Calcineurin inhibitor‐sparing regimens in solid organ transplantation: focus on improving renal function and nephrotoxicity

Abstract

Calcineurin inhibitors are associated with significant nephrotoxicity and chronic kidney damage. Minimization is associated with a modest increase in renal function, but persistent damage is observed on biopsies as long as the CNIs are continued. Avoidance is hampered by lack of experience and possible sirolimus-induced side effects. CNI withdrawal may be the best option by delivering CNIs during the early period of immunologic graft injury and then converting them to less nephrotoxic agents before significant renal damage occurs.

Five-Year Outcomes in Kidney Transplant Patients Converted From Cyclosporine to Everolimus: The Randomized ZEUS Study

“…Late conversion from CNI therapy to an mTOR inhibitor has not shown a renal benefit (26,27), and it is now generally accepted that conversion not later than month 6 posttransplant is advisable and offers most benefit for long-term benefit on renal function (3,28,29). Other, smaller randomized trials have examined the effect of early conversion to everolimus (21) or sirolimus (19,20,30), some of which have provided longer-term follow-up data.…”

“…These efforts have focused on three possible strategies: total avoidance of CNI therapy, low-exposure CNI regimens, or CNI withdrawal (3,4). A key objective for any CNI minimization strategy is the preservation of longterm renal function, which may ultimately lead to improved graft survival but only after many years' follow-up (5).…”

Cell-Free DNA: An Upcoming Biomarker in Transplantation

“…In addition, drug-induced toxicity is an important cause of graft dysfunction in kidney and liver transplantation (1,2). The incidence of acute rejection varies between graft types, with the highest incidence of acute rejection after intestinal, heart, and lung transplantation (approximately 55%, 30-45%, and 35-40%, respectively) (3)(4)(5).…”

Transcriptional Profiling of Belatacept and Calcineurin Inhibitor Therapy in Renal Allograft Recipients

“…One approach to extending allograft survival is to provide adequate maintenance immunosuppression using a non-CNI-based regimen (4,5). Belatacept is a fusion protein that specifically binds to the CD80/86 costimulatory receptors expressed on antigen-presenting cells, thereby blocking their interaction with CD28 on T cells and preventing productive T cell activation.…”