Abstract
Urinary proteome was analyzed and quantified by tandem mass tag (TMT) labeling followed by bioinformatics analysis to study diabetic nephropathy (DN) pathophysiology and to identify biomarkers of a clinical outcome. We included type 2 diabetic normotensive non-obese males with (n = 9) and without (n = 11) incipient DN (microalbuminuria). Sample collection included blood and urine at baseline (control and DN basal) and, in DN patients, after 3 months of losartan treatment (DN treated). Urinary proteome analysis identified 166 differentially abundant proteins between controls and DN patients, 27 comparing DN-treated and DN-basal patients, and 182 between DN-treated patients and controls. The mathematical modeling analysis predicted 80 key proteins involved in DN pathophysiology and 15 in losartan effect, a total of 95 proteins. Out of these 95, 7 are involved in both processes. VCAM-1 and neprilysin stand out of these 7 for being differentially expressed in the urinary proteome. We observed an increase of VCAM-1 urine levels in DN-basal patients compared to diabetic controls and an increase of urinary neprilysin in DN-treated patients with persistent albuminuria; the latter was confirmed by ELISA. Our results point to neprilysin and VCAM-1 as potential candidates in DN pathology and treatment.
Highlights
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) [1]
Incipient DN is characterized by the appearance of microalbuminuria that increases as the disease progresses and may lead to macroalbuminuria and renal failure
We have studied incipient DN male patients before and after losartan treatment, and, in contrast with other studies, we have selected non-obese patients with a good blood pressure and lipid control, with the aim of improving the identification of factors closely related to the pathogenesis of DN
Summary
Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) [1]. Urine proteomic investigations in DN identified potential biomarkers allowing an early detection of DN as well as prediction of normoalbuminuric diabetic patients prone to develop DN [3, 4]. The usefulness of urine proteomics to reveal potential biomarkers was Journal of Diabetes Research evidenced by a multiple proteomic comparison researches in which several proteins differently abundant in patients with DN were identified. This was an important step forward to improve accurate diagnosis and understanding of the disease mechanisms [6, 7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
