Department of Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Diabetes Care. 2013 May;36(5):1248-53. doi: 10.2337/dc12-1298. Epub 2012 Dec 5.
To improve prognosis, it is important to predict the incidence of renal failure and cardiovascular disease in type 2 diabetic patients before the progression to advanced nephropathy. We investigated the predictive effects of urinary liver-type fatty acid-binding protein (L-FABP), which is associated with renal tubulointerstitial damage, in renal and cardiovascular prognosis.
Japanese type 2 diabetic patients (n = 618) with serum creatinine ≤1.0 mg/dL and without overt proteinuria were enrolled between 1996 and 2000 and followed up until 2011. Baseline urinary L-FABP was measured with an enzyme-linked immunosorbent assay. The primary end points were renal and cardiovascular composites (hemodialysis, myocardial infarction, angina pectoris, stroke, cerebral hemorrhage, and peripheral vascular disease). The secondary renal outcomes were the incidence of a 50% decline in estimated glomerular filtration rate (eGFR), progression to an eGFR <30 mL/min/1.73 m(2), and the annual decline rate in eGFR.
During a 12-year median follow-up, 103 primary end points occurred. The incidence rate of the primary end point increased in a stepwise manner with increases in urinary L-FABP. In Cox proportional hazards analysis, the adjusted hazard ratio in patients with the highest tertile of urinary L-FBAP was 1.93 (95% CI 1.13-3.29). This relationship was observed even when analyzed separately in normoalbuminuria and microalbuminuria. Patients with the highest tertile of urinary L-FABP also demonstrated a higher incidence of the secondary renal outcomes.
Our results indicate that urinary L-FABP may be a predictive marker for renal and cardiovascular prognosis in type 2 diabetic patients without advanced nephropathy.
为改善预后，在 2 型糖尿病患者进展为晚期肾病之前预测肾衰竭和心血管疾病的发生非常重要。我们研究了与肾小管间质损伤相关的尿肝型脂肪酸结合蛋白（L-FABP）对肾脏和心血管预后的预测作用。
1996 年至 2000 年间共纳入 618 名血清肌酐≤1.0mg/dL 且无明显蛋白尿的日本 2 型糖尿病患者，并随访至 2011 年。采用酶联免疫吸附试验检测基线尿 L-FABP。主要终点是肾脏和心血管复合终点（血液透析、心肌梗死、心绞痛、中风、脑出血和外周血管疾病）。次要肾脏结局包括 eGFR 下降 50%、进展为 eGFR<30mL/min/1.73m(2)和 eGFR 年下降率。
在 12 年的中位随访期间，发生了 103 个主要终点事件。尿 L-FABP 升高的患者中，主要终点事件的发生率呈逐步增加。在 Cox 比例风险分析中，尿 L-FABP 最高三分位患者的调整后风险比为 1.93（95%CI 1.13-3.29）。即使在正常白蛋白尿和微量白蛋白尿中分别进行分析，也观察到了这种关系。尿 L-FABP 最高三分位的患者也表现出更高的次要肾脏结局发生率。
我们的结果表明，尿 L-FABP 可能是预测无晚期肾病的 2 型糖尿病患者肾脏和心血管预后的标志物。
