微量白蛋白尿
医学
蛋白尿
内科学
危险系数
坎德萨坦
肾脏疾病
糖尿病肾病
置信区间
安慰剂
2型糖尿病
肾功能
泌尿科
糖尿病
血压
内分泌学
肾
病理
血管紧张素II
替代医学
作者
Morten Lindhardt,Frederik Persson,Petra Zürbig,Angélique Stalmach,Harald Mischak,Dick de Zeeuw,Hiddo Lambers Heerspink,Ronald Klein,Trevor J. Orchard,Massimo Porta,John Fuller,Rudolf W. Bilous,Nish Chaturvedi,Hans‐Henrik Parving,Peter Rossing
摘要
Early prevention of diabetic nephropathy is not successful as early interventions have shown conflicting results, partly because of a lack of early and precise indicators of disease development. Urinary proteomics has shown promise in this regard and could identify those at high risk who might benefit from treatment. In this study we investigate its utility in a large type 2 diabetic cohort with normoalbuminuria. We performed a post hoc analysis in the Diabetic Retinopathy Candesartan Trials (DIRECT-Protect 2 study), a multi centric randomized clinical controlled trial. Patients were allocated to candesartan or placebo, with the aim of slowing the progression of retinopathy. The secondary endpoint was development of persistent microalbuminuria (three of four samples). We used a previously defined chronic kidney disease risk score based on proteomic measurement of 273 urinary peptides (CKD273-classifier). A Cox regression model for the progression of albuminuria was developed and evaluated with integrated discrimination improvement (IDI), continuous net reclassification index (cNRI) and receiver operating characteristic curve statistics. Seven hundred and thirty-seven patients were analysed and 89 developed persistent microalbuminuria (12%) with a mean follow-up of 4.1 years. At baseline the CKD273-classifier predicted development of microalbuminuria during follow-up, independent of treatment (candesartan/placebo), age, gender, systolic blood pressure, urine albumin excretion rate, estimated glomerular filtration rate, HbA1c and diabetes duration, with hazard ratio 2.5 [95% confidence interval (CI) 1.4–4.3; P = 0.002] and area under the curve 0.79 (95% CI 0.75–0.84; P < 0.0001). The CKD273-classifier improved the risk prediction (relative IDI 14%, P = 0.002; cNRI 0.10, P = 0.043). In this cohort of patients with type 2 diabetes and normoalbuminuria from a large intervention study, the CKD273-classifier was an independent predictor of microalbuminuria. This may help identify high-risk normoalbuminuric patients for preventive strategies for diabetic nephropathy.
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