Elevated Circulating Pigment Epithelium-Derived Factor Predicts the Progression of Diabetic Nephropathy in Patients With Type 2 Diabetes

Abstract

CONTEXT: Pigment epithelium-derived factor (PEDF), a circulating glycoprotein with antiangiogenic, antioxidative, and anti-inflammatory properties, protects against diabetic nephropathy (DN) in animal models. OBJECTIVE: We investigated whether circulating PEDF predicted the progression of DN in a 4-year prospective study. DESIGN, SETTING, AND PARTICIPANTS: Baseline plasma PEDF levels were measured in type 2 diabetic subjects recruited from the Hong Kong West Diabetes Registry. The role of PEDF in predicting chronic kidney disease (CKD) and albuminuria progression was analyzed using Cox regression analysis. MAIN OUTCOME MEASURE: We evaluated CKD progression, defined as deterioration in CKD staging and a 25% or greater drop in estimated glomerular filtration rate (eGFR) according to International Society of Nephrology statements. RESULTS: At baseline, plasma PEDF levels increased progressively with CKD staging (P for trend <.001; n = 1136). Among 1071 subjects with baseline CKD stage ≤ 3, plasma PEDF levels were significantly higher in those with CKD progression (n = 171) during follow-up than those without (P < .001). Baseline PEDF was independently associated with CKD progression (hazard ratio = 2.76; 95% confidence interval = 1.39-5.47; P = .004), adjusted for age, sex, waist circumference, diabetes duration, hemoglobin A1c, systolic blood pressure, use of antihypertensive drugs, C-reactive protein, and eGFR. Elevated baseline PEDF was also associated with the development of microalbuminuria/albuminuria in a subgroup with normoalbuminuria and eGFR >60 mL/min/1.73 m(2) (n = 462) at baseline (hazard ratio = 2.75; 95% confidence interval = 1.01-7.49; P < .05), even after adjustment for potential confounders. CONCLUSIONS: Elevated PEDF levels may represent a compensatory change in type 2 diabetic patients with renal disease and appear to be a useful marker for evaluating the progression of DN.