Increased serum concentrations of pigment epithelium-derived factor in patients with end-stage renal disease.

To the Editor: Pigment epithelium-derived factor (PEDF), a glycoprotein that belongs to the superfamily of serine protease inhibitors, was first purified from the conditioned media of human retinal pigment epithelial cells; it possesses potent neuronal differentiating activity (1). Recently, PEDF has been shown to be a highly effective inhib-itor of angiogenesis. In cell culture and in animal models, PEDF inhibited endothelial cell (EC) growth and migration and suppressed ischemia-induced neovascularization (1). In addition, PEDF was reported to inhibit tumor necrosis factor-␣-induced or angiotensin II-induced EC activation via its antioxidative properties (2). These observations suggest that PEDF may play a protective role against atherosclerosis by suppressing proliferative inflammatory responses to injuries in ECs. Therefore, characterization of the generation and clearance of PEDF could elucidate the pathophysiological role of this multifunctional protein in vivo. In a recent study of a general population of Japanese residents [mean (SD) age 65.7 (9.3) years; 71 men and 125 women] who showed no clinical evidence of coronary or peripheral arterial occlusive diseases, we found that serum PEDF concentrations showed a distribution, within the reference interval, of 8 to 24 mg/L [mean (SD) 14.6 (3.2) mg/L], and that uric acid (P Ͻ0.001), waist circumference (P ϭ 0.009), insulin (P ϭ 0.019), and triglycerides (P ϭ 0.028) were significant independent determinants of serum PEDF concentrations (3). In a previous study, we also showed that age-and uric acid-adjusted PEDF concentrations were substantially higher in proportion to the accumulation of components of the metabolic syndrome. Furthermore , the expression of PEDF in por-cine liver has been associated with body muscularity and obesity (3). In addition, the concentration of PEDF is down-regulated during the differentiation process of preadipocytes to mature adipocytes (3). These observations suggest that serum PEDF concentrations may increase as a counter-system against coronary risk factors in the metabolic syndrome and that liver and/or adipocytes may be a main source of PEDF in the circulation. However, the clearance of PEDF is not yet characterized, and we do not yet know the relation of serum PEDF concentrations to renal function. Therefore, in this study, we used an ELISA system to investigate whether serum concentrations of PEDF increased in patients with end-stage renal disease (ESRD). The study protocol was approved by our institutional ethics committee, and informed consent was obtained from study participants. We tested 50 patients [mean (SD) age, 60.5 (10.7) years] with clinical manifestations of ESRD— 46 were diagnosed …