Effect of short-term cyclosporine A administration on urinary acidification

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.