Noninvasive Prognostication of Polyomavirus BK Virus-Associated Nephropathy

Background. BK virus-associated nephropathy (BKVN) is associated with an increased risk of graft failure. Methods. Levels of mRNAs encoding proteins implicated in inflammation and fibrosis were measured in urine collected at the time of biopsy diagnosis of BKVN in 29 kidney graft recipients and analyzed for prognosticating graft failure using logistic regression. Results. Ten of 29 BKVN patients had graft failure within 36 months of BKVN diagnosis and the remaining 19 patients did not. Serum creatinine level, BKVN biopsy stage, and urinary cell levels of mRNA for plasminogen activator inhibitor (PAI)-1, vimentin, tissue inhibitor of metalloproteinase-1, fibronectin, granzyme B, or perforin were associated with graft failure. A combination of PAI-1 mRNA level, BKVN biopsy stage, and creatinine level (P=0.0015, by logistic regression) and a combination of PAI-1 mRNA and creatinine levels (P=0.001) were the best-fitting models for prognosticating graft failure, and PAI-1 mRNA level was the only independent predictor (odds ratio, 2.8; 95% confidence interval [CI], 1.1-6.8; P= 0.03) by multivariable analysis. The area under the curve for the combination of PAI-1 mRNA, biopsy, and creatinine was 0.92 (95% CI, 0.80-1.0; P<0.001) by receiver operating characteristic curve analysis, and the area under the curve was 0.92 (95% CI, 0.80-1.0; P<0.001) for the combination of PAI-1 mRNA and creatinine. Graft outcome was correctly predicted in 27 of 29 BKVN patients by either model. Conclusion. Urinary cell level of PAI-1 mRNA, measured at the time of BKVN diagnosis, is an independent prognosticator of graft failure and a prediction model of serum creatinine and PAI-1 mRNA is as accurate as the model that includes the biopsy result.