[Treatment of acute renal failure in Germany: Analysis of current practice]. / Versorgung des akuten Nierenversagens auf deutschen Intensivstationen: Analyse der aktuellen Behandlungspraxis.

BACKGROUND AND OBJECTIVES: There are currently no reliable data on the differential use of renal replacement therapy (RRT) options for critically ill patients with acute renal failure in Germany. PATIENTS AND METHODS: A questionnaire-based survey was delivered to 2265 German intensive care units. The questionnaire contained 19 questions regarding RRT. RESULTS: A total of 423 German intensive care units participated in the survey. The offered modalities of RRT varied significantly: the smaller the facility, the fewer different RRT options were available. Intermittent dialysis procedures were available in only 35% of hospitals with up to 400 beds. In university hospitals, hemodynamically unstable patients were exclusively treated by continuous RRT, whereas in hospitals with up to 400 beds, intermittent RRT was also used. In addition, treatment practice was also dependent on the specialization of the treating physicians: Isolated acute renal failure was treated more often intermittently by nephrologists compared to anesthesiologists (79.7 vs. 43.3%). Nephrologists also used extracorporeal RRT more often in cardiorenal syndrome (54.3 vs. 35.8%), whereas anesthesiologists preferred them in sepsis (37.3 vs. 23.1%). The choice of anticoagulant varied as well: Hospitals with up to 400 beds offered regional citrate anticoagulation in only 50% compared to 90% of university hospitals. CONCLUSIONS: Currently, RRT treatment in acute renal failure on German intensive care units seems to be dependent on the size, local structures, and education of the intensivists rather than patient needs. Our results demonstrate the necessity to establish cross-disciplinary standards for the treatment of acute renal failure in German intensive care units.

[Treatment of acute renal failure in Germany: a structural analysis]. / Versorgung des akuten Nierenversagens in Deutschland--Eine strukturelle Analyse.

INTRODUCTION: There are no reliable data on the structure and practice of the care of critically ill patients with acute renal failure in Germany. METHODS: We carried out a detailed survey by sending a questionnaire to 2265 German Intensive Care Units. The questionnaire contained 19 questions regarding renal replacement therapy. RESULTS: 423 German intensive care units participated in the survey. Most of the ICUs are headed interdisciplinary (47%) or by anesthesiologists (30%), with significant differences depending on the size of the clinic, with primarily interdisciplinary management in smaller clinics. The offered type of renal replacement therapy varies significantly, the smaller the house the fewer methods are available. Thus, intermittent dialysis procedures are offered only in 35% of hospitals with up to 400 beds. The indication for the initiation of acute renal replacement therapy in intensive care is provided predominantly (53%) by an anesthesiologist. A nephrologist is only involved in 22% of all intensive care units. The indication is based primarily on a "clinical criteria", but these are poorly defined. CONCLUSION: Our results demonstrate the need for cross-disciplinary standards for the treatment of acute renal failure in German intensive care units.

Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations.

Management of idiopathic glomerular disease associated with nephrotic syndrome (INS) remains controversial and one of the most complex areas relates to utilization of the drug cyclosporin. This is despite its demonstrated effectiveness in several histologic types of the INS in randomized controlled trials. Cyclosporin is effective in inducing remission of proteinuria in approximately 80% of steroid-sensitive cases of minimal change disease (MCD). Cyclosporin is also effective in both the induction of remission and long-term preservation of renal function in steroid-dependent/-resistant MCD and steroid-resistant focal segmental glomerulosclerosis (FSGS). The overall response rate in FSGS is lower than in MCD, and long-term therapy (>12 months) may be required to both achieve remission and sustain it. Cyclosporin therapy is also of benefit in reducing proteinuria in 70-80% of patients with steroid-resistant membranous nephropathy (MGN). In MGN, the maximum benefit is often delayed compared to MCD (>12 weeks). Cyclosporin is generally well tolerated and safe. The major concern remains the nephrotoxicity, but with careful monitoring of the patient's renal function; minimizing the maintenance dose and utilizing repeat renal biopsy in those receiving long-term therapy, this risk can be minimized. The algorithms have been developed derived from the best evidence in the literature in each of the histologic types to help provide a guide to the integration of cyclosporin into the management of INS for the practicing nephrologist.

Strategies for the treatment of acute renal failure in intensive care units: the aspect of dosing.

Despite all the medical progress, the mortality rate in intensive care units for patients with acute renal failure (ARF) remains high, among specific patient populations, up to 88% [Letourneau I, Dorval M, Belanger R, Legare M, Fortier L, Leblanc M. Acute renal failure in bone marrow transplant patients admitted to the intensive care unit. Nephron Apr 2002; 90 (4), 408-412.]. Recent trial results indicate that patient survival may be improved by adequate renal replacement therapy. In particular, the dose of intermittent and continuous renal replacement therapies has proved to be a significant factor affecting patient survival. Daily intermittent hemodialysis, e.g., is superior to alternate-day intermittent hemodialysis, and with continuous therapies, survival is related to the filtration rate. Further relevant factors include early initiation of renal replacement therapy, choice of biocompatible membranes and the application of bicarbonate-buffered replacement solutions for defined patient groups. The advantages offered by continuous techniques could be demonstrated for individual patient groups; in meta-analyses, advantages were shown for the total population of patients with ARF. Other than for patients with chronic renal failure (NKF-DOQI. Clinical practice guidelines for hemodialysis adequacy. Am J Kid Dis 1997; Vol. 30, 515-566.), there are no current clinical guidelines for a standard treatment of intensive care patients with ARF. Therefore, such a treatment standard still needs to be determined.

COX-2 dependent PGE(2) downregulates alpha(v) integrin expression via the EP(3) receptor in cultured mesangial cells.

BACKGROUND: In experimental glomerulonephritis, inhibition of cyclooxygenase 2 (COX-2) enhances the renocortical expression of pathogenic alpha(v) integrins. AIMS: To study whether this effect is mediated by prostaglandin E(2) (PGE(2)) acting through its EP(3) receptor in cultured rat mesangial cells (MCs). METHODS: MCs were incubated with lipopolysaccharide (LPS), celecoxib, PGE(2), or the selective EP(3) agonist, MB28767. The expression of COX-2, EP(3), and alpha(v) integrin mRNA was measured by reverse transcriptase polymerase chain reaction. RESULTS: LPS upregulated COX-2 expression 2.8-fold and alpha(v) integrin expression twofold. The COX-2 inhibitor celecoxib increased alpha(v) integrin mRNA expression twofold. Both exogenous PGE(2) and the specific EP(3) receptor agonist, MB28767, reduced constitutive alpha(v) integrin mRNA expression to half normal values. COX-2 dependent PGE(2) suppressed the expression of alpha(v) integrin mRNA mediated by the EP(3) receptor in MCs. CONCLUSIONS: These results suggest that COX-2 suppresses the expression of alpha(v) integrins by an increased production of PGE(2) activating its EP(3) receptor in glomerulonephritis.

Aldosterone resistance in kidney transplantation is in part induced by a down-regulation of mineralocorticoid receptor expression.

BACKGROUND: After renal transplantation immunosuppressive drugs-like cyclosporin A (CsA) and FK506 induce either hypoaldosteronism or pseudo-hypoaldosteronism presenting with hyperkalemia and metabolic acidosis. We investigated the relationship between renal allograft function under CsA therapy and plasma aldosterone concentration, potassium- and water homeostasis and mineralocorticoid receptor (MR) expression level in peripheral leukocytes. METHODS: We studied 21 renal transplant patients under CsA therapy and 12 healthy controls. Transplant recipients were studied before and under fludrocortisone treatment. Using quantitative reverse-phase polymerase chain reaction (RT-PCR) specific for the MR, we analyzed the level of expression of MR in peripheral leukocytes. RESULTS: In acidotic transplant recipients (HCO(3) 18.5 +/- 1.2 mM) renal function was only slightly impaired with 2.0 +/- 0.2 mg creatinine/dL when compared with 1.8 +/- 0.3 mg/dL (ns) in non-acidotic patients (HCO(3) 23.0 +/- 2.8 mM). Mean plasma aldosterone levels in renal transplant recipients did not differ from control levels (150 +/- 33 pg/mL vs. 148 +/- 33 pg/mL, ns). In contrast, the expression level of MR in peripheral leukocytes of renal transplant recipients treated with CsA was significantly decreased when compared with healthy controls without renal disease (120 +/- 78 vs. 423 +/- 73 RNA molecules/0.5 microg total RNA, p < 0.01). The level of expression of MR in renal transplant recipients did not differ between acidotic patients and non-acidotic patients (ns). The application of fludrocortisone reversed hyperkalemia and metabolic acidosis without significant effect on MR expression. CONCLUSIONS: The present data demonstrate that hyperkalemia and metabolic acidosis following CsA treatment in kidney transplantation might be associated with a down-regulation of MR expression on peripheral leukocytes. Electrolyte imbalance is reversible on application of fludrocortisone. This observation supports fludrocortisone treatment in transplant patients with severe electrolyte disturbances.

Influence of genetic polymorphisms of the renin-angiotensin system on IgA nephropathy.

BACKGROUND: We evaluated the impact of the three major genetic polymorphisms of the renin-angiotensin system [angiotensinogen (AGT) gene M235T, angiotensin-converting enzyme (ACE) gene-I/D and angiotensin II-type 1 receptor (AT1R) gene A1166C polymorphisms] as risk factors in IgA nephropathy. METHODS: The clinical course of 107 patients with biopsy proven IgA nephropathy followed up for 6.6 +/- 5.8 years was examined. The genetic polymorphisms were determined by PCR amplification. RESULTS: The allele frequencies of the polymorphisms studied were similar in patients and control subjects. AGT-M235T genotype was associated with the presence of nephrotic syndrome (p < 0.05), correlated to the number of antihypertensive drugs agents taken (p < 0.01) and influenced the rate of deterioration of renal function (p < 0.05). Combined analysis of AGT-M235T and ACE-I/D polymorphisms detected an interaction on affecting progression (p < 0.05). ACE-inhibition had a more pronounced effect in certain AGT-M235T and ACE-I/D genotypes (p < 0.05) and their combined analysis showed a synergistic effect (p < 0.01). No association between AT(1)R-A1166C polymorphism and any of the parameters studied was observed. CONCLUSIONS: Our results suggest that angiotensinogen-M235T polymorphism is an important marker of progression in IgA nephropathy in Caucasian patients, especially when analyzed in combination with ACE-I/D polymorphism.

Decreased mineralocorticoid receptor expression in blood cells of kidney transplant recipients undergoing immunosuppressive treatment: cost efficient determination by quantitative PCR.

AIMS: Electrolyte imbalances caused by impaired ion transport are a frequent side effect of immunosuppressive treatment in renal transplant recipients. Clinical symptoms resemble features of hypoaldosteronism, although concentrations of aldosterone are in the normal range. Because immunosuppression might affect the hormone receptor status of cells, mineralocorticoid receptor (hMR) expression by peripheral blood leucocytes (PBL) was studied in these patients. METHODS: Twenty one renal transplant recipients being treated with cyclosporine A and 19 healthy controls were tested. hMR expression was quantified by means of competitive reverse transcription polymerase chain reaction (cRT-PCR) and compared with receptor binding studies with subsequent Scatchard plot analysis carried out previously on 20 renal transplant recipients and 25 controls. Advantages of PCR were summarised and compared with Scatchard plot analysis. RESULTS: Cyclosporine A caused a 37% decrease in hMR molecules on PBL in 75% of renal transplant recipients, and this effect was attributable to the downregulation of hMR transcription. PCR was 99% specific for the detection of hMR in PBL and highly reproducible. CONCLUSIONS: Decreases in hMR protein and RNA in PBL of transplant recipients revealed an inhibitory effect of cyclosporine A on hMR transcription. Because hMR acts as a transcription factor, the expression of several genes involved in electrolyte homeostasis is affected, leading to signs of nephrotoxicity that require therapeutic adjustments. Because of the small volume of blood, the assay can be repeated during treatment and is therefore useful for measuring treatment outcomes. Lower costs and the absence of radioactive challenge are further advantages of the PCR method.

COX-2 inhibition and prostaglandin receptors in experimental nephritis.

BACKGROUND: Renal cyclooxygenases (COX) produce the prostaglandins (PG) E2, I2 and thromboxane (TxA2), which interact with distinct G protein-coupled receptors. We investigated the expression of the three EP receptors EP2, EP3 and EP4 and the receptors for PGI2 (IP) and TxA2 (TP) in rats with passive Heymann nephritis (PHN). We studied their regulation by COX-2 inhibition with celecoxib. MATERIALS AND METHODS: Four groups of Wistar rats were studied: healthy rats (group A), healthy rats treated with celecoxib (group B), rats with PHN (group C), and rats with PHN receiving celecoxib (group D). Expression of the mRNA for all receptors in the renal cortex and for the EP3 receptor in cultured mesangial cells (MCs) was determined by semiquantitative reverse transcriptase polymerase chain reaction. Stable prostaglandin metabolites were measured in the urine by radioimmunoassay. RESULTS: Rats with PHN (group C) showed an 1.8-fold increase of cortical EP3 receptor mRNA expression as compared with controls (group A). In celecoxib-treated PHN rats (group D) the mRNA expression of the EP3 and EP4 receptors was significantly reduced to 1.0-fold and 0.7-fold induction, respectively. Furthermore, the excretion of bicyclo-prostaglandin E2 (PGE2) was inhibited by celecoxib. No changes were observed in the expression of the other PG-receptors. In cultured MC, PGE2 enhanced the EP3 mRNA expression. CONCLUSIONS: These data suggest a predominant role of the EP3 receptor in the transduction of PGE2-actions in PHN. It was concluded that COX-2-dependent PGE2 is able to potentiate its effects in the kidney by up-regulating its own receptors.

Effects of the genetic polymorphisms of the renin-angiotensin system on focal segmental glomerulosclerosis.

BACKGROUND/AIMS: We analyzed the influence of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T and angiotensin-II-type-1 receptor (AT1R) A1166C genetic polymorphisms on the clinical course of focal segmental glomerulosclerosis (FSGS). METHODS: This study consisted of 71 patients with nephrotic syndrome due to biopsy proven FSGS and 100 healthy controls. According to the slope of the reciprocal serum creatinine (1/Cr, >or= or <-0.1 dl x mg(-1) x year(-1)) patients were classified into group A (slow progressors, n = 50) and group B (fast progressors, n = 21). Genotyping was performed using polymerase chain reaction (PCR). RESULTS: There were no relevant differences in the allele frequencies of the investigated polymorphisms between patients with FSGS and controls. Patients carrying the T- allele of the AGT polymorphism required a larger number of antihypertensive agents (MM: 1.35 +/- 1.0 vs. MT/TT: 2.0 +/- 1.2, p < 0.05). The ACE-ID/DD genotypes were more frequently found in patients with fast progression (group A: II: 38.0%, ID/DD: 62.0% vs. group B: II: 14.3%, ID/DD: 85.7%, p < 0.05). The AT1R-A1166C polymorphism was not associated with any of the parameters studied. CONCLUSION: The course of FSGS is in part genetically determined by polymorphisms of the renin-angiotensin-system. The ACE-I/D polymorphism was shown to be a risk factor of progression of renal disease and the AGT-M235T polymorphism was associated with the severity of arterial hypertension.

[Gitelman's syndrome: an important differential diagnosis of hypokalemia]. / Gitelman-Syndrom: Eine wichtige Differenzialdiagnose der Hypokaliämie.

HISTORY AND CLINICAL FINDINGS: A 26-year-old woman presented with fatigue, muscle cramps and weakness. Since the age of 8 years she had moderate hypokalemia of unknown origin that was confirmed on multiple occasions. There was no family history of disease. INVESTIGATIONS: Laboratory tests showed moderate to severe hypokalemia with a serum potassium concentration of 2.7 to 3.0 mmol/l, hypomagnesemia, metabolic alkalosis and pronounced stimulation of the renin-angiotensin-aldosterone system. Despite normal serum calcium levels, urinary calcium excretion was below the detection threshold. Increased natriuresis was observed after administration of furosemide, but not after administration of hydrochlorothiazide. This finding pointed to the presence of a non-functional thiazide-sensitive sodium/chloride cotransporter in the distal convoluted tubule, characteristic for Gitelman's syndrome. Genetic analysis confirmed the diagnosis of Gitelman's syndrome and documented two heterozygous mutations in the gene encoding the sodium/chloride cotransporter. TREATMENT AND COURSE: The patient was treated with 160 mmol potassium and 30 mmol magnesium supplementation per day. Serum potassium was normalized and magnesium serum levels increased. Weakness and fatigue improved markedly. CONCLUSION: Gitelman's syndrome is an important differential diagnosis in the evaluation of the normotensive patient with hypokalemia.

Cytokine removal in septic patients with continuous venovenous hemofiltration.

Despite the progress that has been made in intensive care medicine, multiple organ failure is still associated with high mortality. Apart from the prevention of infectious complications, numerous efforts are being made to improve the treatment of sepsis through adequate antibiotic therapy, the development of new respirator therapies, better control of the hemodynamic situation, and adequate renal replacement therapy. Some authors advocate continuous renal replacement therapy not only for acute renal failure but also for the elimination of inflammatory molecules such as cytokines. Continuous renal replacement therapy improves the cardiovascular hemodynamics in patients with multiple organ failure. Therapeutic options such as volume control, clearance of uremic toxins, correction of acid base disturbances and temperature control are improved. Suitable renal replacement therapy improves not only cardiovascular hemodynamics but also patient survival. In current practice, continuous renal replacement therapy is not used to eliminate mediators such as cytokines. In patients with multiple organ failure and compromised cardiovascular hemodynamics, renal replacement therapy should be carried out as early as possible. In the following review, experimental and clinical findings concerning mediator elimination by continuous and intermittent renal replacement therapy are summarized.

[Glomerulonephritis secondary to chronic infection of a ventriculoatrial shunt]. / Sekundäre Glomerulonephritis bei chronischer Infektion eines ventrikuloatrialen Shunts.

HISTORY AND ADMISSION FINDINGS: A 39-year-old man was referred for assessment of a nephrotic syndrome. He reported deteriorating health with bouts of fever and microhaematuria and proteinuria in the past year. At the age of 24 years a ventriculoatrial shunt had been inserted for an internal hydrocephalus. At another hospital he was given steroids for a nephrotic syndrome suspected of being associated with membranoproliferative glomerulitis, but the disease progressed. On admission he had severe generalised oedema with a temperature of 38,5;C. His general condition was poor. He had no neck stiffness. INVESTIGATIONS: Parameters of inflammation were raised. Serum creatinine and creatinine clearance were normal. Levels of complements C3 and C4 were reduced. The proteinuria was 9g/24h. Renal biopsy revealed type 1 membranoproliferative glomerulonephritis. Micrococcus roseus/varians was demonstrated several times by aerobic blood cultures. TREATMENT AND COURSE: The findings suggested chronically infected ventriculoatrial shunt as cause of the glomerulonephritis. The shunt was, therefore, removed. The same pathogens were grown from it on aerobic culture medium. Six months after removal and replacement of the shunt and treatment of the infection the proteinuria had fallen to 0.45 mg/h; serum creatinine was 1.0 mg/dl. CONCLUSION: When membranoproliferative glomerulonephritis has been demonstrated, secondary forms should be considered in the differential diagnosis. In most cases specific treatment can prevent progression of the renal disease.

HRCT findings of amiodarone pulmonary toxicity: clinical and radiologic regression.

Amiodarone is an antiarrhythmic drug that can cause interstitial pneumonitis leading to pulmonary fibrosis. A 62-year-old man suffering from atrial fibrillation and recurrent dyspnea was treated with amiodarone. After 15 months of treatment, HRCT revealed bilateral interstitial and alveolar opacifications with high-attenuating pleural-parenchymal consolidations, suggesting amiodarone induced pneumonitis. Three months after cessation of amiodarone treatment, HRCT shows complete regression of pneumonitis. Amiodarone pneumonitis can be misinterpreted and mistreated in patients with further underlying diseases. The present case report demonstrates the diagnostic value of HRCT in the diagnosis of interstitial pneumonitis.

[Effect of cyclosporin A on renal function in patients with glomerulonephritis]. / Einfluss von Cyclosporin A auf die Nierenfunktion in der Therapie der Glomerulonephritis.

BACKGROUND AND OBJECTIVE: Cyclosporin A ( CsA) plays a confounding part in the treatment of nephrotic syndrome. Renal hemodynamics and glomerular permselectivity were investigated in patients with glomerulonephritis to analyse the antiproteinuric action of CsA and to differentiate between nephrotoxic and immunosuppressive effects. METHODS: We studied 19 patients with nephrotic syndrome after 6 months of treatment with CsA (membranous glomerulonephritis-MGN, n = 10; focal segmental sclerosing glomerulonephritis - FSGN, n = 5; minimal changes glomerulonephritis - MCGN, n = 4). Patients were studied three times within 3 weeks with (A) and without (B) CsA treatment (A-B-A'). Blood pressure, creatinine, proteinuria, C(In), C(PAH), C(Dex) were measured (analysis according to the model of Deen et al., Am J Physiol. 1985; 249 : 374). RESULTS: GFR (C (In)) increased significantly after withdrawal of CsA from 54 +/- 7.3 to 64 +/- 8.5 ml/min (p < 0.01). Proteinuria increased after withdrawal of cyclosporin (B) between 21 % (MGN) and 45 % (FSGN). After withdrawal of CsA (B) there was no change of FC(dex) in patients with MGN and FSGN. Withdrawal of CsA in patients with MCGN induced a significant decrease in glomerular selectivity in the high molecular range. CONCLUSION: These data demonstrate that CsA is able to induce even in the short term a significant increase in glomerular permselectivity in MCGN. The acute effects on GFR predominantly determined the acute antiproteinuric effects in patients with MGN and FSGN.

Different effects of cyclosporine a and FK506 on potassium transport systems in MDCK cells.

BACKGROUND: Hyperkalemia and metabolic acidosis are common manifestations in patients receiving the immunosuppressive agent cyclosporine A (CsA) and the recently introduced FK506. We compared the acute toxic and antiproliferative effects as well as the effects on the transport activity of Na(+)/K(+)-ATPase and Na(+)/K(+)/2Cl(-) cotransporter of CsA and FK506 in an established cell line of distal/collecting tubule origin (MDCK cells). METHODS: MDCK cells were exposed to various concentrations of CsA or FK506 and the effects on cell viability (MTT test and neutral red uptake), plasma membrane integrity (lactate dehydrogenase (LDH) release) and cell proliferation (bromodeoxyuridine (BrdU) incorporation) were compared. For transport studies, after confluence, MDCK cells were exposed to CsA or FK506 for 48 h in the presence and absence of aldosterone. Ouabain- and bumetanide-sensitive (86)Rubidium uptake measurements were used to study the activity of the Na(+)/K(+)-ATPase and Na(+)/K(+)/2Cl(-) cotransporter at the surface of intact cells. RESULTS: After 24 h of exposure CsA reduced the number of viable cells to 50% at 30 microM, whereas for FK506 2-3 times higher concentrations had to be employed. Similarly, LDH release was stimulated tenfold by 30 microM CsA but only fourfold by 70 microM FK506. In contrast, DNA synthesis was affected at lower concentrations of FK506 than of CsA. In cells treated for 24 h BrdU incorporation was significantly inhibited by 3 microM FK506, whereas a similar inhibition required 10 microM CsA. The transport activity of Na(+)/K(+)-ATPase and of Na(+)/K(+)/2Cl(-) cotransporter were significantly decreased (37 and 63%, respectively) on CsA administration (8 microM). In CsA-treated cells the K(+) channel blockers barium (1 mM), TEA (10 mM) and quinine (1 mM) did not further inhibit the transport activities suggesting that CsA might also act via inhibition of K(+) channels. FK506 at 8 microM had no effect on Na(+)/K(+)-ATPase transport activity but stimulated Na(+)/K(+)/2Cl(-) cotransporter activity by 59%. The stimulatory effect was abolished by K(+) channel blockers indicating that recycling of K(+) might increase by FK506. The simultaneous presence of aldosterone (5 microM) protected the cells from the inhibitory effect of CsA on Na(+)/K(+)-ATPase and Na(+)/K(+)/2Cl(-) cotransporter activity. The stimulatory effect of FK506 on the Na(+)/K(+)/2Cl(-)cotransporter activity was completely abolished in the presence of aldosterone. CONCLUSIONS: Both CsA and FK506 showed acute toxicity in MDCK cells in vitro with the effects of FK506 being less pronounced. CsA and FK506 had different effects on the in vivo transport rates of the Na(+)/K(+)-ATPase and the Na(+)/K(+)/2Cl(-) cotransporter; CsA inhibited the activity of the Na(+)/K(+)-ATPase and the Na(+)/K(+)/2Cl(-) cotransporter whereas FK506 stimulated the activity of Na(+)/K(+)/2Cl(-) cotransporter. These effects were abolished by the application of aldosterone.