A Pilot Study of Urinary Cubilin Shedding in Type 1 Diabetes Mellitus: A Potential Biomarker to Predict Nephropathy.
Source: PubMed, NCBI / U.S. National Library of Medicine
Considering the low sensitivity of microalbuminuria and the increasing prevalence of diabetic nephropathy, biomarker discovery is a priority in diabetes research. We have previously reported increased urinary cubilin shedding preceding microalbuminuria in patients with Type 1 diabetes. In this study, we investigated the predictive value of urinary cubilin as a biomarker in diabetic nephropathy utilizing urine samples collected in one of the largest prospective cohort studies of Type 1 diabetes, Pittsburgh Epidemiology of Diabetes Complications. We measured urinary cubilin by ELISA in urine samples of the participants with normal kidney function and normoalbuminuria obtained at recruitment. Patients were stratified into three groups based on their disease course during a follow-up of > 20 years. Group 1 preserved normal kidney function and normoalbuminuria, Group 2 preserved kidney function but developed macroalbuminuria, and Group 3 progressed to have a > 40% decrease in kidney function during follow-up. We demonstrated that urinary cubilin normalized for creatinine predicted progressive diabetic nephropathy with an area under the receiver operating characteristic curve of 0.81. The urinary cubilin:creatinine ratio was marginally significant across the three groups evaluated by the Kruskal-Wallis test (p = 0.066). The adjusted p value for multiple comparisons of the urinary cubilin:creatinine ratio in comparing the group with > 40% decrease in kidney func
Abstract
Considering the low sensitivity of microalbuminuria and the increasing prevalence of diabetic nephropathy, biomarker discovery is a priority in diabetes research. We have previously reported increased urinary cubilin shedding preceding microalbuminuria in patients with Type 1 diabetes. In this study, we investigated the predictive value of urinary cubilin as a biomarker in diabetic nephropathy utilizing urine samples collected in one of the largest prospective cohort studies of Type 1 diabetes, Pittsburgh Epidemiology of Diabetes Complications. We measured urinary cubilin by ELISA in urine samples of the participants with normal kidney function and normoalbuminuria obtained at recruitment. Patients were stratified into three groups based on their disease course during a follow-up of > 20 years. Group 1 preserved normal kidney function and normoalbuminuria, Group 2 preserved kidney function but developed macroalbuminuria, and Group 3 progressed to have a > 40% decrease in kidney function during follow-up. We demonstrated that urinary cubilin normalized for creatinine predicted progressive diabetic nephropathy with an area under the receiver operating characteristic curve of 0.81. The urinary cubilin:creatinine ratio was marginally significant across the three groups evaluated by the Kruskal-Wallis test (p = 0.066). The adjusted p value for multiple comparisons of the urinary cubilin:creatinine ratio in comparing the group with > 40% decrease in kidney function and the other two groups was 0.05. The urine cubilin:creatinine ratio between the group with > 40% decrease in GFR and preserved kidney function was significant, with a p value of 0.017. We propose that urinary cubilin can be a promising biomarker to predict progressive diabetic nephropathy in patients with Type 1 diabetes. Studies involving larger patient populations are warranted to further validate urinary cubilin shedding as a novel biomarker in predicting progressive diabetic nephropathy.