Mechanisms of lysine-induced acute renal failure in rats

Mechanisms of lysine-induced acute renal failure in rats. We have previously found that lysine produces acute renal failure in rats. To define the acute effects of lysine, rats given lysine at 8.9 mg/kg/min, i.v. for 4.5hr were compared with control rats receiving equiosmolar dextrose. Systemic blood pressure was stable in both groups. Mean intratubular pressure, inulin clearance (C In ), and renal blood flow were determined at 45-min intervals. Intratubular pressures measured with a servonulling micropressure device were elevated by 90min in lysine-treated animals, with tubular heterogeneity, while pressures in dextrose-treated rats were normal and homogeneous. By 135min C In in lysine-treated rats was 45% of C In in dextrose rats. Urine output fell in ly sine-treated rats. Renal blood flow determined by flow probe remained normal in ly sine-treated rats through 135min and did not decline significantly until 180min. Significant dilatation of surface tubules was documented by intravital microscopy beginning at 90min in lysine-treated rats. The sequence of elevated intratubular pressure and tubular dilatation, followed by decreased C In , and then by decreased renal blood flow suggests that lysine produces acute renal failure primarily through tubular obstruction. The tubular obstruction is followed later by an increase in renal vascular resistance. Mecanismes de l'insuffisance renale aigue induite par la lysine chez des rats. Nous prealablement trouvâmes que la lysine entraine une insuffisance renale aigue chez les rats. Afin de definir les effets aigus de la lysine, des rats ayant recu de la lysine a 8,9mg/kg/min i.v. pendant 4.5hr ont ete compares a des rats controles recevant du glucose equimolaire. La pression arterielle systemique etait stable dans les deux groupes. La pression intratubulaire moyenne, la clearance de l'inuline (C In ) et le flux sanguin renal ont ete determines a des intervalles de 45min. Les pressions intratubulaires mesurees avec un appareil a micropression asservi etaient elevees des 90min chez les animaux traites avec la lysine, avec une heterogeneite tubulaire, tandis que les pressions des rats traites au glucose etaient normales et homogenes. Au bout de 135 min, C In des rats traites par la lysine etait de 45% de C In des rats glucose. Le debit urinaire a chute chez les rats traites par la lysine. Le debit sanguin renal determine par une sonde de flux est reste normal chez les rats traites par la lysine pendant 135min, et n'a pas decline significativement jusqu'a 180min. Une dilatation significative des tubules superficiels a ete documentee par microscopie intravitale, comencant a 90min chez les rats traites par la lysine. La sequence de pression intratubulaire elevee et de dilatation tubulaire, suivie par une C In diminuee, puis par une diminution du flux sanguin renal suggere que la lysine entraine une insuffisance renale aigue essentiellement par obstruction tubulaire. L'obstruction tubulaire est suivie plus tard d'une elevation de la resistance vasculaire renale.