Urinary miR-142-3p: a novel biomarker of the progression of IgA nephropathy.

BACKGROUND

The prognosis of IgA nephropathy (IgAN) varies greatly but tends to be poor. The purpose of the present study was to screen for urinary sediment miRNAs that could be used for the non-invasive prediction of IgAN progression and to explore the mechanisms explaining this.

METHODS

We studied two independent cohorts (2014-2015 and 2018-2022) to identify urinary sediment miRNAs that could be used to predict IgAN progression. Bioinformatic analysis and dual-luciferase experiments were used to identify target genes for miR-142-3p. The fibrotic phenotype of tubular epithelial cells was evaluated in HK-2 cells.

RESULTS

In both the training and validation cohorts, the urinary miR-142-3p expression in patients who showed IgAN progression was significantly higher than that in those who did not (P < 0.0001 and P = 0.003, respectively). Multivariate Cox regression analysis showed that high urinary miR-142-3p expression was an independent risk factor for IgAN progression (P < 0.001). Using the International IgA Nephropathy Prediction Tool (IIGANPT) as a reference, we replaced the pathologic indices in the IIGANPT model with the miR-142-3p expression and found that this did not reduce the predictive value of the model (P = 0.228). miR-142-3p is principally expressed in renal tubular epithelial cells, and the in vitro experiments showed that miR-142-3p influences PI3K-AKT pathway activity via inositol polyphosphate-5-phosphatase, thereby playing a role in this cell type's fibrosis phenotype.

CONCLUSIONS

Urinary miR-142-3p is a biomarker for the progression of IgAN and is involved in the exacerbation of renal fibrosis. Urinary miR-142-3p can be used to replace pathologic indices in the IIGANPT without reducing its predictive efficacy, implying that this modified tool could be used to non-invasively predict IgAN progression.