Novel urinary biomarker panel to detect Cyclosporine-induced nephrotoxicity in kidney transplantation

Abstract

Kidney transplantation is the best long-term solution for kidney failure [1]. In 2017, over 20 000 people received kidney transplants in the USA [2]. More than 90% were treated with calcineurin inhibitors (CNI), including cyclosporine. CNI inhibit calcineurin, a protein that activates T-cells by inducing transcription of pro-inflammatory interleukins [1]. CNI reduce acute transplant rejections, but by 10 years, virtually all kidney transplant biopsies show CNI-induced nephrotoxicity [3]. This is partially due to repeated vasoconstriction from CNI, but also through the stimulation of profibrotic cytokines, leading to tubulointerstitial fibrosis and atrophy. Biopsies are only conducted when there are indications of graft failure, but more frequent monitoring of cyclosporine-induced nephrotoxicity could enable early diagnoses and better prognoses [4]. Thus, this viewpoint proposes a panel of urinary biomarkers that may enable early detection and indicate the long-term prognosis of cyclosporine-induced nephrotoxicity. The viewpoint aims to minimize the invasiveness of diagnosis and enable continuous monitoring, allowing frequent observation of cyclosporine-induced nephrotoxicity.