Nicolae M Panduru1, Markku Saraheimo2, Carol Forsblom2, Lena M Thorn2, Daniel Gordin2, Johan Wadén2, Nina Tolonen2, Angelika Bierhaus3, Per M Humpert4, Per-Henrik Groop5. 1. 2nd Clinical Department, "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland Diabetes and Obesity Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland. 2. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland Diabetes and Obesity Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. 3. Department of Medicine I and Clinical Chemistry, University of Heidelberg, Heidelberg, Germany. 4. Stoffwechselzentrum Rhein Pfalz, Mannheim, Germany. 5. Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland Diabetes and Obesity Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland Division of Nephrology, Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia per-henrik.groop@helsinki.fi.
Abstract
OBJECTIVE: We investigated the predictive value of urinary adiponectin (uADP) for the progression of diabetic nephropathy (DN) as well as for the principal determinants of uADP concentrations. RESEARCH DESIGN AND METHODS: uADP was measured in 2,090 patients with type 1 diabetes followed for a median of 5.8 (4.4-6.9) years and in 111 subjects without diabetes. Progression was defined as a change in albuminuria (albumin excretion rate [AER]) to a higher stage or development of end-stage renal disease (ESRD). Various Cox regression and competing risk models were used to evaluate the predictive value of uADP for DN progression. The added predictive benefit to AER or estimated glomerular filtration rate (eGFR) was estimated by the area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), continuous net reclassification improvement (NRI), and other statistical indexes. The determinants of uADP were investigated by multiple regression analyses. RESULTS: uADP was an independent predictor of progression to ESRD (hazard ratio 1.60, P < 0.001) and was an even better predictor than AER (P = 0.04) or as good as eGFR (P = 0.79). Furthermore, uADP added a significant benefit when used together with AER (NRI 0.794, P = 0.03; IDI 0.115, P < 0.0001) or eGFR (NRI 0.637, P < 0.001; IDI 0.087, P < 0.0001). The common determinants of uADP were glycemic control, tubular injury, and AER. CONCLUSIONS: uADP is a strong independent predictor of DN progression from macroalbuminuria to ESRD and adds a significant predictive benefit to current biomarkers in patients with type 1 diabetes.
OBJECTIVE: We investigated the predictive value of urinary adiponectin (uADP) for the progression of diabetic nephropathy (DN) as well as for the principal determinants of uADP concentrations. RESEARCH DESIGN AND METHODS: uADP was measured in 2,090 patients with type 1 diabetes followed for a median of 5.8 (4.4-6.9) years and in 111 subjects without diabetes. Progression was defined as a change in albuminuria (albumin excretion rate [AER]) to a higher stage or development of end-stage renal disease (ESRD). Various Cox regression and competing risk models were used to evaluate the predictive value of uADP for DN progression. The added predictive benefit to AER or estimated glomerular filtration rate (eGFR) was estimated by the area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), continuous net reclassification improvement (NRI), and other statistical indexes. The determinants of uADP were investigated by multiple regression analyses. RESULTS:uADP was an independent predictor of progression to ESRD (hazard ratio 1.60, P < 0.001) and was an even better predictor than AER (P = 0.04) or as good as eGFR (P = 0.79). Furthermore, uADP added a significant benefit when used together with AER (NRI 0.794, P = 0.03; IDI 0.115, P < 0.0001) or eGFR (NRI 0.637, P < 0.001; IDI 0.087, P < 0.0001). The common determinants of uADP were glycemic control, tubular injury, and AER. CONCLUSIONS:uADP is a strong independent predictor of DN progression from macroalbuminuria to ESRD and adds a significant predictive benefit to current biomarkers in patients with type 1 diabetes.
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