Heme Synthesis in Chronic Renal Failure: The Effects of Hemodialysis, Peritoneal Dialysis and Erythropoietin Treatment

Abstract

Increased plasma porphyrins have been described in patients with chronic renal failure (CRF). We measured plasma levels of porphyrins and the activity in erythrocytes of porphobilinogen deaminase (PBG-D), one of the key enzymes in heme biosynthesis, in CRF patients not yet on dialysis and in patients on intermittent hemodialysis (IHD) or chronic ambulatory peritoneal dialysis (CAPD), some of whom were being treated with recombinant human erythropoietin (rHuEPO). In addition, the amount of immuno-detectable PBG-D (Ig PBG-D) per 100 units standard PBG-D activity (Ig PBG-D/100 U) and the total amount of Ig PBG-D, using polyclonal antibodies, were determined in erythrocytes of all patients and controls to detect changes in biodegradation of this enzyme. Plasma porphyrins were increased in CRF patients not yet on dialysis and even higher in both patient groups on dialysis compared with controls. Plasma porphyrins were higher in patients on IHD than in patients on CAPD. The 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 patients on CAPD. Reticulocyte counts were also greater in patients on IHD than in CRF patients not yet on dialysis and patients on CAPD. Ig PBG-D was increased in both groups of patients on dialysis and treated with rHuEPO compared with patients not treated with rHuEPO. In conclusion: (1) in patients on IHD, an increased production of porphyrins is, at least partly, caused by an increased PBG-D activity, and (2) an increased 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 erythroid cell population in which a larger part of PBG-D has not yet been degraded.