Effect of bicarbonate administration on cyclosporine-induced nephrotoxicity in rats.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Zahmatkesh
M
M
Department of Physiology, School of Medicine, Tehran University of Medical Sciences Tehran, Iran. zahmatkm@tums.ac.ir
Kadkhodaee
M
M
Seifi
B
B
Shams
S
S
D000118:Acetylglucosaminidase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology*; D003404:Creatinine / Q000378:metabolism; D016572:Cyclosporine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D011507:Proteinuria / Q000378:metabolism; D051381:Rats
D001639:Bicarbonates; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D000118:Acetylglucosaminidase