Long-Term Impact of Cyclosporin Reduction with MMF Treatment in Chronic Allograft Dysfunction: REFERENECE Study 3-Year Follow Up

Abstract

Calcineurin inhibitor (CNI) toxicity contributes to chronic allograft nephropathy (CAN). In the 2-year, randomized, study, we showed that 50% cyclosporin (CsA) reduction in combination with mycophenolate mofetil (MMF) treatment improves kidney function without increasing the risk for graft rejection/loss. To investigate the long-term effect of this regimen, we conducted a follow up study in 70 kidney transplant patients until 5 years after REFERENCE initiation. The improvement of kidney function was confirmed in the MMF group but not in the control group (CsA group). Four graft losses occurred, 2 in each group (graft survival in the MMF group 95.8% and 90.9% in control group). One death occurred in the control group. There was no statistically significant difference in the occurrence of serious adverse events or acute graft rejections. A limitation is the weak proportion of patient still remaining within the control group. On the other hand, REFERENCE focuses on the CsA regimen while opinions about the tacrolimus ones are still debated. In conclusion, CsA reduction in the presence of MMF treatment seems to maintain kidney function and is well tolerated in the long term.

Risk factors and prognosis of late acute rejection in Chinese kidney transplant recipients

“…Patients with LAR had significantly inferior long‐term allograft survival. This observation echoed the findings in previous reports that LAR had a significantly negative impact on CAN and long‐term allograft outcomes . We were unable to demonstrate a significant difference in overall survival in patients with LAR.…”

“…However, no long‐term outcomes were reported. Similar beneficial results with slowing of renal function deterioration without additional risk of acute rejections were also observed in patients with chronic allograft dysfunction with the use of high dose MMF(2 g daily), as in the Reference study and both high dose MMF(2 g daily) and Prednisolone (not less than 10 mg daily) in the Creeping Creatinine Study . Protocol biopsy has been suggested to help to select a low risk group which would benefit from CsA minimization without an increase in rejection .…”

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

“…No acute rejection episodes were observed, and only one patient in each group lost a graft. At 5 years, kidney function had improved in the MMF group, whereas it was impaired in the CsA group [16]. At 5 years, graft survival was 95.8% in the MMF group and 90.9% in the CsA group [16].…”

“…A few studies have assessed the impact of reducing CNI dose on kidney function under the umbrella of introducing MPA . One of the largest studies conducted has been a French randomized prospective study that included 101 kidney transplant patients who had been recipients of a graft for at least 1 year and had presented with a negative slope of 1/serum creatinine .…”

Manejo da doença crônica do enxerto renal

“…22 In another approach, the cyclosporine dose was halved after the addition of MMF, which also resulted in stabilization of the renal function in the group with the reduced cyclosporine dose, whereas those on the full dose experienced progressive worsening. 23 Strategies with mTOR inhibitors have been published. 13,[24][25][26] To date, the most robust study demonstrated that patients with glomerular filtration rates (GFR) > 40 mL/min had improvement of renal function and lower rate of neoplastic diseases 24 months after conversion to sirolimus, compared with controls.…”