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

Abstract

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.