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 HCO3 20 +/- 0.9 mEq/l) while those treated for 3 days did not (Blood pH 7.39 +/- 0.01, HCO3 24 +/- 1.0 mEq/l). Fractional HCO3 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 pCO2 in a highly alkaline urine was impaired in both groups (urinary pCO2 61 +/- 2.3 mmHg and 50 +/- 2.5 mmHg in rats treated with CyA for 3 and 8 days, respectively as compared to controls 72 +/- 3.0 mmHg, p less than 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 mu ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000652:urine; D003524:Cyclosporins / Q000008:administration & dosage / Q000633:toxicity*; D004573:Electrolytes / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology / Q000652:urine; D051381:Rats; D012964:Sodium / Q000494:pharmacology; D017693:Sodium Bicarbonate; D013431:Sulfates / Q000494:pharmacology; D013997:Time Factors; D014556:Urine / Q000032:analysis*
D001639:Bicarbonates; D003524:Cyclosporins; D004573:Electrolytes; D013431:Sulfates; D000643:Ammonium Chloride; C012036:sodium sulfate; D002245:Carbon Dioxide; D017693:Sodium Bicarbonate; D012964:Sodium; D011188:Potassium