Effect of bicarbonate administration on cyclosporine-induced nephrotoxicity in rats

Cyclosporine (CsA) is known to cause metabolic and distal tubular acidosis. There is some evidence that CsA reduces net HCO(3)(-) absorption. The aim of this study was to elucidate whether bicarbonate administration prevented CsA-induced functional or structural nephrotoxicity.

Seven days after uninephrectomy, 20 rats were divided into 4 groups. NaHCO(3) (0.28 mol/L) was added in drinking water for 7 days, whereas control rats received regular tap water. The bicarbonate pretreated rats were administered either CsA (50 mg/kg intraperitoneally) or vehicle daily for a week. At the end of the procedure, animals were placed in metabolic cages for 24 hours after which we measured creatinine clearance (Ccr), urinary total proteins, pH, and N-acetyl-beta-D-glucosaminidase (NAG) activity. The kidney was fixed in formaldehyde.

Ccr was significantly affected by the administration of CsA. The effects of CsA on serum pH and HCO(3)(-) concentration were prevented by pretreatment with NaHCO(3). However, it did not affect the CsA-induced increased urinary NAG activity or decreased Ccr. There was no protection of CsA-induced changes in renal tissues by NaHCO(3).

Overall NaHCO(3) administration did not prevent CsA-induced changes in Ccr and NAG activity. These data suggested involvement of factors other than acid-base status in CsA-induced nephrotoxicity. However, correction of acidosis should still be considered for patients receiving CsA because acidosis exacerbates tissue damage.