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.