Regulation of porphyrin and heme metabolism in the kidney.

Heme biosynthetic capacity within the kidney is localized mainly within the cells of the proximal convoluted tubule. Porphyrin accumulation in response to porphyrinogenic agents occurs predominantly in the cortical nephrons and decreases dramatically in the medullary region. This pattern of heme biosynthetic capacity correlates with the distribution of mixed function oxidase activities in the kidney. The regulation of heme biosynthesis in kidney cells is qualitatively comparable with that observed in liver, but differs with respect to the time required to realize induction of ALA synthetase in response to porphyrinogenic chemicals. This refractoriness may reflect a substantially greater ratio of regulatory or uncommitted heme to overall heme biosynthetic activity in renal cells, as compared with the hepatocyte. Studies on the mechanisms of trace metal-induced renal porphyria support the view that the kidney can play an important, even predominant, role in the etiology of excess urinary porphyrins excreted as a result of disordered porphyrin metabolism. Evidence from clinical studies suggests that the kidney may also play an important role in the etiology and manifestations of inherited and acquired forms of human porphyria.