Tacrolimus Monotherapy is Safe in Immunologically Low-Risk Kidney Transplant Recipients: A Randomized-Controlled Pilot Study

Abstract

In this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, www.trialregister.nl]. Low immunological risk was defined as maximal 3 HLA mismatches and the absence of panel reactive antibodies. Six months after transplantation, recipients were randomized if eGFR >30 ml/min, proteinuria <50 mg protein/mmol creatinine, no biopsy-proven rejection after 3 months, and no lymphocyte depleting therapy given. Recipients were randomized to tacrolimus/mycophenolate mofetil (TAC/MMF) or to taper and discontinue MMF at month 9 (TACmono). 79 of the 121 recipients were randomized to either TACmono (n = 38) or TAC/MMF (n = 41). Mean recipient age was 59 years and 59% received a living donor transplant. The median follow-up was 62 months. After randomization, 3 TACmono and 4 TAC/MMF recipients experienced a biopsy-proven rejection. At 5 years follow-up, patient survival was 84% in TACmono versus 76% in TAC/MMF with death-censored graft survival of 97% for both groups and no differences in eGFR and proteinuria. Eleven TACmono recipients had an infectious episode versus 22 TAC/MMF recipients (p < 0.03). Donor-specific anti-HLA antibodies were not detected during follow-up in both groups. Tacrolimus monotherapy in selected immunologically low-risk kidney transplant recipients appears safe and reduces the number of infections.

Transplant Candidates of 70+ Years Have Superior Survival If Receiving Pre-Emptively a Living Donor Kidney

“…Recently, it was shown in a small RCT that immunologically low-risk elderly recipients could be safely managed with tacrolimus monotherapy one year after transplantation. The results showed significantly fewer infections and a much better COVID vaccination response while medication adherence improved with fewer gastro-intestinal side effects [24]. Though these results indicate that the aged immune system of the elderly allows for and benefits from less intense immune suppression, confirmation in a larger study is required.…”

The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients

“…In a recent study, immunological low-risk patients, of whom the majority were elderly, were randomized for continuing standard immune suppression vs. tacrolimus monotherapy at 1 year after transplantation [34]. This feasibility study showed that after discontinuation of MMF, DSA remained undetectable for at least 4 years, infections were reduced, and vaccination responses to SARS-CoV-19 were superior [35].…”

Transplant Trial Watch

“…In a recent pilot study, researchers from Erasmus Medical Centre in the Netherlands investigated the ability to withdraw MMF in low immunological-risk recipients by 9 months following renal transplant [ 4 ]. A pre-planned sub-study investigated responses to the pneumococcal, tetanus and influenza vaccines at 12-month post-transplant [ 5 ].…”