Renin mRNA expression and renal dysfunction in tacrolimus-induced acute nephrotoxicity.
Tacrolimus is a superior immunosuppressive agent and has markedly improved the short-term outcome of renal allografts. Despite the beneficial effects of maintaining immunotolerance in organ transplant recipients, it has well-characterized side effects on renal hemodynamics in the early phase. The mechanism of tacrolimus-induced acute nephrotoxicity is still unclear. The purpose of this study was to elucidate the role of renin-angiotensin system (RAS) in tacrolimus-induced acute nephrotoxicity. We examined the renal mRNA levels of renin in order to elucidate the relationship between plasma renin activity (PRA) and tacrolimus-induced renal dysfunction. Daily administration of tacrolimus (4 mg/kg/day) for 2 weeks in spontaneously hypertensive rats (SHR) significantly increased BUN and plasma creatinine (P-Cr) level, while endogenous creatinine clearance (Ccr) significantly decreased in tacrolimus treated rats. Regarding tubular function data, fractional excretion of Na (FENa) and fractional excretion of K were higher in the tacrolimus treated group. Renin mRNA levels in the renal cortex in tacrolimus treated rats significantly increased when compared to the vehicle-treated rats. Ccr level was inversely proportional to PRA, with a high correlation coeffecient. The rise in PRA significantly correlated with increase in FENa by liner regression. Therefore, the results indicate that RAS is involved in the tacrolimus-induced acute nephrotoxicity.
Nakatani
Tatsuya
T
Department of Urology, Osaka City University Graduate School of Medicine, Osaka, Japan.
Uchida
Junji
J
Iwai
Tomoaki
T
Matsumura
Kentaro
K
Naganuma
Toshihide
T
Kuratsukuri
Katsuyuki
K
Sugimura
Kazunobu
K
D000818:Animals; D003404:Creatinine / Q000378:metabolism; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000235:genetics*; D007684:Kidney Tubules / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011918:Rats, Inbred SHR; D012044:Regression Analysis; D012083:Renin / Q000097:blood / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D016559:Tacrolimus / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects
D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D003404:Creatinine; D012083:Renin; D016559:Tacrolimus