A systematic literature review and meta-analysis evaluated modifiable risk factors for the development of BK polyoma virus-associated complications.

Abstract

BK polyomavirus-associated nephropathy (BKPyVAN) remains a significant cause of kidney graft injury. Several risk factors are suggested, mostly based on monocentric or retrospective studies. By performing a systematic literature review and comprehensive meta-analysis we sought to provide solid assumptions and test the reproducibility of known modifiable clinical risk factors for BKPyV. Literature search included Medline, Embase and Cochrane Register of Controlled Trials. Research question was defined with PICOTS framework. Pro- and retrospective clinical studies reporting BKPyV complications in adult kidney transplant recipients were included. Odds, hazard, or risk ratios were directly extracted or calculated. Endpoints were biopsy-proven-, presumptive BKPyVAN, BKPyV-DNAemia and events leading to treatment. Pooled risks were calculated with random effects models. Bias risks were assessed with QUIPS tools, funnel plots and I² statistics. We identified 6,690 publications and included 165 encompassing 197,029 total patients. Twenty-nine studies were graded as high risk for bias. The number of included studies was highest for anti-thymocyte globulin vs. IL-2RA (78 studies), tacrolimus versus cyclosporine (54 studies), and ABO-incompatible transplantation (32 studies). Corticosteroids were significantly associated with three out of four endpoints: tacrolimus and anti-thymocyte globulin with two, and tacrolimus levels, blood group ABO-incompatible transplantation, rituximab, mycophenolate mofetil, mTOR inhibitors, and ureteral stents with one each. We were not able to identify a single independent risk factor for all endpoints, reflecting the complexity in predicting BKPyV-related complications in kidney transplant recipients. Rather than a single drug or procedure, insufficient net immune control over BKPyV replication in donor kidney may significantly promote BKPyV complications.