Proteomic characterization of obesity-related nephropathy

BACKGROUND: Nephropathy related to obesity lacks a pathophysiological understanding and definite diagnostic pathways by biomarkers. METHODS: In this study we investigated the association between urinary peptides and body mass index (BMI) and renal function in proteome data sets from 4015 individuals. RESULTS: A total of 365 urinary peptides were identified to be significantly associated with BMI. The majority of these peptides were collagen fragments. In addition, most of the peptides also demonstrated a significant concordant association with estimated glomerular filtration rate (eGFR) in the investigated cohort, with the presence of diabetes exhibiting no significant association. A new classifier was developed, based on 150 urinary peptides, that enabled the distinction of non-obese subjects with preserved kidney function from obese, non-diabetic subjects with eGFR >45 mL/min/1.73 m(2) in an independent cohort, with an area under the curve of 0.93. CONCLUSIONS: On a molecular level, the data strongly suggest a link between obesity and fibrosis, which may be a major cause of obesity-related nephropathy.