The pathophysiological mechanisms involved in the genesis of diabetic nephropathy (DN) have not been fully elucidated. Nonetheless it is well established that oxidative stress plays a key role in the development of this complication in type 1 diabetes mellitus (T1D). The study of biochemical pathways associated with the development of DN in humans is complicated by the need of renal biopsy. Recently the development of more sensitive techniques of molecular biology has increased the use of urine as a reliable sample source to the study of renal diseases. Our group has been conducting systematic collection of urine samples from T1D patients in order to identify new biomarkers of kidney function evolution and to elucidate pathophysiological mechanisms of DN. Previous work from our laboratory have shown increased expression of the gene encoding the thioredoxin interacting protein (TXNIP) in the urinary sediment of T1D considered as "decliners" (patients with a decrease of the estimated glomerular filtration rate [eGFR]>5 mL/min/1.73m2 per year) versus "non decliners" patients. This project aims to expand the use of urine as a tool to study DN, specifically evaluating: (1) the cellular profile of urinary sediment of T1D patients with different degrees of renal disease using flow cytometry; (2) the gene expression profile of the urinary sediment of "decliners" compared to "non decliners" patients; (3) the expression of urine micro RNAs (miRNAs) related to genes of pro-oxidant pathways and its association with the evolution of DN and (4) the expression of these miRNAs in cultured human mesangial and tubular cells, to evaluate the origin of these miRNAs in renal tissue. To this end we collected since 2013 urine samples from 68 T1D patients with varying degrees of DN. New samples continue to be collected, as well as the biochemical and clinical data of patients, in order to evaluate the association of the molecular and cellular results with the evolution of renal function.
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