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Analysis of Circulating and Urinary Levels of hsa-miRNA-770-5p in Diabetic Nephropathy
Dimitar Nikolov1, Georgi Nikolov1, Mariela Geneva-Popova2
1Second Department of Internal Diseases, Faculty of Medicine, Clinic of Nephrology, University Hospital "St. George", Medical University-Plovdiv, 4002 Plovdiv, Bulgaria.
Background:
Diabetic nephropathy (DN), also referred to as diabetic kidney disease, represents one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and remains a leading cause of end-stage renal disease worldwide. Conventional clinical markers, including albuminuria and estimated glomerular filtration rate (eGFR), are widely used for diagnosis and staging but may have limited sensitivity for detecting early renal injury and predicting disease progression. In recent years, circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers that reflect underlying molecular mechanisms of diabetic nephropathy and may complement traditional clinical indicators.
Objective:
The present study aimed to evaluate serum and urinary levels of hsa-miRNA-770-5p across different stages of diabetic nephropathy and to assess its potential diagnostic value in relation to established indicators of renal function.
Methods:
A total of 257 participants were included and divided into four groups: healthy controls, patients with T2DM without nephropathy, patients with T2DM and DN in CKD stages I-II, and patients with DN undergoing maintenance hemodialysis (MHD). Serum and urinary levels of miRNA-770-5p were measured using quantitative real-time polymerase chain reaction (qPCR) and analyzed using the 2-ΔΔCt method. Statistical analyses included comparisons between groups using ANOVA, correlation analyses with renal function parameters such as eGFR and proteinuria/albuminuria, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance.
Results:
Serum levels of miRNA-770-5p were significantly elevated in patients with DN and in patients undergoing maintenance hemodialysis compared with healthy controls and patients with T2DM without nephropathy. In contrast, urinary levels of miRNA-770-5p were markedly reduced in patients with DN. Serum levels in patients with T2DM without nephropathy were slightly lower than those observed in healthy controls. Significant correlations were identified between miRNA-770-5p levels and renal function parameters, including eGFR and proteinuria/albuminuria, supporting the biological relevance of this microRNA in renal injury. ROC curve analysis demonstrated good discriminatory ability for differentiating DN from T2DM without nephropathy (serum AUC = 0.82; urine AUC = 0.79).
Conclusions:
hsa-miRNA-770-5p demonstrates distinct and opposite patterns in serum and urine that correlate with the severity of diabetic nephropathy. The complementary changes observed in circulating and urinary levels support the potential of miRNA-770-5p as a non-invasive biomarker that may complement conventional clinical markers and provide additional insight into the molecular mechanisms involved in the development and progression of diabetic nephropathy.
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