Urine and Blood-Derived MicroRNAs in Patients with Kidney Cancer: A Review of Clinical Utility and Recent Developments

Renal cell carcinoma (RCC) is frequently detected incidentally, and no widely adopted noninvasive biomarkers are available for RCC diagnosis or prognosis. In this regard, cell-free microRNAs (cfmiRs) have emerged as promising candidates due to their stability in biological fluids. In this narrative review, we summarize translational studies published from 2010 to 2025 that evaluated serum, plasma, or urinary cfmiRs for RCC diagnosis, prognosis, recurrence surveillance, or treatment-response monitoring. Forty-two studies met inclusion criteria, comprising 3454 patients with RCC and 2445 healthy donors. Twenty-nine studies assessed diagnostic performance, fewer evaluated prognostic applications, and none examined treatment-response monitoring. Multi-miRNA panels generally reported higher performance than single-miRNA assays. Serum was the most frequently studied biofluid in this review (n = 26), followed by urine (n = 12) and plasma (n = 4). Urinary biomarkers demonstrated high specificity and the practical advantage of noninvasive collection. Although limited in number, prognostic studies identified associations between cfmiRs and overall survival, recurrence-free survival, metastasis-free survival, and other clinically relevant outcomes. However, substantial heterogeneity in study design, assay methods, and reporting limited comparisons across studies. Current evidence supports continued evaluation of cfmiRs as adjunctive biomarkers alongside imaging or histopathology, but multicenter validation, standardized methods, and more robust evidence are required before clinical implementation.