Abstract
Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). We explored the possibility of using urinary miRNA as non-invasive biomarkers for CKD. We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. Patients were followed for 16.2 ± 15.5 months. Patients with diabetic glomerulosclerosis had lower urinary miR-15 expression, while those with IgA nephropathy had higher urinary miR-17 expression, than other diagnosis groups. Baseline proteinuria had significant inverse correlation with urinary expression of miR-15, miR-192, and miR-216a; baseline renal function correlated with urinary expression of miR-15, miR-17, miR-192, and miR-217. The rate of renal function decline correlated with urinary expression of miR-21 (r=0.301, p=0.026) and miR-216a (r=0.515, p < 0.0001). Patients with a high urinary expression of miR-21 and miR-216a had better dialysis-free survival than those with low expression (log rank test, p=0.005 and p=0.003, respectively). Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure. Our results suggest that urinary miRNA profiling has the potential of further development as biomarkers of CKD.
Highlights
Chronic kidney disease (CKD) is a debilitating and costly medical condition
We have previously reported that urinary expression of miR-200a, miR-200b and miR-429 were downregulated in patients with IgA nephropathy, and the degree of reduction correlated with disease severity and rate of progression [13], while patients with active lupus nephritis had lower urinary expression of miR200a, miR-200c, miR-141, miR-429 and miR-192 than healthy controls [14]
Most of the baseline clinical and biochemical parameters were highly comparable between the diagnosis groups, except patients with diabetic glomerulosclerosis had more proteinuria (p < 0.0001) and marginally more tubulointerstitial scarring (p = 0.09) than the other groups
Summary
The clinical course is characterized by persistent proteinuria after an initial insult to the kidney, followed by progressive decline in renal function [1]. Evidence indicates that miRNAs play a role in the pathogenesis of many human diseases [6,7]. Evidence indicates that microRNAs (miRNA) play a role in the pathogenesis of chronic kidney diseases (CKD). Methods: We quantified miRNA expression in urinary sediment of 56 CKD patients who underwent kidney biopsy. The rate of renal function decline correlated with urinary expression of miR-21 (r = 0.301, p = 0.026) and miR-216a (r = 0.515, p < 0.0001). Conclusions: Urinary miR-21 and miR-216a expression correlated with the rate of renal function decline and risk of progression to dialysis-dependent renal failure.
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