Can you have a cake and eat it? Comparing reducing mycophenolate versus switching to everolimus for kidney transplants with new-onset BKPyV-DNAemia.

BK polyomavirus remains a vexing issue in kidney transplantation. There are no antiviral drugs, and solely reducing immunosuppression is recommended for management. However, evidence from randomized controlled studies lacks defining clearance of BK polyomavirus-DNAemia and/or nephropathy as a primary outcome. In this arena of strong opinions, hesitancy, and poor industry interest, Caillard et al. from 16 centers in France take the bull by the horns and present compelling data on clearance of new-onset BK polyomavirus-DNAemia at 6 months after randomizing 130 kidney transplant patients 1:1 to reduced calcineurin inhibitors plus reduced mycophenolate or switching to everolimus. Although both protocols preserve renal allograft function, the mycophenolate arm performs better numerically and kinetically. Thus, everolimus cannot unfold its presumed antiviral effect. The study has potential to serve as new reference for reducing immunosuppression, being neither "mycophenolate first" nor "calcineurin inhibitors first," but "first both." The bar has been set very high now for other interventions alone or on top of "first both."