Acidosis and weight loss are induced by cyclosporin A in uninephrectomizedrats

The effects of cyclosporin A (CyA, 50 mg/kg body weight) or its commercial vehicle (cremophor) on the acid-base regulation of uninephrectomized rats w ere assessed for 7 days and in non-nephrectomized rats for 15 days. CyA ind uced a marked systemic acidosis, accompanied by decreases in blood PCO2 and plasma bicarbonate. Untreated uninephrectomized rats did not show the acid osis. In CyA-treated rats the urine pH decreased (control 6.65+/-0.06 vs. C yA 6.18+/-0.08, P<0.01) as well as urinary bicarbonate (non-nephrectomized rats 7.50+/-1.88 mM vs. uninephrectomy plus CyA 0.75+/-0.06 mM; P<0.01), su ggesting partial renal compensation of systemic acidosis. Titratable acidit y increased in CyA-treated rats (control 21.6+/-1.2 vs. CyA 63.3+/-12.0 mu Eq/l; P<0.001). Phosphate, glucose, and osmolar clearances were not signifi cantly altered in non-nephrectomized rats treated with CyA for 15 days. The re was a striking de crease in body weight in CyA-treated rats (control 274 .0+/-3.8 vs. CyA 225.0+/-5.1 g; P<0.01), but compensatory growth of the rem aining kidney was not prevented by this drug or by its vehicle. In summary, CyA induced a severe metabolic acidosis in uninephrectomized rats that was not compensated by the remaining kidney, in spite of the well-preserved co mpensatory weight gain of this organ. Loss of body weight was significant i n CyA treated animals.