Abstract
BackgroundPatients with Type 1 Diabetes (T1D) are particularly vulnerable to development of Diabetic nephropathy (DN) leading to End Stage Renal Disease. Hence a better understanding of the factors affecting kidney disease progression in T1D is urgently needed. In recent years microRNAs have emerged as important post-transcriptional regulators of gene expression in many different health conditions. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease.Methods and FindingsWe studied urine microRNA profiles with qPCR in 40 T1D with >20 year follow up 10 who never developed renal disease (N) matched against 10 patients who went on to develop overt nephropathy (DN), 10 patients with intermittent microalbuminuria (IMA) matched against 10 patients with persistent (PMA) microalbuminuria. A Bayesian procedure was used to normalize and convert raw signals to expression ratios. We applied formal statistical techniques to translate fold changes to profiles of microRNA targets which were then used to make inferences about biological pathways in the Gene Ontology and REACTOME structured vocabularies. A total of 27 microRNAs were found to be present at significantly different levels in different stages of untreated nephropathy. These microRNAs mapped to overlapping pathways pertaining to growth factor signaling and renal fibrosis known to be targeted in diabetic kidney disease.ConclusionsUrinary microRNA profiles differ across the different stages of diabetic nephropathy. Previous work using experimental, clinical chemistry or biopsy samples has demonstrated differential expression of many of these microRNAs in a variety of chronic renal conditions and diabetes. Combining expression ratios of microRNAs with formal inferences about their predicted mRNA targets and associated biological pathways may yield useful markers for early diagnosis and risk stratification of DN in T1D by inferring the alteration of renal molecular processes.
Highlights
Diabetic nephropathy (DN) is the leading cause of End Stage Renal Disease (ESRD) in the Western world, accounting for more than 40% of cases
Urinary microRNA profiles differ across the different stages of diabetic nephropathy
Patients with either type 1 (T1D) or 2 (T2D) diabetes are at risk of DN, but the disease burden is higher in the former group [1]
Summary
Diabetic nephropathy (DN) is the leading cause of End Stage Renal Disease (ESRD) in the Western world, accounting for more than 40% of cases. There have been no comprehensive studies examining miRNA signatures in human urine in relation to either longitudinal clinical outcomes and/or the level of urinary albumin, which is the current gold standard for detecting and staging diabetic nephropathy in the clinic. The goal of this pilot study is to identify the differences on urinary miRNA profiles in patients with long standing T1D who were either free from diabetic nephropathy or had developed variable degrees of albuminuria after long follow-up. We hypothesized that urinary microRNA profile of patients will differ in the different stages of diabetic renal disease
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