Abstract
BackgroundPatients with both diabetes mellitus (DM) and kidney disease could have diabetic nephropathy (DN) or non-diabetic renal disease (NDRD). IgA nephropathy (IgAN) and membranous nephropathy (MN) are the major types of NDRD. No ideal noninvasive diagnostic model exists for differentiating them. Our study sought to construct diagnostic models for these diseases and to identify noninvasive biomarkers that can reflect the severity and prognosis of DN.MethodsThe diagnostic models were constructed using logistic regression analysis and were validated in an external cohort by receiver operating characteristic curve analysis method. The associations between these microRNAs and disease severity and prognosis were explored using Pearson correlation analysis, Cox regression, Kaplan–Meier survival curves, and log-rank tests.ResultsOur diagnostic models showed that miR-95-3p, miR-185-5p, miR-1246, and miR-631 could serve as simple and noninvasive tools to distinguish patients with DM, DN, DM with IgAN, and DM with MN. The areas under the curve of the diagnostic models for the four diseases were 0.995, 0.863, 0.859, and 0.792, respectively. The miR-95-3p level was positively correlated with the estimated glomerular filtration rate (p < 0.001) but was negatively correlated with serum creatinine (p < 0.01), classes of glomerular lesions (p < 0.05), and scores of interstitial and vascular lesions (p < 0.05). However, the miR-631 level was positively correlated with proteinuria (p < 0.001). A low miR-95-3p level and a high miR-631 level increased the risk of progression to end-stage renal disease (p = 0.002, p = 0.011).ConclusionsThese four microRNAs could be noninvasive tools for distinguishing patients with DN and NDRD. The levels of miR-95-3p and miR-631 could reflect the severity and prognosis of DN.
Highlights
The incidence of diabetes mellitus (DM) has gradually increased with the development of a social economy, and the number of patients with diabetes is expected to exceed 693 million by 2045 [1]
The microRNA profiling of global urinary sediment from patients in the different groups is shown in Supplementary Fig. S1
The volcano plots of microRNAs evaluated in the screening phase are reported in Supplementary Figs
Summary
The incidence of diabetes mellitus (DM) has gradually increased with the development of a social economy, and the number of patients with diabetes is expected to exceed 693 million by 2045 [1]. The gold standard for distinguishing DN and NDRD is renal biopsy, but it cannot be performed routinely because of its invasiveness, Received: 18 August 2020 Revised: 20 May 2021 Accepted: 1 June 2021. Patients with both diabetes mellitus (DM) and kidney disease could have diabetic nephropathy (DN) or nondiabetic renal disease (NDRD). METHODS: The diagnostic models were constructed using logistic regression analysis and were validated in an external cohort by receiver operating characteristic curve analysis method The associations between these microRNAs and disease severity and prognosis were explored using Pearson correlation analysis, Cox regression, Kaplan–Meier survival curves, and log-rank tests.
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