Association of JC polyomavirus viruria with nephrolithiasis from a clinical observation and in vitro calcium oxalate monohydrate crystal-cell adhesion assays

Abstract Nephrolithiasis is a prevalent urological disease with complicated pathogenesis. Accumulating evidence suggests microbes may participate in stone formation. JC polyomavirus (JCPyV) commonly infects humans and persists latently in renal tubular epithelial cells with intermittent urinary shedding. However, the association between JCPyV viruria and nephrolithiasis remains unclear. We enrolled 188 nephrolithiasis patients and 194 stone-free controls. Urinary JCPyV DNA was detected by qPCR. We characterized JCPyV DNA kinetics in JCPyV‑exposed HK‑2 cells and assessed changes in calcium oxalate monohydrate (COM) crystal‑cell adhesion upon JCPyV exposure. Statistical analyses included chi-square tests, logistic regression and independent-sample tests. Urinary JCPyV positivity was higher in patients than controls (59.04% vs. 33.51%). After adjusting for age and sex, JCPyV viruria remained associated with nephrolithiasis (OR = 2.52, 95%CI:1.63–3.87, P < 0.001). Persistent detection of JCPyV DNA was observed in JCPyV‑exposed HK‑2 cells, and JCPyV exposure significantly promoted COM crystal adhesion to tubular cells. JCPyV viruria was significantly associated with nephrolithiasis in this cross-sectional study. While in vitro data show JCPyV exposure enhances COM crystal adhesion, these cellular findings cannot confirm JCPyV as a causal driver. Collectively, our findings provide preliminary evidence to guide further research linking JCPyV to kidney stones.