Profiling of five urinary exosomal miRNAs for the differential diagnosis of patients with diabetic kidney disease and focal segmental glomerulosclerosis

Abstract

Objective: The objective of this study is to investigate the diagnostic utility of microRNAs (miRNAs) for distinguishing between urine samples from patients with Diabetic Kidney Disease (DKD) and those with Focal Segmental Glomerulosclerosis (FSGS).

Methods: In this multicentric, cross-sectional investigation, we enrolled patients diagnosed with DKD, individuals with primary biopsy-proven FSGS, and healthy controls. The top 5 miRNAs (hsa-mir-21, hsa-mir-30a, hsa-mir-193a, hsa-mir-196a, hsa-mir-200a) were selected to quantify miRNAs in urine samples. Isolation of targeted miRNAs was performed from urinary exosomes, and the quantitative profile of the isolated miRNAs was measured by RT-qPCR. The ΔΔCt method was implemented to calculate the fold differences between disease and control samples.

Results: Thirteen DKD patients, 11 FSGS patients, and 14 healthy controls were included in this study. Hsa-mir-21 and hsa-mir-30a exhibited distinct regulation in both groups, with upregulation observed in FSGS and downregulation in DKD (hsa-mir-21 in DKD (0.668 ± 0.25, p < 0.0005) and FSGS (2.267 ± 1.138, p < 0.0077); hsa-mir-30a in DKD (0.874 ± 0.254, p = 0.079) and FSGS (1.378 ± 0.312, p < 0.0006)). Hsa-mir-193a exhibited significant dysregulation in DKD (1.017 ± 0.413, p < 0.029) but not in FSGS (4.18 ± 1.528, p = 0.058). Hsa-mir-196a and hsa-mir-200a showed upregulation in patient groups (hsa-mir-196a in DKD (1.278 ± 0.527, p = 0.074) and FSGS (2.47 ± 0.911, p < 0.0003); hsa-mir-200a in DKD (1.909 ± 0.825, p = 0.082) and FSGS (1.301 ± 0.358, p < 0.008)).

Conclusion: Specific miRNAs, particularly miR-21, miR-30a, miR-196a, and miR-200a, might play a role in the pathogenesis of kidney diseases and could potentially serve as biomarkers to distinguish between FSGS and DKD patients.