Clearance of pentosidine, an advanced glycation end product, by different modalities of renal replacement therapy

We recently demonstrated that pentosidine, an advanced glycation end product,accumulates markedly as albumin-linked form (P-alb) and in free-form (P-free) in the plasma of patients with end-stage renal failure. The present study was undertaken to examine the clearance of P-alb and P-free by different modalities of renal replacement therapy, that is, hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), and renal transplantation. HD cleared P-free (9.4 +/- 4.3 nmol/kg/HD) but not P-alb, by diffusion but not by membrane adsorption, whereas CAPD cleared both P-alb (4.03 +/- 2.01 nmol/kg/day) and P-free (2.43 +/- 1.24 nmol/kg/day). Plasma total pentosidine levels were significantly (P < 0.05) lower in CAPD (0.97 +/- 0.41 nmol/ml) than in HD (1.19 +/- 0.41 nmol/ml), as the result of a lower serum albumin level in the former patients. Indeed, P-alb expressed per mg albumin was virtually identical in HD and CAPD. By contrast, P-free was significantly lower in CAPD than in HD. P-alb levels were significantly correlated with plasma P-free levels in both HD and CAPD patients, but not in the CAPD dialysate. Pentosidine transport across the peritoneum occurs mainly by diffusion, both as P-alb and P-free. Interestingly, peritoneal P-alb clearance (0.17 +/- 0.07 ml/min) significantly (P < 0.00001) exceeded albumin clearance (0.11 +/- 0.05 ml/min). P-alb levels being significantly higher (P < 0.0005) in the peritoneal fluid (36.28 +/- 18.55 pmol/mg) than in the serum (27.12 +/- 11.71 pmol/mg), thus raises the possibility of a facilitated diffusion of P-alb or an active transport mechanism for protein-linked pentosidine into the peritoneal cavity. After renal transplantation, plasma P-free fell rapidly, remained barely detectable after one month, and returned to normal at six months. By contrast, P-alb fell more slowly and remained significantly above normal at six months, but returned eventually to normal levels. These findings demonstrate that: (1) both HD and CAPD remove P-free; (2) the peritoneal clearance of P-alb might contribute to the lower level of plasma pentosidine in CAPD than in HD patients; and (3) renal transplantation is the best therapeutic modality to normalize both P-alb and P-free levels.