Plasma microRNA-186 and proteinuria in focal segmental glomerulosclerosis

Abstract

Background: MicroRNAs (miRNAs) are stable in circulation, and their unique expression profiles can serve as fingerprints for various diseases. This study explored whether plasma miRNAs could be used as biomarkers to evaluate disease activity in patients with focal segmental glomerulosclerosis (FSGS).

Study design: Retrospective and prospective cohorts.

Setting & participants: 78 patients with FSGS with nephrotic proteinuria (protein excretion > 3.5g/24 h), 35 patients with FSGS in complete remission, 63 patients with membranous nephropathy, 59 patients with diabetic nephropathy, and 69 apparently healthy controls were recruited. Plasma samples from 51 other patients with FSGS with nephrotic proteinuria were collected prospectively before and after steroid treatment.

Predictors: Plasma miRNA concentration.

Outcomes: Complete remission (protein excretion < 0.4g/24 h), or no response (sustained protein excretion > 3.5g/24 h after 8 weeks of steroid treatment).

Measurements: Quantitative reverse transcription-polymerase chain reaction analysis of plasma miRNAs.

Results: Increases in miR-125b, miR-186, and miR-193a-3p levels were identified in a pooled plasma sample of 9 patients with FSGS compared with that of 9 healthy controls and were confirmed with individual samples from patients with FSGS (n=32) and healthy controls (n=30). Areas under the receiver operating characteristic curves of miR-125b, miR-186, miR-193a-3p, and the 3 miRNAs in combination were 0.882, 0.789, 0.910, and 0.963, respectively. miR-125b and miR-186 concentrations were significantly lower in patients with FSGS in complete remission (n=35) than those with nephrotic proteinuria (n=37). In a prospective study, miR-125b and miR-186 levels declined markedly in patients with FSGS with complete remission (n=29), but not those with no response (n=22), after steroid treatment. Plasma miR-125b and miR-186 levels were not elevated in patients with membranous nephropathy (n=63) and diabetic nephropathy (n=59) regardless of degree of proteinuria. Last, plasma miR-186, but not miR-125b, level was correlated with degree of proteinuria in patients with FSGS (151 samples).

Limitations: Relatively small cohort size.

Conclusions: Plasma miR-186 may be a biomarker for FSGS with nephrotic proteinuria.

Keywords: Plasma miR-186; biomarkers; circulating miRNAs; expression profile; focal segmental glomerulosclerosis (FSGS); kidney disease; microRNA (miRNA); nephrotic syndrome; noncoding RNA; proteinuria; remission.