Acidosis and weight loss are induced by cyclosporin A in uninephrectomized rats.
The effects of cyclosporin A (CyA, 50 mg/kg body weight) or its commercial vehicle (cremophor) on the acid-base regulation of uninephrectomized rats were assessed for 7 days and in non-nephrectomized rats for 15 days. CyA induced a marked systemic acidosis, accompanied by decreases in blood PCO(2) and plasma bicarbonate. Untreated uninephrectomized rats did not show the acidosis. In CyA-treated rats the urine pH decreased (control 6. 65+/-0.06 vs. CyA 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), suggesting partial renal compensation of systemic acidosis. Titratable acidity increased in CyA-treated rats (control 21.6+/-1.2 vs. CyA 63.3+/-12.0 microEq/l; P<0.001). Phosphate, glucose, and osmolar clearances were not significantly altered in non-nephrectomized rats treated with CyA for 15 days. There was a striking decrease 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 remaining 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 compensatory weight gain of this organ. Loss of body weight was significant in CyA-treated animals.
Jaramillo-Juárez
F
F
Centro Básico, Universidad Autónoma de Aguascalientes, Mexico.
Rodríguez-Vázquez
M L
ML
Namorado
M C
MC
Martín
D
D
Reyes
J L
JL
D000138:Acidosis / Q000139:chemically induced*; D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects* / Q000097:blood / Q000652:urine; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000097:blood / Q000652:urine; D008297:Male; D009392:Nephrectomy; D014677:Pharmaceutical Vehicles / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015431:Weight Loss / Q000187:drug effects*
D007166:Immunosuppressive Agents; D014677:Pharmaceutical Vehicles; C022131:cremophor; D011092:Polyethylene Glycols; D016572:Cyclosporine