Urine Proteome Specific for Eye Damage Can Predict Kidney Damage in Patients With Type 2 Diabetes: A Case-Control and a 5.3-Year Prospective Cohort Study

OBJECTIVE The predictive value of microalbuminuria (MAU) for kidney damage is limited in type 2 diabetes (T2D). We studied whether a urine proteome specific for sight-threatening proliferative diabetic retinopathy (PDR) is an indicator to predict chronic renal insufficiency (CRI) in patients with T2D. RESEARCH DESIGN AND METHODS A shotgun urine proteomic analysis was performed in patients with MAU and PDR (case subjects) and in patients with MAU and a duration of T2D for > 10 years but without any degree of retinopathy (control subjects). In the cohort study, 210 patients with T2D with an estimated glomerular filtration rate (eGFR) >= 80 mL/min/1.73m(2) were followed for a median of 5.3 years. Urine proteins specific for PDR were used for predicting CRI (eGFR <60 mL/min/1.73 m(2)). RESULTS The top two urine proteins with the highest difference in ratio of case subjects to control subjects were haptoglobin (8.7 times; P < 0.0001) and alpha-2-macroglobulin (5.7 times; P < 0.0001). In the cohort study, patients with baseline urinary haptoglobin >= 20 ng/min (haptoglobinuria) had a higher incidence of CRI than those without (hazard ratio [95% CI] 3.27 [1.41-7.58]; P = 0.006). The overall CRI rate was 3.2% for patients without haptoglobinuria or MAU, 9.5% for those with MAU, and 13.3% for those with haptoglobinuria. The highest rate for CRI (22.4%) was in patients with both MAU and haptoglobinuria (P < 0.001). CONCLUSIONS Urine haptoglobin, which is specific for PDR, is a novel biomarker and complement to urine albumin for predicting kidney damage in patients with T2D.