Effect of short-term cyclosporine A administration on urinary acidification

D. C. Batlle, C. Gutterman, J. Tarka, R. Prasad

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35 Scopus citations

Abstract

This study was designed to investigate the short-term effect of cyclosporine A (CyA) at a dose of 25 mg/kg body weight, on urinary acidification and renal potassium handling. Rats treated with CyA for 8 days developed metabolic acidosis (Blood pH 7.34 ± 0.01, Blood HCO 3 20 ± 0.9 mEq/l) while those treated for 3 days did not (Blood pH 7.39 ± 0.01, HCO 3 24 ± 1.0 mEq/l). Fractional HCO 3 excretion was low in both groups indicating that bicarbonate reabsorption in the proximal nephron was unimpaired. Distal hydrogen ion secretion evaluated by the ability to increase urinary pCO 2 in a highly alkaline urine was impaired in both groups (urinary pCO 2 61 ± 2.3 mmHg and 50 ± 2.5 mmHg in rats treated with CyA for 3 and 8 days, respectively asd compared to controls 72 ± 3.0 mmHg, p < 0.01). Under basal conditions, renal potassium excretion was lower in CyA treated rats than in controls. This was observed in association with a decrease in GFR in rats treated with CyA for 8 days (GFR 1.3 ± 0.3 ml/min) but not in those treated for 3 days (GFR 2.2 ± 0.4 ml/min). Rats treated with CyA for 3 days were able to increase potassium excretion normally in response to both sodium sulfate infusion and to an acute potassium infusion. In rats treated with CyA for 8 days, acute potassium loading failed to elicit an increase in fractional potassium excretion (from 32 ± 5.3 to 28 ± 2.3%) despite an increase in plasma K (from 3.0 ± 0.2 to 8.4 ± 0.3 mEq/l) and urine flow (from 11 to 36 μml/min). We conclude that CyA administration results in a decrease in the rate of hydrogen ion secretion by the collecting tubule. This defect in distal acidification can be disclosed by the finding of a subnormal pCO 2 in a highly alkaline urine. CyA administration can also impair distal potassium secretion as evaluated by a lack of a rise in potassium excretion in response to an acute potassium infusion. These experimental findings suggest that a voltage-dependent defect in hydrogen ion and potassium secretion underlies, at least in part, the hyperkalemic metabolic acidosis found in some patients chronically treated with CyA.

Original languageEnglish (US)
JournalClinical Nephrology
Volume25
Issue numberSUPPL. 1
StatePublished - Jan 1 1986

ASJC Scopus subject areas

  • Nephrology

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