Kidney microRNA-21 Expression and Kidney Function in IgA Nephropathy.

Rationale & Objective: Previous studies have suggested that microRNA-21 (miR-21) plays an important role in kidney fibrosis. We examined the relationship between intrarenal miR-21 level and rate of kidney function loss in immunoglobulin A nephropathy (IgAN).

Study Design: Prospective cohort study.

Setting & Participants: 40 patients with IgAN and 10 with hypertensive nephrosclerosis as controls.

Predictors: miR-21 levels in kidney biopsy specimen and urinary sediment, quantified as ratio to the housekeeping gene.

Outcomes: Kidney event-free survival and rate of kidney function decline.

Analytic Approach: Time-to-event and correlation analysis.

Results: The IgAN group had significantly higher intrarenal miR-21 expression compared with the hypertensive nephrosclerosis group (1.71 [IQR, 0.99-2.77] vs 0.31 [IQR, 0.25-1.32];  < 0.0001), but urinary miR-21 levels were similar. Intrarenal miR-21 expression had significant but modest correlation with severity of glomerulosclerosis ( = 0.293;  = 0.05) and tubulointerstitial fibrosis ( = 0.341;  = 0.03). Patients with high intrarenal miR-21 expression had significantly higher risk for developing kidney end points compared with those with low expression (log-rank test,  = 0.017). Univariate Cox analysis showed that intrarenal miR-21 expression significantly predicted the development of kidney end points (unadjusted HR, 1.586; 95% CI, 1.179-2.134;  = 0.002). However, the result was just short of statistical significance after adjusting for the severity of histologic damage ( = 0.06). There was also a significant correlation between intrarenal miR-21 expression and the slope of kidney function decline by univariate analysis ( = -0.399;  = 0.02).

Limitations: Small sample size; uncertain cellular origin of miR-21.

Conclusions: We found that intrarenal miR-21 expression is increased in patients with IgAN, modestly correlated with the severity of histologic damage, and predictive of subsequent kidney function loss.