Calcineurin inhibitor-sparing regimens based on mycophenolic acid after kidney transplantation

Abstract

Summary The use of calcineurin inhibitors (CNIs) has dramatically reduced the number of acute rejections and improved kidney allograft survival. However, CNIs can also cause kidney damage and several adverse events. This has prompted transplant physicians to use CNI‐sparing regimens. CNI withdrawal, minimization, or avoidance protocols have been conducted using mycophenolic acid (MPA), and/or mammalian‐target‐of‐rapamycin inhibitors, and/or belatacept. Herein, we review the outcomes of minimizing, withdrawing, or avoiding CNIs when giving mycophenolic acid to de novo and maintenance kidney transplant patients. Protocols on CNI withdrawal, when based on MPA without mammalian‐target‐of‐rapamycin inhibitors (mTORi) or belatacept, in de novo and maintenance kidney transplant patients, are associated with an increased risk of acute rejection. Consequently, these strategies have been abandoned and are not recommended. Protocols on CNI minimization show a beneficial impact of kidney function and acceptable acute rejection rates mainly in patients who have been recipients of a graft for >3–5 years. However, no significant improvement to graft survival has been observed.

The need for minimization strategies: current problems of immunosuppression

“…As pointed out by Kamar et al . in this issue, MPA‐based minimization leads to better renal function . Although there have been several studies of the potential for CNI‐free protocols with MPA and steroids, complete CNI avoidance or withdrawal over the first 3 years has been associated with an increased rejection risk and worse outcomes in prospective randomized studies .…”

Long‐term outcome after early cyclosporine withdrawal in kidney transplantation: ten years after

“…Furthermore, the incidence of de novo Class II DSA, which is known to have a negative impact on graft survival, 18 was assessed for the first time in a CNI-sparing study. 8 significantly increased in the MMF group. These results suggest that CsA withdrawal is not only associated with a higher incidence of AR, but carries an important risk of chronic rejection in the long term, in accordance with a previous report.…”

“…The analysis for cause biopsies performed after one year postgraft showed that chronic rejection was more frequently observed in the MMF group. Furthermore, the incidence of de novo Class II DSA, which is known to have a negative impact on graft survival, was assessed for the first time in a CNI‐sparing study . Their occurrence significantly increased in the MMF group.…”

“…Several other studies investigated CNI‐sparing strategies and systematic reviews and meta‐analyses recently unraveled this issue . One meta‐analysis specifically focused on strategies involving MMF .…”

Recent advances in kidney transplantation: a viewpoint from the Descartes advisory board*

“…Thus, CNI avoidance, withdrawal or minimization protocols have been conducted using MPA and/or mammalian target of rapamycin inhibitors. Despite promising short-term results, these approaches were associated with more acute rejection and the appearance of de novo donor-specific Abs [ 60 , 61 ]. More recently, the administration of belatacept was associated with better long-term kidney function, as well as better graft and patient survival [ 62 ].…”