HEME-SYNTHESIS IN CHRONIC-RENAL-FAILURE - THE EFFECTS OF HEMODIALYSIS, PERITONEAL-DIALYSIS AND ERYTHROPOIETIN TREATMENT

Increased plasma porphyrins have been described in patients with chron ic renal failure (CRF). We measured plasma levels of porphyrins and th e activity in erythrocytes of porphobilinogen deaminase (PBG-D), one o f the key enzymes in heme biosynthesis, in CRF patients not yet on dia lysis and in patients on intermittent hemodialysis (IHD) or chronic am bulatory peritoneal dialysis (CAPD), some of whom were being treated w ith recombinant human erythropoietin (rHuEPO). In addition, the amount of immuno-detectable PBG-D (Ig PBG-D) per 100 units standard PBG-D ac tivity (Ig PBG-D/100 U) and the total amount of Ig PBG-D, using polycl onal antibodies, were determined in erythrocytes of all patients and c ontrols to detect changes in biodegradation of this enzyme. Plasma por phyrins were increased in CRF patients not yet on dialysis and even hi gher in both patient groups on dialysis compared with controls. Plasma porphyrins were higher in patients on IHD than in patients on CAPD. T he activity of PBG-D was increased and Ig PBG-D/100 U was decreased in patients on IHD compared with CRF patients not yet on dialysis and pa tients on CAPD. Reticulocyte counts were also greater in patients on I HD than in CRF patients not yet on dialysis and patients on CAPD. Ig P BG-D was increased in both groups of patients on dialysis and treated with rHuEPO compared with patients not treated with rHuEPO. In conclus ion: (1) in patients on IHD, an increased production of porphyrins is, at least partly, caused by an increased PBG-D activity, and (2) an in creased PBG-D activity and a decrease in Ig PBG-D/100 U in patients on IHD could be explained by the presence of a (relatively) young erythr oid cell population in which a larger part of PBG-D has not yet been d egraded.