Leflunomide in the treatment of BK polyomavirus associated nephropathy in kidney transplanted patients - A systematic review

BK polyomavirus (BKPyV) associated nephropathy (BKVAN) is seen in about 5% of renal transplant patients and can lead to chronic graft failure or graft loss. No effective therapy is available. Leflunomide has shown promising results in BKVAN. We performed a systematic review about the use of leflunomide for the treatment of BKVAN. The recommendations of the Cochrane Handbook of systematic Reviews were followed. Due to different study designs and endpoints nometa-analysiswas performed. The literature search for primary studies yielded 274 results. Finally, twelve studieswere includedwith a total of 267 patients. Clearance of BKPyV viremia was reported in 33.3% to 92.3% of cases and 27 graft losses (10.1%). The included studies were very heterogeneous, especially in terms of leflunomide dosing. Pharmacokinetics seem to have an important impact on the efficacy of leflunomide in BKVAN. There was no correlation between leflunomide serum levels and virus reduction. New adverse events of leflunomide have been described, e.g. haemolytic anaemia and thrombotic microangiopathy. Overall, the risk of bias in the studies was assessed as high and the quality of evidence was rated low. The role of leflunomide in BKVAN remains unclear, but further studies seem reasonable and should address pharmacokinetic aspects. (C) 2020 Elsevier Inc. All rights reserved.