver transplant patient: case report.

    Science.gov (United States)

    Riveiro-Barciela, M; Campos-Varela, I; Tovar, J L; Vargas, V; Simón-Talero, M; Ventura-Cots, M; Crespo, M; Bilbao, I; Castells, L

    2011-12-01

    Nephrotoxicity is one of the most common side effects of long-term immunosuppressive therapy with calcineurin inhibitors. We describe a case of distal renal tubular acidosis secondary to tacrolimus administration. A 43-year-old man with end-stage liver disease due to hepatitis C and B virus infections and alcoholic cirrhosis received a liver transplantation under immunosuppressive treatment with tacrolimus and mycophenolate mofetil. In the postoperative period, the patient developed hyperkalemic hyperchloremic metabolic acidosis, with a normal serum anion gap and a positive urinary anion gap, suggesting distal renal tubular acidosis. We excluded other causes of hyperkalemia. Administration of intravenous bicarbonate, loop diuretics, and oral resin exchanger corrected the acidosis and potassium levels. Distal renal tubular acidosis is one of several types of nephrotoxicity induced by tacrolimus treatment, resulting from inhibition of potassium secretion in the collecting duct. Treatment to correct the acidosis and hyperkalemia should be promptly initiated, and the tacrolimus dose adjusted when possible.

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

    Science.gov (United States)

    Hansen, J M; Løkkegaard, H; Høy, C E; Fogh-Andersen, N; Olsen, N V; Strandgaard, S

    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 volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR 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 transplant recipients treated with a low maintenance dose of CsA had a well-preserved renal functional reserve, and dietary supplementation with fish oil in these patients did not improve renal function.

  7. Gastrin stimulates renal dopamine production by increasing the renal tubular uptake of l-DOPA.

    Science.gov (United States)

    Jiang, Xiaoliang; Zhang, Yanrong; Yang, Yu; Yang, Jian; Asico, Laureano D; Chen, Wei; Felder, Robin A; Armando, Ines; Jose, Pedro A; Yang, Zhiwei

    2017-01-01

    Gastrin is a peptide hormone that is involved in the regulation of sodium balance and blood pressure. Dopamine, which is also involved in the regulation of sodium balance and blood pressure, directly or indirectly interacts with other blood pressure-regulating hormones, including gastrin. This study aimed to determine the mechanisms of the interaction between gastrin and dopamine and tested the hypothesis that gastrin produced in the kidney increases renal dopamine production to keep blood pressure within the normal range. We show that in human and mouse renal proximal tubule cells (hRPTCs and mRPTCs, respectively), gastrin stimulates renal dopamine production by increasing the cellular uptake of l-DOPA via the l-type amino acid transporter (LAT) at the plasma membrane. The uptake of l-DOPA in RPTCs from C57Bl/6J mice is lower than in RPTCs from normotensive humans. l-DOPA uptake in renal cortical slices is also lower in salt-sensitive C57Bl/6J than in salt-resistant BALB/c mice. The deficient renal cortical uptake of l-DOPA in C57Bl/6J mice may be due to decreased LAT-1 activity that is related to its decreased expression at the plasma membrane, relative to BALB/c mice. We also show that renal-selective silencing of Gast by the renal subcapsular injection of Gast siRNA in BALB/c mice decreases renal dopamine production and increases blood pressure. These results highlight the importance of renal gastrin in stimulating renal dopamine production, which may give a new perspective in the prevention and treatment of hypertension. Copyright © 2017 the American Physiological Society.

  8. Auxin induces cell proliferation in an experimental model of mammalian renal tubular epithelial cells.

    Science.gov (United States)

    Cernaro, Valeria; Medici, Maria Antonietta; Leonello, Giuseppa; Buemi, Antoine; Kohnke, Franz Heinrich; Villari, Antonino; Santoro, Domenico; Buemi, Michele

    2015-06-01

    Indole-3-acetic acid is the main auxin produced by plants and plays a key role in the plant growth and development. This hormone is also present in humans where it is considered as a uremic toxin deriving from tryptophan metabolism. However, beyond this peculiar aspect, the involvement of auxin in human pathophysiology has not been further investigated. Since it is a growth hormone, we evaluated its proliferative properties in an in vitro model of mammalian renal tubular epithelial cells. We employed an experimental model of renal tubular epithelial cells belonging to the LLC-PK1 cell line that is derived from the kidney of healthy male pig. Growth effects of auxin against LLC-PK1 cell lines were determined by a rapid colorimetric assay. Increasing concentrations of auxin (to give a final concentration from 1 to 1000 ng/mL) were added and microplates were incubated for 72 h. Each auxin concentration was assayed in four wells and repeated four times. Cell proliferation significantly increased, compared to control cells, 72 h after addition of auxin to cultured LLC-PK1 cells. Statistically significant values were observed when 100 ng/mL (p auxin influences cell growth not only in plants, where its role is well documented, but also in mammalian cell lines. This observation opens new scenarios in the field of tissue regeneration and may stimulate a novel line of research aiming at investigating whether this hormone really influences human physiology and pathophysiology and in particular, kidney regeneration.

  9. The Effect of Connective Tissue Growth Factor on Human Renal Tubular Epithelial Cell Transdifferentiation

    Institute of Scientific and Technical Information of China (English)

    张春; 朱忠华; 邓安国

    2004-01-01

    To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of α-smooth muscle actin (α-SMA) were assessed by indirect immuno-fluorescence, and the percentage of α-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of α-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of α-SMA were markedly stronger than that in negative controls. The percentages of α-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9 %, 65.5 % vs 2.4 %, P<0.01) . α-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).

  10. Chronic glucose infusion causes sustained increases in tubular sodium reabsorption and renal blood flow in dogs.

    Science.gov (United States)

    Brands, Michael W; Bell, Tracy D; Rodriquez, Nancy A; Polavarapu, Praveen; Panteleyev, Dmitriy

    2009-02-01

    This study tested the hypothesis that inducing hyperinsulinemia and hyperglycemia in dogs, by infusing glucose chronically intravenously, would increase tubular sodium reabsorption and cause hypertension. Glucose was infused for 6 days (14 mg.kg(-1).min(-1) iv) in five uninephrectomized (UNX) dogs. Mean arterial pressure (MAP) and renal blood flow (RBF) were measured 18 h/day using DSI pressure units and Transonic flow probes, respectively. Urinary sodium excretion (UNaV) decreased significantly on day 1 and remained decreased over the 6 days, coupled with a significant, sustained increase in RBF, averaging approximately 20% above control on day 6. Glomerular filtration rate and plasma renin activity (PRA) also increased. However, although MAP tended to increase, this was not statistically significant. Therefore, the glucose infusion was repeated in six dogs with 70% surgical reduction in kidney mass (RKM) and high salt intake. Blood glucose and plasma insulin increased similar to the UNX dogs, and there was significant sodium retention, but MAP still did not increase. Interestingly, the increases in PRA and RBF were prevented in the RKM dogs. The decrease in UNaV, increased RBF, and slightly elevated MAP show that glucose infusion in dogs caused a sustained increase in tubular sodium reabsorption by a mechanism independent of pressure natriuresis. The accompanying increase in PRA, together with the failure of either RBF or PRA to increase in the RKM dogs, suggests the site of tubular reabsorption was before the macula densa. However, the volume retention and peripheral edema suggest that systemic vasodilation offsets any potential renal actions to increase MAP in this experimental model in dogs.

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

    Directory of Open Access Journals (Sweden)

    Young Larry

    2011-03-01

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

  12. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways.

    Science.gov (United States)

    Nagai, Junya; Takano, Mikihisa

    2014-08-15

    Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as a clinically important antibiotic class because of their reliable efficacy and low cost. However, the clinical use of aminoglycosides is limited by their nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot of studies on characterization of the renal transport system for aminoglycosides so far reported involved various in-vivo and in-vitro techniques. Early studies revealed that aminoglycosides are taken up through adsorptive endocytosis in renal epithelial cells. Subsequently, it was found that megalin, a multiligand endocytic receptor abundantly expressed on the apical side of renal proximal tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin has been suggested to be a promising molecular target for the prevention of aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports have indicated that aminoglycosides are transported via a pathway that does not require endocytosis, such as non-selective cation channel-mediated entry, in cultured renal tubular cells as well as cochlear outer hair cells. In this commentary article, we review the cellular transport of aminoglycosides in renal epithelial cells, focusing on endocytosis-dependent and -independent pathways.

  13. Endogenous ouabain in renal Na(+) handling and related diseases.

    Science.gov (United States)

    Manunta, Paolo; Messaggio, Elisabetta; Casamassima, Nunzia; Gatti, Guido; Carpini, Simona Delli; Zagato, Laura; Hamlyn, John M

    2010-12-01

    The Na(+) pump and its Endogenous modulator Ouabain (EO) can be considered as an ancestral enzymatic system, conserved among species ranging from Drosophila to humans, related to Na handling. In this review, we examine how EO is linked with vascular function in hypertension and if it impacts the pathogenesis of heart and renal failure. Moreover, the molecular mechanism of endogenous ouabain-linked hypertension involves the sodium pump/sodium-calcium exchanger duet. Biosynthesis of EO occurs in adrenal glands and is under the control of angiotensin II, ACTH and epinephrine. Elevated concentrations of EO and in the sub-nanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure. Experimental data suggest that the Na/K-ATPase α(2)-catalytic subunit causes EO-induced vasoconstriction. Finally, maneuvers that promote Na depletion, as diuretic therapy or reduced Na intake, raise the EO levels. Taken together, these findings suggest a key role for EO in body Na homeostasis.

  14. 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

    volunteers (N = 9) and two groups of stable long-term kidney-transplanted patients treated with maintenance low-dose CsA (3.0 +/- 0.6 mg/kg; N = 9) or without CsA (N = 9). After an overnight fast, the subjects were water loaded, and clearance studies were performed, postponing morning medication. GFR...... 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...

  15. Renal tubular reabsorption of sodium and water during infusion of low-dose dopamine in normal man

    DEFF Research Database (Denmark)

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

    1990-01-01

    1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates...... 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...

  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

    1. Using the renal clearance of lithium (CLi) as an index of proximal tubular outflow of sodium and water, together with simultaneous measurements of effective renal plasma flow, glomerular filtration rate (GFR) and sodium clearance (CNa), renal function and the tubular segmental reabsorption rates...... 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...

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

    Science.gov (United States)

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

    1992-01-01

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

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

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    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.

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

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    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.

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

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    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.

  1. Effect of hepatitis B virus X gene on apoptosis and immune molecules of renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    王轩

    2013-01-01

    Objective To investigate the effect of hepatitis B virus X(HBX)gene on apoptosis and immune moleculesof human proximal renal tubular epithelial cell line(HK-2).Methods The eukaryotic vector pcDNA3.1-myc-HBX containing HBX gene was transiently transfected into

  2. 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.

  3. Renal tubular acidosis type II associated with vitamin D deficiency presenting as chronic weakness.

    Science.gov (United States)

    Ali, Yaseen; Parekh, Amila; Baig, Mirza; Ali, Taseen; Rafiq, Tazeen

    2014-08-01

    Chronic vitamin D deficiency, though common in the elderly, is often under diagnosed and when progressing to renal tubular acidosis type II (RTA 2) can cause several simultaneous electrolyte imbalances that may present with weakness and pain as chief symptoms. We present such a case that after months of evaluation and symptomatic treatment did not lead to an effective establishment of the etiology causing chronic weakness and body pain in an elderly female patient. Eventually, after a careful review of the patient's history, repeat physical examinations, laboratory data evaluation, and diagnostic testing led to the establishment of the diagnosis of proximal RTA 2 associated with vitamin D deficiency, which caused the patient to develop several remarkable secondary electrolyte imbalances such as hypokalemia, hypocalcemia, hypophosphatemia, acidemia, hyperparathyroidism, with weakness and body pain.

  4. Long-term follow-up in distal renal tubular acidosis with sensorineural deafness.

    Science.gov (United States)

    Peces, R

    2000-11-01

    A 20-year-old man presented with failure to thrive and bilateral genu valgum. On the basis of growth failure, skeletal deformity, hyperchloremic metabolic acidosis with alkaline urine and hypokalemia, nephrocalcinosis, and hearing loss, a diagnosis of distal renal tubular acidosis (DRTA) with sensorineural deafness was made. The genu valgum was treated by corrective osteotomy. Skeletal deformity was corrected and impaired growth improved after sustained therapy of metabolic acidosis with alkali supplementation. During an 8-year follow-up period the patient's glomerular filtration rate remained stable, the nephrocalcinosis did not progress, and his height increased 10 cm. Although nephrolithiasis led to atrophy of the right kidney, at last follow-up, when the patient was 44 years old, his creatinine clearance was 50 ml/min per 1.73 m2 body surface.

  5. [Urolithiasis due to renal tubular acidosis associated with Sjögren's syndrome].

    Science.gov (United States)

    Umekawa, T; Esa, A; Uemura, T; Kohri, K; Kurita, T; Ishikawa, Y; Iguchi, M; Kataoka, K

    1990-03-01

    We encountered 4 patients with urolithiasis due to renal tubular acidosis (RTA) associated with Sjögren's syndrome. Laboratory results about RTA in 4 patients with Sjögrenhs syndrome were not significantly different from those in patients who suffered from urolithiasis due to RTA without Sjögren's syndrome. The incidence of urolitiasis in these cases was suspected to be higher than that in RTA patients without Sjögren's syndrome, because all 4 patients in this study had urolithiasis. When we examine patients with bilateral and multiple urolithiasis, particularly in middle-aged women, we should bear in mind that RTA and Sjögren's syndrome may exist in the background.

  6. 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.

  7. Hypokalemic periodic paralysis associated with thyrotoxicosis, renal tubular acidosis and nephrogenic diabetes insipidus.

    Science.gov (United States)

    Im, Eun Joo; Lee, Jung Min; Kim, Ji Hyun; Chang, Sang Ah; Moon, Sung Dae; Ahn, Yu Bae; Son, Hyun Shik; Cha, Bong Yun; Lee, Kwang Woo; Son, Ho Young

    2010-01-01

    A 19-year-old girl presented at our emergency room with hypokalemic periodic paralysis. She had a thyrotoxic goiter and had experienced three paralytic attacks during the previous 2 years on occasions when she stopped taking antithyroid drugs. In addition to thyrotoxic periodic paralysis (TPP), she had metabolic acidosis, urinary potassium loss, polyuria and polydipsia. Her reduced ability to acidify urine during spontaneous metabolic acidosis was confirmed by detection of coexisting distal renal tubular acidosis (RTA). The polyuria and polydipsia were caused by nephrogenic diabetes insipidus, which was diagnosed using the water deprivation test and vasopressin administration. Her recurrent and frequent paralytic attacks may have been the combined effects of thyrotoxicosis and RTA. Although the paralytic attack did not recur after improving the thyroid function, mild acidosis and nephrogenic DI have been remained subsequently. Patients with TPP, especially females with atypical metabolic features, should be investigated for possible precipitating factors.

  8. Transient distal renal tubular acidosis following hump nosed viper bite: Two cases from Sri Lanka

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    Ranga M Weerakkody

    2016-01-01

    Full Text Available Hump-nosed viper (Hypnale hypnale; HNV is one of the six major snake species in Sri Lanka that cause envenomation. Nephrotoxicity, coagulopathy, and neurotoxicity are wellrecognized features of its envenomation. Type 4 renal tubular acidosis (RTA4 has only once been described previously in this condition, and we report two further cases. Two patients aged 53 and 51 presented following HNV bites with acute kidney injury and microangiopathic hemolytic anemia. Both underwent multiple cycles of hemodialysis until the polyuric phase was reached. Despite polyuria, both patients developed resistant hyperkalemia that needed further hemodialysis. The urinary pH, arterial pH, delta ratio, and transtubular potassium gradient confirmed RTA4. HNV venom has been shown to damage the proximal convoluted tubules in animal studies, but not the distal convoluted tubule, and hence the mechanism of our observation in these two patients is unclear. Unexplained hyperkalemia in recovery phase of HNV bite should raise suspicions of RTA4.

  9. Sjogren's syndrome with distal renal tubular acidosis presenting as hypokalaemic paralysis.

    Science.gov (United States)

    Vaidya, Gaurang; Ganeshpure, Swapnil

    2012-10-19

    A young lady with a history of repeated episodes of generalised weakness and fatigue presented to our hospital with similar symptoms and was found to have severe hypokalaemia. She had been previously diagnosed as hypokalaemic periodic paralysis but during this presentation she had also started complaining of the classic sicca-complex of Sjogren's syndrome, which was not present previously. On subsequent investigations she was found to have normal anion-gap metabolic acidosis with positive urine anion gap consistent with the diagnosis of distal renal tubular acidosis (RTA). It was thus concluded that the distal RTA secondary to Sjogren's syndrome was the cause of severe hypokalaemia in our patient. By presenting this case we aim to not only highlight one of the rare presentations of Sjogren's syndrome but also the favourable response of our patient to potassium replacement alone.

  10. 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.

  11. 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

  12. 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.

  13. Competitive inhibition of renal tubular secretion of ciprofloxacin and metabolite by probenecid

    Science.gov (United States)

    Landersdorfer, Cornelia B; Kirkpatrick, Carl M J; Kinzig, Martina; Bulitta, Jürgen B; Holzgrabe, Ulrike; Jaehde, Ulrich; Reiter, Andreas; Naber, Kurt G; Rodamer, Michael; Sörgel, Fritz

    2010-01-01

    AIMS Probenecid influences transport processes of drugs at several sites in the body and decreases elimination of several quinolones. We sought to explore extent, time course, and mechanism of the interaction between ciprofloxacin and probenecid at renal and nonrenal sites. METHODS A randomized, two-way crossover study was conducted in 12 healthy volunteers (in part previously published Clin Pharmacol Ther 1995; 58: 532–41). Subjects received 200 mg ciprofloxacin as 30-min intravenous infusion without and with 3 g probenecid divided into five oral doses. Drug concentrations were analysed by liquid chromatography–tandem mass spectrometry and high-performance liquid chromatography. Ciprofloxacin and its 2-aminoethylamino-metabolite (M1) in plasma and urine with and without probenecid were modelled simultaneously with WinNonlin®. RESULTS Data are ratio of geometric means (90% confidence intervals). Addition of probenecid reduced the median renal clearance from 23.8 to 8.25 l h−1[65% reduction (59, 71), P ciprofloxacin and from 20.5 to 8.26 l h−1 (66% reduction (57, 73), P ciprofloxacin nonrenal clearance by 8% (1, 14) (P ciprofloxacin and M1 by probenecid. The affinity for the renal transporter was 4.4 times higher for ciprofloxacin and 3.6 times higher for M1 than for probenecid, based on the molar ratio. Probenecid did not affect volume of distribution of ciprofloxacin or M1, nonrenal clearance or intercompartmental clearance of ciprofloxacin. CONCLUSIONS Probenecid inhibited the renal tubular secretion of ciprofloxacin and M1, probably by a competitive mechanism and due to reaching >100-fold higher plasma concentrations. Formation of M1, nonrenal clearance and distribution of ciprofloxacin were not affected. PMID:20233180

  14. Chronic hepatitis B serum promotes apoptotic damage in human renal tubular cells

    Institute of Scientific and Technical Information of China (English)

    Cun-Liang Deng; Xin-Wen Song; Hai-Jun Liang; Chen Feng; Yun-Jian Sheng; Ming-Yong Wang

    2006-01-01

    AIM: To investigate the effect of the serum of patients with chronic hepatitis B (CHB) on apoptosis of renal tubular epithelial cells in vitro and to study the role of hepatitis B virus (HBV) and transforming growth factor-β1 (TGF-β1) in the pathogenesis of hepatitis B virus associated glomerulonephritis (HBV-GN).METHODS: The levels of serum TGF-β1 were measured by specific enzyme linked immunosorbent assay (ELISA) and HBV DNA was tested by polymerase chain reaction (PCR) in 44 patients with CHB ,and 20 healthy persons as the control. The normal human kidney proximal tubular cell (HK-2) was cultured together with the sera of healthy persons, CHB patients with HBV-DNA negative(20 cases) and HBV-DNA positive (24 cases) for up to 72 h. Apoptosis and Fas expression of the HK-2 were detected by flow cytometer.RESULTS: The apoptosis rate and Fas expression of HK-2 cells were significantly higher in HBV DNA positive serum group 19.01±5.85% and 17.58±8.35%, HBV DNA negative serum group 8.12±2.80% and 6.96 ± 2.76% than those in control group 4.25±0.65% and 2.33 ± 1.09%, respectively (P < 0.01). The apoptosis rate and Fas expression of HK-2 in HBV DNA positive serum group was significantly higher than those in HBV DNA negative serum (P < 0.01). Apoptosis rate of HK-2 cells in HBV DNA positive serum group was positively correlated with the level of HBV-DNA (r = 0.657). The level of serum TGF-β1 in CHB group was 163.05 ± 91.35 μg/L, significantly higher as compared with 81.40 ± 40.75 μg/L in the control group (P < 0.01).CONCLUSION: The serum of patients with chronic hepatitis B promotes apoptotic damage in human renal tubular cells by triggering a pathway of Fas up-regulation. HBV and TGF-β1 may play important roles in the mechanism of hepatitis B virus associated glomerulonephritis.

  15. 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.

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

    Science.gov (United States)

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

    2015-07-01

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

  17. FGF23 regulates renal sodium handling and blood pressure

    OpenAIRE

    Andrukhova, Olena; Slavic, Svetlana; Smorodchenko, Alina; Zeitz, Ute; Shalhoub, Victoria; Lanske, Beate; Pohl, Elena E.; Erben, Reinhold G.

    2014-01-01

    Fibroblast growth factor-23 (FGF23) is a bone-derived hormone regulating renal phosphate reabsorption and vitamin D synthesis in renal proximal tubules. Here, we show that FGF23 directly regulates the membrane abundance of the Na+:Cl− co-transporter NCC in distal renal tubules by a signaling mechanism involving the FGF receptor/αKlotho complex, extracellular signal-regulated kinase 1/2 (ERK1/2), serum/glucocorticoid-regulated kinase 1 (SGK1), and with-no lysine kinase-4 (WNK4). Renal sodium (...

  18. 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 < 0.01), but positively correlated with superoxide dismutase, glutathione and mitochondrial membrane potential (r = 0.807, 0.815, 0.739; each P < 0.01). We postulate that prohibitin acts as a positive regulator of mechanisms that counteract oxidative stress and extracellular matrix accumulation and therefore has an antioxidative effect.

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice

    Science.gov (United States)

    Yang, Guannan; Zhao, Zongjiang; Zhang, Xinxue; Wu, Amin; Huang, Yawei; Miao, Yonghui; Yang, Meijuan

    2017-01-01

    Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

  1. Effect of berberine on the renal tubular epithelial-to-mesenchymal transition by inhibition of the Notch/snail pathway in diabetic nephropathy model KKAy mice.

    Science.gov (United States)

    Yang, Guannan; Zhao, Zongjiang; Zhang, Xinxue; Wu, Amin; Huang, Yawei; Miao, Yonghui; Yang, Meijuan

    2017-01-01

    Renal tubular epithelial-to-mesenchymal transition (EMT) and renal tubular interstitial fibrosis are the main pathological changes of diabetic nephropathy (DN), which is a common cause of end-stage renal disease. Previous studies have suggested that berberine (BBR) has antifibrotic effects in the kidney and can reduce apoptosis and inhibit the EMT of podocytes in DN. However, the effect of BBR on the renal tubular EMT in DN and its mechanisms of action are unknown. This study was performed to explore the effects of BBR on the renal tubular EMT and the molecular mechanisms of BBR in DN model KKAy mice and on the high glucose (HG)-induced EMT in mouse renal tubular epithelial cells. Our results showed that, relative to the model mice, the mice in the treatment group had an improved general state and reduced blood glucose and 24-h urinary protein levels. Degradation of renal function was ameliorated by BBR. We also observed the protective effects of BBR on renal structural changes, including normalization of an index of renal interstitial fibrosis and kidney weight/body weight. Moreover, BBR suppressed the activation of the Notch/snail pathway and upregulated the α-SMA and E-cadherin levels in DN model KKAy mice. BBR was further found to prevent HG-induced EMT events and to inhibit the HG-induced expression of Notch pathway members and snail1 in mouse renal tubular epithelial cells. Our findings indicate that BBR has a therapeutic effect on DN, including its inhibition of the renal tubular EMT and renal interstitial fibrosis. Furthermore, the BBR-mediated EMT inhibition occurs through Notch/snail pathway regulation.

  2. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells

    Science.gov (United States)

    Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis. PMID:27936102

  3. AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells.

    Science.gov (United States)

    Yoshinaga, Tomoyo; Uwabe, Kenichiro; Naito, Shoichi; Higashino, Kenichi; Nakano, Toru; Numata, Yoshito; Kihara, Akio

    2016-01-01

    Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis. In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus. Initial screening was performed with the immortalized HK-2 renal tubule epithelial cell line. The most promising compounds were further tested in RPTEC primary renal tubule epithelial cells. We found that the synthetic lipid AM251 suppressed two hallmark events associated with EMT, the upregulation of collagen 1A1 (COL1A1) and downregulation of E-cadherin. Though AM251 is known to act as an antagonist for the cannabinoid receptor type 1 (CB1) and an agonist for the G protein-coupled receptor 55 (GRP55), the suppression of EMT by AM251 was not mediated through either receptor. Microarray analyses revealed that AM251 inhibited induction of several EMT transcription factors such as SNAIL1, which is the key inducer of EMT, and the AP-1 transcription factors FOSB and JUNB. Activation of SMAD2/3 and p38 mitogen-activated protein kinase (MAPK) was inhibited by AM251, with greater inhibition of the latter, indicating that AM251 acted upstream of SMAD/p38 MAPK in the TGF-β signaling pathway. Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis.

  4. Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

    Science.gov (United States)

    Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

    2013-02-01

    The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

  5. 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.

  6. Connexin 30 deficiency impairs renal tubular ATP release and pressure natriuresis.

    Science.gov (United States)

    Sipos, Arnold; Vargas, Sarah L; Toma, Ildikó; Hanner, Fiona; Willecke, Klaus; Peti-Peterdi, János

    2009-08-01

    In the renal tubule, ATP is an important regulator of salt and water reabsorption, but the mechanism of ATP release is unknown. Several connexin (Cx) isoforms form mechanosensitive, ATP-permeable hemichannels. We localized Cx30 to the nonjunctional apical membrane of cells in the distal nephron and tested whether Cx30 participates in physiologically important release of ATP. We dissected, partially split open, and microperfused cortical collecting ducts from wild-type and Cx30-deficient mice in vitro. We used PC12 cells as ATP biosensors by loading them with Fluo-4/Fura Red to measure cytosolic calcium and positioning them in direct contact with the apical surface of either intercalated or principal cells. ATP biosensor responses, triggered by increased tubular flow or by bath hypotonicity, were approximately three-fold greater when positioned next to intercalated cells than next to principal cells. In addition, these responses did not occur in preparations from Cx30-deficient mice or with purinergic receptor blockade. After inducing step increases in mean arterial pressure by ligating the distal aorta followed by the mesenteric and celiac arteries, urine output increased 4.2-fold in wild-type mice compared with 2.6-fold in Cx30-deficient mice, and urinary Na(+) excretion increased 5.2-fold in wild-type mice compared with 2.8-fold in Cx30-deficient mice. Furthermore, Cx30-deficient mice developed endothelial sodium channel-dependent, salt-sensitive elevations in mean arterial pressure. Taken together, we suggest that mechanosensitive Cx30 hemichannels have an integral role in pressure natriuresis by releasing ATP into the tubular fluid, which inhibits salt and water reabsorption.

  7. 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.

  8. Sequenciamento total do exoma como ferramenta de diagnóstico de acidose tubular renal distal

    Directory of Open Access Journals (Sweden)

    Paula Cristina Barros Pereira

    2015-12-01

    Full Text Available Resumo Objetivo A acidose tubular renal distal (ATRd é caracterizada por acidose metabólica devido à excreção renal de ácido prejudicada. O objetivo deste artigo é apresentar o diagnóstico genético de quatro crianças com ATRd com uso do sequenciamento total do exoma. Métodos Selecionamos duas famílias não relacionadas, quatro crianças com ATRd e seus pais, para fazer o sequenciamento total do exoma. A audição foi preservada em ambas as crianças da família um, porém em nenhuma criança da família dois, na qual um par de gêmeas teve perda auditiva severa. Fizemos o sequenciamento total do exoma em dois conjuntos de amostras e confirmamos os achados com o método de sequenciamento de Sanger. Resultados Duas mutações foram identificadas nos genes ATP6V0A4 e ATP6V1B1. Na família um, detectamos uma nova mutação no éxon 13 do gene ATP6V0A4 com uma alteração em um nucleotídeo único GAC → TAC (c.1232G>T que causou substituição de ácido aspártico por tirosina na posição 411. Na família dois, detectamos uma mutação recorrente do homozigoto com inserção de um par de bases (c.1149_1155insC no éxon 12 do gene ATP6V1B1. Conclusão Nossos resultados confirmam o valor do sequenciamento total do exoma para o estudo de nefropatias genéticas complexas e permitem a identificação de mutações novas e recorrentes. Adicionalmente, demonstramos claramente pela primeira vez a aplicação desse método molecular em doenças tubulares renais.

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

    Science.gov (United States)

    Xiao, Yun; Liu, Jishi; Peng, Yu; Xiong, Xuan; Huang, Ling; Yang, Huixiang; Zhang, Jian; Tao, Lijian

    2016-01-01

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

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

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    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.

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

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; 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...

  12. 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.

  13. Increased risk of abnormal proximal renal tubular function with HIV infection and antiretroviral therapy.

    Science.gov (United States)

    Dauchy, Frédéric-Antoine; Lawson-Ayayi, Sylvie; de La Faille, Renaud; Bonnet, Fabrice; Rigothier, Claire; Mehsen, Nadia; Miremont-Salamé, Ghada; Cazanave, Charles; Greib, Carine; Dabis, Francois; Dupon, Michel

    2011-08-01

    Abnormal kidney function is common in the course of human immunodeficiency virus (HIV) infection. Here, we performed a cross-sectional analysis using 399 patients within the Aquitaine cohort (a hospital-based cohort of HIV-1-infected patients receiving routine clinical management) to estimate the prevalence of proximal renal tubular dysfunction (PRTD) associated with HIV infection. These patients did not differ statistically by sociodemographics, median age, years since HIV diagnosis, AIDS stage, or median CD4 cell count from the entire 3080 patient cohort. Antiretroviral therapy was received by 352 patients, with 256 given tenofovir (TDF); 325 had undetectable HIV plasma viral load, and 26 were diagnosed with PRTD. In multivariate analysis, significant independent associations were found between PRTD and age (odds ratio (OR) 1.28 per 5-year increase), atazanavir (OR 1.28 per year of exposure), and TDF (OR 1.23 per year) treatment. Among patients having received TDF-containing regimens over a 5-year period, PRTD remained significantly associated with TDF exposure when treatment was ongoing (OR 5.22) or had been discontinued (OR 11.49). Thus, cumulative exposure to TDF and/or atazanavir was associated with an increased risk of PRTD, with concern about its reversibility in patients with HIV.

  14. 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.

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

    Science.gov (United States)

    Ueda, Norishi

    2015-01-01

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

  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. Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin-Mediated Kidney Injury.

    NARCIS (Netherlands)

    Swelm, R.P. van; Wetzels, J.F.; Verweij, V.G.; Laarakkers, C.M.; Pertijs, J.C.; Wijst, J.A. van der; Thevenod, F.; Masereeuw, R.; Swinkels, D.W.

    2016-01-01

    Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal adm

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

    OpenAIRE

    Margarita Irene Rocha-Gómez; Samuel Zaltzman-Girshëvich; Silvestre García-de la Puente

    2015-01-01

    La acidosis tubular renal se caracteriza por acidosis metabólica hiperclorémica. El diagnóstico del tipo de acidosis tubular renal se realiza mediante la medición del transporte tubular máximo de bicarbonato y de la capacidad de acidificación urinaria; sin embargo, estas pruebas son invasivas y requieren determinaciones especializadas. Objetivo: comparar la utilidad de la recolección urinaria de dos horas, una prueba relativamente simple y al alcance de muchos laboratorios, con la medició...

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

    Directory of Open Access Journals (Sweden)

    Huei-Fen Jheng

    2015-10-01

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

  20. The renal handling of hemoglobin. I. Glomerular filtration.

    Science.gov (United States)

    Bunn, H F; Esham, W T; Bull, R W

    1969-05-01

    The glomerular filtration of hemoglobin (alpha(2)beta(2)) was studied under conditions in which its dissociation into alphabeta dimers was experimentally altered. Rats receiving hemoglobin treated with the sulfhydryl reagent bis(N-maleimidomethyl) ether (BME) showed a much lower renal excretion and prolonged plasma survival as compared with animals injected with untreated hemoglobin. Plasma disappearance was also prolonged in dogs receiving BME hemoglobin. Gel filtration data indicated that under physiological conditions, BME hemoglobin had impaired subunit dissociation. In addition, BME hemoglobin showed a very high oxygen affinity and a decreased rate of auto-oxidation. Glomerular filtration was enhanced under conditions which favor the dissociation of hemoglobin into dimers. Cat hemoglobin, which forms subunits much more extensively than canine hemoglobin, was excreted more readily by the rat kidney. The renal uptake of (59)Fe hemoglobin injected intra-arterially into rabbits varied inversely with the concentration of the injected dose.

  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. Cell-specific delivery of a transforming growth factor-beta type I receptor kinase inhibitor to proximal tubular cells for the treatment of renal fibrosis

    NARCIS (Netherlands)

    Prakash, Jai; de Borst, Martin H.; van Loenen - Weemaes, Annemiek M.; Lacombe, Marie; Opdam, Frank; van Goor, Harry; Meijer, Dirk K. F.; Moolenaar, Frits; Poelstra, Klaas; Kok, Robbert J.

    2008-01-01

    Purpose. Activation of tubular epithelial cells by transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of renal tubulointerstitial fibrosis. We developed a renally accumulating conjugate of a TGF-beta type-I receptor kinase inhibitor (TKI) and evaluated its

  3. Pharmacogenetics May Influence Tacrolimus Daily Dose, But Not Urinary Tubular Damage Markers In The Long-Term Period After Renal Transplantation

    Directory of Open Access Journals (Sweden)

    Stefanović Nikola Z.

    2015-10-01

    Full Text Available Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP 3A5 (6986A>G and ABCB1 (3435C>T polymorphisms on tacrolimus (TAC dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients.

  4. 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.

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

    Science.gov (United States)

    Stroo, Ingrid; Claessen, Nike; Teske, Gwendoline J D; Butter, Loes M; Florquin, Sandrine; Leemans, Jaklien C

    2015-01-01

    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.

  6. Fibroblast Growth Factor 23: a Bridge Between Bone Minerals and Renal Volume Handling

    NARCIS (Netherlands)

    Humalda, Jelmer Kor

    2016-01-01

    The work in this thesis addresses the interaction between the phosphate-regulating hormone Fibroblast Growth Factor 23 (FGF-23) as key player in bone-mineral homeostasis and renal volume handling, mainly in the context of the renin-angiotensin-aldosterone system (RAAS). First, we elaborate on the ro

  7. 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.

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

    Science.gov (United States)

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

    2016-02-01

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

  9. Long-term leptin treatment exerts a pro-apoptotic effect on renal tubular cells via prostaglandin E2 augmentation.

    Science.gov (United States)

    Hsu, Yung-Ho; Cheng, Chung-Yi; Chen, Yen-Cheng; Chen, Tso-Hsiao; Sue, Yuh-Mou; Tsai, Wei-Lun; Chen, Cheng-Hsien

    2012-08-15

    Adipokine leptin reportedly acts on the kidney in pathophysiological states. However, the influence of leptin on renal tubular epithelial cells is still unclear. Gentamicin, a widely used antibiotic for the treatment of bacterial infection, can cause nephrotoxicity. This study aims to investigate the influence of long-term leptin treatment on gentamicin-induced apoptosis in rat renal tubular cells (NRK-52E) and mice. We monitored apoptosis and molecular mechanisms using annexin V/ propidium iodide staining and small interfering RNA transfection. In NRK-52E cells, leptin reduced gentamicin-induced apoptosis at 24h, but significantly increased apoptosis at 48 h. Long-term treatment of leptin decreased Bcl-x(L) expression and increased caspase activity in gentamicin-treated NRK-52E cells. Leptin also increased the expression of cyclooxygenase-2 (COX-2) and its product, prostaglandin E(2) (PGE(2)), in a dose-dependent manner. The COX-2 inhibitor, NS398 (N-[2-(Cyclohexyloxy)-4- nitrophenyl]methanesulfonamide), blocked PGE(2) augmentation and the pro-apoptotic effects of leptin. The addition of PGE(2) recovered the pro-apoptotic effect of leptin in NS398-treated NRK-52E cells. In a mouse animal model, a 10 day leptin treatment significantly increased gentamicin-induced apoptotic cells in proximal tubules. NS398 treatment inhibited this in vivo pro-apoptotic effect of leptin. Results reveal that long-term elevation of leptin induces COX-2-mediated PGE(2) augmentation in renal tubular cells, and then increases these cells' susceptibility to gentamicin-induced apoptosis.

  10. 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

    unaffected by acute surgical denervation of the kidneys. In contrast, chronic renal denervation or infusion of phentolamine (5 micrograms kg-1 min-1) into the renal artery eliminated the increase in APR and FPR during RVP elevation to 20 mmHg. Chronic, but not acute renal denervation depleted renal tissue...

  11. Insufici??ncia renal aguda em pacientes com doen??a glomerular: aspectos histol??gicos e papel da necrose tubular aguda

    OpenAIRE

    Tavares, Maria Brand??o

    2011-01-01

    A insufici??ncia renal aguda ?? comum em pacientes com s??ndrome nefr??tica, podendo requerer terapia de substitui????o renal e ser irrevers??vel. A insufici??ncia renal aguda nesses pacientes pode ser precipitada por processos infecciosos, hipovolemia, drogas nefrot??xicas; entretanto na maioria dos casos a etiologia n??o ?? identificada e a insufici??ncia renal aguda ?? considerada idiop??tica. A necrose tubular aguda foi associada ?? insufici??ncia renal aguda em adultos com les??o m??nima...

  12. Renal sodium handling and haemodynamics are equally affected by hyperinsulinaemia in salt-sensitive and salt-resistant hypertensives

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Donker, AJM; Gans, ROB

    2001-01-01

    Objective It is well-known that insulin induces renal sodium retention. It is not yet known whether insulin's renal effects are involved in the development of salt-sensitive hypertension. We assessed the effects of insulin on renal sodium handling and haemodynamics in 10 salt-sensitive (SS) and 10 s

  13. Renal sodium handling and haemodynamics are equally affected by hyperinsulinaemia in salt-sensitive and salt-resistant hypertensives

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Donker, AJM; Gans, ROB

    Objective It is well-known that insulin induces renal sodium retention. It is not yet known whether insulin's renal effects are involved in the development of salt-sensitive hypertension. We assessed the effects of insulin on renal sodium handling and haemodynamics in 10 salt-sensitive (SS) and 10

  14. Local synthesis of interferon-alpha in lupus nephritis is associated with type I interferons signature and LMP7 induction in renal tubular epithelial cells.

    Science.gov (United States)

    Castellano, Giuseppe; Cafiero, Cesira; Divella, Chiara; Sallustio, Fabio; Gigante, Margherita; Pontrelli, Paola; De Palma, Giuseppe; Rossini, Michele; Grandaliano, Giuseppe; Gesualdo, Loreto

    2015-03-22

    Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level. We performed immunohistochemical analysis for MXA-protein and in situ hybridization to detect interferon-alpha signature and production in human lupus nephritis. Through microarray studies, we analyzed the gene expression profile of renal tubular epithelial cells, stimulated with interferon-alpha. We validated microarray results through real-time polymerase chain reaction, flow cytometry on renal tubular epithelial cells, and through immunohistochemical analysis and confocal microscopy on renal biopsies. Type I interferons signature was characterized by MXA-specific staining in renal tubular epithelial cells; in addition, in situ hybridization showed that renal tubular epithelial cells were the major producers of interferon-alpha, indicating a potential autocrine effect. Whole-genome expression profile showed interferon-alpha induced up-regulation of genes involved in innate immunity, protein ubiquitination and switching to immunoproteasome. In accordance with the in vitro data, class IV lupus nephritis showed up-regulation of the immunoproteasome subunit LMP7 in tubular epithelial cells associated with type I interferon signature. Our data indicate that type I interferons might have a pathogenic role in lupus nephritis characterized by an autocrine effect of interferon-alpha on renal tubular epithelial cells. Therefore we hypothesize that inhibition of type I interferons might represent a therapeutic target to prevent tubulo-interstitial damage in patients with lupus nephritis.

  15. Role of TNF-associated cytokines in renal tubular cell apoptosis induced by hyperoxaluria.

    Science.gov (United States)

    Horuz, Rahim; Göktaş, Cemal; Çetinel, Cihangir A; Akça, Oktay; Aydın, Hasan; Ekici, Işın D; Albayrak, Selami; Sarıca, Kemal

    2013-06-01

    Crystal-cell interaction has been reported as one of the most crucial steps in urinary stone formation. Hyperoxaluria-induced apoptotic changes in renal tubular epithelial cells is the end-stage of this interaction. We aimed to evaluate the possible pathways responsible in the induction of apoptosis within the involved cells by assessing the receptoral expression of three different pathways. 16 male Spraque-Dowley rats were divided into two groups: Group 1 (n:8) received only distilled water; Group 2 (n:8) received 0.75 % ethylene glycol (EG) in their daily water to induce hyperoxaluria for 2 weeks. After 24 h urine collection, all animals were euthenized and right kidneys were removed and fixed for immunohistochemical evaluation. Oxalate and creatinine levels (in 24 h-urine) and FAS, tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand (TRAIL) and TRAIL receptor-2 expressions (in tissue) have been assessed. In addition to TNF (p = 0.0007) expression; both FAS (p = 0.0129 ) and FASL (p = 0.032) expressions significantly increased in animals treated with EG. The expressions of TRAIL (p = 0.49) and TRAIL-R2 (p = 0.34) receptors did not change statistically after hyperoxaluria induction. Although a positive correlation with cytokine expression density and 24 h-urinary oxalate expression (mg oxalate/mg creatinine) has been assessed with TNF (p = 0.04, r = 0.82), FAS (p = 0.05, r = 0.80), FAS-L (p = 0.04, r = 0.82); no correlation could be demonstrated between TRAIL and TRAIL R2 expressions. Our results indicate that apoptosis induced by oxalate is possibly mediated via TNF and FAS pathways. However, TRAIL and TRAIL-R2 seemed to have no function in the cascade. Correlation with urinary oxalate levels did further strengthen the findings.

  16. Elevated D-glucose concentrations modulate TGF-beta 1 synthesis by human cultured renal proximal tubular cells. The permissive role of platelet-derived growth factor.

    OpenAIRE

    Phillips, A.O.; Steadman, R.; Topley, N; Williams, J. D.

    1995-01-01

    Interstitial fibrosis is a marker of progression of renal impairment in diabetic nephropathy. Transforming growth factor (TGF)-beta 1 is one of a group of pro-fibrotic cytokines and growth factors that have been associated with the development of interstitial fibrosis. We have examined the modulating influence of glucose on the production of TGF-beta 1 by cultured human proximal tubular cells. Incubation of growth-arrested human proximal tubular cells (HPTC) (72 hours in serum free medium) in...

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

    DEFF Research Database (Denmark)

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

    1989-01-01

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

  18. Hyperosmolarity enhanced susceptibility to renal tubular fibrosis by modulating catabolism of type I transforming growth factor-beta receptors.

    Science.gov (United States)

    Chiang, Tai-An; Yang, Yu-Lin; Yang, Ya-Ying; Hu, Min-Hsiu; Wu, Pei-Fen; Liu, Shu-Fen; Huang, Ruay-Ming; Liao, Tung-Nan; Hung, Chien-Ya; Hung, Tsung-Jen; Lee, Tao-Chen

    2010-03-01

    Hyperosmolarity plays an essential role in the pathogenesis of diabetic tubular fibrosis. However, the mechanism of the involvement of hyperosmolarity remains unclear. In this study, mannitol was used to evaluate the effects of hyperosmolarity on a renal distal tubule cell line (MDCK). We investigated transforming growth factor-beta receptors and their downstream fibrogenic signal proteins. We show that hyperosmolarity significantly enhances the susceptibility to exogenous transforming growth factor (TGF)-beta1, as mannitol (27.5 mM) significantly enhanced the TGF-beta1-induced increase in fibronectin levels compared with control experiments (5.5 mM). Specifically, hyperosmolarity induced tyrosine phosphorylation on TGF-beta RII at 336 residues in a time (0-24 h) and dose (5.5-38.5 mM) dependent manner. In addition, hyperosmolarity increased the level of TGF-beta RI in a dose- and time-course dependent manner. These observations may be closely related to decreased catabolism of TGF-beta RI. Hyperosmolarity significantly downregulated the expression of an inhibitory Smad (Smad7), decreased the level of Smurf 1, and reduced ubiquitination of TGF-beta RI. In addition, through the use of cycloheximide and the proteasome inhibitor MG132, we showed that hyperosmolarity significantly increased the half-life and inhibited the protein level of TGF-beta RI by polyubiquitination and proteasomal degradation. Taken together, our data suggest that hyperosmolarity enhances cellular susceptibility to renal tubular fibrosis by activating the Smad7 pathway and increasing the stability of type I TGF-beta receptors by retarding proteasomal degradation of TGF-beta RI. This study clarifies the mechanism underlying hyperosmotic-induced renal fibrosis in renal distal tubule cells. (c) 2010 Wiley-Liss, Inc.

  19. 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.

  20. Cell-specific delivery of a transforming growth factor-beta type I receptor kinase inhibitor to proximal tubular cells for the treatment of renal fibrosis.

    Science.gov (United States)

    Prakash, Jai; de Borst, Martin H; van Loenen-Weemaes, Annemiek M; Lacombe, Marie; Opdam, Frank; van Goor, Harry; Meijer, Dirk K F; Moolenaar, Frits; Poelstra, Klaas; Kok, Robbert J

    2008-10-01

    Activation of tubular epithelial cells by transforming growth factor-beta (TGF-beta) plays an important role in the pathogenesis of renal tubulointerstitial fibrosis. We developed a renally accumulating conjugate of a TGF-beta type-I receptor kinase inhibitor (TKI) and evaluated its efficacy in vitro and in vivo. TKI was conjugated to the protein Lysozyme (LZM) via a platinum-based linker. TKI-LZM was evaluated in human tubular cells (HK-2) for its anti-fibrotic activity. Plasma, kidney and urine drug levels after a single intravenous dose of TKI-LZM in rats were determined by HPLC or immunodetection. Anti-fibrotic effects of TKI-LZM were examined in the unilateral ureteral obstruction (UUO) model. TKI-LZM conjugate was successfully synthesized at an 1:1 drug/carrier ratio, and inhibited TGF-beta1-induced procollagen-1alpha1 gene expression in HK-2 cells. In vivo, TKI-LZM accumulated rapidly in tubular cells and provided a local depot for 3 days. Interestingly, a single dose of TKI-LZM inhibited the activation of tubular cells and fibroblasts in UUO rats and reduced renal inflammation. In contrast, free TKI at an equimolar (low) dosage exhibited little effects. Inhibition of TGF-beta signaling by local drug delivery is a promising antifibrotic strategy, and demonstrated the important role of tubular activation in renal fibrosis.

  1. Disparate effects of roscovitine on renal tubular epithelial cell apoptosis and senescence: implications for autosomal dominant polycystic kidney disease.

    Science.gov (United States)

    Park, Jin-Young; Park, See-Hyoung; Weiss, Robert H

    2009-01-01

    Control of apoptosis in autosomal dominant polycystic kidney disease (ADPKD) and in at least some cancers is likely regulated by the endogenous cyclin kinase inhibitor p21, levels of this protein being decreased in ADPKD and increased in many malignancies. The cyclin kinase inhibitor roscovitine has shown efficacy in treatment of murine PKD. We asked how a single agent can be efficacious in both PKD and cancer. Renal tubular epithelial cells were incubated at diverse roscovitine concentrations; apoptosis and senescence were measured. Subsequently, levels of pro- and antiapoptotic proteins were evaluated. Renal tubular epithelial cells exposed to 'low' concentrations of roscovitine showed minimal apoptosis in association with markedly increased levels of the antiapoptotic protein p21, and these cells became senescent. Conversely, cells exposed to 'high' levels of roscovitine became apoptotic. The mechanism of antiapoptosis and senescence with 'low'-dose roscovitine involves augmentation of the antiapoptotic proteins. Data in this study provide a mechanistic explanation of how roscovitine is effective in PKD, and suggest that further study of this agent should focus on assessment of dose response. Furthermore, our discovery of senescence induced by a PKD effective drug suggests a new area of therapeutic investigation in this disease. (c) 2008 S. Karger AG, Basel.

  2. 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.

  3. Alpha-enolase on apical surface of renal tubular epithelial cells serves as a calcium oxalate crystal receptor

    Science.gov (United States)

    Fong-Ngern, Kedsarin; Thongboonkerd, Visith

    2016-10-01

    To search for a strategy to prevent kidney stone formation/recurrence, this study addressed the role of α-enolase on apical membrane of renal tubular cells in mediating calcium oxalate monohydrate (COM) crystal adhesion. Its presence on apical membrane and in COM crystal-bound fraction was confirmed by Western blotting and immunofluorescence staining. Pretreating MDCK cells with anti-α-enolase antibody, not isotype-controlled IgG, dramatically reduced cell-crystal adhesion. Immunofluorescence staining also confirmed the direct binding of purified α-enolase to COM crystals at {121} > {100} > {010} crystal faces. Coating COM crystals with urinary proteins diminished the crystal binding capacity to cells and purified α-enolase. Moreover, α-enolase selectively bound to COM, not other crystals. Chemico-protein interactions analysis revealed that α-enolase interacted directly with Ca2+ and Mg2+. Incubating the cells with Mg2+ prior to cell-crystal adhesion assay significantly reduced crystal binding on the cell surface, whereas preincubation with EDTA, a divalent cation chelator, completely abolished Mg2+ effect, indicating that COM and Mg2+ competitively bind to α-enolase. Taken together, we successfully confirmed the role of α-enolase as a COM crystal receptor to mediate COM crystal adhesion at apical membrane of renal tubular cells. It may also serve as a target for stone prevention by blocking cell-crystal adhesion and stone nidus formation.

  4. 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

  5. TWEAK Activates the Non-Canonical NFκB Pathway in Murine Renal Tubular Cells: Modulation of CCL21

    Science.gov (United States)

    Sanz, Ana B.; Sanchez-Niño, Maria D.; Izquierdo, Maria C.; Jakubowski, Aniela; Justo, Pilar; Blanco-Colio, Luis M.; Ruiz-Ortega, Marta; Selgas, Rafael; Egido, Jesús; Ortiz, Alberto

    2010-01-01

    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 NFκB activation suggestive of engagement of the non-canonical NFκB pathway. We now explore TWEAK-induced activation of NFκB2 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 TNFα activated different DNA-binding NFκB complexes. TWEAK-induced sustained NFκB activation was associated with NFκB2 p100 processing to p52 via proteasome and nuclear translocation and DNA-binding of p52 and RelB. TWEAK, but not TNFα 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 NFκB2-dependent chemokine, CCL19, was upregulates by TWEAK, but not by TNFα. However, both cytokines promoted chemokine RANTES expression (3-fold mRNA at 24 h). In vivo, TWEAK induced nuclear NFκB2 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 NFκB activation and CCL21 expression in tubular cells thus promoting

  6. 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.

  7. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Wetzels, J.F.M.; Joles, J.A.; Christensen, E.I.; Verroust, P.J.; Li, D.; Oliver, N.; Xu, L.; Kok, R.J.; Goldschmeding, R.

    2010-01-01

    Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal ex

  8. Renal tubular epithelial-mesenchymal transition in kidney fibrosis%肾小管上皮间充质转化与肾脏纤维化

    Institute of Scientific and Technical Information of China (English)

    王来亮; 罗群

    2014-01-01

    Epithelial-mesenchymal transition ( EMT) , a process by which differentiated epithelial cells under-go a phenotypic conversion that gives rise to the matrix-producing fibroblasts and myofibroblasts, is increasingly recognized as an integral part of tissue fibrogenesis after injury.However, the degree to which renal tubular epithelial EMT contributes to kidney fibrosis remains a matter of intense debate and is likely to be context-dependent.Renal tubular EMT is an adap-tive response of epithelial cells to a hostile or changing microenvironment and is regulated by many factors.Several intrace-llular signal transduction pathways such as transforming growth factor-β( TGF-β)/Smad and Wnt/β-catenin signaling are essential in controlling the process of renal tubular epithelial EMT which are potential targets of antifibrotic therapy present-ly.This review highlights the current understanding of renal tubular epithelial EMT and its underlying mechanisms to stimu-late further discussion on its role in the pathogenesis of renal interstitial fibrosis.

  9. RENAL TUBULAR SENSITIVITY TO ATRIAL-NATRIURETIC-FACTOR IN ESSENTIAL-HYPERTENSION

    NARCIS (Netherlands)

    JANSSEN, WMT; DEZEEUW, D; VANDERHEM, GK; DEJONG, PE

    1994-01-01

    Objective: To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension. Design: Nine healthy volunteers and six patients with essential hypertension were studied on four test

  10. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

  12. 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.

  13. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  15. 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

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis

    NARCIS (Netherlands)

    D. Mul (Dick); F.K. Grote (Floor); J.R. Goudriaan; S.M.P.F. de Muinck Keizer-Schrama (Sabine); J.M. Wit (Jan); W. Oostdijk (Wilma)

    2010-01-01

    textabstractBackground: Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. Objective: To investigate the clinical, growth and laboratory parameters in children

  18. Lysosomal Changes in Renal Proximal Tubular Epithelial Cells of Male Sprague Dawley Rats Following Decalin Exposure

    Science.gov (United States)

    1990-01-01

    decalin-treated animal. Note large, pale, rcd-staining lysosome (-). An exfoliated epithelial cell can iu- seen in the tubular lumen containing large...photomicrograph contains an exfoliated epithelial cell (-) with enlarged, intact lysosomes. The tubule on the left half of the photomicrograph contains an...metabolism of proteins. In: Cytology , GH Bourne and JF Danielli (eds). Academ- The Kidney: Physiology and Pathophysiology, DW ic Press, NY, pp. 251-300. - ~- i :- d .L n .- 2

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

    Science.gov (United States)

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

    2015-01-01

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

  20. 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.

  1. Handling and staging of renal cell carcinoma: the International Society of Urological Pathology Consensus (ISUP) conference recommendations

    NARCIS (Netherlands)

    Trpkov, K.; Grignon, D.J.; Bonsib, S.M.; Amin, M.B.; Billis, A.; Lopez-Beltran, A.; Samaratunga, H.; Tamboli, P.; Delahunt, B.; Egevad, L.; Montironi, R.; Srigley, J.R.; Hulsbergen-van de Kaa, C.A.

    2013-01-01

    The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and

  2. Handling and staging of renal cell carcinoma: the International Society of Urological Pathology Consensus (ISUP) conference recommendations

    NARCIS (Netherlands)

    Trpkov, K.; Grignon, D.J.; Bonsib, S.M.; Amin, M.B.; Billis, A.; Lopez-Beltran, A.; Samaratunga, H.; Tamboli, P.; Delahunt, B.; Egevad, L.; Montironi, R.; Srigley, J.R.; Hulsbergen-van de Kaa, C.A.

    2013-01-01

    The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and

  3. Malondialdehyde, antioxidant enzymes, and renal tubular functions in children with iron deficiency or iron-deficiency anemia.

    Science.gov (United States)

    Altun, Demet; Kurekci, Ahmet Emin; Gursel, Orhan; Hacıhamdioglu, Duygu Ovunc; Kurt, Ismail; Aydın, Ahmet; Ozcan, Okan

    2014-10-01

    We aimed to investigate the effects of iron deficiency (ID) or iron-deficiency anemia (IDA) on oxidative stress and renal tubular functions before and after treatment of children. A total of 30 children with a diagnosis of IDA constituted the IDA group and 32 children with a diagnosis of ID constituted the ID group. Control group consisted 38 age-matched children. Serum ferritin, soluble transferrin receptor (sTfR), serum, and urinary sodium (Na), potassium (K), calcium (Ca), phosphorus (P), creatinine (Cr), uric acid (UA), urinary N-acetyl-β-D-glucosaminidase (NAG) levels, and intra-erythrocyte malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) levels were measured before and after iron therapy in the IDA and ID groups, whereas it was studied once in the control group. We have divided the study group in groups according to age (infants <2 years, children 3-9 years, and adolescents 10-15 years). Patients with IDA (infant, adolescent) and ID (infant, children, and adolescent) had a significantly high level of MDA in post-treatment period in comparison to those of healthy control. Patients with IDA (children, adolescent) and ID (infant, children) had a significantly high level of pre-treatment GSH-Px than controls. Post-treatment SOD was lower in IDA (children and adolescent) groups than control and post-treatment CAT was lower in IDA and ID (adolescent) groups than control. These findings show that ferrous sulfate used in the treatment of ID or IDA could lead to oxidative stress; however, a marked deterioration of in proximal renal tubular functions was not seen.

  4. 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.

  5. Extracellular vesicles released from mesenchymal stromal cells modulate miRNA in renal tubular cells and inhibit ATP depletion injury.

    Science.gov (United States)

    Lindoso, Rafael S; Collino, Federica; Bruno, Stefania; Araujo, Dayana S; Sant'Anna, Julliana F; Tetta, Ciro; Provero, Paolo; Quesenberry, Peter J; Vieyra, Adalberto; Einicker-Lamas, Marcelo; Camussi, Giovanni

    2014-08-01

    The mechanisms involved in renal repair by mesenchymal stromal cells (MSCs) are not entirely elucidated. The paracrine secretion of bioactive molecules has been implicated in the protective effects. Besides soluble mediators, MSCs have been shown to release extracellular vesicles (EVs), involved in renal repair process for different injury models. EVs have been shown to mediate communication between cells through the transference of several molecules, like protein, bioactive lipids, mRNA, and microRNAs (miRNAs). The miRNAs are noncoding RNAs that posttranscriptionally modulate gene expression and are involved in the regulation of several cellular processes, including those related to repair. The aim of the present study was to investigate the role of MSC-EVs in the modulation of miRNAs inside renal proximal tubular epithelial cells (PTECs) in an in vitro model of ischemia-reperfusion injury induced by ATP depletion. In this model we evaluated whether changes in miRNA expression were dependent on direct miRNA transfer or on transcription induction by MSC-EVs. The obtained results showed an enhanced incorporation of MSC-EVs in injured PTECs with protection from cell death. This biological effect was associated with EV-mediated miRNA transfer and with transcriptional modulation of miRNAs expressed by injured PTECs. Prediction of miRNA targets showed that miRNAs modulated in PTECs are involved in process of renal recovery with downregulation of coding-mRNAs associated with apoptosis, cytoskeleton reorganization, and hypoxia, such as CASP3 and 7, SHC1 and SMAD4. In conclusion, these results indicate that MSC-EVs may transfer and modulate the expression of several miRNAs involved in the repair and recovery process in PTECs.

  6. Genetics Home Reference: SLC4A1-associated distal renal tubular acidosis

    Science.gov (United States)

    ... a shortage of red blood cells ( anemia ). Hemolytic anemia can lead to unusually pale skin (pallor), extreme tiredness (fatigue), ... breakdown of these abnormal red blood cells may lead to hemolytic anemia. Some people have nonhereditary forms of distal renal ...

  7. Renal hemodynamics, tubular function, and response to low-dose dopamine during acute hypoxia in humans

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal; Hansen, J M; Kanstrup, I L

    1993-01-01

    , heart rate, and plasma norepinephrine. Effective renal plasma flow (ERPF) decreased at HA by 10% (P sodium clearance (CNa), and urine flow remained unchanged compared with SL. Dopamine at SL and HA increased ERPF by 47% (P

  8. 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.

  9. 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.......3-31.0)% (P sodium clearance (CNa), but glomerular filtration rate and urine flow rate remained unchanged. 3. Dopamine increased CNa to similar values on the three study days. CLi increased to 40.9 (35.5-46.5) ml/min (endogenous lithium, P

  10. 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.

  11. 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.

  12. L-Carnitine Protects Renal Tubular Cells Against Calcium Oxalate Monohydrate Crystals Adhesion Through Preventing Cells From Dedifferentiation

    Directory of Open Access Journals (Sweden)

    Shujue Li

    2016-08-01

    Full Text Available Background/Aims: The interactions between calcium oxalate monohydrate (COM crystals and renal tubular epithelial cells are important for renal stone formation but still unclear. This study aimed to investigate changes of epithelial cell phenotype after COM attachment and whether L-carnitine could protect cells against subsequent COM crystals adhesion. Methods: Cultured MDCK cells were employed and E-cadherin and Vimentin were used as markers to estimate the differentiate state. AlexaFluor-488-tagged COM crystals were used in crystals adhesion experiment to distinguish from the previous COM attachment, and adhesive crystals were counted under fluorescence microscope, which were also dissolved and the calcium concentration was assessed by flame atomic absorption spectrophotometry. Results: Dedifferentiated MDCK cells induced by transforming growth factor β1 (TGF-β1 shown higher affinity to COM crystals. After exposure to COM for 48 hours, cell dedifferentiation were observed and more subsequent COM crystals could bind onto, mediated by Akt/GSK-3β/Snail signaling. L-carnitine attenuated this signaling, resulted in inhibition of cell dedifferentiation and reduction of subsequent COM crystals adhesion. Conclusions: COM attachment promotes subsequent COM crystals adhesion, by inducing cell dedifferentiation via Akt/GSK-3β/Snail signaling. L-carnitine partially abolishes cell dedifferentiation and resists COM crystals adhesion. L-carnitine, may be used as a potential therapeutic strategy against recurrence of urolithiasis.

  13. Pentavalent antimonial nephrotoxicity in the rat Disfunção tubular renal em ratos tratados com antimoniais pentavalentes

    Directory of Open Access Journals (Sweden)

    Joel Paulo R. Veiga

    1990-08-01

    Full Text Available Aspects of the renal function were assessed in rats treated with the pentavalent antimonials Glucantime (Meglumine Antimoniate, Rhodia or Pentostam (Sodium Stibogluconate, Wellcome. In dose of 30 mg of Sb v (Glucantime or Pentostam by 100 mg of weight by day for 30 days, renal functional changes were observed consisting of disturbances in urine concentrating capacity. Such disturbances were expressed by significantly low values of urine osmolality as compared to the basal values previous to the drugs. The decrease in urine osmolality was associated to a significant increase in urinary flow and in negative free-water clearance. There was no alteration in osmolar clearance and in fractional excretion of sodium. These observations suggest an interference of the drugs in the action of the antidiuretic hormone. The disturbance in urine concentration was reversible after a seven days period without the drugs administration. No significant histopathological alterations were observed in the kidneys of the rats treated with the drugs. On the other hand, the rats treated with a high dose of Pentostam (200 mg/100 grams of weight/day showed the functional and the histopathological alterations of the acute tubular necrosis.Estudou-se a função renal de ratos tratados com Glucantime (Antimoniato de Meglumine, Rhodia e Pentostam (Estibogluconato de Sódio, Wellcome na dose de 30 mg de Sb v por 100 g de peso por dia, durante 30 dias. Observou-se um distúrio na concentração urinária, que foi reversível 7 dias após cessada a administração das drogas. O estudo histopatológico do rim, por meio da microscopia óptica, não evidenciou alterações significativas. Por outro lado, ratos tratados com altas doses dos antimoniais (200 mg de Sb v por 100 g de peso por dia mostraram alterações funcionais e histopatológicas renais compatíveis com necrose tubular aguda.

  14. 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.

  15. 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

  16. An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis.

    Science.gov (United States)

    Morris, R C

    1968-07-01

    In adult patients with hereditary fructose intolerance (HFI) fructose induces a renal acidification defect characterized by (a) a 20-30% reduction in tubular reabsorption of bicarbonate (T HCO(3) (-)) at plasma bicarbonate concentrations ranging from 21-31 mEq/liter, (b) a maximal tubular reabsorption of bicarbonate (Tm HCO(3) (-)) of approximately 1.9 mEq/100 ml of glomerular filtrate, (c) disappearance of bicarbonaturia at plasma bicarbonate concentrations less than 15 mEq/liter, and (d) during moderately severe degrees of acidosis, a sustained capacity to maintain urinary pH at normal minima and to excrete acid at normal rates. In physiologic distinction from this defect, the renal acidification defect of patients with classic renal tubular acidosis is characterized by (a) just less than complete tubular reabsorption of bicarbonate at plasma bicarbonate concentrations of 26 mEq/liter or less, (b) a normal Tm HCO(3) (-) of approximately 2.8 mEq/100 ml of glomerular filtrate, and (c) during acidosis of an even severe degree, a quantitatively trivial bicarbonaturia, as well as (d) a urinary pH of greater than 6. That the fructose-induced renal acidification defect involves a reduced H(+) secretory capacity of the proximal nephron is supported by the magnitude of the reduction in T HCO(3) (-) (20-30%) and the simultaneous occurrence and the persistence throughout administration of fructose of impaired tubular reabsorption of phosphate, alpha amino nitrogen and uric acid.A reduced H(+) secretory capacity of the proximal nephron also appears operative in two unrelated children with hyperchloremic acidosis, Fanconi's syndrome, and cystinosis. In both, T HCO(3) (-) was reduced 20-30% at plasma bicarbonate concentrations ranging from 20-30 mEq/liter. The bicarbonaturia disappeared at plasma bicarbonate concentrations ranging from 15-18 mEq/liter, and during moderate degrees of acidosis, urinary pH decreased to less than 6, and the excretion rate of acid was normal.

  17. 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...

  18. Metformin inhibits advanced glycation end products (AGEs)-induced renal tubular cell injury by suppressing reactive oxygen species generation via reducing receptor for AGEs (RAGE) expression.

    Science.gov (United States)

    Ishibashi, Y; Matsui, T; Takeuchi, M; Yamagishi, S

    2012-11-01

    Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in tubulointerstitial damage in diabetic nephropathy. Recently, metformin has been shown to ameliorate tubular injury both in cell culture and diabetic animal model. However, effects of metformin on AGEs-induced tubular cell apoptosis and damage remain unknown. We examined here whether and how metformin could block the AGEs-RAGE-elicited tubular cell injury in vitro. Gene expression level was evaluated by real-time reverse-transcription polymerase chain reactions. Reactive oxygen species (ROS) generation was measured with dihydroethidium staining. Apoptosis was evaluated by DNA fragmentation and annexin V expression level. AGEs upregulated RAGE mRNA levels and subsequently increased ROS generation and intercellular adhesion molecule-1, monocyte chemoattractant protein-1 and transforming growth factor-β gene expression in human renal proximal tubular cells, all of which were significantly blocked by the treatment of 0.01 and 0.1 mM metformin. Compound C, an inhibitor of AMP-activated protein kinase significantly blocked the effects of metformin on RAGE gene expression and ROS generation in AGEs-exposed tubular cells. Furthermore, metformin dose-dependently inhibited the AGEs-induced apoptotic cell death of tubular cells; 1 mM metformin completely suppressed the pro-apoptotic effects of AGEs in 2 different assay systems. Our present study suggests that metformin could inhibit the AGEs-induced apoptosis and inflammatory and fibrotic reactions in tubular cells probably by reducing ROS generation via suppression of RAGE expression through AMP-activated protein kinase activation. Metformin may protect against tubular cell injury in diabetic nephropathy by blocking the AGEs-RAGE-ROS axis.

  19. Effects of Escherichia Coli Subtilase Cytotoxin and Shiga Toxin 2 on Primary Cultures of Human Renal Tubular Epithelial Cells

    Science.gov (United States)

    Márquez, Laura B.; Velázquez, Natalia; Repetto, Horacio A.; Paton, Adrienne W.; Paton, James C.; Ibarra, Cristina; Silberstein, Claudia

    2014-01-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) cause post-diarrhea Hemolytic Uremic Syndrome (HUS), which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB) that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC) and compare its effects with those produced by Shiga toxin type 2 (Stx2), in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2. PMID:24466317

  20. Resveratrol ameliorates hyperglycemia-induced renal tubular oxidative stress damage via modulating the SIRT1/FOXO3a pathway.

    Science.gov (United States)

    Wang, Xueling; Meng, Linghang; Zhao, Long; Wang, Zengfu; Liu, Haiying; Liu, Gang; Guan, Guangju

    2017-04-01

    Oxidative stress plays an important role in the development and progression of diabetic nephropathy (DN). We aimed to investigate if resveratrol (RSV) could ameliorate hyperglycemia-induced oxidative stress in renal tubules via modulating the SIRT1/FOXO3a pathway. The effects of RSV on diabetes rats were assessed by periodic acid-Schiff, Masson staining, immunohistochemistry, and western blot analyses. Additionally, oxidative indicators (such as catalase, superoxide dismutase, reactive oxygen species, and malondialdehyde), the deacetylase activity of SIRT1 and protein expressions of SIRT1, FOXO3a, and acetylated-FOXO3a were measured. These indicators were similarly evaluated in an in vitro study. Furthermore, the silencing of SIRT1 was used to confirm its role in the resistance to oxidative stress and the relationship between SIRT1 and FOXO3a in vitro. After 16weeks of RSV treatment, the renal function and glomerulosclerosis of rats with DN was dramatically ameliorated. RSV treatment increased SIRT1 deacetylase activity, subsequently decreasing the expression of acetylated-FOXO3a and inhibiting the oxidative stress caused by hyperglycemia both in vivo and in vitro. The silencing of SIRT1 in HK-2 cells aggravated the high glucose-induced oxidative stress and overexpression of acetylated-FOXO3a; RSV treatment failed to protect against these effects. RSV modulates the SIRT1/FOXO3a pathway by increasing SIRT1 deacetylase activity, subsequently ameliorating hyperglycemia-induced renal tubular oxidative stress damage. This mechanism provides the basis for a new approach to developing an effective DN treatment, which is of great clinical significance for reducing the morbidity and mortality associated with DN. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Effects of Escherichia coli subtilase cytotoxin and Shiga toxin 2 on primary cultures of human renal tubular epithelial cells.

    Directory of Open Access Journals (Sweden)

    Laura B Márquez

    Full Text Available Shiga toxin (Stx-producing Escherichia coli (STEC cause post-diarrhea Hemolytic Uremic Syndrome (HUS, which is the most common cause of acute renal failure in children in many parts of the world. Several non-O157 STEC strains also produce Subtilase cytotoxin (SubAB that may contribute to HUS pathogenesis. The aim of the present work was to examine the cytotoxic effects of SubAB on primary cultures of human cortical renal tubular epithelial cells (HRTEC and compare its effects with those produced by Shiga toxin type 2 (Stx2, in order to evaluate their contribution to renal injury in HUS. For this purpose, cell viability, proliferation rate, and apoptosis were assayed on HRTEC incubated with SubAB and/or Stx2 toxins. SubAB significantly reduced cell viability and cell proliferation rate, as well as stimulating cell apoptosis in HRTEC cultures in a time dependent manner. However, HRTEC cultures were significantly more sensitive to the cytotoxic effects of Stx2 than those produced by SubAB. No synergism was observed when HRTEC were co-incubated with both SubAB and Stx2. When HRTEC were incubated with the inactive SubAA272B toxin, results were similar to those in untreated control cells. Similar stimulation of apoptosis was observed in Vero cells incubated with SubAB or/and Stx2, compared to HRTEC. In conclusion, primary cultures of HRTEC are significantly sensitive to the cytotoxic effects of SubAB, although, in a lesser extent compared to Stx2.

  2. 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

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

    NARCIS (Netherlands)

    M. Asselman (Marino)

    2008-01-01

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

  4. Determinants of tubular bone marrow-derived cell engraftment after renal ischemia/reperfusion in rats

    NARCIS (Netherlands)

    Broekema, M; Harmsen, MC; Koerts, JA; Petersen, AH; van Luyn, MJA; Navis, G; Popa, ER

    2005-01-01

    Background. Ischemia/reperfusion (I/R) injury is a major cause of acute renal failure (ARF). ARF is reversible, due to an innate regenerative process, which is thought to depend partly on bone marrow-derived progenitor cells. The significance of these cells in the repair process has been questioned

  5. 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.

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

    Science.gov (United States)

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

    2016-03-01

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

  7. Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

    Science.gov (United States)

    Reed, Galen D.; von Morze, Cornelius; Verkman, Alan S.; Koelsch, Bertram L.; Chaumeil, Myriam M.; Lustig, Michael; Ronen, Sabrina M.; Bok, Robert A.; Sands, Jeff M.; Larson, Peder E. Z.; Wang, Zhen J.; Larsen, Jan Henrik Ardenkjær; Kurhanewicz, John; Vigneron, Daniel B.

    2016-01-01

    In vivo spin spin relaxation time (T2) heterogeneity of hyperpolarized [13C,15N2]urea in the rat kidney was investigated. Selective quenching of the vascular hyperpolarized 13C signal with a macromolecular relaxation agent revealed that a long-T2 component of the [13C,15N2]urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the [13C,15N2]urea to be distinguished via multi-exponential analysis. The T2 response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized [13C,15N2]urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-13C-cyclopropane-2H8. Large T2 increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis. Therefore, [13C,15N2]urea relaxometry is sensitive to two steps of the renal urea handling process: glomerular filtration and the inner-medullary urea transporter (UT)-A1 and UT-A3 mediated urea concentrating process. Simple motion correction and subspace denoising algorithms are presented to aid in the multi exponential data analysis. Furthermore, a T2-edited, ultra long echo time sequence was developed for sub-2 mm3 resolution 3D encoding of urea by exploiting relaxation differences in the vascular and filtrate pools. PMID:27570835

  8. Oral erdosteine administration attenuates cisplatin-induced renal tubular damage in rats.

    Science.gov (United States)

    Yildirim, Zeki; Sogut, Sadik; Odaci, Ersan; Iraz, Mustafa; Ozyurt, Huseyin; Kotuk, Mahir; Akyol, Omer

    2003-02-01

    The effect of oral erdosteine on tissue malondialdehyde (MDA) and nitric oxide (NO) levels, and catalase (CAT), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities are investigated in the cisplatin model of acute renal failure in rats. A single dose of cisplatin caused kidney damage manifested by kidney histology as well as increases in plasma creatinine and blood urea nitrogen (BUN) levels. Treatment with free radical scavenger erdosteine attenuated increases in plasma creatinine and BUN, and tissue MDA and NO levels, and provided a histologically-proven protection against cisplatin-induced acute renal failure. Erdosteine also reduced depletion in the tissue CAT, GSH-Px, and SOD activities. These results show that erdosteine may be a promising drug for protection against cisplatin-induced nephrotoxicity. However, further studies with different doses of erdosteine are warranted for clarifying the issue.

  9. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3

    OpenAIRE

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

    2015-01-01

    Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na+/H+ exchanger isoform 3 (NHE3) localization and phosphorylation, resul...

  10. 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.

  11. Pathology of spontaneous tubular proteinuria evaluated by renal scintigraphy {sup 99m}-Tc-dimercaptosuccinic acid (DMSA). Second report. Evaluation of urinary excretion and urinary bladder uptake images

    Energy Technology Data Exchange (ETDEWEB)

    Matsuyama, Takeshi; Hosaki, Tomoko; Shimizu, Mariko [Fussa Hospital, Tokyo (Japan)] [and others

    2000-03-01

    The significance of DMSA uptake in the urinary bladder and %uptake in renal scintigrams with {sup 99m}Tc-DMSA in spontaneous tubular proteinuria was reassessed. The subjects were 10 patients in whom DMSA uptake in the urinary bladder could be clearly evaluated among 15 cases that were tentatively diagnosed as having spontaneous tubular proteinuria and in which renal scintigraphy was performed with DMSA. All of the patients were male children and their mean age was 9 years 11 months. No morphological abnormalities in the kidneys could be detected in any of the cases, and %uptake of DMSA was very low. Urinary excretion and uptake of the nuclide in the urinary bladder was significantly increased. In view of the pharmacokinetics of DMSA, the patients' disease appeared to be complicated by failure of the proximal tubule epithelial cells to resorb low-molecular-weight proteins, and the failure of active transport on the vascular lumen side of the cells. As a result, urinary excretion was increased and marked uptake in the urinary bladder was induced. Accordingly, when %uptake of DMSA cannot be measured, it is necessary to determine the extent of uptake in the urinary bladder. When images showing abnormal uptake are obtained, the possibility of diseases associated with functional failure at the proximal tubular level, such as spontaneous tubular proteinuria, is quite high. (K.H.)

  12. Hypokalemia-Induced Rhabdomyolysis as a result of Distal Renal Tubular Acidosis in a Pregnant Woman: A Case Report and Literature Review

    Directory of Open Access Journals (Sweden)

    Manasawee Srisuttayasathien

    2015-01-01

    Full Text Available Rhabdomyolysis in pregnancy is a rare occurrence. The manifestation of distal renal tubular acidosis (RTA for the first time during adulthood is uncommon. According to a review of the literature, pregnancy may predispose individuals to rhabdomyolysis due to hypokalemia. A reduction in interstitial potassium ions could decrease muscular blood flow and lead to muscle injury. This report describes the case of a pregnant woman with rhabdomyolysis induced by hypokalemia resulting from distal RTA. The patient subsequently delivered a healthy newborn.

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

    DEFF Research Database (Denmark)

    Olsen, Niels Vidiendal

    1998-01-01

    remained unchanged by pretreatment with metoprolol, and a comparison of dopamine and dobutamine in doses producing similar increases in cardiac output demonstrated that only dopamine increased ERPF. These findings indicate that indirect haemodynamic effects secondary to increases in cardiac contractility...... at these high doses. Although not affecting the percentage increase in CNa, metoprolol suppressed the absolute, maximal response to non-pressor doses of dopamine, suggesting that a reduced adrenergic beta(1) receptor activity may indirectly affect the natriuretic response, probably by decreasing renal perfusion...

  14. 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.

  15. Influence of consumption of cadmium-polluted rice or Jinzu River water on occurrence of renal tubular dysfunction and/or Itai-itai disease.

    Science.gov (United States)

    Kobayashi, Etsuko; Suwazono, Yasushi; Dochi, Mirei; Honda, Ryumon; Kido, Teruhiko

    2009-03-01

    The aim of this study was to clarify whether consumption of cadmium (Cd)-polluted rice or Jinzu River water exerted any influence on the occurrence of renal tubular dysfunction and/or Itai-itai disease. From the participants of health examinations conducted in 1967 and 1968, 3,078 subjects who had resided for >30 years in the present hamlet and were aged >50 years were selected as the target population and were divided according to their residence in 55 hamlets. In a multiple regression analysis, the regression coefficients between rice-Cd concentration and prevalence of abnormal urinary findings (proteinuria, glucosuria, or proteinuria with glucosuria) or patients with Itai-itai disease were statistically significant between both sexes. The correlation between the prevalence of users of Jinzu River water and the occurrence of glucosuria in men as well as abnormal urinary findings in women was not statistically significant. We surmise that eating Cd-polluted rice and drinking and/or cooking with Jinzu River water influenced the occurrence of Itai-itai disease. The occurrence of renal tubular dysfunction is likely to have also been influenced by both factors, with eating Cd-polluted rice having a greater impact on the occurrence of renal tubular dysfunction as compared to drinking and/or cooking with Jinzu River water.

  16. Cobalt Chloride Induces Expression and Function of Breast Cancer Resistance Protein (BCRP/ABCG2) in Human Renal Proximal Tubular Epithelial Cell Line HK-2.

    Science.gov (United States)

    Nishihashi, Katsuki; Kawashima, Kei; Nomura, Takami; Urakami-Takebayashi, Yumiko; Miyazaki, Makoto; Takano, Mikihisa; Nagai, Junya

    2017-01-01

    The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2. Cobalt chloride treatment significantly increased the mRNA expression of not only glucose transporter 1 (GLUT1), a typical HIF-1 target gene mRNA, but also ABCG2 mRNA in HK-2 cells. The BCRP inhibitor Ko143-sensitive accumulation of BCRP substrates such as Hoechst33342 and mitoxantrone was significantly enhanced by cobalt chloride treatment. In addition, treatment with cobalt chloride significantly increased the Ko143-sensitive accumulation of fluorescein isothiocyanate-labeled methotrexate in HK-2 cells. Furthermore, cobalt chloride treatment attenuated the cytotoxicity induced by mitoxantrone and methotrexate, which might be, at least in part, due to the increase in BCRP-mediated transport activity via HIF-1 activation. These findings indicate that HIF-1 activation protects renal proximal tubular cells against BCRP substrate-induced cytotoxicity by enhancing the expression and function of BCRP in renal proximal tubular cells.

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

    Science.gov (United States)

    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

  18. Epinephrine Evokes Renalase Secretion via a-Adrenoceptor/NF-κB Pathways in Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Feng Wang

    2014-08-01

    Full Text Available Background/Aims: Renalase is a recently discovered, kidney-specific monoamine oxidase that metabolizes circulating catecholamines. These findings present new insights into hypertension and chronic kidney diseases. Previous data demonstrated that renalase was mainly secreted from proximal tubules which could be evoked by catecholamines. The purpose of this study is to investigate whether renalase expression is induced by epinephrine via a-adrenoceptor/NFκB pathways. Methods: HK2 cells were utilized to explore renalase expression in response to epinephrine in vitro. Phentolamine, an a-adrenoceptor antagonist, and Tosyl Phenylalanyl Chloromethyl Ketone (TPCK were used to block a-adrenoceptor and to knock down the transcription factor NFκB, respectively. Renalase expression was analyzed using Western blot and quantitative PCR. Results: Both protein and mRNA levels of renalase in HK2 cells increased in response to epinephrine (PConclusion: Epinephrine evokes renalase secretion via a-adrenoceptor/NF-κB pathways in renal proximal tubular epithelial cells.

  19. Deafness and renal tubular acidosis in mice lacking the K-Cl co-transporter Kcc4.

    Science.gov (United States)

    Boettger, Thomas; Hübner, Christian A; Maier, Hannes; Rust, Marco B; Beck, Franz X; Jentsch, Thomas J

    2002-04-25

    Hearing depends on a high K(+) concentration bathing the apical membranes of sensory hair cells. K(+) that has entered hair cells through apical mechanosensitive channels is transported to the stria vascularis for re-secretion into the scala media(). K(+) probably exits outer hair cells by KCNQ4 K(+) channels(), and is then transported by means of a gap junction system connecting supporting Deiters' cells and fibrocytes() back to the stria vascularis. We show here that mice lacking the K(+)/Cl(-) (K-Cl) co-transporter Kcc4 (coded for by Slc12a7) are deaf because their hair cells degenerate rapidly after the beginning of hearing. In the mature organ of Corti, Kcc4 is restricted to supporting cells of outer and inner hair cells. Our data suggest that Kcc4 is important for K(+) recycling() by siphoning K(+) ions after their exit from outer hair cells into supporting Deiters' cells, where K(+) enters the gap junction pathway. Similar to some human genetic syndromes(), deafness in Kcc4-deficient mice is associated with renal tubular acidosis. It probably results from an impairment of Cl(-) recycling across the basolateral membrane of acid-secreting alpha-intercalated cells of the distal nephron.

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

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    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.

  1. 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.

  2. Renal glucose handling in diabetes and sodium glucose cotransporter 2 inhibition

    Directory of Open Access Journals (Sweden)

    Resham Raj Poudel

    2013-01-01

    Full Text Available The kidneys play a major role in glucose homeostasis through its utilization, gluconeogenesis, and reabsorption via sodium glucose cotransporters (SGLTs. The defective renal glucose handling from upregulation of SGLTs, mainly the SGLT2, plays a fundamental role in the pathogenesis of type 2 diabetes mellitus. Genetic mutations in a SGLT2 isoform that results in benign renal glycosuria, as well as clinical studies with SGLT2 inhibitors in type 2 diabetes support the potential of this approach. These studies indicate that inducing glycosuria by suppressing SGLT2 can reduce plasma glucose and A1c levels, as well as decrease weight, resulting in improved β-cell function and enhanced insulin sensitivity in liver and muscle. Because the mechanism of SGLT2 inhibition is independent of insulin secretion and sensitivity, these agents can be combined with other antidiabetic agents, including exogenous insulin. This class represents a novel therapeutic approach with potential for the treatment of both type 2 and type 1 diabetes.

  3. 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.

  4. Problemas renales de la cirrosis Renal problems of cirrhosis

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    Alvaro García

    1992-02-01

    Full Text Available Presentamos una revisión actualizada y condensada acerca de los problemas renales más relevantes que ocurren en la cirrosis tales como las alteraciones en el manejo del sodio y del agua, el tratamiento de la ascitis y el edema y el enfoque de la falla renal que ocurre en esta enfermedad, es decir síndrome hepato-renal y necrosis tubular aguda.

    We present a condensed and updated review on the most common renal problems occurring in cirrhosis such as the handling of sodium and water, the treatment of ascites and edema and the approach to the renal failure that frequently takes place in this disease, namely hepato-renal syndrome and acute tubular necrosis.

  5. Elucidation of the distal convoluted tubule transcriptome identifies new candidate genes involved in renal Mg2+ handling.

    NARCIS (Netherlands)

    Baaij, J.H.F. de; Groot Koerkamp, M.J.; Lavrijsen, M.; Zeeland, F. van; Meijer, H.; Holstege, F.C.; Bindels, R.J.M.; Hoenderop, J.G.J.

    2013-01-01

    The kidney plays a key role in the maintenance of Mg(2+) homeostasis. Specifically, the distal convoluted tubule (DCT) is instrumental in the fine-tuning of renal Mg(2+) handling. In recent years, hereditary Mg(2+) transport disorders have helped to identify important players in DCT Mg(2+) homeostas

  6. 肾小管上皮细胞损伤的研究进展%Progress in research of renal tubular epithelial cell injury

    Institute of Scientific and Technical Information of China (English)

    彭单单

    2013-01-01

    肾小管上皮细胞(RTEC)是肾小管间质的主要细胞,具有旺盛的代谢活性和潜在的增殖能力,并能分泌多种细胞因子.RTEC损伤,不仅是引起急性肾衰竭的直接原因,而且是导致慢性肾衰竭、贫血、肾性骨病等不可逆的终末期肾病的主要原因和共同病理过程.防治RTEC损伤对于减缓或逆转肾间质纤维化进展具有重要意义.%Renal tubular epithelial cell (RTEC) is the major cell type in renal tubulointerstitium. It has strong metabolic activity and proliferative potency. It secretes a variety of cytokines. RTEC injury is not only the direct cause of acute renal failure, but also the main reason of renal interstitial fibrosis (RIF) and the common pathological process of irreversible end-stage renal diseases such as chronic renal failure, anemia and renal osteodystrophy. Prevention and treatment of RTEC injury is of great significance in slowing down and reversing the progress of RIF.

  7. Caffeine-induced diuresis and natriuresis is independent of renal tubular NHE3.

    Science.gov (United States)

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

    2015-06-15

    Caffeine is one of the most widely consumed behavioral substances. We have previously shown that caffeine- and theophylline-induced inhibition of renal reabsorption causes diuresis and natriuresis, an effect that requires functional adenosine A1 receptors. In this study, we tested the hypothesis that blocking the Gi protein-coupled adenosine A1 receptor via the nonselective adenosine receptor antagonist caffeine changes Na(+)/H(+) exchanger isoform 3 (NHE3) localization and phosphorylation, resulting in diuresis and natriuresis. We generated tubulus-specific NHE3 knockout mice (Pax8-Cre), where NHE3 abundance in the S1, S2, and S3 segments of the proximal tubule was completely absent or severely reduced (>85%) in the thick ascending limb. Consumption of fluid and food, as well as glomerular filtration rate, were comparable in control or tubulus-specific NHE3 knockout mice under basal conditions, while urinary pH was significantly more alkaline without evidence for metabolic acidosis. Caffeine self-administration increased total fluid and food intake comparably between genotypes, without significant differences in consumption of caffeinated solution. Acute caffeine application via oral gavage elicited a diuresis and natriuresis that was comparable between control and tubulus-specific NHE3 knockout mice. The diuretic and natriuretic response was independent of changes in total NHE3 expression, phosphorylation of serine-552 and serine-605, or apical plasma membrane NHE3 localization. Although caffeine had no clear effect on localization of the basolateral Na(+)/bicarbonate cotransporter NBCe1, pretreatment with DIDS inhibited caffeine-induced diuresis and natriuresis. In summary, NHE3 is not required for caffeine-induced diuresis and natriuresis.

  8. Effect of low-osmolar contrast medium iopromide and iso-osmolar iodixanol on DNA fragmentation in renal tubular cell culture.

    Science.gov (United States)

    Ludwig, Ulla; Connemann, Julia; Keller, Frieder

    2013-12-01

    Intravascular administration of iodinated contrast media continues to be a common cause of hospital-acquired acute kidney injury. Accumulating evidence suggests that radiocontrast agent-induced nephrotoxicity is associated with increased oxidative stress, which leads to renal tissue damage with DNA fragmentation. We therefore tested whether an iso-osmolar contrast medium (iodixanol) causes less oxidative DNA damage to renal tubular cells than a low-osmolar contrast medium (iopromide). HK-2 cells (human proximal renal tubular cell line) were incubated at different time points (10 min-2 h) with increasing concentrations (20-120 mg/ml iodine) of iodixanol or of iopromide. Oxidative DNA damage to renal tubular cells was measured by alkaline comet assay (single-cell gel electrophoresis). Both iso- and low-osmolar contrast agents induced time- and concentration-dependent DNA fragmentation. DNA fragmentation was maximal at 2 h with 120 mg/ml iodine for iopromide (32 ± 27 tail moments) and iodixanol (46 ± 41 tail moments); both were significantly different from the control value with 3.15 ± 1.6 tail moments (Student's t test; p DNA fragmentation than iopromide (ANOVA for 1 h p = 0.039 and 2 h p = 0.025, respectively). We were able to demonstrate for the first time that an iso-osmolar contrast medium induced even greater oxidative stress and DNA damage than a low-osmolar agent in HK-2 cells. This could provide an explanation for the nephrotoxicity that also is observed with iodixanol in clinical practice.

  9. 1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells.

    Science.gov (United States)

    Rinaldo, Christine Hanssen; Gosert, Rainer; Bernhoff, Eva; Finstad, Solrun; Hirsch, Hans H

    2010-11-01

    Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-O-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithelial cells were infected with BKV-Dunlop, and CMX001 was added 2 h postinfection (hpi). The intracellular and extracellular BKV DNA load was determined by quantitative PCR. Viral gene expression was examined by quantitative reverse transcription-PCR, Western blotting, and immunofluorescence microscopy. We also examined host cell viability, proliferation, metabolic activity, and DNA replication. The titration of CMX001 identified 0.31 μM as the 90% effective concentration (EC(90)) for reducing the extracellular BKV load at 72 hpi. BKV large T antigen mRNA and protein expression was unaffected at 24 hpi, but the intracellular BKV genome was reduced by 90% at 48 hpi. Late gene expression was reduced by 70 and 90% at 48 and 72 hpi, respectively. Comparisons of CMX001 and cidofovir EC(90)s from 24 to 96 hpi demonstrated that CMX001 had a more rapid and enduring effect on BKV DNA and infectious progeny at 96 hpi than cidofovir. CMX001 at 0.31 μM had little effect on overall cell metabolism but reduced bromodeoxyuridine incorporation and host cell proliferation by 20 to 30%, while BKV infection increased cell proliferation in both rapidly dividing and near-confluent cultures. We conclude that CMX001 inhibits BKV replication with a longer-lasting effect than cidofovir at 400× lower levels, with fewer side effects on relevant host cells in vitro.

  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. 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.

  12. 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.

  13. Distal renal tubular acidosis in Filipino children, caused by mutations of the anion-exchanger SLC4A1 (AE1, Band 3) gene.

    Science.gov (United States)

    Anacleto, Francisco E; Bruce, Lesley J; Clayton, Peter; Hegde, Shivram; Resontoc, Lourdes P; Wrong, Oliver

    2010-01-01

    To describe the clinical features and genetic basis of distal renal tubular acidosis (dRTA) in Filipino children. Clinical description and gene analysis of affected members of 7 families. In all affected children, the disease was associated with mutations of the SLC4A1 gene that codes for the bicarbonate/chloride anion-exchanger 1 (AE1, band 3) protein situated in the red cell membrane and the alpha-intercalated (proton-secreting) cell of the renal collecting duct. In 2 families, affected children were homozygous for a substitution of aspartic acid for glycine in residue 701 of the AE1 protein (G701D); in the other 5 families, affected children were compound heterozygotes of this mutation with the AE1 mutation (Delta400-408) that causes Southeast Asian ovalocytosis (SAO). All affected children had morphological red cell changes that closely resembled SAO, including the children who were homozygous for G701D and did not have the SAO mutation. Homozygous G701D thus produces morphological red cell changes that are not readily distinguishable from SAO. The parents of all 7 families were originally domiciled in the islands of the Visayas group in the central part of the Philippine archipelago. Recessive renal tubular acidosis in Filipinos is usually caused by SLC4A1 mutations, commonly G701D. 2010 S. Karger AG, Basel.

  14. Insulin-like growth factor-1 enhances epidermal growth factor receptor activation and renal tubular cell regeneration in postischemic acute renal failure.

    Science.gov (United States)

    Lin, J J; Cybulsky, A V; Goodyer, P R; Fine, R N; Kaskel, F J

    1995-06-01

    Growth factors such as insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and hepatocyte growth factor have been shown to accelerate the recovery from postischemic acute renal failure (ARF) with a concomitant increase in DNA synthesis. Interactions between growth factors have been demonstrated in a number of in vitro studies. This study examined the effect of exogenous IGF-1 on the DNA synthesis and EGF receptor (EGF-R) activation in postischemic rat kidneys. Thirty minutes after the relief of 30-minute total occlusion of the left renal artery in anesthetized 225 to 300 gm Sprague-Dawley rats, either IGF-1 (75 micrograms/kg) or normal saline solution (NS, 0.2 ml) was given by intravenous bolus, followed by twice daily subcutaneous injections of IGF-1 (50 micrograms/kg) or 0.2 ml NS for 4 days, respectively, in IGF-1-Tx) and NS treated (NS-Tx) groups (n = 8 each). On the day after the completion of treatment, inulin clearance (ml/kg/min) of the postischemic kidneys in the IGF-1-Tx group was significantly higher (p < 0.01) than inulin clearance of kidneys in the NS-Tx group. This was associated with improved kidney morphology. IGF-1 treatment also enhanced the labeling index of 5-bromo-2'-deoxyuridine (percent of stained tubule cells), a marker for active DNA synthesis, in the outer medulla of postischemic kidneys at 1 day and 2 days after the injury. EGF-R tyrosine phosphorylation (which reflects receptor activation) increased in postischemic kidneys in both NS-Tx (n = 5) and IGF-1-Tx (n = 3) groups 1 day after the injury as compared with nonischemic contralateral kidneys. In the IGF-1-Tx group there was also increased iodine 125-labeled EGF binding and EGF-R protein. Our results demonstrate a beneficial effect of IGF-1 on postischemic ARF. Furthermore, they suggest that EGF-R activation is involved in tubular regeneration and that IGF-1 may enhance EGF-R activation by increasing EGF-R expression.

  15. Handling and staging of renal cell carcinoma: the International Society of Urological Pathology Consensus (ISUP) conference recommendations.

    Science.gov (United States)

    Trpkov, Kiril; Grignon, David J; Bonsib, Stephen M; Amin, Mahul B; Billis, Athanase; Lopez-Beltran, Antonio; Samaratunga, Hemamali; Tamboli, Pheroze; Delahunt, Brett; Egevad, Lars; Montironi, Rodolfo; Srigley, John R

    2013-10-01

    The International Society of Urologic Pathology 2012 Consensus Conference on renal cancer, through working group 3, focused on the issues of staging and specimen handling of renal tumors. The conference was preceded by an online survey of the International Society of Urologic Pathology members, and the results of this were used to inform the focus of conference discussion. On formal voting a ≥65% majority was considered a consensus agreement. For specimen handling it was agreed that with radical nephrectomy specimens the initial cut should be made along the long axis and that both radical and partial nephrectomy specimens should be inked. It was recommended that sampling of renal tumors should follow a general guideline of sampling 1 block/cm with a minimum of 3 blocks (subject to modification as needed in individual cases). When measuring a renal tumor, the length of a renal vein/caval thrombus should not be part of the measurement of the main tumor mass. In cases with multiple tumors, sampling should include at a minimum the 5 largest tumors. There was a consensus that perinephric fat invasion should be determined by examining multiple perpendicular sections of the tumor/perinephric fat interface and by sampling areas suspicious for invasion. Perinephric fat invasion was defined as either the tumor touching the fat or extending as irregular tongues into the perinephric tissue, with or without desmoplasia. It was agreed upon that renal sinus invasion is present when the tumor is in direct contact with the sinus fat or the loose connective tissue of the sinus, clearly beyond the renal parenchyma, or if there is involvement of any endothelium-lined spaces within the renal sinus, regardless of the size. When invasion of the renal sinus is uncertain, it was recommended that at least 3 blocks of the tumor-renal sinus interface should be submitted. If invasion is grossly evident, or obviously not present (small peripheral tumor), it was agreed that only 1 block was

  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. 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.

  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. SIRT1 activator ameliorates the renal tubular injury induced by hyperglycemia in vivo and in vitro via inhibiting apoptosis.

    Science.gov (United States)

    Wang, Xue-Ling; Wu, Li-Yan; Zhao, Long; Sun, Li-Na; Liu, Hai-Ying; Liu, Gang; Guan, Guang-Ju

    2016-10-01

    . These findings indicated that the increased expression of SIRT1, mediated by RSV, is a possible mechanism by which RSV prevents renal tubular injury in diabetic nephropathy (DN). So RSV has great clinical significance and could provide the basis for the new way to effective treatment to contain the morbidity and mortality associated with DN. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  20. 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.

  1. Renal Tubular Acidosis

    Science.gov (United States)

    ... Disease Chronic Kidney Disease (CKD) What Is Chronic Kidney Disease? Causes of CKD Tests & Diagnosis Managing CKD Eating Right Preventing CKD What If My Kidneys Fail? Clinical Trials Anemia High Blood Pressure Heart ... Nephropathy Kidney Disease in Children Childhood Nephrotic Syndrome Hemolytic ...

  2. Renal Tubular Acidosis

    Science.gov (United States)

    ... Looking for Health Lessons? Visit KidsHealth in the Classroom What Other Parents Are Reading Your Child's Development ( ... may involve stopping use of the drug or changing the dosage. If an underlying disease or other ...

  3. Altered renal distal tubule structure and renal Na(+) and Ca(2+) handling in a mouse model for Gitelman's syndrome.

    NARCIS (Netherlands)

    Loffing, J.; Vallon, V.; Loffing-Cueni, D.; Aregger, F.; Richter, K.H.; Pietri, L.; Bloch-Faure, M.; Hoenderop, J.G.J.; Shull, G.E.; Meneton, P.; Kaissling, B.

    2004-01-01

    Gitelman's syndrome, an autosomal recessive renal tubulopathy caused by loss-of-function mutations in the thiazide-sensitive NaCl co-transporter (NCC) of the distal convoluted tubule (DCT), is characterized by mild renal Na(+) wasting, hypocalciuria, hypomagnesemia, and hypokalemic alkalosis. For ga

  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. 肌酐代谢产物对肾小管上皮细胞凋亡的影响%Effect of metabolites of creatinine on the apoptosis of renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    胡白瑛

    2013-01-01

    目的 研究肌酐产物是否能促进肾小管上皮细胞凋亡.方法 原代培养人肾小管上皮细胞,将肌酐产物与肾小管上皮细胞共同培养,对肾小管上皮细胞进行形态学观察;抽提DNA进行琼脂糖电泳观察有无梯形条带.结果 肾小管上皮细胞在肌酐产物作用下逐渐变小、变圆、固缩,最后漂浮死亡,但胞膜始终完整;肌酐产物导致肾小管上皮细胞凋亡,琼脂糖凝胶中有DNA梯形条带,加入谷胱甘肽(GSH)未见DNA梯形条带.结论 肌酐产物促进肾小管上皮细胞凋亡,GSH可阻断之.%Objective To study the effect of metabolites of creatinine on the apoptosis of renal tubular epithelial cells. Methods Renal tubular epithelia were cultured in vitro. The metabolites of creatinine and renal tubular epithelial cells were incubated together. The morphological change of renal tubular epithelial cells was observed. Gel electrophoresis of DNA extracted from that to observe bands of apoptotsis. Results Affected by metabolites of creatinine, renal tubular epithelial cells showed characters of apoptosis (smaller, round, pyknosis and death), but the cell membrane was always integral. Agarose gel electrophoresis revealed the appearance of DNA ladder, which disappeared with the addition of GSH. Conclusion The metabolites of creatinine can induce the apoptosis of renal tubular epithelial cells, which could be reversed by GSH.

  6. Cellular adaptive response of distal renal tubular cells to high-oxalate environment highlights surface alpha-enolase as the enhancer of calcium oxalate monohydrate crystal adhesion.

    Science.gov (United States)

    Kanlaya, Rattiyaporn; Fong-Ngern, Kedsarin; Thongboonkerd, Visith

    2013-03-27

    Hyperoxaluria is one of etiologic factors of calcium oxalate kidney stone disease. However, response of renal tubular cells to high-oxalate environment remained largely unknown. We applied a gel-based proteomics approach to characterize changes in cellular proteome of MDCK cells induced by 10mM sodium oxalate. A total of 14 proteins were detected as differentially expressed proteins. The oxalate-induced up-regulation of alpha-enolase in whole cell lysate was confirmed by 2-D Western blot analysis. Interaction network analysis revealed that cellular adaptive response under high-oxalate condition involved stress response, energy production, metabolism and transcriptional regulation. Down-regulation of RhoA, which was predicted to be associated with the identified proteins, was confirmed by immunoblotting. In addition, the up-regulation of alpha-enolase on apical surface of renal tubular epithelial cells was also confirmed by immunoblotting of the isolated apical membranes and immunofluorescence study. Interestingly, blockage of alpha-enolase expressed on the cell surface by antibody neutralization significantly reduced the number of calcium oxalate monohydrate (COM) crystals adhered on the cells. These results strongly suggest that surface alpha-enolase plays an important role as the enhancer of COM crystal binding. The increase of alpha-enolase expressed on the cell surface may aggravate kidney stone formation in patients with hyperoxaluria. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Mitochondrial dysfunction contributes to the cytotoxicity induced by tentacle extract from the jellyfish Cyanea capillata in rat renal tubular epithelial NRK-52E cells.

    Science.gov (United States)

    Wang, Tao; He, Qian; Xiao, Liang; Wang, Qianqian; Zhang, Bo; Wang, Beilei; Liu, Guoyan; Zheng, Jiemin; Yu, Bentong; Zhang, Liming

    2013-11-01

    Our previous studies have shown that tentacle extract (TE) from the jellyfish Cyanea capillata could induce a delayed jellyfish envenomation syndrome with severe multiple organ dysfunctions, among which renal injury with tubular necrosis seemed to be most serious. So, in this study, we aimed to explore the toxic effect of TE on rat renal tubular epithelial NRK-52E cells. Based on the previous findings that TE could cause oxidative damage in erythrocytes, the effects of TE on cell oxidative stress conditions, including ROS production and lipid peroxidation, and mitochondrial dysfunction associated with cell death were investigated in NRK-52E cells. The results showed that TE caused cell morphological change and decreased cell viability through induction of apoptosis and necrosis in NRK-52E cells. Meanwhile, ROS overproduction and mitochondrial membrane potential decrease were found before the cell death occurred. It was concluded that TE could induce cytotoxicity, especially apoptosis and necrosis, in NRK-52E cells, and mitochondrial dysfunction and ROS overproduction might play important roles in the process of cell injury and death.

  8. 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.

  9. Human renal tubular cells contain CD24/CD133 progenitor cell populations: Implications for tubular regeneration after toxicant induced damage using cadmium as a model.

    Science.gov (United States)

    Shrestha, Swojani; Somji, Seema; Sens, Donald A; Slusser-Nore, Andrea; Patel, Divyen H; Savage, Evan; Garrett, Scott H

    2017-09-15

    The proximal tubules of the kidney are target sites of injury by various toxicants. Cadmium (Cd(+2)), an environmental nephrotoxicant can cause adverse effects and overt renal damage. To decipher the mechanisms involved in nephrotoxicity, an in vitro model system is required. Mortal cultures of human proximal tubule (HPT) cells have served, as models but are difficult to acquire and do not lend themselves to stable transfection. The immortalized human proximal tubule cell line HK-2, has served as a model but it lacks vectorial active transport and shows signs of lost epithelial features. Recently a new proximal tubule cell line was developed, the RPTEC/TERT1, and the goal of this study was to determine if this cell line could serve as a model to study nephrotoxicity. Global gene expression analysis of this cell line in comparison to the HK-2 and HPT cells showed that the RPTEC/TERT1 cells had gene expression patterns similar to HPT cells when compared to the HK-2 cells. The HPT and the RPTEC/TERT1 cell line had an increased population of stem/progenitor cells co-expressing CD24 and CD133 when compared to the HK-2 cells. The level of expression of cadherins, claudins and occludin molecules was also similar between the RPTEC/TERT1 and the HPT cells. Acute exposure to Cd(+2) resulted in necrosis of the RPTEC/TERT1 cells when compared to the HK-2 cells which died by apoptosis. Thus, the RPTEC/TERT1 cells are similar to HPT cells and can serve as a good model system to study mechanisms involved in toxicant induced renal damage. Copyright © 2017 Elsevier Inc. All rights reserved.

  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. Identification of Tubular Heparan Sulfate as a Docking Platform for the Alternative Complement Component Properdin in Proteinuric Renal Disease

    NARCIS (Netherlands)

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

    2011-01-01

    Properdin binds to proximal tubular epithelial cells (PTEC) and activates the complement system via the alternative pathway in vitro. Cellular ligands for properdin in the kidney have not yet been identified. Because properdin interacts with solid-phase heparin, we investigated whether heparan sulfa

  12. 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

  13. 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

  14. Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

    DEFF Research Database (Denmark)

    Reed, Galen D; von Morze, Cornelius; Verkman, Alan S

    2016-01-01

    originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the [(13)C,(15)N2]urea to be distinguished via multi-exponential analysis. The T2 response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized [(13)C,(15...

  15. Adaptive strategies for post-renal handling of urine in birds

    DEFF Research Database (Denmark)

    Laverty, Gary; Skadhauge, Erik

    2008-01-01

    coprodeum and portions of the hindgut (colon or rectum and ceca). This presents a potential problem in that hyperosmotic ureteral urine in contact with the permeable epithelia of these tissues would counteract renal osmotic work. This review describes and provides examples of different strategies used...... functions like a mammalian urinary bladder, preserving the osmotic concentrating work of the kidney; 3. an interaction strategy, in which post-renal transport processes are hormonally regulated in order to optimize renal function under varying conditions of salt or water stress; 4. the salt gland strategy...... some species in this group are relatively good renal concentrators, and would be predicted to have post-renal mechanisms to preserve this work. This new synthesis illustrates the marked diversity of adaptive mechanisms used by avian species to maintain osmotic homeostasis....

  16. Effect of inhibition of nitric oxide synthase on blood pressure and renal sodium handling in renal denervated rats

    Directory of Open Access Journals (Sweden)

    F. Xavier

    2000-03-01

    Full Text Available The role of sympathetic nerve activity in the changes in arterial blood pressure and renal function caused by the chronic administration of NG-nitro-L-arginine methyl ester (L-NAME, an inhibitor of nitric oxide (NO synthesis, was examined in sham and bilaterally renal denervated rats. Several studies have demonstrated that sympathetic nerve activity is elevated acutely after L-NAME administration. To evaluate the role of renal nerve activity in L-NAME-induced hypertension, we compared the blood pressure response in four groups (N = 10 each of male Wistar-Hannover rats weighing 200 to 250 g: 1 sham-operated vehicle-treated, 2 sham-operated L-NAME-treated, 3 denervated vehicle-treated, and 4 denervated L-NAME-treated rats. After renal denervation or sham surgery, one control week was followed by three weeks of oral administration of L-NAME by gavage. Arterial pressure was measured weekly in conscious rats by a tail-cuff method and renal function tests were performed in individual metabolic cages 0, 7, 14 and 21 days after the beginning of L-NAME administration. L-NAME (60 mg kg-1 day-1 progressively increased arterial pressure from 108 ± 6.0 to 149 ± 12 mmHg (P<0.05 in the sham-operated group by the third week of treatment which was accompanied by a fall in creatinine clearance from 336 ± 18 to 222 ± 59 µl min-1 100 g body weight-1 (P<0.05 and a rise in fractional urinary sodium excretion from 0.2 ± 0.04 to 1.62 ± 0.35% (P<0.05 and in sodium post-proximal fractional excretion from 0.54 ± 0.09 to 4.7 ± 0.86% (P<0.05. The development of hypertension was significantly delayed and attenuated in denervated L-NAME-treated rats. This was accompanied by a striking additional increase in fractional renal sodium and potassium excretion from 0.2 ± 0.04 to 4.5 ± 1.6% and from 0.1 ± 0.015 to 1.21 ± 0.37%, respectively, and an enhanced post-proximal sodium excretion compared to the sham-operated group. These differences occurred despite an

  17. Glomerular hyperfiltration in type 1 diabetes mellitus results from primary changes in proximal tubular sodium handling without changes in volume expansion.

    NARCIS (Netherlands)

    Vervoort, G.M.M.; Veldman, B.A.J.; Berden, J.H.M.; Smits, P.; Wetzels, J.F.M.

    2005-01-01

    BACKGROUND: Glomerular hyperfiltration plays a role in the pathophysiology of diabetic nephropathy. An increase in the glomerular filtration rate (GFR) could result from primary actions at the glomerular/vascular level or could be the consequence of a primary increase in proximal tubular sodium

  18. 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.

  19. Contamination of renal patients’ hospital chart covers with vancomycin resistant enterococci: Handle with care

    Directory of Open Access Journals (Sweden)

    Edward Zimbudzi

    2011-10-01

    Full Text Available BackgroundVancomycin-­‐resistant enterococci(VREhave been increasingly associated with patients with renal failureattending large metropolitan teaching hospitals.Monash Medical Center has been following guidelines issued by the Department of Human Services to reduce the spread of VRE, but unfortunately this has had limited impact, especially in the renalunit.In an attempt to investigate the causes of the sustained VRE prevalence in the renal unit, this study sought to determine if renal patient chart covers were contaminated with VRE and iftherewasanygeneticsimilaritytopatientVREisolates.MethodUsingconveniencesampling,chartcoversofpatientscolonisedorinfectedwithVREwereswabbedfromJulytoSeptember2010(n=46.Sampleswerealsocollectedfromchartcoversofnon-­‐VREpatients.MoleculartypingofallmatchingVREpatientandchartisolateswasperformedusingpulsedfieldgelelectrophoresis(PFGEbythepublichealthlaboratory(MicrobiologicalDiagnosticUnit,UniversityofMelbourne.ResultsNoneofthepatientswhowereVREnegative(n=14hadcontaminatedchartcovers.VREwasrecoveredfromtwodrugchartcovers(patientAandBfromthe31VREpositivepatientssampled.Onepatient(patientCwasmisidentifiedasaVREpatientfortwoweeksandwassubjecttocontactprecautionswhilebeingdialysed,yetthreecharttypesbelongingtothispatientwerefoundtobecontaminatedwithVRE.ConclusionThefindingsofthisstudydemonstratethatitispossibleforpatients’hospitalchartcoverstobecontaminatedwithVREeventhoughtherewasnogeneticsimilaritytothecurrentpatientstrain.Inthisregard,thestudyrevealsthatpatientchartsmayhaveanimportantroleinspreadingVRE.

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

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    Xin-Xin Pang

    2016-07-01

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

  1. Role of the distal convoluted tubule in renal Mg(2+) handling: molecular lessons from inherited hypomagnesemia

    NARCIS (Netherlands)

    Ferre, S.; Hoenderop, J.G.J.; Bindels, R.J.M.

    2011-01-01

    In healthy individuals, Mg(2+) homeostasis is tightly regulated by the concerted action of intestinal absorption, exchange with bone, and renal excretion. The kidney, more precisely the distal convoluted tubule (DCT), is the final determinant of plasma Mg(2+) concentrations. Positional cloning strat

  2. Proximal tubular dysfunction is associated with chronic allograft nephropathy and decreased long-term renal-graft survival

    NARCIS (Netherlands)

    Camara, N.O.S.; Silva, M.S.; Nishida, S.; Pereira, A.B.; Pacheco-Silva, A.

    2004-01-01

    Background: Chronic allograft nephropathy is the major cause of graft loss after the first year of transplantation. Although many conditions are associated with its development, there is no method that can anticipate its risk in patients with good renal function. Methods: We prospectively studied 92

  3. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells.

    Science.gov (United States)

    Liang, Jie; Chen, Fuxue; Gu, Fu; Liu, Xin; Li, Feng; Du, Dongshu

    2017-04-01

    The kidney is essential in the maintenance of in vivo homeostasis by body fluid and electrolyte conservation and metabolic waste removal. Previously, we reported the expression of a novel G protein family (Tas2rs), which includes bitter taste receptors, in the kidney tubule system, including the nephrons and the collecting duct system. Bitter taste receptors could affect kidney function via Ca(2+) intake. Alkaloids such as phenylthiocarbamide stimulate these receptors and cause an increase in Ca(2+) intake. In this study, we determined the expression of bitter taste receptors in the immature kidney and small intestine and in primary renal epithelial cells and M-1 (collecting tubule cell line) cells, by using QPCR and immunostaining. We found no expression of bitter taste receptors in the immature kidney and small intestine several days after birth; the relative abundance of Tas2rs transcripts varied depending on the developmental stage. Tas2rs were expressed in primary renal epithelial cells and M-1 cells. The traditional Chinese medicinal plant extracts phellodendrine and coptisine caused a rapid rise in intracellular Ca(2+) concentration, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. Thus, phellodendrine and coptisine could change the physiological status of renal cells in vitro by mediation of bitter taste receptors in a PLC-dependent manner. Our results provide new insights on the expression and role of bitter taste receptors in renal development and function.

  4. Gallic acid ameliorates renal functions by inhibiting the activation of p38 MAPK in experimentally induced type 2 diabetic rats and cultured rat proximal tubular epithelial cells.

    Science.gov (United States)

    Ahad, Amjid; Ahsan, Haseeb; Mujeeb, Mohd; Siddiqui, Waseem Ahmad

    2015-10-05

    Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats. GA (25 mg/kgbw and 50 mg/kgbw, p.o.) treatment for 16 weeks post induction of diabetes led to a significant reduction in the levels of blood glucose, HbA1c, serum creatinine, blood urea nitrogen and proteinuria as well as a significant reduction in the levels of creatinine clearance. GA significantly inhibited the renal p38 MAPK and nuclear factor kappa B (N-κB) activation as well as significantly reduced the levels of renal transforming growth factor beta (TGF-β) and fibronectin. Treatment with GA resulted in a significant reduction in the serum levels of proinflammatory cytokines viz. interleukin 1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α). Moreover, GA significantly lowered renal pathology and attenuated renal oxidative stress. In cultured rat NRK 52E proximal tubular epithelial cells, GA treatment inhibited high glucose induced activation of p38 MAPK and NF-κB as well as suppressed proinflammatory cytokine synthesis. The results of the present study provide in vivo and in vitro evidences that the p38 MAPK pathway plays an important role in the pathogenesis of DN, and GA attenuates the p38 MAPK-mediated renal dysfunction in HFD/STZ induced type 2 diabetic rats.

  5. Histopathological characterization of renal tubular and interstitial changes in 5/6 nephrectomized marmoset monkeys (Callithrix jacchus).

    Science.gov (United States)

    Suzuki, Yui; Yamaguchi, Itaru; Myojo, Kensuke; Kimoto, Naoya; Imaizumi, Minami; Takada, Chie; Sanada, Hiroko; Takaba, Katsumi; Yamate, Jyoji

    2015-01-01

    Common marmosets (Callithrix jacchus) have become a useful animal model, particularly for development of biopharmaceuticals. While various renal failure models have been established in rodents, there is currently no acceptable model in marmosets. We analyzed the damaged renal tubules and tubulointerstitial changes (inflammation and fibrosis) of 5/6 nephrectomized (Nx) common marmosets by histopathological/immunohistochemical methods, and compared these findings to those in 5/6 Nx SD rats. In Nx marmosets and rats sacrificed at 5 and 13 weeks after Nx, variously dilated and atrophied renal tubules were seen in the cortex in common; however, the epithelial proliferating activity was much less in Nx marmosets. Furthermore, the degrees of inflammation and fibrosis seen in the affected cortex were more severe and massive in Nx marmosets with time-dependent increase. Interestingly, inflammation in Nx marmosets, of which degree was less in Nx rats, consisted of a large number of CD3-positive T cells and CD20-positive B cells (occasionally forming follicles), and a few CD68-positive macrophages. Based on these findings, lymphocytes might contribute to the progressive renal lesions in Nx marmosets. Fibrotic areas in Nx marmosets comprised myofibroblasts expressing vimentin and α-smooth muscle actin (α-SMA), whereas along with vimentin and α-SMA expressions, desmin was expressed in myofibroblasts in Nx rats. This study shows that there are some differences in renal lesions induced by Nx between marmosets and rats, which would provide useful, base-line information for pharmacology and toxicology studies using Nx marmosets.

  6. 'Endotoxin tolerance': TNF-alpha hyper-reactivity and tubular cytoresistance in a renal cholesterol loading state.

    Science.gov (United States)

    Zager, R A; Johnson, A C M; Lund, S

    2007-03-01

    The term 'endotoxin tolerance' defines a state in which prior endotoxin (lipopolysaccharide (LPS)) exposure induces resistance to subsequent LPS attack. However, its characteristics within kidney have not been well defined. Hence, this study tested the impact of LPS 'preconditioning' (LPS-PC; 18 or 72 h earlier) on: (i) selected renal inflammatory mediators (tumor necrosis factor (TNF)-alpha, interleukin-10 (IL-10), monocyte chemotactic protein-1 (MCP-1), inducible nitric oxide synthase (iNOS), Toll-like receptor 4 (TLR4); protein or mRNA); (ii) cholesterol homeostasis (a stress reactant); and (iii) isolated proximal tubule (PT) vulnerability to hypoxia or membrane cholesterol (cholesterol oxidase/esterase) attack. Two hours post LPS injection, LPS-PC mice manifested reduced plasma TNF-alpha levels, consistent with systemic LPS tolerance. However, in kidney, paradoxical TNF-alpha hyper-reactivity (protein/mRNA) to LPS existed, despite normal TLR4 protein levels. PT TNF-alpha levels paralleled renal cortical results, implying that PTs were involved. LPS-PC also induced: (i) renal cortical iNOS, IL-10 (but not MCP-1) mRNA hyper-reactivity; (ii), PT cholesterol loading, and (iii) cytoresistance to hypoxia and plasma membrane cholesterol attack. A link between cholesterol homeostasis and cell LPS responsiveness was suggested by observations that cholesterol reductions in HK-2 cells (methylcyclodextrin), or reductions in HK-2 membrane fluidity (A2C), blunted LPS-mediated TNF-alpha/MCP-1 mRNA increases. In sum: (i) systemic LPS tolerance can be associated with renal hyper-responsiveness of selected components within the LPS signaling cascade (e.g., TNF-alpha, iNOS, IL-10); (ii) PT cytoresistance against hypoxic/membrane injury coexists; and (iii) LPS-induced renal/PT cholesterol accumulation may mechanistically contribute to each of these results.

  7. Effects of nebivolol versus metoprolol on sodium sensitivity and renal sodium handling in hypertensive Hispanic postmenopausal women.

    Science.gov (United States)

    Preston, Richard A; Afshartous, David; Materson, Barry J; Rodco, Rolando; Alonso, Alberto B

    2014-08-01

    Several consistent lines of evidence indicate an association between sodium sensitivity and impaired nitric oxide bioactivity. Nevertheless, whether restoring nitric oxide in humans by pharmacological means can ameliorate sodium sensitivity has not been investigated. Because nebivolol has been demonstrated to increase nitric oxide bioactivity in both laboratory and clinical investigations, we hypothesized that nebivolol might ameliorate sodium sensitivity and improve renal sodium handling in comparison to metoprolol. We therefore conducted a randomized, 2-treatment-period crossover trial in 19 Hispanic postmenopausal women with hypertension to determine the comparative effects of nebivolol versus metoprolol on (1) 24-hour ambulatory blood pressure response to an increase in dietary sodium from 5 days of low sodium to 5 days of high sodium, (2) renal natriuretic response to a 1-L saline challenge, and (3) asymmetrical dimethylarginine. Clinic blood pressure and heart rate were significantly reduced after 4 weeks of treatment with both nebivolol and metoprolol. Twenty-four–hour mean systolic blood pressure increased sharply from low sodium to high sodium for both nebivolol and metoprolol. Nevertheless, the increases in blood pressure did not differ between the 2 drugs: 7.7 (3.1, 12.3) mm Hg with metoprolol and 9.3 (4.6, 13.9) mm Hg with nebivolol (P=0.63). Furthermore, we observed no differences between the drugs in natriuretic response to saline challenge or asymmetrical dimethylarginine. In a sodium-sensitive population, at doses sufficient to produce reductions in blood pressure and heart rate, nebivolol did not demonstrate a significant effect on sodium sensitivity or sodium handling compared with metoprolol.

  8. 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.

  9. Matrilysin (MMP-7) Inhibition of BMP-7 Induced Renal Tubular Branching Morphogenesis Suggests a Role in the Pathogenesis of Human Renal Dysplasia

    Science.gov (United States)

    Harju-Baker, Susanna; Rims, Cliff; Sheen, Joong-Hyuk; Liapis, Helen

    2012-01-01

    Congenital renal dysplasia (RD) is a severe form of congenital renal malformation characterized by disruption of normal renal development with cyst formation, reduced or absent nephrons, and impaired renal growth. The authors previously identified that matrilysin (matrix metalloproteinase–7) was overexpressed in a microarray gene expression analysis of human RD compared to normal control kidneys. They now find that active matrilysin gene transcription and protein synthesis occur within dysplastic tubules and epithelial cells lining cysts in human RD by RT-PCR and immunohistochemistry. Similar staining patterns were seen in obstructed kidneys of pouch opossums that show histological features similar to that of human RD. In vitro, matrilysin inhibits formation of branching structures in mIMCD-3 cells stimulated by bone morphogenetic protein–7 (BMP-7) but does not inhibit hepatocyte growth factor–stimulated branching. BMP-7 signaling is essential for normal kidney development, and overexpression of catalytically active matrilysin in human embryonic kidney 293 cells reduces endogenous BMP-7 protein levels and inhibits phosphorylation of BMP-7 SMAD signaling intermediates. These findings suggest that matrilysin expression in RD may be an injury response that disrupts normal nephrogenesis by impairing BMP-7 signaling. PMID:22215634

  10. Mitochondrial Fission Increases Apoptosis and Decreases Autophagy in Renal Proximal Tubular Epithelial Cells Treated with High Glucose.

    Science.gov (United States)

    Lee, Wen-Chin; Chiu, Chien-Hua; Chen, Jin-Bor; Chen, Chiu-Hua; Chang, Hsueh-Wei

    2016-11-01

    The aim of this study was to examine the effect of mitochondrial morphogenesis changes on apoptosis and autophagy of high-glucose-treated proximal tubular epithelial cells (HK2). Cell viability, apoptosis, and mitochondrial morphogenesis were examined using crystal violet, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL), and mitotracker staining, respectively. High glucose inhibited cell viability and induced mitochondrial fission in HK2 cells. After depleting mitofusin 1 (MFN1), the MFN1(-) HK2 cells (fission type) became more susceptible to high-glucose-induced apoptosis and mitochondrial fragmentation observed by TUNEL and mitotracker assays. In siMFN2 HK2 cells (fission type), mitochondria were highly fragmented (>80% fission rate) with or without high-glucose treatment; however, siFIS1 (mitochondrial fission protein 1) HK2 cells (fusion type) exhibited little fragmentation (High-glucose treatment induced autophagy, characterized by the formation of autophagosome and microtubule-associated protein light chain 3 (LC3) B-II, as observed by transmission electron microscopy and western blotting, respectively. LC3B-II levels decreased in both MFN1(-) and siMFN2 HK2 cells, but increased in siFIS1 HK2 cells. Moreover, autophagy displays a protective role against high-glucose-induced cell death based on cotreatment with autophagy inhibitors (3-methyladenine and chloroquine). Mitochondrial fission may increase apoptosis and decrease autophagy of high-glucose-treated HK2 cells.

  11. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik

    1996-01-01

    to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra......-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p ....5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p peritoneal and renal clearances of 99m...

  12. Imaging Renal Urea Handling in Rats at Millimeter Resolution using Hyperpolarized Magnetic Resonance Relaxometry

    CERN Document Server

    Reed, Galen D; Verkman, Alan S; Koelsch, Bertram L; Chaumeil, Myriam M; Lustig, Michael; Ronen, Sabrina M; Sands, Jeff M; Larson, Peder E Z; Wang, Zhen J; Larsen, Jan Henrik Ardenkjær; Vigneron, Daniel B

    2015-01-01

    \\textit{In vivo} spin spin relaxation time ($T_2$) heterogeneity of hyperpolarized \\textsuperscript{13}C urea in the rat kidney was investigated. Selective quenching of the vascular hyperpolarized \\textsuperscript{13}C signal with a macromolecular relaxation agent revealed that a long-$T_2$ component of the \\textsuperscript{13}C urea signal originated from the renal extravascular space, thus allowing the vascular and renal filtrate contrast agent pools of the \\textsuperscript{13}C urea to be distinguished via multi-exponential analysis. The $T_2$ response to induced diuresis and antidiuresis was performed with two imaging agents: hyperpolarized \\textsuperscript{13}C urea and a control agent hyperpolarized bis-1,1-(hydroxymethyl)-1-\\textsuperscript{13}C-cyclopropane-$^2\\textrm{H}_8$. Large $T_2$ increases in the inner-medullar and papilla were observed with the former agent and not the latter during antidiuresis suggesting that $T_2$ relaxometry may be used to monitor the inner-medullary urea transporter (UT)-...

  13. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik Sahl

    1996-01-01

    to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra......-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p ....5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p peritoneal and renal clearances of 99m...

  14. 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.

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

    Science.gov (United States)

    Al-Haggar, Mohammad; Sakamoto, Osamu; Shaltout, Ali; El-Hawary, Amany; Wahba, Yahya; Abdel-Hadi, Dina

    2011-01-01

    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.

  16. Should blood gas analysis be part of the diagnostic workup of short children? Auxological data and blood gas analysis in children with renal tubular acidosis.

    Science.gov (United States)

    Mul, D; Grote, F K; Goudriaan, J R; de Muinck Keizer-Schrama, S M P F; Wit, J M; Oostdijk, W

    2010-01-01

    Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. To investigate the clinical, growth and laboratory parameters in children with RTA to estimate the possible value of laboratory screening for this disorder in infants and children referred for short stature according to a recent guideline. Retrospective chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands and 3 centers in Belgium. The current guideline for short stature detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6 per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and above 3 years, respectively. Sensitivity was 17/30 and 12/24 for a -2.0 SDS cutoff for weight and body mass index, respectively. In infants and toddlers diagnosed before 3 years of age, the mean weight loss was 1.5 SD, and 0.8 SDS in older children. In short children >3 years RTA was extremely rare, always associated with clinical symptoms, and rarely detected by blood gas analysis. According to our data a decreasing weight SDS for age is a sufficient indication to perform blood gas analysis in children 3 years of age. Copyright © 2010 S. Karger AG, Basel.

  17. Overexpression of angiotensinogen downregulates aquaporin 1 expression via modulation of Nrf2–HO-1 pathway in renal proximal tubular cells of transgenic mice

    Directory of Open Access Journals (Sweden)

    Shiao-Ying Chang

    2016-09-01

    Full Text Available Introduction: We aimed to examine the regulation of aquaporin 1 expression in an angiotensinogen transgenic mouse model, focusing on underlying mechanisms. Methods: Male transgenic mice overexpressing rat angiotensinogen in their renal proximal tubular cells (RPTCs and rat immortalised RPTCs stably transfected with rat angiotensinogen cDNA were used. Results: Angiotensinogen-transgenic mice developed hypertension and nephropathy, changes that were either partially or completely attenuated by treatment with losartan or dual renin–angiotensin system blockade (losartan and perindopril, respectively, while hydralazine prevented hypertension but not nephropathy. Decreased expression of aquaporin 1 and heme oxygenase-1 and increased expression of nuclear factor erythroid 2-related factor 2 (Nrf2 and sodium–hydrogen exchanger 3 were observed in RPTCs of angiotensinogen-transgenic mice and in angiotensinogen-transfected immortalised RPTCs. These parameters were normalised by dual renin–angiotensin system blockade. Both in vivo and in vitro studies identified a novel mechanism in which angiotensinogen overexpression in RPTCs enhances the cytosolic accumulation of Nrf2 via the phosphorylation of pGSK3β Y216. Consequently, lower intranuclear Nrf2 levels are less efficient to trigger heme oxygenase-1 expression as a defence mechanism, which subsequently diminishes aquaporin 1 expression in RPTCs. Conclusions: Angiotensinogen-mediated downregulation of aquaporin 1 and Nrf2 signalling may play an important role in intrarenal renin–angiotensin system-induced hypertension and kidney injury.

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

    Science.gov (United States)

    Ueda, Kohei; Fujiki, Katsunori; Shirahige, Katsuhiko; Gomez-Sanchez, Celso E.; Fujita, Toshiro; Nangaku, Masaomi; Nagase, Miki

    2017-01-01

    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. PMID:24491541

  19. Efecto citotóxico de la toxina shiga tipo 2 y su subunidad b en células epiteliales tubulares renales humanas en cultivo Cytotoxic effect of Shiga toxin type 2 and its B subunit on human renal tubular epithelial cell cultures

    Directory of Open Access Journals (Sweden)

    Virginia Pistone Creydt

    2005-04-01

    Full Text Available Escherichia coli enterohemorrágica productora de toxina Shiga (Stx causa diarrea acuosa, colitis hemorrágica y síndrome urémico hemolítico (SUH. En Argentina, el SUH es la principal causa de insuficiencia renal en niños. El objetivo de este trabajo fue estudiar la toxicidad de Stx tipo 2 (Stx2 y su subunidad B (Stx2B en células epiteliales tubulares renales humanas (CERH, en presencia y ausencia de factores inflamatorios. Los efectos citotóxicos se evaluaron como alteración de la funcionalidad del epitelio; daños histológicos; viabilidad celular; síntesis de proteínas y apoptosis celular. Los resultados muestran que Stx2 regula el pasaje de agua a través de CERH a tiempos menores de 1h de incubación. A tiempos mayores, hasta 72 hs, el estudio de la morfología, la viabilidad, la síntesis de proteínas y la apoptosis demostró que las CERH fueron sensibles a la acción citotóxica de Stx2 y Stx2B de una manera dosis y tiempo dependiente. Estos efectos fueron potenciados por lipopolisacáridos bacterianos (LPS, IL-1b, y butirato.Shiga toxin (Stx-producing E.coli causing watery diarrhea, hemorrhagic colitis and hemolytic-uremic syndrome (HUS. In Argentina, HUS is the most common cause of acute renal failure in children. The purpose of the present study was to examine the cytotoxicity of Stx type 2 (Stx2 and its B subunit (Stx2B on human renal tubular epithelial cells (HRTEC, in the presence and absence of inflammatory factors. Cytotoxic effects were assessed in terms of functionality of the epithelium, histological damage, cell viability, protein synthesis and cellular apoptosis. Results show that Stx2 regulates the passage of water through the HRTEC within an incubation period of 1h. Within longer periods, up to 72 hours, the study of morphology, viability, protein synthesis and apoptosis shows that HRTEC were sensitive to the cytotoxic action of Stx2 and Stx2B in a dose- and time-dependent manner. These effects were potentiated by

  20. Renal expression of parvalbumin is critical for NaCl handling and response to diuretics

    Science.gov (United States)

    Belge, Hendrica; Gailly, Philippe; Schwaller, Beat; Loffing, Johannes; Debaix, Huguette; Riveira-Munoz, Eva; Beauwens, Renaud; Devogelaer, Jean-Pierre; Hoenderop, Joost G.; Bindels, René J.; Devuyst, Olivier

    2007-01-01

    The distal convoluted tubule (DCT) plays an essential role in the reabsorption of NaCl by the kidney, a process that can be inhibited by thiazide diuretics. Parvalbumin (PV), a Ca2+-binding protein that plays a role in muscle fibers and neurons, is selectively expressed in the DCT, where its role remains unknown. We therefore investigated the renal phenotype of PV knockout mice (Pvalb−/−) vs. wild-type (Pvalb+/+) littermates. PV colocalized with the thiazide-sensitive Na+-Cl− cotransporter (NCC) in the early DCT. The Pvalb−/− mice showed increased diuresis and kaliuresis at baseline with higher aldosterone levels and lower lithium clearance. Acute furosemide administration increased diuresis and natriuresis/kaliuresis, but, surprisingly, did not increase calciuria in Pvalb−/− mice. NaCl supplementation of Pvalb−/− mice increased calciuria at baseline and after furosemide. The Pvalb−/− mice showed no significant diuretic response to hydrochlorothiazide, but an accentuated hypocalciuria. A decreased expression of NCC was detected in the early DCT of Pvalb−/− kidneys in the absence of ultrastructural and apoptotic changes. The PV-deficient mice had a positive Ca2+ balance and increased bone mineral density. Studies in mouse DCT cells showed that endogenous NCC expression is Ca2+-dependent and can be modulated by the levels of PV expression. These results suggest that PV regulates the expression of NCC by modulating intracellular Ca2+ signaling in response to ATP in DCT cells. They also provide insights into the Ca2+-sparing action of thiazides and the pathophysiology of distal tubulopathies. PMID:17804801

  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. Renal mucinous tubular and spindle cell carcinoma: two cases report and review of the literature%肾黏液性小管状和梭形细胞癌2例报道并文献复习

    Institute of Scientific and Technical Information of China (English)

    Zhifeng Wei; Zhengyu Zhang; Jingping Ge; Jianping Gao; Wenquan Zhou

    2012-01-01

    We reported the clinical and pathologic features of two different types of renal mucinous tubular and spindle cell. carcinoma (MTSCC). The first patient was incidentally discovered by health examination, with lower nuclear grade, no part and distant metastasis. The second patient presented with persistence hyperpyrexia, part and distant metastasis, and high nuclear grade. Surgery were both performed successfully. The first patient had no recurrences and no distant metastases. The second patient died of multiple organ failure 3 months postoperatively. Although MTSCC is usually a low potential malignancy carcinoma, high malignancy may occur and lead to a fatal course. So it needs a proper management and prognostication.

  3. 丹参注射液对梗阻性肾病梗阻解除后肾间质纤维化的影响%Salvia miltiorrhiza injection treatment on renal tubular interstitial fibrosis of obstructive nephropathy

    Institute of Scientific and Technical Information of China (English)

    王昭辉; 白遵光; 杨海峰

    2012-01-01

    目的:研究丹参注射液对梗阻性肾病梗阻解除后肾间质纤维化的影响.方法:将22只新西兰兔随机分为假手术组、造模组和丹参组,假手术组予术后普通喂养,造模组在解除梗阻后给予生理盐水腹腔注射,丹参组在解除梗阻后给予丹参注射液腹腔注射,观察三组的基本情况、血清学指标及肾间质病变情况.结果:丹参组血清肌酐(Cr)、尿素氮(Bun)含量较对照组低,P<0.05;丹参组病理标本中上皮细胞病变减轻,炎症细胞浸润较对照组少,间质增生减少,间质面积较对照组减少,P<0.05.结论:丹参注射液可以改善梗阻性肾病梗阻解除后肾间质纤维化情况,促进肾功能的恢复.%Aim:To explore the affect of Salvia miltiorrhiza injection treatment on renal tubular interstitial fibrosis. Methods: New Zealand rabbits were randomly divided into fake operational group control group and Salvia miltiorrhiza group, Salvia miltiorrhiza group was given Salvia miltiorrhiza injection by in-traperitoneal route after relief of obstruction lately 2 weeks, compared three groups of serological markers and renal tubular interstitial fibrosis. Results; The Blood creatinine levels and Blood urea nitrogen levels in Salvia miltiorrhiza group is lower than those of the control group(P <0. 05) ,the renal tubular interstitial level of Salvia miltiorrhiza group lower than control group ( P <0. 05 ). Conclusion: Salvia miltiorrhiza injection can improve renal tubulointerstitial fibrosis in obstructive nephropathy obstruction, promote recovery of renal function.

  4. 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

  5. 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

  6. 黏液样小管状及梭形细胞肾癌的CT诊断%CT diagnosis of mucinous tubular and spindle cell renal carcinoma

    Institute of Scientific and Technical Information of China (English)

    王秀玲; 张宗军; 夏秋媛; 陆珍风; 季学满

    2016-01-01

    Objective:To discuss the CT manifestations of mucinous tubular and spindle cell renal carcinoma (MTSRCC)and to improve the understanding of this tumor.Methods:The CT features of 8 patients with surgery and pa-thology proven MTSRCC were retrospectively analyzed.Non-enhanced and triphasic enhanced CT scanning were performed in all of the 8 patients.The size,location,density in plain CT and the enhanced pattern and degree of the tumor,as well as the adjacent involvement,retroperitoneal lymph node and distant metastasis were analyzed.Results:All of the 8 patients with MTSRCC presented as single,well-defined,oval or round mass with the mean maximum diameter as 4.53cm (1.8 ~7.6cm).Iso-attenuation or slightly hyper-attenuation of the tumor was revealed on plain CT in 7 cases,and hypo-attenuation in 1 case.Association with nephrolithiasis in 1 case.No intra-tumoral hemorrhage or calcification was identified.Tumor showed as gradually mild enhancement after contrast administration,homogeneous enhancement was showed in 6 patients and heterogeneous enhancement in 2 patients.The enhancement degree was apparently less than that of normal renal cortex. The mean CT value of the tumor in these 8 patients increased at cortico-medullary phase and delayed phase was 26.2HU and 33.6HU respectively.The ratio of tumor and renal cortex in cortico-medullary phase and delayed phase was 21.54%and 33.28% respectively.Conclusion:MTSRCC is a rarely seen renal neoplasm with low degree malignancy,which predomi-nantly presents in adult women.The CT features include well-defined,mass,necrosis and calcification are seldom,could be associated with nephrolithiasis,iso-attenuated on plain CT and with progressively mild enhancement.%目的:探讨黏液样小管状及梭形细胞肾癌(MTSRCC)的 CT 表现,提高对该病的认识。方法:回顾性分析8例经手术病理证实的 MTSRCC 的 CT 表现,8例均行 MSCT 平扫及三期增强扫描。分析病灶大小、位置、形态、平

  7. Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats.

    Science.gov (United States)

    Costa, E L; Almeida, A R; Netto, F M; Gontijo, J A R

    2005-12-01

    The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 microL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 +/- 26 microL min-1 100 g body weight-1) and captopril-treated (903 +/- 72 microL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

  8. Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Costa E.L.

    2005-01-01

    Full Text Available The present study evaluated the acute effect of the intraperitoneal (ip administration of a whey protein hydrolysate (WPH on systolic arterial blood pressure (SBP and renal sodium handling by conscious spontaneously hypertensive rats (SHR. The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 176.6 ± 4.9 mmHg, N = 8, P = 0.001 and 1.0 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 163.8 ± 5.9 mmHg, N = 8, P = 0.0018. Creatinine clearance decreased significantly (P = 0.0084 in the WPH-treated group (326 ± 67 µL min-1 100 g body weight-1 compared to 0.15 M NaCl-treated (890 ± 26 µL min-1 100 g body weight-1 and captopril-treated (903 ± 72 µL min-1 100 g body weight-1 rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 ± 0.019% compared to 0.126 ± 0.041 and 0.66 ± 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033. Similarly, the fractional potassium excretion in WPH-treated rats (0.25 ± 0.05% was significantly lower (P = 0.0063 than in control (0.91 ± 0.15% and captopril-treated rats (1.24 ± 0.30%, respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE-inhibiting in vitro activity (IC50 = 0.68 mg/mL. The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

  9. Renal tubular and adrenal medullary tumors in the 2-year rat study with canagliflozin confirmed to be secondary to carbohydrate (glucose) malabsorption in the 15-month mechanistic rat study.

    Science.gov (United States)

    De Jonghe, Sandra; Johnson, Mark D; Mamidi, Rao N V S; Vinken, Petra; Feyen, Bianca; Lammens, Godelieve; Proctor, Jim

    2017-09-12

    During preclinical development of canagliflozin, an SGLT2 inhibitor, treatment-related pheochromocytomas, renal tubular tumors (RTT), and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. In a previous 6-month rat mechanistic study, feeding a glucose free diet prevented canagliflozin effects on carbohydrate malabsorption as well as the increase in cell proliferation in adrenal medulla and kidneys, implicating carbohydrate malabsorption as the mechanism for tumor formation. In this chronic study male Sprague-Dawley rats were dosed orally with canagliflozin at high dose-levels (65 or 100 mg/kg/day) for 15 months and received either a standard diet or a glucose-free diet. Canagliflozin-dosed rats on standard diet showed presence of basophilic renal tubular tumors (6/90) and an increased incidence of adrenal medullary hyperplasia (35/90), which was fully prevented by feeding a glucose-free diet (no RTT's; adrenal medullary hyperplasia in ≤5/90). These data further confirm that kidney and adrenal medullary tumors in the 2-year rat study were secondary to carbohydrate (glucose) malabsorption and were not due to a direct effect of canagliflozin on these target tissues. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. 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.

    Science.gov (United States)

    Kimura, Hideki; Mikami, Daisuke; Kamiyama, Kazuko; Sugimoto, Hidehiro; Kasuno, Kenji; Takahashi, Naoki; Yoshida, Haruyoshi; Iwano, Masayuki

    2014-11-14

    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.

  11. 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.

  12. 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

  13. Clinical value analysis of renal tubular epithelium and renal local pathological changes on kidney stone formation%肾小管上皮及肾脏局部病理改变对肾结石形成的临床价值分析

    Institute of Scientific and Technical Information of China (English)

    邓武成

    2015-01-01

    目的:探讨肾小管上皮及肾脏局部病理改变在肾结石形成中的作用机制。方法:选取89例肾结石患者作为实验组,90例肾癌患者的肾标本作为对照组,检测两组肾小管上皮的骨桥蛋白、骨形成蛋白‐2(BM P‐2)和II型胶原的表达情况。结果:实验组患者结石多以混合的形式存在;两组肾小管上皮及肾脏局部病理改变中均可见骨桥蛋白表达,实验组高于对照组,差异有统计学意义,骨桥蛋白主要在肾集合管和肾小管上皮细胞胞浆内表达;BM P‐2、II型胶原在肾小管上皮及肾脏病理局部组织中均未见表达。结论:骨桥蛋白在肾结石患者的肾小管上皮细胞中表达, BM P‐2、II型胶原未见表达,因此肾小管上皮及肾脏局部病理改变时骨桥蛋白可能促进肾结石的形成。%Objective:To study the role of renal tubular epithelium and kidney local pathological changes in kidney stone formation .Methods:89 cases of renal calculi patients were selected as the experimental group ,90 cases of patients with renal cell carcinoma renal specimens as control group ,the expression of renal tubular epithelial osteopontin ,bone morphogenetic protein‐2 (BMP‐2) and type II collagen were detected .Results:The calculi mostly existed in the form of mixture ,including of mixture was the calcium calculi (91 .01% ) ,calcium oxalate calculi (84 .27% ) ,uric acid/uric acid salt (14 .61% ) ,carbonate apatite (8 .99% ) ,and ammonium magnesium phosphate hexahydrate (11 .24% ) .Osteopontin was expressed in both two groups and the experimental group was significantly higher than that in the control group .Osteopontin was mainly expressed in the cytoplasm of renal collecting renal tu‐bular epithelial cells .Expression of BMP‐2 and collagen II were not observed in renal tubular epithelial or renal path‐ological local tissues .Conclusion:Osteopontin is expressed in the renal tubular epithelial cells

  14. 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.

  15. Proximal tubular hypertrophy and enlarged glomerular and proximal tubular urinary space in obese subjects with proteinuria.

    Directory of Open Access Journals (Sweden)

    Ana Tobar

    Full Text Available BACKGROUND: Obesity is associated with glomerular hyperfiltration, increased proximal tubular sodium reabsorption, glomerular enlargement and renal hypertrophy. A single experimental study reported an increased glomerular urinary space in obese dogs. Whether proximal tubular volume is increased in obese subjects and whether their glomerular and tubular urinary spaces are enlarged is unknown. OBJECTIVE: To determine whether proximal tubules and glomerular and tubular urinary space are enlarged in obese subjects with proteinuria and glomerular hyperfiltration. METHODS: Kidney biopsies from 11 non-diabetic obese with proteinuria and 14 non-diabetic lean patients with a creatinine clearance above 50 ml/min and with mild or no interstitial fibrosis were retrospectively analyzed using morphometric methods. The cross-sectional area of the proximal tubular epithelium and lumen, the volume of the glomerular tuft and of Bowman's space and the nuclei number per tubular profile were estimated. RESULTS: Creatinine clearance was higher in the obese than in the lean group (P=0.03. Proteinuria was similarly increased in both groups. Compared to the lean group, the obese group displayed a 104% higher glomerular tuft volume (P=0.001, a 94% higher Bowman's space volume (P=0.003, a 33% higher cross-sectional area of the proximal tubular epithelium (P=0.02 and a 54% higher cross-sectional area of the proximal tubular lumen (P=0.01. The nuclei number per proximal tubular profile was similar in both groups, suggesting that the increase in tubular volume is due to hypertrophy and not to hyperplasia. CONCLUSIONS: Obesity-related glomerular hyperfiltration is associated with proximal tubular epithelial hypertrophy and increased glomerular and tubular urinary space volume in subjects with proteinuria. The expanded glomerular and urinary space is probably a direct consequence of glomerular hyperfiltration. These effects may be involved in the pathogenesis of obesity

  16. Effects of a long-acting formulation of octreotide on renal function and renal sodium handling in cirrhotic patients with portal hypertension: a randomized, double-blind, controlled trial

    DEFF Research Database (Denmark)

    Ottesen, LH; Aagaard, N K; Kiszka-Kanowitz, M;

    2001-01-01

    . The patients were in sodium steady state at the time of study. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured by a constant infusion clearance technique. Renal sodium handling was determined by lithium and sodium clearance measurements. Therapeutic serum levels...... during octreotide treatment were not significantly different from those of placebo. In addition, no changes in free water clearance, urinary flow rate, or 24-hour Na excretion were demonstrated. A significant increase of mean arterial pressure (+5 mm Hg; P ... of octreotide along with a reduction of insulin-like growth factor I (IGF-I) (P filtration fraction (GFR/ERPF). Changes in clearance and extraction fraction of sodium and lithium...

  17. 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)

  18. Hepatitis B Virus Infection and the Kidney: Renal Abnormalities in HBV Patients, Antiviral Drugs Handling, and Specific Follow-Up

    Directory of Open Access Journals (Sweden)

    Gilbert Deray

    2015-01-01

    Full Text Available Chronic hepatitis B virus (CHB infection is one of the most common causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC worldwide. Many patients with CHB have variable degrees of functional renal impairment, and approximately 2 to 15% of patients on hemodialysis have CHB. Several therapeutic regimens have been developed in the past years, among which oral nucleoside and nucleotide analogues have been demonstrated to be efficient and well tolerated. However, they all are excreted in the urine and may thus require dosage adjustment in patients with decreased renal function. Furthermore, a number of them may in addition be toxic to the kidneys, especially in those patients presenting with renal insufficiency.

  19. Renal acidification defects in medullary sponge kidney

    DEFF Research Database (Denmark)

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

    1988-01-01

    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...

  20. The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop and thiazide diuretics.

    Science.gov (United States)

    Lee, Chien-Te; Ng, Hwee-Yeong; Lee, Yueh-Ting; Lai, Li-Wen; Lien, Yeong-Hau H

    2016-02-01

    Calbindin-D28k (CBD-28k) is a calcium binding protein located in the distal convoluted tubule (DCT) and plays an important role in active calcium transport in the kidney. Loop and thiazide diuretics affect renal Ca and Mg handling: both cause Mg wasting, but have opposite effects on Ca excretion as loop diuretics increase, but thiazides decrease, Ca excretion. To understand the role of CBD-28k in renal Ca and Mg handling in response to diuretics treatment, we investigated renal Ca and Mg excretion and gene expression of DCT Ca and Mg transport molecules in wild-type (WT) and CBD-28k knockout (KO) mice. Mice were treated with chlorothiazide (CTZ; 50 mg · kg(-1) · day(-1)) or furosemide (FSM; 30 mg · kg(-1) · day(-1)) for 3 days. To avoid volume depletion, salt was supplemented in the drinking water. Urine Ca excretion was reduced in WT, but not in KO mice, by CTZ. FSM induced similar hypercalciuria in both groups. DCT Ca transport molecules, including transient receptor potential vanilloid 5 (TRPV5), TRPV6, and CBD-9k, were upregulated by CTZ and FSM in WT, but not in KO mice. Urine Mg excretion was increased and transient receptor potential subfamily M, member 6 (TRPM6) was upregulated by both CTZ and FSM in WT and KO mice. In conclusion, CBD-28k plays an important role in gene expression of DCT Ca, but not Mg, transport molecules, which may be related to its being a Ca, but not a Mg, intracellular sensor. The lack of upregulation of DCT Ca transport molecules by thiazides in the KO mice indicates that the DCT Ca transport system is critical for Ca conservation by thiazides.

  1. Efeito do extrato bruto das folhas de Echinodorus Macrophyllus e de frações semipurificadas sobre a função renal em ratos com necrose tubular aguda induzida por gentamicina

    OpenAIRE

    Gustavo Pereira Cosenza

    2010-01-01

    A Echinodorus macrophyllus (E. macrophyllus), família alismatacea, é uma espécie nativa do Brasil onde é conhecida por chapéu de couro, chá mineiro e erva de pântano. O objetivo deste trabalho foi avaliar o possível efeito do extrato bruto das folhas de E. macrophyllus (EB) e de frações dele extraídos (FAE, FB e FAq) sobre a função renal em ratos normais e em ratos com necrose tubular aguda (NTA) induzida por gentamicina (GT). O EB, obtido por percolação, foi submetido à extração com acetato ...

  2. 30-MM Tubular Projectile

    Science.gov (United States)

    1984-10-01

    Suiza tubular projectile 20 9. Inspection of Hispano Suiza sabot 21 10. Inspection of GAU-8 sabot 22 11. Firing data - 30-rn tubular projectile (Hispano... Suiza 23 copper banded) 12. Firing data - 30-m tubular projectile (GAU-8 plastic 24 banded) 13. Firing data - 30-m tubular projectile (GAU-8 copper 25...42 13. In-flight Hispano Suiza tubular projectiles 43 14. In-flight C4U-8 (plastic) tubular projectile 44 15. In-flight GCU-8 (copper) tubular

  3. 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.

  4. CNNM2, encoding a basolateral protein required for renal Mg2+ handling, is mutated in dominant hypomagnesemia

    NARCIS (Netherlands)

    Stuiver, M.; Lainez, S.; Will, C.; Terryn, S.; Gunzel, D.; Debaix, H.; Sommer, K.; Kopplin, K.; Thumfart, J.; Kampik, N.B.; Querfeld, U.; Willnow, T.E.; Nemec, V.; Wagner, C.A.; Hoenderop, J.G.J.; Devuyst, O.; Knoers, N.V.A.M.; Bindels, R.J.M.; Meij, I.C.; Muller, D.

    2011-01-01

    Familial hypomagnesemia is a rare human disorder caused by renal or intestinal magnesium (Mg(2+)) wasting, which may lead to symptoms of Mg(2+) depletion such as tetany, seizures, and cardiac arrhythmias. Our knowledge of the physiology of Mg(2+) (re)absorption, particularly the luminal uptake of

  5. The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer

    DEFF Research Database (Denmark)

    Daugaard, G; Strandgaard, S; Holstein-Rathlou, N H

    1987-01-01

    Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable...

  6. Effect of progesterone on renal sodium handling in man: relation to aldosterone excretion and plasma renin activity.

    Science.gov (United States)

    Oparil, S; Ehrlich, E N; Lindheimer, M D

    1975-08-01

    1. The effect of progesterone on renal haemodynamics and intrarenal sodium handing was evaluated in thirteen normal men on a constant diet. Clearances were measured during maximal water diuresis and again 4-7 days later, this time 3 h after progesterone was given intramuscularly. Seven additional studies were performed 3 days after progesterone administration. Another four tests were performed on volunteers who had manifested renal 'escape' from the sodium-retaining effect of deoxycorticosterone acetate. 2. In acute progesterone studies glomerular filtration rate was unchanged, whereas effective renal plasma flow increased, so that filtration fraction decreased significantly. A similar in crease in urinary sodium occurred whether subjects received a low or high sodium diet. Indices which related to the distal delivery of filtrate (fractional urine flow and the sum of fractional free water and sodium clearances) increased significantly in both groups. The progesterone-induced increase in sodium excretion was not related to changes in plasma renin activity, renin substrate or urinary aldosterone. After 3 days of progesterone, the increase of sodium excretion was less than in the acute studies and urinary aldosterone increased tow- to four-fold. Progesterone failed to produce an acute increse in urinary sodium in subjects hyperexpanded by administration of exogenous mineralocorticoids. 3. Results suggest that the acute natriuretic action of progesterone is in part independent of aldosterone inhibition and that progesterone may inhibit sodium reabsorption at proximal as well as distal sites in the nephron.

  7. The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Sung Min Ju

    2015-01-01

    Full Text Available Apigenin is a member of the flavone subclass of flavonoids present in fruits and vegetables. Apigenin has long been considered to have various biological activities, such as antioxidant, anti-inflammatory, and antitumorigenic properties, in various cell types. Cisplatin was known to exhibit cytotoxic effect to renal cells by inducing apoptosis through activation of p53. The present study investigated the antiapoptotic effects of apigenin on the cisplatin-treated human renal proximal tubular epithelial (HK-2 cells. HK-2 cells were pretreated with apigenin (5, 10, 20 μM for 1 h and then treated with 40 μM cisplatin for various times. Apigenin inhibited the cisplatin-induced apoptosis of HK-2 cells. Interestingly, apigenin itself exerted cytostatic activity because of its ability to induce cell cycle arrest. Apigenin inhibited caspase-3 activity and PARP cleavage in cisplatin-treated cells. Apigenin reduced cisplatin-induced phosphorylation and expression of p53, with no significant influence on production of ROS that is known to induce p53 activation. Furthermore, apigenin promoted cisplatin-induced Akt phosphorylation, suggesting that enhanced Akt activation may be involved in cytoprotection. Taken together, these results suggest that apigenin ameliorates cisplatin-induced apoptosis through reduction of p53 activation and promotion of PI3K/Akt pathway in HK-2 cells.

  8. Reliability of Tubular Joints

    DEFF Research Database (Denmark)

    Sørensen, John Dalsgaard; Thoft-Christensen, Palle

    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...

  9. 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

  10. 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

  11. 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

  12. Renal cysteine conjugate C-S lyase mediated toxicity of halogenated alkenes in primary cultures of human and rat proximal tubular cells.

    Science.gov (United States)

    McGoldrick, Trevor A; Lock, Edward A; Rodilla, Vicente; Hawksworth, Gabrielle M

    2003-07-01

    Proximal tubular cells from human (HPT) and rat (RPT) kidneys were isolated, grown to confluence and incubated with S-(1,2-dichlorovinyl)- l-cysteine (DCVC), S-(1,2,2-trichlorovinyl)- l-cysteine (TCVC), S-(1,1,2,2-tetrafluoroethyl)- l-cysteine (TFEC) and S-(2-chloro-1,1-difluorethyl)- l-cysteine (CDFEC), the cysteine conjugates of nephrotoxicants. The cultures were exposed to the conjugates for 12, 24 and 48 h and the toxicity determined using the MTT assay. All four conjugates caused dose-dependent toxicity to RPT cells over the range 50-1,000 microM, the order of toxicity being DCVC>TCVC>TFEC=CDFEC. The inclusion of aminooxyacetic acid (AOAA; 250 microM), an inhibitor of pyridoxal phosphate-dependent enzymes such as C-S lyase, afforded protection, indicating that C-S lyase has a role in the bioactivation of these conjugates. In HPT cultures only DCVC caused significant time- and dose-dependent toxicity. Exposure to DCVC (500 microM) for 48 h decreased cell viability to 7% of control cell values, whereas co-incubation of DCVC (500 microM) with AOAA (250 microM) resulted in cell viability of 71%. Human cultures were also exposed to S-(1,2-dichlorovinyl)-glutathione (DCVG). DCVG was toxic to HPT cells, but the onset of toxicity was delayed compared with the corresponding cysteine conjugate. AOAA afforded almost complete protection from DCVG toxicity. Acivicin (250 microM), an inhibitor of gamma-glutamyl transferase (gamma-GT), partially protected against DCVG (500 microM)-induced toxicity at 48 h (5% viability and 53% viability in the absence and presence of acivicin, respectively). These results suggest that DCVG requires processing by gamma-GT prior to bioactivation by C-S lyase in HPT cells. The activity of C-S lyase, using TFEC as a substrate, and glutamine transaminase K (GTK) was measured in rat and human cells with time in culture. C-S lyase activity in RPT and HPT cells decreased to approximately 30% of fresh cell values by the time the cells reached

  13. Targeting apoptosis in acute tubular injury.

    Science.gov (United States)

    Ortiz, Alberto; Justo, Pilar; Sanz, Ana; Lorz, Corina; Egido, Jesús

    2003-10-15

    Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in acute renal failure. Acute tubular necrosis is the most frequent form of parenchymal acute renal failure. The main causes are ischemia-reperfusion, sepsis and nephrotoxic drugs. Exogenous factors such as nephrotoxic drugs and bacterial products, and endogenous factors such as lethal cytokines promote tubular cell apoptosis. Such diverse stimuli engage intracellular death pathways that in some cases are stimulus-specific. We now review the role of apoptosis in acute renal failure, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis.

  14. 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

    Real function, plasma renin concentration (PRC) and prostaglandin (PG) excretion rate was studied in groups of Sprague-Dawley (SPRD) and Wistar (WIST) rats anesthetized with either Halothane-N2O or Inactin. Conscious rats were used as controls. A. In Halothane-N2O anesthesia inulin clearance (CIN......) 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...

  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. 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.

  17. How to differentiate renal senescence from chronic kidney disease in clinical practice.

    Science.gov (United States)

    Musso, Carlos G; Jauregui, Jose R

    2016-09-01

    Renal aging is frequently confused with chronic nephropathy in clinical practice, since there are some similarities between them, particularly regarding reduced glomerular filtration rate (GFR). However, there are many differences between these two entities which can help any practitioner to distinguish between them, such as: GFR deterioration rate, hematocrit, renal handling of urea, creatinine and some electrolytes, tubular acidification, urinalysis, and renal imaging. Differentiation between renal aging and chronic renal disease is crucial in order to avoid unnecessary medicalization of what is a physiological change associated with the healthy aging process, and the potential harmful consequences of such overdiagnosis. A recently described equation (HUGE), as well as an adequate nephrological evaluation and follow up can help physicians to distinguish both entities.

  18. 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.

  19. Reduction of oxalate-induced renal tubular epithelial (NRK-52E cell injury and inhibition of calcium oxalate crystallisation in vitro by aqueous extract of Achyranthes aspera

    Directory of Open Access Journals (Sweden)

    Aggarwal Anshu

    2010-01-01

    Full Text Available Despite considerable progress in medical therapy, there is no satisfactory drug to treat kidney stones. Therefore, this study is aimed to look for an alternative treatment by using Achyranthes aspera. Here, the inhibitory potency of A. aspera 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 in vitro. Data are expressed as mean values of three independent experiments (each in triplicate and analysed by the analysis of variance (P < 0.05 to estimate the differences between values of extracts tested. A. aspera extract exhibited a concentration-dependent inhibition of the growth of CaOx crystals but a similar pattern of inhibition was not observed with increase in the plant extract concentration for the nucleation assay. When NRK 52E cells were injured by exposure to oxalate for 72 hours, A. aspera extract prevented the injury in a dose-dependent manner. On treatment with the different concentrations of the plant, the cell viability increased and the lactate dehydrogenase (LDH release decreased in a concentration-dependent manner. These studies indicate that A. aspera extract besides having a cytoprotective role also has a potential to inhibit both nucleation and the growth of the CaOx crystals and can prove to be a potent candidate for phytotherapy against urolithiasis.

  20. 虫草菌液对糖尿病肾病肾小管上皮细胞转分化的影响%Effect of Cordyceps sinensis liquid on diabetic nephropathy renal tubular epithelial cell transdifferentiation

    Institute of Scientific and Technical Information of China (English)

    刘彤葳; 周盾; 郝春艳

    2014-01-01

    Objective To discuss the effect of Cordyceps sinensis liquid on Diabetic Nephropathy renal tubular epithelial cell transdifferentiation.Methods Diabetic Nephropathy renal tubular epithelial cells were treated with different dose of Cordyceps sinensis liquid and high glucose,and divided into five groups.Control group was added 5.5 mmol/L D-glucose,High glucose group was added 30 mmol/L D-glucose, Experimental group 1 was added 30 mmol/L D-glucose and 5μg/mL Cordyceps sinensis liquid,Experimental group 2 was added 30 mmol/L D-glucose and 10 μg/mL Cordyceps sinensis liquid,Experimental group 3 was added 30 mmol/L D-glucose and 20 μg/mL Cordyceps sinensis liquid.The expression of E-cadherin protein,FN protein,α-SMA protein and ILK protein in each group were detected by western blot. Results Compared with control group,the expression of E-cadherin protein in high glucose was decreased significantly(P<0.01),and with the addition of Cordyceps bacteria increases,E-cadherin protein expression in three Experiment group were gradually increased(P<0.01).Compared with control group,the expression ofα-SMA protein and FN protein in High glucose group were increased significantly (P <0.01 ),and both two protein in Experiment group 2 and Experiment 3 were significantly lower than High glucose group(P<0.01).Compared with control group,the expression of ILK protein in high glucose group was significantly higher(P<0.01 ),and its expression in Experiment group 3 was significantly lower than High glucose group (P<0.01 ). Conclusion Cordyceps sinensis liquid can inhibit diabetic nephropathy renal tubular epithelial cell translating into myofibroblast,then inhibit renal tubule interstitial fibrosis.%目的:探讨虫草菌液对糖尿病肾病肾小管上皮细胞转分化的影响。方法将不同浓度的虫草菌液和高糖作用于人近端肾小管上皮细胞,根据加入剂量和组份不同分成以下5组:对照组给予5.5 mmol/L D-葡萄糖;高糖组给予30 mmol

  1. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  2. 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.

  3. STANDARDIZATION OF AN IN VITRO MODEL OF DIABETIC NEPHROPATHY IN RENAL TUBULAR CELLS AND INVESTIGATION OF THE ROLE OF ALDOSE REDUCTASE PATHWAY IN HIGH GLUCOSE-INDUCED RENAL CELL INJURY

    OpenAIRE

    El Gamal, Heba

    2015-01-01

    Diabetic nephropathy (DN) is the leading cause of end stage renal disease, and one of the most serious microvascular complications of diabetes mellitus. Increase in the shift of glucose into the aldose reductase pathway during diabetes leads to accumulation of sorbitol and fructose in the cells, and causes an imbalance in the associated cofactors, which in turn cause deleterious events such as oxidative stress, endoplasmic reticulum (ER) stress and cell death in the kidney. The objective of t...

  4. Nitro-oleic acid ameliorates oxygen and glucose deprivation/re-oxygenation triggered oxidative stress in renal tubular cells via activation of Nrf2 and suppression of NADPH oxidase.

    Science.gov (United States)

    Nie, Huibin; Xue, Xia; Liu, Gang; Guan, Guangju; Liu, Haiying; Sun, Lina; Zhao, Long; Wang, Xueling; Chen, Zhixin

    2016-01-01

    Nitroalkene derivative of oleic acid (OA-NO2), due to its ability to mediate revisable Michael addition, has been demonstrated to have various biological properties and become a therapeutic agent in various diseases. Though its antioxidant properties have been reported in different models of acute kidney injury (AKI), the mechanism by which OA-NO2 attenuates intracellular oxidative stress is not well investigated. Here, we elucidated the anti-oxidative mechanism of OA-NO2 in an in vitro model of renal ischemia/reperfusion (I/R) injury. Human tubular epithelial cells were subjected to oxygen and glucose deprivation/re-oxygenation (OGD/R) injury. Pretreatment with OA-NO2 (1.25 μM, 45 min) attenuated OGD/R triggered reactive oxygen species (ROS) generation and subsequent mitochondrial membrane potential disruption. This action was mediated via up-regulating endogenous antioxidant defense components including superoxide dismutase (SOD1), heme oxygenase 1 (HO-1), and γ-glutamyl cysteine ligase modulatory subunits (GCLM). Moreover, subcellular fractionation analyses demonstrated that OA-NO2 promoted nuclear translocation of nuclear factor-E2- related factor-2 (Nrf2) and Nrf2 siRNA partially abrogated these protective effects. In addition, OA-NO2 inhibited NADPH oxidase activation and NADPH oxidase 4 (NOX4), NADPH oxidase 2 (NOX2) and p22(phox) up-regulation after OGD/R injury, which was not relevant to Nrf2. These results contribute to clarify that the mechanism of OA-NO2 reno-protection involves both inhibition of NADPH oxidase activity and induction of SOD1, Nrf2-dependent HO-1, and GCLM.

  5. The Unappreciated Role of Extrarenal and Gut Sensors in Modulating Renal Potassium Handling: Implications for Diagnosis of Dyskalemias and Interpreting Clinical Trials

    Directory of Open Access Journals (Sweden)

    Murray Epstein

    2016-05-01

    Full Text Available In addition to the classic and well-established “feedback control” of potassium balance, increasing investigative attention has focused on a novel and not widely recognized complementary regulatory paradigm for maintaining potassium homeostasis—the “feed-forward control” of potassium balance. This regulatory mechanism, initially defined in rumen, has recently been validated in normal human subjects. Studies are being conducted to determine the location for this putative potassium sensor and to evaluate potential signals, which might increase renal potassium excretion. Awareness of this more updated integrative control mechanism for potassium homeostasis is ever more relevant today, when the medical community is increasingly focused on the challenges of managing the hyperkalemia provoked by renin–angiotensin–aldosterone system inhibitors (RAASis. Recent studies have demonstrated a wide gap between RAASi prescribing guidelines and real-world experience and have highlighted that this gap is thought to be attributable in great part to hyperkalemia. Consequently we require a greater knowledge of the complexities of the regulatory mechanisms subserving potassium homeostasis. Sodium polystyrene sulfonate has long been the mainstay for treating hyperkalemia, but its administration is fraught with challenges related to patient discomfort and colonic necrosis. The current and imminent availability of newer potassium binders with better tolerability and more predictive dose–response potassium removal should enhance the management of hyperkalemia. Consequently it is essential to better understand the intricacies of mammalian colonic K+ handling. We discuss colonic transport of K+ and review evidence for potassium (BK channels being responsible for increased stool K+ in patients with diseases such as ulcerative colitis.

  6. Effect of glucagon infusion on the renal clearance of amylase relative to creatinine.

    Science.gov (United States)

    Tedesco, F J; Davila, E; Gardner, L B

    1978-10-01

    Recent data seem to support a tubular defect as the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon has been proposed by some to be an important factor in this phenomenon. To examine the role of glucagon as this "tubular dysfunction factor", we investigated the effect of intravenously infused glucagon on the fractional excretion of amylase and the tubular handling of a low molecular weight protein, beta2 microglobulin, in normal, healthy volunteers. At glucagon levels far in excess of those seen in pancreatitis, the clearance ratio of beta2 microglobulin relative to creatinine increased, whereas the clearance ratio of amylase relative to creatinine did not increase above the normal range. The dissociation between beta2 microglobulin clearance and amylase clearance allows one to question the theory that tubular dysfunction is the mechanism of the elevated renal clearance of amylase relative to creatinine in acute pancreatitis. Glucagon does not appear to be the sole factor responsible for the elevation of renal clearance of amylase relative to creatinine in acute pancreatitis.

  7. FARMACOFISIOLOGÍA RENAL

    Directory of Open Access Journals (Sweden)

    Musso CG

    2014-03-01

    Full Text Available Renal physiology plays a key role in the pharmacokinetics of many drugs. Knowledge of the particularities of each nephron function (filtration, secretion, reabsorption and excretion and each of renal tubular transport mechanisms (simple diffusion, facilitated diffusion, facilitated transport, active transport, endocytosis and pinocytosis is fundamental to achieve better management of drug prescriptions.

  8. Effects of insulin detemir and NPH insulin on renal handling of sodium, fluid retention and weight in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Hendriksen, K V; Jensen, Tonny Joran; Oturai, P;

    2012-01-01

    In type 2 diabetic patients, insulin detemir (B29Lys(ε-tetradecanoyl),desB30 human insulin) induces less weight gain than NPH insulin. Due to the proposed reduction of tubular action by insulin detemir, type 2 diabetic patients should have increased urinary sodium excretion, thereby reducing extr...

  9. Tubular apocrine adenoma.

    Science.gov (United States)

    Toribio, J; Zulaica, A; Peteiro, C

    1987-04-01

    We report a case of tubular apocrine adenoma located on the scalp, with characteristics of syringocystadenoma papilliferum in the superior part of the lesion. An interesting feature of the growth is its connective tissue involvement.

  10. Renal sodium avidity in heart failure: from pathophysiology to treatment strategies.

    Science.gov (United States)

    Mullens, Wilfried; Verbrugge, Frederik Hendrik; Nijst, Petra; Tang, Wai Hong Wilson

    2017-02-23

    Increased neurohumoral stimulation resulting in excessive sodium avidity and extracellular volume overload are hallmark features of decompensated heart failure. Especially in case of concomitant renal dysfunction, the kidneys often fail to elicit effective natriuresis. While assessment of renal function is generally performed by measuring serum creatinine-a surrogate for glomerular filtration-, this only represents part of the nephron's function. Alterations in tubular sodium handling are at least equally important in the development of volume overload and congestion. Venous congestion and neurohumoral activation in advanced HF further promote renal sodium and water retention. Interestingly, early on, before clinical signs of heart failure are evident, intrinsic renal derangements already impair natriuresis. This clinical review discusses the importance of heart failure (HF) induced changes in different nephron segments. A better understanding of cardiorenal interactions which ultimately result in sodium avidity in HF might help to treat and prevent congestion in chronic and acute HF.

  11. Role of the glomerular-tubular imbalance with tubular predominance in the arterial hypertension pathophysiology.

    Science.gov (United States)

    Fox, María Ofelia Barber; Gutiérrez, Ernesto Barber

    2013-09-01

    In previous investigations we caused renal tubular reabsorption preponderance relating to the glomerular filtration (Glomerular-tubular imbalance) and we observed that this fact conducted to volume expansion and development of arterial hypertension, in rats that previously were normotens. We based on this evidence and other which are reflected in the literature arrived at the following hypothesis: a greater proportion of tubular reabsorption relating to the filtered volume is the base of the establishment of the glomerular-tubular imbalance with tubular predominance (GTI-T), which favors to the Na(+)-fluid retention and volume expansion. All of which conduced to arterial hypertension. These facts explain a primary hypertensive role of the kidney, consistent with the results of renal transplants performed in different lines of hypertensive rats and their respective controls and in humans: hypertension can be transferred with the kidney. GTI-T aims to be, a common phenomenon involved in the hypertension development in the multiple ways which is manifested the hypertensive syndrome. In secondary hypertension, GTI-T is caused by significant disruptions of hormone secretions that control renal function, or obvious vascular or parenchymal damage of these organs. In primary hypertension the GTI-T has less obvious causes inherently developed in the kidney, including humoral, cellular and subcellular mechanisms, which may insidiously manifest under environmental factors influence, resulting in insidious development of hypertension. This would explain the state of prehypertension that these individuals suffer. So it has great importance to study GTI-T before the hypertension is established, because when hypertensive state is established, other mechanisms are installed and they contribute to maintain the hypertension. Our hypothesis may explaining the inability of the kidneys to excrete salt and water in hypertension, as Guyton and colleagues have expressed and constitutes a

  12. Pitfalls and Limitations of Radionuclide Renal Imaging in Adults.

    Science.gov (United States)

    Keramida, Georgia; James, Jacqueline M; Prescott, Mary C; Peters, Adrien Michael

    2015-09-01

    To understand pitfalls and limitations in adult renography, it is necessary to understand firstly the physiology of the kidney, especially the magnitude and control of renal blood flow, glomerular filtration rate and tubular fluid flow rate, and secondly the pharmacokinetics and renal handling of the three most often used tracers, Tc-99m-mercaptoacetyltriglycine (MAG3), Tc-99m-diethylene triamine pentaacetic acid (DTPA) and Tc-99m-dimercaptosuccinic acid (DMSA). The kidneys may be imaged dynamically with Tc-99m-MAG3 or Tc-99m-DTPA, with or without diuretic challenge, or by static imaging with Tc-99m-DMSA. Protocols are different according to whether the kidney is native or transplanted. Quantitative analysis of dynamic data includes measurement of renal vascularity (important for the transplanted kidney), absolute tracer clearance rates, differential renal function (DRF) and response to diuretic challenge. Static image reveals functional renal parenchymal damage, both focal and global, is useful in the clinical management of obstructive uropathy, renal stone disease and hypertension (under angiotensin converting enzyme inhibition), and is the preferred technique for determining DRF. Diagnosis based on morphological appearances is important in transplant management. Even though nuclear medicine is now in the era of hybrid imaging, renal imaging remains an important subspecialty in nuclear medicine and requires a sound basing in applied physiology, the classical supporting discipline of nuclear medicine.

  13. 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.

  14. 缺氧对肾小管上皮细胞分泌外泌体的影响%Effect of hypoxia on exosomes in renal tubular epithelial cells

    Institute of Scientific and Technical Information of China (English)

    郭艳霞; 宋秀珍; 周秋根

    2015-01-01

    目的 观察缺氧对肾小管上皮细胞分泌外泌体的影响,探讨外泌体在缺氧致肾脏损伤中的作用及机制.方法 (1)常氧(21%O2)及缺氧(1%O2)分别处理大鼠肾小管上皮细胞(NRK-52E)48 h,收集细胞上清液并使用高速梯度离心法分离外泌体.采用透射电镜、纳米示踪分析、Western印迹、蛋白浓度定量鉴定并比较两组外泌体的基本特性.(2)在共培养实验中,以不同浓度(1、10、50、100、300 mg/L)的常氧外泌体、缺氧外泌体分别干预脂多糖(LPS)诱导的大鼠原代腹腔巨噬细胞,使用实时荧光定量PCR与酶联免疫吸附试验(ELISA)法分别检测巨噬细胞白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、诱导型氮氧化物合酶(iNOS)水平;使用Western印迹法检测巨噬细胞磷酸化(p)STAT/STAT及细胞因子信号传导抑制蛋白1 (SOCS1)的蛋白表达;最后,使用实时荧光定量PCR法检测常氧外泌体与缺氧外泌体中炎性反应相关微RNA(microRNA,miR)的表达差异.结果 (1)离心得到的囊泡具有外泌体典型的结构,粒径小于150 nm,表达外泌体标志蛋白CD63,说明分离得到外泌体.缺氧对肾小管上皮细胞分泌的外泌体形态、粒径分布比例无明显影响,但提高了外泌体的分泌量.(2)缺氧外泌体相比于常氧外泌体促进了LPS诱导的M1型巨噬细胞IL-6、TNF-α、iNOS的表达和分泌(均P<0.01),同时提高STAT的磷酸化水平并减少SOCS1的蛋白表达(均P<0.01);对炎性反应相关microRNA检测发现缺氧外泌体中miR-155、miR-27a表达量较常氧外泌体明显升高(P<0.05).结论 缺氧可改变外泌体的生物学功能,表现为协同促进LPS诱导的M1型巨噬细胞的表型转化,这可能是慢性肾脏病微炎性反应状态持续的原因之一.%Objective To explore the effect of hypoxia on exosomes secreted by renal tubular epithelial cells and the function of exosomes in chronic kidney diseases.Methods (1) The supernatant of

  15. Espirales tubulares para turbinas

    Directory of Open Access Journals (Sweden)

    Editorial, Equipo

    1958-07-01

    Full Text Available Para el suministro y fabricación de las espirales tubulares que debían alimentar las turbinas del aprovechamiento hidroeléctrico de Brownlee, que constituye el primero de los cuatro saltos del grupo Hells Canyon, del río Snake, la conocida factoría S. Morgan Smith, especializada en la construcción de turbinas y material a ellas accesorio, se encargó del estudio, fabricación y montaje de cuatro de estas espirales tubulares de 5,50 m de diámetro máximo.

  16. Polarity of stimulation and secretion of transforming growth factor-beta 1 by cultured proximal tubular cells.

    OpenAIRE

    Phillips, A.O.; Steadman, R.; Morrisey, K.; Williams, J. D.

    1997-01-01

    Proximal tubular epithelial cells are the most abundant cells in the renal cortex, and recent studies suggest that they may play an important role in initiating pathological changes in renal disease. Transforming growth factor (TGF)-beta 1 has been implicated as a major factor controlling the development and progression of renal fibrosis in numerous diseases, including diabetic nephropathy. We have recently demonstrated that human proximal tubular epithelial cells synthesize and secrete TGF-b...

  17. 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

  18. 2型糖尿病肾病患者肾小管功能相关因素分析%In patients with type 2 diabetes kidney disease clinical factors associated with renal tubular function analysis

    Institute of Scientific and Technical Information of China (English)

    贾晓炜; 栾进; 张南雁; 李岚; 赵琳; 贾贺堂

    2013-01-01

    Objective To discuss the clinical implications of urinary β2 microglobulin(U - β2 - MG)and its related factors in T2 Diabetes Mellitus patients with diabetic nephropathy( DN). Methods We collected 171 diagnosed DN patients (male 109, female 62). Correlation analysis of U - β2 - MG and the other clinical test items was made. Correlation analysis was made again after we divided patients into three groups: simple DM , DM with hypertension, DM with hypertension and hyperlipidemia. Results Positive correlation between levels of U - β2 - MG and indices as A1 β, IgG, al - MG, level of SCr and SBP was found. Within group DM, levels of U - β2 - MG had an significantly positive correlation with levels of CHO、HDL、BUN, while showing negative correlation with GFR. In the group of DM with hypertension, there was a positive correlation with levels of U - β2 - MG and those of SBP,CHO,LDL, SCr, and a negative correlation with GFR . In the last group, there was an significantly positive correlation between levels of U - β2 -MG and DBP, LDL, BUN, and still a negative correlation with level of U - β2 - MG and GFR. Conclusions Damage of Tubule interstitial is easily found in DN patients. U - β2 - MG was negatively correlated with GFR, indicating that U - β2 - MG has already increased when GFR slightly decreased. The produce of U - β2 - MG is closely related to the level of blood glucose ,blood pressure, and lipid level. U - β2 - MG was significantly associated with CHO, LDL - C, SCr, which showed that early active control of blood lipid might have positive effects on the prognosis of DN, especially in aspect of avoiding renal tubular damage.%目的 探讨2型糖尿病肾病患者尿β2微球蛋白(U-β2-MG)的相关因素及临床意义.方法 收集DN患者171例,并分析U-β2-MG与临床各观察指标的相关性.进一步将患者分为单纯糖尿病、糖尿病合并高血压病、糖尿病合并高血压和高脂血症三组再进行相关分析.结果

  19. Homozygous SLC2A9 mutations cause severe renal hypouricemia.

    Science.gov (United States)

    Dinour, Dganit; Gray, Nicola K; Campbell, Susan; Shu, Xinhua; Sawyer, Lindsay; Richardson, William; Rechavi, Gideon; Amariglio, Ninette; Ganon, Liat; Sela, Ben-Ami; Bahat, Hilla; Goldman, Michael; Weissgarten, Joshua; Millar, Michael R; Wright, Alan F; Holtzman, Eliezer J

    2010-01-01

    Hereditary hypouricemia may result from mutations in the renal tubular uric acid transporter URAT1. Whether mutation of other uric acid transporters produces a similar phenotype is unknown. We studied two families who had severe hereditary hypouricemia and did not have a URAT1 defect. We performed a genome-wide homozygosity screen and linkage analysis and identified the candidate gene SLC2A9, which encodes the glucose transporter 9 (GLUT9). Both families had homozygous SLC2A9 mutations: A missense mutation (L75R) in six affected members of one family and a 36-kb deletion, resulting in a truncated protein, in the other. In vitro, the L75R mutation dramatically impaired transport of uric acid. The mean concentration of serum uric acid of seven homozygous individuals was 0.17 +/- 0.2 mg/dl, and all had a fractional excretion of uric acid >150%. Three individuals had nephrolithiasis, and three had a history of exercise-induced acute renal failure. In conclusion, homozygous loss-of-function mutations of GLUT9 cause a total defect of uric acid absorption, leading to severe renal hypouricemia complicated by nephrolithiasis and exercise-induced acute renal failure. In addition to clarifying renal handling of uric acid, our findings may provide a better understanding of the pathophysiology of acute renal failure, nephrolithiasis, hyperuricemia, and gout.

  20. Kollektiv Handling

    DEFF Research Database (Denmark)

    Toubøl, Jonas

    2012-01-01

    Boganmeldelse af Flemming Ibsen, Laust Høgedahl & Steen Sheuer: Kollektiv Handling. Faglig organisering og skift af fagforening. Nyt fra Samfundsvidenskaberne, Frederiksberg, 2012.......Boganmeldelse af Flemming Ibsen, Laust Høgedahl & Steen Sheuer: Kollektiv Handling. Faglig organisering og skift af fagforening. Nyt fra Samfundsvidenskaberne, Frederiksberg, 2012....

  1. Insuficiencia renal aguda.

    OpenAIRE

    Carlos Hernán Mejía

    2009-01-01

    Acute renal failure (ARF) is a clinic syndrome characterized by decline in renal function occurring over a short time period. Is a relatively common complication in hospitalized critically ill patients and is associated with high morbidity and mortality. ARF has often a multi-factorial etiology syndrome usually approached diagnostically as pre-renal, post-renal, or intrinsic ARF. Most intrinsic ARF is caused by ischemia or nephrotoxins and is classically associated with acute tubular necrosis...

  2. 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.

  3. Acute renal injury and tubular acidosis caused by intravenous voriconazole%静脉应用伏立康唑致急性肾损伤及肾小管性酸中毒

    Institute of Scientific and Technical Information of China (English)

    周晓明; 陈愉; 冯学威; 赵立

    2012-01-01

    1例80岁男性患者因术后感染给予亚胺培南西司他汀钠、万古霉素、卡泊芬净、米卡芬净及美罗培南,效果不佳,后治疗改为联用美罗培南1.0 g,1次/8 h静脉滴注及伏立康唑200 mg(首日剂量400 mg,1次/12 h),1次/12 h静脉滴注.第5~9天,实验室检查示血清肌酐(SCr)154~208 μmol/L,尿素氮(BUN)24.3~35.9 mmol/L,血清胱抑素C 4.54~5.44 mg/L;血pH值7.18~7.34,氯离子122~130 mmol/L,钾离子3.4~4.1 mmol/L,标准碳酸氢盐波动于12~15 mmol/L,实际碳酸氢盐 13~14 mmol/L,阴离子间隙13~14 mmol/L.尿分析示红细胞3.8~4.8个/HP,蛋白±,pH值保持在5.5.诊断为肾小管性酸中毒、急性肾损伤.第9天,伏立康唑用法改为每晨静脉滴注200 mg,每晚鼻饲给药200 mg.调整用法后第3天患者出现高氯性酸中毒、低钾血症,第11天停用伏立康唑,美罗培南继续应用.停药2 d后,患者血清SCr及BUN水平升至最高,分别达282 μmol/L及49.4 mmol/L,随后逐渐降低,分别于停药后第25天和停药后34天降至正常,血气分析各项指标于停药后第25天基本恢复正常.%An 80-year-old male; patient was given imipenem/cilastatin, vancomycin, caspofungin, micafungin, and meropenem for post-operative infections, but these had no effect. The treatment was then switched to an IV infusion of meropenem 1. 0 g every 8 hours combined with an IV infusion of voriconazole 400 mg every 12 hours on the first day followed by 200 mg every 12 hours. On days 5-9 of treatment, the laboratory tests showed the following levels; serum creatine ( SCr ) 154-208 (xmol/L, blood urea nitrogen ( BUN ) 24.3-35.9 mmol/L, serum cystatin C 4. 54-5.44 mg/L, blood pH 7. 18-7. 34, Cl" 122-130 mmol/L, K*3.4-4. 1 mmol/L, standard bicarbonate 12-15 mmol/L, actual bicarbonate 13-14 mmol/L,anion gap 13-14 mmol/L. Urinalysis revealed the following levels; RBC connt 3. 8-4. 8 cells/HP, protein ?, and pH 5. 5. Acute renal tubular acidosis and acute renal injury were

  4. Urinary proteins of tubular origin: basic immunochemical and clinical aspects.

    Science.gov (United States)

    Scherberich, J E

    1990-01-01

    A variety of tubular marker proteins, as compared to healthy controls, are excreted at an increased rate in the urine of patients with renal damage. Beside cytoplasmic glutathione-S-transferase and lysosomal beta-N-acetyl-glucosaminidase (beta-NAG) the majority of kidney-related urine proteins derives from membrane surface components of the most vulnerable proximal tubule epithelia, among them ala-(leu-gly)-aminopeptidase, gamma-glutamyl transpeptidase (GGT), the tubular portion of angiotensinase A, the major brush border glycoprotein 'SGP-240' and adenosine-deaminase-binding protein. Urinary tissue proteins, e.g. brush border (BB) microvilli, are immunologically identical with those antigens prepared from cell membranes of the human kidney itself. BB antigens are shed into the urine of patients with glomerulonephritis, interstitial nephritis, systemic diseases, e.g. systemic lupus erythematosus (SLE), diabetes mellitus and multiple myeloma, arterial hypertension, infectious diseases (malaria, AIDS) and after operations, renal grafting and administration of X-ray contrast media, aminoglycosides or certain cytostatics (cis-platinum). Tissue proteinuria of tubular proteins is determined by enzyme-kinetic or quantitative immunological assays applying either poly- or monoclonal antikidney antibodies. Clinical, ultrastructural and histochemical studies support the idea that both 'soluble' and high-molecular-weight membrane particles (vacuolar blebs, greater than 10(6) dalton) as well as microfilamental components of the epithelial cytoskeleton contribute to tubular 'histuria' which appears as a sensitive parameter in monitoring tubular damage under clinical conditions at a very early phase.

  5. Markers of tubular dysfunction.

    Science.gov (United States)

    Piscator, M

    1989-03-01

    Since the first description of tubular proteinuria in 1958, much progress has been made with regard to diagnostic means for detecting small changes in the function of the proximal tubule. Small increases in the excretion of low-molecular-weight proteins can now be determined with great accuracy. Determination of total protein is an economic way of screening large populations but does not give specific information on the type of damage. Determinations of glucose, phosphate and amino acids are relatively insensitive methods, since their excretion is also dependent on diet and nutritional status. Determination of high-molecular-weight enzymes released from damaged tubular cells may be of use for studies of acute as well as chronic effects of nephrotoxic agents, but more data are needed.

  6. Maternal drugs and neonatal renal failure

    Directory of Open Access Journals (Sweden)

    M Sahay

    2014-01-01

    Full Text Available Maternal use of drugs during pregnancy may cause irreversible renal failure in the newborn. This report highlights the adverse effect of telmisartan during the last trimester of pregnancy. The neonate presented with oliguric renal failure and the renal histology showed proximal tubular dysgenesis.

  7. 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.

  8. Macrophage Chemotaxis in Anti-tubular Basement Membrane-Induced Interstitial Nephritis in Guinea Pigs

    NARCIS (Netherlands)

    Kennedy, Thomas L.; Merrow, Martha; Phillips, S. Michael; Norman, Michael; Neilson, Eric G.

    1985-01-01

    Interstitial renal lesions containing T cells and macrophages develop after 14 days in guinea pigs immunized to produce anti-tubular basement membrane-induced interstitial nephritis. We serially examined the renal venous and systemic arterial sera from such animals to determine if chemotactic factor

  9. Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis

    NARCIS (Netherlands)

    Gonzalez, Julien; Mouttalib, Sofia; Delage, Christine; Calise, Denis; Maoret, Jean-Jose; Pradere, Jean-Philippe; Klein, Julie; Buffin-Meyer, Benedicte; Van der Veen, Betty; Charo, Israel F.; Heeringa, Peter; Duchene, Johan; Bascands, Jean-Loup; Schanstra, Joost-Peter

    2013-01-01

    Most end-stage renal disease kidneys display accumulation of extracellular matrix (ECM) in the renal tubular compartment (tubular interstitial fibrosis - TIF) which is strongly correlated with the future loss of renal function. Although inflammation is a key event in the development of TIF, it can a

  10. 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。

  11. 阿德福韦酯致肾小管酸中毒并低磷骨软化症3例临床分析%Renal tubular acidosis and secondary hypophosphatemic osteomalacia caused by adefovir dipivoxil: 3 cases report

    Institute of Scientific and Technical Information of China (English)

    吴丹; 巴建明; 谷伟军; 金楠; 杨国庆; 母义明; 窦京涛; 吕朝晖

    2012-01-01

    Objective To analyze the clinical characteristics and treatment of 3 patients with renal tubular acidosis ( RTA ) and secondary hypophosphatemic osteomalacia caused by adefovir dipivoxil, and to raise awareness of renal tubular dysfunction caused by adefovir dipivoxil. Methods The clinical data and treatment of 3 patients with RTA and hypophosphatemic osteomalacia caused by adefovir dipivoxil were reviewed and summarized. Results Three patients were hospitalized with the chief complaint of progressive systemic aggravation of bone pain. When they came to our hospital, they all lied in bed and could hardly walk. Laboratory tests showed acidic blood ( pH = 7. 329 - 7. 381 ), alkaline urine ( pH = 6. 5 - 8. 0 ), hypophosphatemia ( 0. 42 - 0. 68 mmol/L ), hypokalemia ( 3. 08 - 3. 5mmol/L ), higher level of alkaline phosphatase ( 185. 1 - 247. 7U/L ), and normal serum calcium and PTH. They all had osteoporosis. Case 1 was diagnosed as renal tubular acidosis, and case 2 and case 3 were diagnosed as Fanconi syndrome because they had glycosuria, proteinuria, and aminoaciduria. All the 3 patients had secondary hypophosphatemic osteomalacia. According to their medical history, laboratory tests, and the history of long-term oral administration of adefovir dipivoxil, we considered that the injury of renal tubular was caused by adefovir dipivoxil. The initial treatment was to withdraw adefovir dipivoxil and to use other antivirals instead.Effective managements including the supplementation of neutral phosphorus mixture, active vitamin D, potassium citrate, and sodium bicarbonate were given according to the different biochemical abnormality. The follow-up showed that their clinical symptoms ameliorated significantly, and bone pain relieved. They could walk without any help. The biochemical indicators gradually returned to normal. Conclusion Impairment of renal function during the treatment of adfovir dipivoxil for patients with hepatitis B is not rare in clinical practice. Renal

  12. 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

  13. Drug-induced renal disease.

    Science.gov (United States)

    Curtis, J R

    1979-11-01

    The clinical manifestations of drug-induced renal disease may include all the manifestations attributed to natural or spontaneous renal diseases such as acute renal failure, chronic renal failure, acute nephritic syndrome, renal colic, haematuria, selective tubular defects, obstructive nephropathy, etc. It is therefore vital in any patient with renal disease whatever the clinical manifestations might be, to obtain a meticulous drug and toxin inventory. Withdrawal of the offending drug may result in amelioration or cure of the renal disorder although in the case of severe renal failure it may be necessary to utilise haemodialysis or peritoneal dialysis to tide the patient over the period of acute renal failure. Analgesic nephropathy is an important cause of terminal chronic renal failure and it is therefore vital to make the diagnosis as early as possible. The pathogenesis of some drug-induced renal disorders appears to be immunologically mediated. There are many other pathogenetic mechanisms involved in drug-induced renal disorders and some drugs may under appropriate circumstances be responsible for a variety of different nephrotoxic effects. For example, the sulphonamides have been incriminated in examples of crystalluria, acute interstitial nephritis, acute tubular necrosis, generalised hypersensitivity reactions, polyarteritis nodosa and drug-induced lupus erythematosus.

  14. Tubular Injury in a Rat Model of Type 2 Diabetes Is Prevented by Metformin

    OpenAIRE

    Takiyama, Yumi; Harumi, Tatsuo; Watanabe, Jun; Fujita, Yukihiro; Honjo, Jun; Shimizu, Norihiko; Makino, Yuichi; Haneda, Masakazu

    2011-01-01

    OBJECTIVE Chronic hypoxia has been recognized as a key regulator in renal tubulointerstitial fibrosis, as seen in diabetic nephropathy, which is associated with the activation of hypoxia-inducible factor (HIF)-1α. We assess here the effects of the biguanide, metformin, on the expression of HIF-1α in diabetic nephropathy using renal proximal tubular cells and type 2 diabetic rats. RESEARCH DESIGN AND METHODS We explored the effects of metformin on the expression of HIF-1α using human renal pro...

  15. 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.``

  16. 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.

  17. Management of renal disease in pregnancy.

    Science.gov (United States)

    Podymow, Tiina; August, Phyllis; Akbari, Ayub

    2010-06-01

    Although renal disease in pregnancy is uncommon, it poses considerable risk to maternal and fetal health. This article discusses renal physiology and assessment of renal function in pregnancy and the effect of pregnancy on renal disease in patients with diabetes, lupus, chronic glomerulonephritis, polycystic kidney disease, and chronic pyelonephritis. Renal diseases occasionally present for the first time in pregnancy, and diagnoses of glomerulonephritis, acute tubular necrosis, hemolytic uremic syndrome, and acute fatty liver of pregnancy are described. Finally, therapy of end-stage renal disease in pregnancy, dialysis, and renal transplantation are reviewed.

  18. 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.

  19. Cystinosis (ctns) zebrafish mutant shows pronephric glomerular and tubular dysfunction

    Science.gov (United States)

    Elmonem, Mohamed A.; Khalil, Ramzi; Khodaparast, Ladan; Khodaparast, Laleh; Arcolino, Fanny O.; Morgan, Joseph; Pastore, Anna; Tylzanowski, Przemko; Ny, Annelii; Lowe, Martin; de Witte, Peter A.; Baelde, Hans J.; van den Heuvel, Lambertus P.; Levtchenko, Elena

    2017-01-01

    The human ubiquitous protein cystinosin is responsible for transporting the disulphide amino acid cystine from the lysosomal compartment into the cytosol. In humans, Pathogenic mutations of CTNS lead to defective cystinosin function, intralysosomal cystine accumulation and the development of cystinosis. Kidneys are initially affected with generalized proximal tubular dysfunction (renal Fanconi syndrome), then the disease rapidly affects glomeruli and progresses towards end stage renal failure and multiple organ dysfunction. Animal models of cystinosis are limited, with only a Ctns knockout mouse reported, showing cystine accumulation and late signs of tubular dysfunction but lacking the glomerular phenotype. We established and characterized a mutant zebrafish model with a homozygous nonsense mutation (c.706 C > T; p.Q236X) in exon 8 of ctns. Cystinotic mutant larvae showed cystine accumulation, delayed development, and signs of pronephric glomerular and tubular dysfunction mimicking the early phenotype of human cystinotic patients. Furthermore, cystinotic larvae showed a significantly increased rate of apoptosis that could be ameliorated with cysteamine, the human cystine depleting therapy. Our data demonstrate that, ctns gene is essential for zebrafish pronephric podocyte and proximal tubular function and that the ctns-mutant can be used for studying the disease pathogenic mechanisms and for testing novel therapies for cystinosis. PMID:28198397

  20. 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

  1. 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.

  2. Renal involvement in antiphospholipid syndrome.

    Science.gov (United States)

    Pons-Estel, Guillermo J; Cervera, Ricard

    2014-02-01

    Renal involvement can be a serious problem for patients with antiphospholipid syndrome (APS). However, this complication has been poorly recognized and studied. It can be present in patients who have either primary or systemic lupus erythematosus-associated APS. Clinical and laboratory features of renal involvement in APS include hypertension, hematuria, acute renal failure, and progressive chronic renal insufficiency with mild levels of proteinuria that can progress to nephrotic-range proteinuria. The main lesions are renal artery stenosis, venous renal thrombosis, and glomerular lesions (APS nephropathy) that may be acute (thrombotic microangiopathy) and/or chronic (arteriosclerosis, arterial fibrous intimal hyperplasia, tubular thyroidization, arteriolar occlusions, and focal cortical atrophy). APS can also cause end-stage renal disease and allograft vascular thrombosis. This article reviews the range of renal abnormalities associated with APS, and their diagnosis and treatment options.

  3. Renal tubule cell repair following acute renal injury.

    Science.gov (United States)

    Humes, H D; Lake, E W; Liu, S

    1995-01-01

    Experimental data suggests the recovery of renal function after ischemic or nephrotoxic acute renal failure is due to a replicative repair process dependent upon predominantly paracrine release of growth factors. These growth factors promote renal proximal tubule cell proliferation and a differentiation phase dependent on the interaction between tubule cells and basement membrane. These insights identify the molecular basis of renal repair and ischemic and nephrotoxic acute renal failure, and may lead to potential therapeutic modalities that accelerate renal repair and lessen the morbidity and mortality associated with these renal disease processes. In this regard, there is a prominent vasoconstrictor response of the renal vasculature during the postischemic period of developing acute renal failure. The intravenous administration of pharmacologic doses of atrial natriuretic factor (ANF) in the postischemic period have proven efficacious by altering renal vascular resistance, so that renal blood flow and glomerular filtration rate improve. ANF also appears to protect renal tubular epithelial integrity and holds significant promise as a therapeutic agent in acute renal failure. Of equal or greater promise are the therapeutic interventions targeting the proliferative reparative zone during the postischemic period. The exogenous administration of epidermal growth factor or insulin-like growth factor-1 in the postischemic period have effectively decreased the degree of renal insufficiency as measured by the peak serum creatinine and has hastened renal recovery as measured by the duration of time required to return the baseline serum creatinine values. A similarly efficacious role for hepatocyte growth factor has also been recently demonstrated.

  4. 急性缺糖缺氧通过增强胆碱酯酶表达促进肾小管细胞的炎性损伤%Acute oxygen and glucose deprivation promotes inflammatory injury of renal tubular cells by enhancing the expression of cholinesterase

    Institute of Scientific and Technical Information of China (English)

    吴明; 吴乐锋; 李明利; 陆俊福; 赖凯; 徐迹; 刘芬; 冯永文

    2016-01-01

    Objective To investigate the injury mechanism of renal tubular cells induced by acute oxygen and glucose depri-vation. Methods Isolation and culture of rat kidney macrophages and renal epithelial cells,constructing co-cultivating model of lacking Oxygen and sugar(Oxygen and glucose deprivation,OGD),Cells were devided into control group and OGD group,and were given OGD treatment for 1 hour,and then carried out normal culture for up to 24 hours in each group. the expression of TNF al-pha,IL-1 beta,IL-10 in supernatant fluid was detected by ELISA,the viability of renal tubular cells was determined by MTT,the expression of mRNA and protein of acetylcholine esterase (AChE) were determined by RT-qPCR and Western Blot respectively. Results The levels of TNF alpha (pg/ml) in the supernatant fluid in cultivation system were (231.67±36.28) in control group VS (428.67±43.16)(P<0.05) in OGD group,the levels of IL-1β (pg/ml) were (116.67±21.64) in control group VS (219.63±43.86) in OGD group(P<0.05),the levels of IL-10 (pg/ml) were (235.67±39.35) in control group VS (432.67±49.72) in OGD group (P<0. 01). The viability of renal tubular cells was (88.41±18.25) VS (46.98±13.87)(P<0.01);The levels of mRNA and protein of AChE in OGD group were higher than those in control group,they were raised (3.82±0.73) and (2.17±0.46) times respectively (P<0.01). Conclusion Acute oxygen and glucose deprivation enhances the expression of cholinesterase in renal macrophages ,the acute in-jury of renal tubular cells induced by OGD was mediated through inflammatory mediators.%目的:探讨急性缺糖缺氧导致肾小管细胞损伤的机制。方法分离培养大鼠肾内巨噬细胞、肾小管上皮细胞,构建两者共培养(transwell)模型,细胞分成对照组及缺糖缺氧(Oxygen and glucose deprivation,OGD)组,给予缺糖缺氧处理细胞1h后再正常培养24h,ELISA法检测两组上清液TNF-α,IL-1β和IL-10的浓度,噻唑蓝(MTT)检测肾小

  5. 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

  6. 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.

  7. Tubular organ epithelialisation

    Directory of Open Access Journals (Sweden)

    Rhea Saksena

    2016-12-01

    Full Text Available Hollow, tubular organs including oesophagus, trachea, stomach, intestine, bladder and urethra may require repair or replacement due to disease. Current treatment is considered an unmet clinical need, and tissue engineering strategies aim to overcome these by fabricating synthetic constructs as tissue replacements. Smart, functionalised synthetic materials can act as a scaffold base of an organ and multiple cell types, including stem cells can be used to repopulate these scaffolds to replace or repair the damaged or diseased organs. Epithelial cells have not yet completely shown to have efficacious cell–scaffold interactions or good functionality in artificial organs, thus limiting the success of tissue-engineered grafts. Epithelial cells play an essential part of respective organs to maintain their function. Without successful epithelialisation, hollow organs are liable to stenosis, collapse, extensive fibrosis and infection that limit patency. It is clear that the source of cells and physicochemical properties of scaffolds determine the successful epithelialisation. This article presents a review of tissue engineering studies on oesophagus, trachea, stomach, small intestine, bladder and urethral constructs conducted to actualise epithelialised grafts.

  8. 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.

  9. [Renal toxicity of antiviral drugs].

    Science.gov (United States)

    Frasca', Giovanni M; Balestra, Emilio; Tavio, Marcello; Morroni, Manrico; Manarini, Gloria; Brigante, Fabiana

    2012-01-01

    Highly effective and powerful antiviral drugs have been introduced into clinical practice in recent years which are associated with an increased incidence of nephrotoxicity. The need of combining several drugs, the fragility of the patients treated, and the high susceptibility of the kidney are all factors contributing to renal injury. Many pathogenetic mechanisms are involved in the nephrotoxicity of antiviral drugs, including drug interaction with transport proteins in the tubular cell; direct cytotoxicity due to a high intracellular drug concentration; mitochondrial injury; and intrarenal obstruction or stone formation due to the low solubility of drugs at a normal urinary pH. As a result, various clinical pictures may be observed in patients treated with antiviral drugs, ranging from tubular dysfunction (Fanconi syndrome, renal tubular acidosis, nephrogenic diabetes insipidus) to acute renal failure (induced by tubular necrosis or crystal nephropathy) and kidney stones. Careful attention should be paid to prevent renal toxicity by evaluating the glomerular filtration rate before therapy and adjusting the drug dosage accordingly, avoiding the combination with other nephrotoxic drugs, and monitoring renal parameters on a regular basis while treating patients.

  10. Intervention in growth factor activated signaling pathways by renally targeted kinase inhibitors

    NARCIS (Netherlands)

    Fretz, Marjan M.; Dolman, M. E. (Emmy) M.; Lacombe, Marie; Prakash, Jai; Nguyen, Tri Q.; Goldschmeding, Roel; Pato, Janos; Storm, Gert; Hennink, Wim E.; Kok, Robbert J.

    2008-01-01

    Cell-specific targeting to renal tubular cells is an interesting approach to enhance the accumulation of drugs in the kidney. Low molecular weight proteins are rapidly filtered and extensively accumulate in proximal tubular cells. We therefore have used lysozyme (LZM,14 kDa) as a tubular

  11. Renal Expression and Urinary Excretion of Na-K-2Cl Cotransporter in Obstructive Nephropathy

    Directory of Open Access Journals (Sweden)

    Anabel Brandoni

    2017-01-01

    Full Text Available Renal damage due to urinary tract obstruction accounts for up to 30% of acute kidney injury in paediatrics and adults. Bilateral ureteral obstruction (BUO is associated with polyuria and reduced urinary concentrating capacity. We investigated the renal handling of water and electrolytes together with the renal expression and the urinary excretion of the Na-K-Cl cotransporter (NKCC2 after 1 (BUO-1, 2 (BUO-2, and 7 (BUO-7 days of release of BUO. Immunoblotting and immunohistochemical studies showed that NKCC2 expression was upregulated in apical membranes both from BUO-2 and from BUO-7 rats. The apical membrane expression, where NKCC2 is functional, may be sufficient to normalize water, potassium, sodium, and osmolytes tubular handling. NKCC2 abundance in homogenates and mRNA levels of NKCC2 was significantly decreased in almost all groups suggesting a decrease in the synthesis of the transporter. Urinary excretion of NKCC2 was increased in BUO-7 groups. These data suggest that the upregulation in the expression of NKCC2 in apical membranes during the postobstructive phase of BUO could contribute to improving the excretion of sodium and consequently also the excretion of potassium, osmolytes, and water. Moreover, the increase in urinary excretion of NKCC2 in BUO-7 group could be a potential additional biomarker of renal function recovery.

  12. 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.

  13. Handling Metalloproteinases.

    Science.gov (United States)

    Fridrich, Sven; Karmilin, Konstantin; Stöcker, Walter

    2016-02-02

    Substrate cleavage by metalloproteinases involves nucleophilic attack on the scissile peptide bond by a water molecule that is polarized by a catalytic metal, usually a zinc ion, and a general base, usually the carboxyl group of a glutamic acid side chain. The zinc ion is most often complexed by imidazole nitrogens of histidine side chains. This arrangement suggests that the physiological pH optimum of most metalloproteinases is in the neutral range. In addition to their catalytic metal ion, many metalloproteinases contain additional transition metal or alkaline earth ions, which are structurally important or modulate the catalytic activity. As a consequence, these enzymes are generally sensitive to metal chelators. Moreover, the catalytic metal can be displaced by adventitious metal ions from buffers or biological fluids, which may fundamentally alter the catalytic function. Therefore, handling, purification, and assaying of metalloproteinases require specific precautions to warrant their stability. Copyright © 2016 John Wiley & Sons, Inc.

  14. 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

  15. 高糖通过TGF-β1/Smad信号通路介导肾小管上皮细胞1型胶原合成的机制探讨%High glucose stimulate collagen Ⅰ synthesis in renal tubular epithelial cells via activated TGF-β/Smad signaling pathway

    Institute of Scientific and Technical Information of China (English)

    孙辽

    2008-01-01

    目的 探讨高糖对肾小管上皮细胞1型胶原(Collagen Ⅰ)合成影响的分子机制.结果 体外培养的大鼠近端肾小管上皮细胞(NRK52E细胞)分为四组:甘露醇组、高糖组、高糖+TGF-β1中和抗体组、高糖+IsG1对照组.ELISA法检测细胞培养上清中TGF-β1的浓度,细胞免疫化学结果 检测p-Smad2/3核表达水平,RT-PCR和Western blot结果 分别检测Collagen Ⅰ mRNA和蛋白的表达.结果 高糖以时间依赖方式上调Collagen Ⅰ mRNA表达.高糖刺激NRK52E细胞24 h和48 h后内源性TGF-β1合成明显增加,约为甘露醇对照组的3倍.与刺激前和甘露醇组比较,高糖刺激24 h可显著上调NRK52E细胞p-Smad2/3核表达水平(t=4.2,t=3.25,P<0.01).TGF-β1中和抗体能抑制高糖介导的p-Smad2/3核表达及Collagen Ⅰ蛋白的表达(t=3.12,t=3.02,P<0.01).结论 高糖通过TGF-β/Smad信号通路介导肾小管上皮细胞Collagen Ⅰ的合成.%Objective To investigate the molecular mechanisms that high glucose stimulate collagen Ⅰ synthesis in renal tubular epi-thelial cells. Methods Normal rat pwximal tubular epithelial (NRK52E) cells were cultured grown in RPMI-1640 medium and were divid-ed four groups: mannitol group, high glucose group, high glucose + neutralizing TGF-β1 antibody group, high glucose + IgG1 group. TGF-β1 in the supematant of cultured cells were measured by enzyme-linked immunosorbent assay (ELISA). Nuclear expression of p-Smad2/3 were examined by immunocytochemistry. Expression of collagen Ⅰ mRNA was detected by RT-PCR. Expression of collagen Ⅰ pro-tein was detected by Western blot. Results High glucose up-regulated the expression of collagen Ⅰ mRNA by time-dependent manor. Com-pared with mannitol group, high glucose markedly increased the level of TGF-β1 in supernatant of cultured cell after 24h and 48h and upreg-ulated p-Smad2/3 nuclear expression(t =4. 2, t = 3.25, P <0.01). Neutralizing TGF-β1 antibody inhibited high glucose- induced p-Smad2

  16. 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.

  17. Regulation of renal function and blood pressure control by P2 purinoceptors in the kidney.

    Science.gov (United States)

    Van Beusecum, Justin; Inscho, Edward W

    2015-04-01

    Kidneys are important regulators of extracellular fluid volume (ECFV) homeostasis. ECFV is a key regulatory component of long-term blood pressure control influenced by controlling tubular sodium transport. In recent decades, renal P2 purinoceptors (P2 receptors) have come to the forefront as a mechanism for regulating ECFV. P2 receptors are broadly distributed in renal tubular and vascular elements where they confer segmental control of renal vascular resistance, autoregulation, and tubular reabsorption. Activation or impairment of renal P2 purinoceptors is implicated in the regulating blood pressure or causing renal pathologies including hypertension. In this brief review, we discuss the role of renal vascular and tubular P2 purinoceptors in the regulation of renal hemodynamics, maintenance of ECFV, regulation of sodium reabsorption and the control of blood pressure.

  18. Tenofovir-related nephrotoxicity in human immunodeficiency virus-infected patients: three cases of renal failure, Fanconi syndrome, and nephrogenic diabetes insipidus.

    Science.gov (United States)

    Karras, Alexandre; Lafaurie, Matthieu; Furco, André; Bourgarit, Anne; Droz, Dominique; Sereni, Daniel; Legendre, Christophe; Martinez, Frank; Molina, Jean-Michel

    2003-04-15

    We report 3 cases of renal toxicity associated with use of the antiviral agent tenofovir. Renal failure, proximal tubular dysfunction, and nephrogenic diabetes insipidus were observed, and, in 2 cases, renal biopsy revealed severe tubular necrosis with characteristic nuclear changes. Patients receiving tenofovir must be monitored closely for early signs of tubulopathy (glycosuria, acidosis, mild increase in the plasma creatinine level, and proteinuria).

  19. 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

  20. 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

  1. 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.

  2. Intrarenal hemodynamics and impaired tubular functions in patients with systemic lupus erythematosus

    OpenAIRE

    A N Maksudova; Liya Aleksandrovna Khusnutdinova; I G Salikhov

    2010-01-01

    Objective. To identify intrarenal hemodynamic disorders in patients with systemic lupus erythematosus (SLE), to assess their prognostic role, and to reveal an association between tubular dysfunction and intraglomerular hemodynamics. Subjects and methods. Twenty-nine SLE patients, 86.2% of them were diagnosed as having a renal lesion, were examined. The levels of ethanolamine, uric acid, calcium, and phosphorus were determined in their daily urine and serum; the renal functional reserve (RF...

  3. 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.

  4. Renal Glycosuria without Hyperglycemia in Cyclosporine-Treated Rats

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    Chang Hwa Lee

    2012-06-01

    Conclusion: Glycosuria may occur without hyperglycemia in cyclosporine administration. We suggest that cyclosporine may decrease tubular reabsorption of glucose in renal tubular epithelial cells, and then glycosuria could be induced by the altered glucose transporter expressions. We will analyze the glucose transporters in proximal tubule of rat kidney.

  5. 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.

  6. 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.

  7. Renal dysfunctions in glomerulonephropathy with rapidly declined renal failure.

    Science.gov (United States)

    Futrakul, N; Pochanugool, C; Sitprija, V; Singkhwa, V; Futrakul, P; Yenrudi, S; Sensirivatana, R; Watana, D; Poshyachinda, M

    1996-07-01

    Eight patients aged between 5 and 26 years developed rapid deterioration of renal function and became oliguric/anuric with duration ranging from 1 to 21 days. The initial functional assessment revealed severe degree of glomerular, tubular, and vascular dysfunctions. The magnitude of renal dysfunction was quantified and expressed in terms of a clinical score. The degree of glomerular and tubular dysfunctions were inversely proportional to the renal plasma flow and peritubular capillary blood flow (PTCB), respectively. Similar findings have been observed in a variety of severe glomerulonephropathies. In this aspect, it is likely that the reduction of peritubular capillary blood flow and tubulointerstitial disease are interrelated. Further evidence to support the primary role of reduction of PTCB in inducing tubulointerstitial disease is provided by the following: (a) Reduction of PTCB is documented in mesangial proliferative nephrosis with steroid resistance prior to the detection of tubulointerstitial disease. (b) Ischemic insult can induce tubulointerstitial disease in experimental setting of renal artery occlusion in animal, (c) Improved tubular function can be achieved following the increase in PTCB with the enhanced renal perfusion therapy.

  8. 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.

  9. A Simple Tubular Reactor Experiment.

    Science.gov (United States)

    Hudgins, Robert R.; Cayrol, Bertrand

    1981-01-01

    Using the hydrolysis of crystal violet dye by sodium hydroxide as an example, the theory, apparatus, and procedure for a laboratory demonstration of tubular reactor behavior are described. The reaction presented can occur at room temperature and features a color change to reinforce measured results. (WB)

  10. Competition by meperidine for the organic cation renal excretory system.

    Science.gov (United States)

    Acara, M; Gessner, T; Trudnowski, R J

    1981-07-01

    Renal tubular excretory transport of meperidine was studied using the Sperber preparation in chickens. When urine samples from infused and uninfused kidneys were analyzed for meperidine by gas chromatography, meperidine was always present in greater amounts in the urine from the infused kidney, demonstrating active tubular excretion. Meperidine at an infusion rate of 1 mumole/min, also inhibited the excretion of the organic cations choline and acetylcholine, indicating occupation of the renal organic cation excretory system in the chicken.

  11. Renal hücreli karsinom tanılı bir olguda tekrarlayan hiperkalemi atakları

    OpenAIRE

    Alp, A.; Akdam, H; Ünsal, A; Uyanık, Ö; Ayhan, M; Çulhacı, N; Akar, H; Yeniçerioğlu, Y

    2014-01-01

    Hyperkalemia is one of the most urgent entities in clinical practice. The importance of hyperkalemia arises from its cardiovascular effects that can be mortal. Relapsing hyperkalemia is rare and usually associated with renal disorders. Renal tubular acidosis is one of them. Although Type 4 renal tubular acidosis is generally associated with diabetes mellitus, this entity also may accompanied by other disorders. Renal cell carcinoma is the most common type of kidney cancer in adults and recent...

  12. FISIOPATOLOGÍA DE LA INSUFICIENCIA RENAL AGUDA POR CISPLATINO

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    Rodriguez Macías EL

    2013-09-01

    Full Text Available Cisplatin is one of the major antineoplastic used for treatment of tumors such as testicular, ovarian, cervical, lung, bladder and head, among others. It has been described various types of toxicities induced by cisplatin, but the renal is the main one. This toxicity consist sof an acute reduction in renal plasma flow and a decline in glomerular filtration and installation of a tubular necrosis, with predominant involvement of the distal tubules and accumulation of cellular debris (lumen obstruction. Other mechanisms involved in renal injury are microangiopathy and pro-inflammatory mediators. We conclude that the nephrotoxicity caused by cisplatin can induce renal failure in which tubular structural damage predominates.

  13. Urinary tubular protein-based biomarkers in the rodent model of cisplatin nephrotoxicity: a comparative analysis of serum creatinine, renal histology, and urinary KIM-1, NGAL, and NAG in the initiation, maintenance, and recovery phases of acute kidney injury.

    Science.gov (United States)

    Sinha, Vikash; Vence, Luis M; Salahudeen, Abdulla K

    2013-03-01

    Several biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared. To compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI. Sprague-Dawley rats (300-350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed. A significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P CP to discern the time course and pattern of expression.

  14. 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.

  15. 原发性干燥综合征合并肾小管酸中毒并发骨软化症的临床特征及诊治%Clinical Manifestation and Diagnosis of Osteomalacia in Patients with Primary Sjgren's Syndrom and Renal Tubular Acidosis

    Institute of Scientific and Technical Information of China (English)

    李凤翱; 马中书; 邱明才; 韩红玲; 贾红蔚; 崔瑾; 汤绍芳; 戴晨琳; 高桦; 郑方遒; 朱梅

    2012-01-01

    Objective To summarize the clinical manifestations and treatment of osteomalacia in patients with primary Sjogren's Syndrom and renal tubular acidosis. Methods The clinical data of 20 patients suffered from this disease and admitted in our hospital from 2003 to 2008 were analyzed retrospectively. Results All these 20 patients experienced decayed tooth, tiredness, and boneache. Among them 15 patients had had thirsty feelings and 10 suffered from scheroma. According to the clinical manifestations, bone X - ray findings, and bone mineral density, these 20 patients were divided into severe bone disease group ( n = 10 ) and mild bone disease group ( n = 10 ). The comparison of rheumatic immunological index between these two groups concluded that the positive rates of SSA and SSB and the concentration of globulin in severe group were higher than those in mild group, although the difference was not statistically significant ( P > 0. 05 ). Antinuclear antibody, rheumatoid factor, andγglobulin in severe group were significantly higher than those in mild group ( P <0. 05 ). Infiltration of lympocytes and deposition of immunoglobulin complexes were found both in kidney and muscular biopsy tissues. Tiredness and boneache were resolved after treatment. Conclusion For osteomalacia caused by the combination of primary Sjogren's syndrome and renal tubular acidosis , active immunosuppressive treatment and supplementation of large - dose vitamin D in active form may be feasible in addition to conventional acidity correction and calcium supplementation,%目的 探讨原发性干燥综合征、肾小管酸中毒并发骨软化症的临床特点和治疗效果.方法 回顾性分析天津医科大学总医院内分泌科2003-2008年收治的20例原发性干燥综合征、肾小管酸中毒并发骨软化症患者的临床资料.结果 20例患者均有龋齿、乏力、骨痛,15例患者有口干症状,10例患者有眼干症状.依据临床表现、骨X线和骨密度检查结果,20

  16. 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

  17. Rupture of Renal Transplant

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    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.

  18. Intestinal absorption and renal reabsorption of calcium throughout postnatal development.

    Science.gov (United States)

    Beggs, Megan R; Alexander, R Todd

    2017-04-01

    Calcium is vital for many physiological functions including bone mineralization. Postnatal deposition of calcium into bone is greatest in infancy and continues through childhood and adolescence until peek mineral density is reached in early adulthood. Thereafter, bone mineral density remains static until it eventually declines in later life. A positive calcium balance, i.e. more calcium absorbed than excreted, is crucial to bone deposition during growth and thus to peek bone mineral density. Dietary calcium is absorbed from the intestine into the blood. It is then filtered by the renal glomerulus and either reabsorbed by the tubule or excreted in the urine. Calcium can be (re)absorbed across intestinal and renal epithelia via both transcellular and paracellular pathways. Current evidence suggests that significant intestinal and renal calcium transport changes occur throughout development. However, the molecular details of these alterations are incompletely delineated. Here we first briefly review the current model of calcium transport in the intestine and renal tubule in the adult. Then, we describe what is known with regard to calcium handling through postnatal development, and how alterations may aid in mediating a positive calcium balance. The role of transcellular and paracellular calcium transport pathways and the contribution of specific intestinal and tubular segments vary with age. However, the current literature highlights knowledge gaps in how specifically intestinal and renal calcium (re)absorption occurs early in postnatal development. Future research should clarify the specific changes in calcium transport throughout early postnatal development including mediators of these alterations enabling appropriate bone mineralization. Impact statement This mini review outlines the current state of knowledge pertaining to the molecules and mechanisms maintaining a positive calcium balance throughout postnatal development. This process is essential to achieving

  19. 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

  20. 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

  1. Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease.

    Directory of Open Access Journals (Sweden)

    Shunsaku Nakagawa

    Full Text Available In chronic kidney disease (CKD, progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1, lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL, SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.

  2. Early detection of tubular dysfunction.

    Science.gov (United States)

    Piscator, M

    1991-11-01

    The determination of low-molecular-weight proteins in urine as a tool for early detection of damage to the proximal tubules is briefly discussed. Beta 2-microglobulin, retinol-binding protein and alpha 1-microglobulin are at present the most widely used markers for tubular dysfunction. The determination of beta 2-microglobulin has earlier been the method of choice, but due to its instability at low pH there are certain disadvantages. Available data indicate that alpha 1-microglobulin may replace beta 2-microglobulin for screening purposes. The low-molecular-weight proteins are at present the best markers for early detection of tubular dysfunction; other constituents are not as well suited for this, even if the determination of urine enzymes has its supporters.

  3. Miopatias associadas a agregados tubulares

    Directory of Open Access Journals (Sweden)

    Mary Souza Carvalho

    1993-09-01

    Full Text Available Os autores relatam a caso de paciente de 58 anos de idade do sexo masculino, com quadro de características miastênicas tanto clínica como eletromiograficamente, no qual a biópsia muscular com histoquímica e microscopia eletrônica permitiu fazer o diagnostico de miopatia associada a agregados tubulares. É chamada a atenção para o fato de que as alterações anátomo-patológicas encontradas podem estar presentes em um grupo heterogêneo de pacientes com grande variedade de sintomas, não havendo portanto motivo para considerar-se a existência de uma miopatia com agregados tubulares, já que os achados anátomo-patológicos são inespecíficos e não configuram moléstia específica.

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Expression of renal cubilin and its potential role in tubulointerstitial inflammation induced by albumin overload

    Institute of Scientific and Technical Information of China (English)

    Jurong YANG; Yani HE; Haiying SHEN; Hanlu DING; Kailong LI; Huiming WANG

    2008-01-01

    cubilin nucleotide markedly reduced expression of MCP-1 and RANTES. Cubilin was required for handling a greater amount of protein in nephrotic status and albumin-induced production of MCP-1 and RANTES by renal tubular cells, which further initiated tubulointerstitial inflammation in proteinuric disease.

  6. Isolation and characterization of a primary proximal tubular epithelial cell model from human kidney by CD10/CD13 double labeling.

    Directory of Open Access Journals (Sweden)

    Cynthia Van der Hauwaert

    Full Text Available Renal proximal tubular epithelial cells play a central role in renal physiology and are among the cell types most sensitive to ischemia and xenobiotic nephrotoxicity. In order to investigate the molecular and cellular mechanisms underlying the pathophysiology of kidney injuries, a stable and well-characterized primary culture model of proximal tubular cells is required. An existing model of proximal tubular cells is hampered by the cellular heterogeneity of kidney; a method based on cell sorting for specific markers must therefore be developed. In this study, we present a primary culture model based on the mechanical and enzymatic dissociation of healthy tissue obtained from nephrectomy specimens. Renal epithelial cells were sorted using co-labeling for CD10 and CD13, two renal proximal tubular epithelial markers, by flow cytometry. Their purity, phenotypic stability and functional properties were evaluated over several passages. Our results demonstrate that CD10/CD13 double-positive cells constitute a pure, functional and stable proximal tubular epithelial cell population that displays proximal tubule markers and epithelial characteristics over the long term, whereas cells positive for either CD10 or CD13 alone appear to be heterogeneous. In conclusion, this study describes a method for establishing a robust renal proximal tubular epithelial cell model suitable for further experimentation.

  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. 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 phosphodies......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......). LPS-induced fall in GFR and proximal tubular outflow were sustained on day 2. Furthermore, LPS-treated rats showed a marked increase in fractional distal water excretion, despite significantly elevated levels of plasma vasopressin (AVP). Semiquantitative immunoblotting showed that LPS increased......-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...

  9. Ciprofloxacin-Induced Renal Failure

    Directory of Open Access Journals (Sweden)

    Audra Fuller

    2015-10-01

    Full Text Available Acute renal failure (ARF is a common diagnosis in hospitalized patients, particularly in intensive care units (ICU. Determining the cause and contributing factors associated with ARF is crucial during treatment. The etiology is complex, and several factors often contribute to its development. Medications can cause acute tubular necrosis, acute interstitial nephritis, and crystal-induced or post-obstructive nephropathy. There have been several case reports of ARF secondary to fluoroquinolones. Here we report the development of acute renal failure within a few days of initiating oral ciprofloxacin therapy and briefly describe the different types of renal failure secondary to fluoroquinolone administration. Clinical studies demonstrate that using fluoroquinolones with other potentially nephrotoxic medications requires monitoring of renal function to limit the renal toxicity with these medications. Also, the risk-benefit profile of patients requiring fluoroquinolones should be considered.

  10. Effects of receptor-mediated endocytosis and tubular protein composition on volume retention in experimental glomerulonephritis

    DEFF Research Database (Denmark)

    Kastner, Christian; Pohl, Marcus; Sendeski, Mauricio

    2009-01-01

    Human glomerulonephritis (GN) is characterized by sustained proteinuria, sodium retention, hypertension, and edema formation. Increasing quantities of filtered protein enter the renal tubule, where they may alter epithelial transport functions. Exaggerated endocytosis and consequent protein overl...... mechanism of channel activation which may involve the action of filtered plasma proteases....... and channels involved in volume regulation were altered in GN, and 2) proximal tubular endocytosis may influence locally as well as downstream expressed tubular transporters and channels. Effects of anti-glomerular basement membrane GN were studied in controls and megalin-deficient mice with blunted proximal...

  11. 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

  12. Citrato y litiasis renal

    OpenAIRE

    2013-01-01

    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 rena...

  13. Effects of different concentrations of hydroxyethyl starch 130/0.4 applied for different time periods on injury to human renal tubular epithelial cells%不同浓度和时间应用羟乙基淀粉130/0.4对人肾小管上皮细胞损伤的影响

    Institute of Scientific and Technical Information of China (English)

    邵芹; 段满林; 李仁奇; 王琛

    2015-01-01

    Objective To evaluate the effects of different concentrations of hydroxyethyl starch (HES) 130/0.4 applied for different time periods on injury to human renal tubular epithelial cells.Methods Human renal kidney epithelial cells HK-2 at the logarithmic growth phase were seeded in 96-well plates at a density of 1 × 105 cells/ml (0.1 ml/well),in culture flasks (5 ml/flask) or in cluture dishes (5 ml/dish).HK-2 cells were randomly divided into 4 groups (n=49 each) using a random number table:control group (group C) and 0.3%,1.5% and 3.0% HES 130/0.4 groups (H1,H2 and H3 groups).In H1,H2 and H3 groups,HK-2 cells were incubated with 0.3%,1.5% and 3.0% HES 130/0.4,respectively.The equal volume of PBS was added to the culture medium in group C.At day 1,3,5 and 7 of incubation,the cell viability was measured.At day 3,5 and 7 of incubation,cell apoptosis was detected,and apoptosis rate was calculated.On day 7 of incubation,the cells were stained with toluidine blue for examination of intracellular HES deposition (under light microscope) and pathological changes (with transmission electron microscope).Results Compared with group C,the cell viability was significantly decreased on day 5 and 7 of incubation,and apoptosis rate was increased on day 3,5 and 7 of incubation in group H3,and no significant difference was detected in the parameters mentioned above in H1 and H2 groups.Microscopic examination showed that intracellular HES deposition was observed in H2 and H3 groups,and pathological changes were obvious,and apoptotic cells were also found in H3 group.Conclusion Application of high-concentration HES 130/0.4 for a long period can lead to injury to human renal tubular epithelial cells,however,application of high-or low-concentration HES 130/0.4 for a short period produces no influence on the cells.%目的 评价不同浓度和时间应用羟乙基淀粉130/0.4(HES 130/0.4)对人肾小管上皮细胞损伤的影响.方法 人肾小管上皮细胞HK-2细胞

  14. IgA肾病患者肾小管中P-gp表达与肾脏病理及肾功能损害的相关性%The effects of renal tubular P-gp expression on pathological lesion and renal function in IgA nephropathy

    Institute of Scientific and Technical Information of China (English)

    杨汝春; 王永钧; 鲁盈; 厉春萍; 朱晓玲

    2011-01-01

    Objective To explore the effects of P- glycoprotein (P- gp) expression in renal tubules on renal pathological lesion and renal function in progression of Ig Anephropathy (IgAN). Methods One hungdred and eighty eight(188) patients with primary IgAN diagnosed by renal biopsy were studied. Clinical data, including age, sex; serum creatinine level (Scr), creatinine clearance rate (Ccr), 24h urinary excretion of protien(24hUP) and Blood urea nitrogen(BUN) were detected before renal biopsy. The assessment of renal pathological lesion was according to Lee SM and Katafuchi semiquantitative scoring system. Immuno-histochemistry was performed to detect the expression of P- gp in nephridial tissue. The relationship between P- gp expressions and Scr, Ccr, 24hUP, BUN, or pathological lesion semiquantitative scores were analyzed. Results P- gp expression level in kidney of IgAN patients showed statistically significant negative correlations with Ccr, and significant negative correlations with 24hUP, Scr, BUN and pathological lesion semiquantitative scores. Conclusion P- gp expression and transport Mediated by P- gp possibly participate in protecting renal function and preventing progression ofkidney pathological injury.%目的 通过对IgA肾病肾小管中P-糖蛋白(P-glycoprotein,P-gp)表达与肾脏病理损害相关性的研究,探讨肾小管功能及其损伤在IgA肾病进展中的作用的关系.方法以经肾活检诊断的188例原发性IgA肾病患者为研究对象,肾活检前检查患者24h尿蛋白(24hUP)、肌酐清除率(Ccr)、血肌(Scr)、尿素氮(BuN)等.肾脏病理损害主要参考Lee分级、Katafuchi半定量积分标准和Andreoli病理活动性/慢性指数评分标准.采用免疫组化方法测定肾组织中P-gp表达,统计分析肾小管P-gp蛋白表达与肾脏病理损害积分以及患者肾功能的相关性.结果 IgA肾病肾小管中P-gp表达与肾脏病理损害Lee分级和Katafuchi半定量积分均呈显著负相关,P-gp与肾小

  15. Miopatias associadas a agregados tubulares

    OpenAIRE

    Mary Souza Carvalho; Lusvarghi,Edgard S.; Ângela Lobo F. Levy; Paulo N. Borsoi Salum; Consuelo J. Rodrigues; José Antonio Levy

    1993-01-01

    Os autores relatam a caso de paciente de 58 anos de idade do sexo masculino, com quadro de características miastênicas tanto clínica como eletromiograficamente, no qual a biópsia muscular com histoquímica e microscopia eletrônica permitiu fazer o diagnostico de miopatia associada a agregados tubulares. É chamada a atenção para o fato de que as alterações anátomo-patológicas encontradas podem estar presentes em um grupo heterogêneo de pacientes com grande variedade de sintomas, não havendo por...

  16. Inhibition of monocyte chemoattractant protein-1 expression in tubular epithelium attenuates tubulointerstitial alteration in rat Goodpasture syndrome.

    Science.gov (United States)

    Okada, H; Moriwaki, K; Kalluri, R; Imai, H; Ban, S; Takahama, M; Suzuki, H

    2000-03-01

    To examine the role of monocyte chemoattractant protein-1 (MCP-1) expressed by tubular epithelium in tubulointerstitial alterations in situ, the level of MCP-1 mRNA in tubular epithelium was lowered selectively in the rat model of Goodpasture syndrome (GPS). Intravenously administered antisense oligodeoxynucleotide (ODN) is taken up by renal tubular epithelium and has been found to block expression of target genes in rats. MCP-1 antisense ODN was injected into GPS rats every second day from days 27 to 35 after immunization (this represents the time when renal MCP-1 mRNA level was increased and interstitial mononuclear cell infiltration was aggravated). In addition to a reduction in the level of tubular MCP-1 mRNA, antisense ODN treatment attenuated monocyte infiltration significantly and preserved renal function in GPS rats. However, ODN injection did not affect glomerular MCP-1 expression and glomerular histopathology, and there were no significant changes in the urinary protein excretion rate. Our findings provide direct evidence that MCP-1, expressed by tubular epithelium, plays a pivotal role in mediating secondary tubulointerstitial alterations in the GPS model.

  17. 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.

  18. [Nucleotide receptors and renal function].

    Science.gov (United States)

    Jankowski, Maciej

    2014-01-01

    Kidney plays a key role in homeostasis of human body. It has heterogenic structure and is characterized by complicated vascular beds and numbers of sympathetic nerves endings. Nucleotides receptors are involved in the regulation of blood flow, a fundamental process for renal function. Plasma is filtrated in renal glomerulus and activity of nucleotides receptors located on cells of glomerular filter modifies the physi- cochemical properties of filter and affects the filtration process. Electrolytes, water and low molecular weight molecules are reabsorbed from tubular fluid or secreted into fluid in proximal and distal tubules. Glomerular filtration rate and activity of tubular processes are regulated via nucleotides receptors by glomerulotubularbalance and tubuloglomerular feedback. Nucleotides receptors are involved in systemic regulation of blood pressure and carbohydrate metabolism.

  19. 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.

  20. Renal function assessment in heart failure.

    Science.gov (United States)

    Pérez Calvo, J I; Josa Laorden, C; Giménez López, I

    2017-03-01

    Renal function is one of the most consistent prognostic determinants in heart failure. The prognostic information it provides is independent of the ejection fraction and functional status. This article reviews the various renal function assessment measures, with special emphasis on the fact that the patient's clinical situation and response to the heart failure treatment should be considered for the correct interpretation of the results. Finally, we review the literature on the performance of tubular damage biomarkers.

  1. Tubular dysfunction after peritonectomy and chemohyperthermic treatment with cisplatin.

    Science.gov (United States)

    La Manna, Gaetano; Virzì, Salvatore; Deraco, Marcello; Capelli, Irene; Accorsi, Alma; Dalmastri, Vittorio; Comai, Giorgia; Bonomi, Serena; Grassi, Antonio; Selva, Saverio; Feliciangeli, Giorgio; Scolari, Maria; Stefoni, Sergio

    2006-01-01

    Peritoneal carcinomatosis has always been regarded as a contraindication in traditional cancer surgery treatment; however, good results have been reported by using new combined medical-surgical loco-regional techniques. Peritonectomy and chemohyperthermic perfusion with cisplatinum (CIIP) seem to play a central role in obtaining a better survival rate than with the traditional procedures, even though there is a cisplatinum nephrotoxic effect. The aim of this study was to investigate entity and type of renal injury after CIIP. Forty-two patients (12 males and 30 females) with recurrent or primary peritoneal carcinomatosis who underwent peritonectomy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy with cisplatin were enrolled. A significant worsening in renal function was observed on the third post-operative day and this condition then persisted for three months. A reduction in estimated-Glomerular Filtration Rate (e-GFR) and an alteration in the albumin:creatinine ratio proved tubular injury. On the third post-operative day after cisplatinum administration, a high toxicity peak was found following platinum free fraction excretion. Proximal tubular injury was confirmed even at the three month analysis. A significant correlation between the total protein reduction rate and the decrease in renal function was established. In relation to that, the platinum free fraction could increase because of a binding protein shortage and the nephrotoxic effect could be enhanced due to platinum accumulation within the post-operative period. This finding suggests that the higher the protein reduction is, the lower the e-GFR determination is at three months.

  2. Handling sharps and needles

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000444.htm Handling sharps and needles To use the sharing features ... Health Administration. OSHA fact sheet: protecting yourself when handling contaminated sharps. Updated January 2011. Available at: www. ...

  3. Inhibition of gentamicin–induced renal tubular cell necrosis

    OpenAIRE

    Tavafi, Majid

    2012-01-01

    Gentamicin nephrotoxicity limit its usage against gram negative bacteria. Most researches showed that antioxidant agents improved gentamicin nephrotoxicity. According to these investigations oxidative stress play a central role in the mechanism of gentamicin induced nephrotoxicity. Recently Rafieian-Kopaei and colleagues showed that erythropoietin significantly ameliorated serum creatinine, blood urea nitrogen and tubal necrosis in gentamicin induced nephrotoxicity in rat. One of the advantag...

  4. Endothelial protein C receptor in renal tubular epithelial cells and ...

    African Journals Online (AJOL)

    Jane

    2011-07-20

    Jul 20, 2011 ... placenta, heart, liver and lung endothelial cell. However, there ... The effects of some reagents (high glucose, tumor necrosis factor–α and interleukin-1β) were measured by .... functional domains, including N terminal signal peptide ..... endothelial cell protein C receptor (EPCR) 23bp insert in patients with.

  5. 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.

  6. 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.

  7. 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

  8. 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