Department of Medicine (E.H., C.-Y.Y., P.C.H.L., Y.-C.W., C.H.Y.F., W.-S.C., A.X., K.S.L.L., Queen Mary Hospital; Research Centre of Heart, Brain, Hormones, and Healthy Aging (E.H., A.X., K.S.L.L.); and State Key Laboratory of Pharmaceutical Biotechnology (A.X., K.S.L.L.), The University of Hong Kong, Hong Kong, China.
J Clin Endocrinol Metab. 2014 Nov;99(11):E2169-77. doi: 10.1210/jc.2014-2235. Epub 2014 Aug 28.
Pigment epithelium-derived factor (PEDF), a circulating glycoprotein with antiangiogenic, antioxidative, and anti-inflammatory properties, protects against diabetic nephropathy (DN) in animal models.
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.
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.
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.
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.
色素上皮衍生因子（PEDF）是一种具有抗血管生成、抗氧化和抗炎作用的循环糖蛋白，可在动物模型中预防糖尿病肾病（DN）。
我们在一项为期 4 年的前瞻性研究中，研究了循环 PEDF 是否可以预测 DN 的进展。
设计、地点和参与者：从香港西部糖尿病登记处招募的 2 型糖尿病患者中测量基线血浆 PEDF 水平。使用 Cox 回归分析分析 PEDF 在预测慢性肾脏病（CKD）和白蛋白尿进展中的作用。
我们评估了 CKD 进展，根据国际肾脏病学会的声明，定义为 CKD 分期恶化和估算肾小球滤过率（eGFR）下降 25%或更多。
在基线时，血浆 PEDF 水平随 CKD 分期逐渐升高（趋势 P <.001；n = 1136）。在基线 CKD 分期≤3 的 1071 例患者中，随访期间发生 CKD 进展（n = 171）的患者血浆 PEDF 水平明显高于未发生进展者（P <.001）。基线 PEDF 与 CKD 进展独立相关（风险比=2.76；95%置信区间=1.39-5.47；P =.004），调整年龄、性别、腰围、糖尿病病程、糖化血红蛋白、收缩压、降压药物使用、C 反应蛋白和 eGFR。在基线时具有正常白蛋白尿和 eGFR >60 mL/min/1.73 m 2（n = 462）的亚组中，基线时升高的 PEDF 也与微量白蛋白尿/白蛋白尿的发生相关（风险比=2.75；95%置信区间=1.01-7.49；P <.05），即使在调整了潜在混杂因素后也是如此。
升高的 PEDF 水平可能代表 2 型糖尿病肾病患者的代偿性变化，似乎是评估 DN 进展的有用标志物。
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