Abnormalities of heme biosynthesis in experimental acute renal failure

Several abnormalities of porphyrin metabolism have been described in patients with end-stage renal failure. Because the heme biosynthetic pathway in acute renal failure has not been studied hitherto, an experimental model was therefore induced in 30 dogs by ligation and transection of both ureters. Forty-eight h after this procedure, anemia and uremia developed, erythrocyte aminolevulinate dehydratase activity decreased, and plasma porphyrins increased in these 30 dogs, whereas seven sham-operated animals did not exhibit any alteration of these parameters. Uremic plasma showed a capacity to inhibit aminolevulinate dehydratase activity (mean, 11.1 +/- 5.8%) when incubated in vitro with erythrocytes from healthy dogs. Such findings are similar to those reported in uremic patients on hemodialysis or on continuous ambulatory peritoneal dialysis. Twenty-three of the 30 animals underwent a hemodialysis session (180 min) 48 h after ureteral ligation, using a polyacrylonitrile membrane dialyzer. In addition to reducing serum creatinine and urea levels, this procedure significantly reduced plasma porphyrin values. However, the activity of erythrocyte aminolevulinate dehydratase and the plasma capacity to inhibit this enzyme were not modified after the hemodialysis session. This results described here show that some of the abnormalities of heme biosynthesis described in chronic renal failure are detected early in an experimental model of acute renal failure. This study also confirms that, although most plasma porphyrins circulate bound to proteins, hemodialysis may reduce levels of plasma porphyrins when a high permeability membrane is used.