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Gitelman syndrome is a rare hereditary disorder of the thiazide-sensitive NaCl transporter in the distal renal tubular cells, but mimicking of such hereditary tubular disorders has been described in different autoimmune diseases (Sjögren syndrome, SLE, ...). A 62-year-old woman with painful red eyes and sicca syndrome presented at the ophthalmological department. The diagnostic evaluation identified a Sjögren syndrome with early endophthalmitis as the reason for the red eyes. Results of laboratory examination indicated severe hypokalemia, metabolic alkalosis and hypomagnesemia, although this had not been seen years earlier. Together with the urine analysis, a rare case of an acquired Gitelman syndrome was diagnosed. Substitution with potassium and magnesium improved the initial symptoms of weakness, but renal electrolyte wasting persisted even after treatment of Sjögren syndrome. In patients with autoimmune disease, laboratory analysis of serum electrolytes should be performed because different acquired tubular disorders can lead to severe hypokalemia.

BACKGROUND The development of metabolic alkalosis was described recently in patients with hypernatremia. However, the causes for this remain unknown. The current study serves to clarify whether metabolic alkalosis develops in vitro after removal of free water from plasma and whether this can be predicted by a mathematical model. MATERIALS AND METHODS Ten serum samples of healthy humans were dehydrated by 29 % by vacuum centrifugation corresponding to an increase of the contained concentrations by 41 %. Constant partial pressure of carbon dioxide at 40 mmHg was simulated by mathematical correction of pH [pH(40)]. Metabolic acid-base state was assessed by Gilfix' base excess subsets. Changes of acid-base state were predicted by the physical-chemical model according to Watson. RESULTS Evaporation increased serum sodium from 141 (140-142) to 200 (197-203) mmol/L, i.e., severe hypernatremia developed. Acid-base analyses before and after serum concentration showed metabolic alkalosis with alkalemia: pH(40): 7.43 (7.41 to 7.45) vs 7.53 (7.51 to 7.55), p = 0.0051; base excess: 1.9 (0.7 to 3.6) vs 10.0 (8.2 to 11.8), p = 0.0051; base excess of free water: 0.0 (- 0.2 to 0.3) vs 17.7 (16.8 to 18.6), p = 0.0051. The acidifying effects of evaporation, including hyperalbuminemic acidosis, were beneath the alkalinizing ones. Measured and predicted acid-base changes due to serum evaporation agreed well. CONCLUSIONS Evaporation of water from serum causes concentrational alkalosis in vitro, with good agreement between measured and predicted acid-base values. At least part of the metabolic alkalosis accompanying hypernatremia is independent of renal function.

BACKGROUND: Humoral alloresponses may contribute to chronic allograft nephropathy (CAN) in a subset of kidney transplant recipients. For chronic humoral rejection, the efficacy of rescue therapy with tacrolimus and mycophenolate mofetil has been suggested. METHODS: Eleven recipients with C4d-positive CAN (index biopsy performed after a median of 3 years posttransplantation), who had been on cyclosporine A-based immunosuppression, were converted to tacrolimus, and if not part of basal therapy, to mycophenolate mofetil. We evaluated the effect of this tacrolimus/mycophenolate mofetil rescue therapy on clinical outcomes and on alloantibody formation detected with flow cytometric testing of panel-reactive antibody. RESULTS: Tacrolimus/mycophenolate mofetil rescue therapy (plus anti-rejection treatment in six recipients with additional signs of acute cellular rejection) failed to prevent progressive deterioration of graft function. Four patients returned to dialysis after 4 to 18 months. Serial post-transplant serology detected HLA class I and/or II reactivity in seven recipients. Tacrolimus/mycophenolate mofetil therapy did not affect the time course of alloantibody levels. One patient with C4d-positive transplant glomerulopathy, who did not respond to tacrolimus/mycophenolate mofetil rescue therapy, developed nephroticrange proteinuria associated with a rapid decline of allograft function. Despite considerable reduction in alloantibody levels and nearly complete clearance of C4d deposits, immunoadsorption failed to prevent graft failure in this patient. CONCLUSION: Our data argue against the efficacy of tacrolimus/mycophenolate mofetil rescue therapy in established C4d-positive chronic allograft dysfunction. Prospective trials are needed to evaluate whether early initiation of this or other antihumoral strategies are capable of effectively preventing alloantibody-mediated chronic graft injury.

Tubular atrophy is a common histological feature of chronic renal failure, and epithelial cell death by apoptosis might play an important role in its pathogenesis. Angiotensin II contributes to the progressive nature of many kidney diseases and treatment with angiotensin converting enzyme inhibitors preserves the structure of the tubulointerstitial compartment in human and experimental renal diseases.Primary cultures of human renal proximal tubular epithelial cells were co-incubated with angiotensin II alone or in combination with the angiotensin II AT1 receptor antagonist losartan or/and the AT2 antagonist PD123319. Apoptosis was determined after 20 hours by TUNEL staining and flow cytometry.Angiotensin II at concentrations of 10(-9) M induced apoptosis (control vs. angiotensin II 4 +/- 3% vs. 73 +/- 11%; p0.05). This effect was completely offset by co-incubation with the angiotensin II AT2 receptor blocker at concentrations 10(-7) M (control vs. PD123319 4 +/- 3% vs. 8 +/- 3%; p0.05); AT1 blockade was ineffective in apoptosis inhibition. When both angiotensin receptors were blocked, no additional effect on apoptosis inhibition could be detected.We provided evidence, that physiological concentrations of angiotensin II can induce apoptosis of human renal proximal tubule epithelial cells. This effect is mediated via AT2 receptors.