Transplant Trial Watch

Adverse Outcomes of Tacrolimus Withdrawal in Immune-Quiescent Kidney Transplant Recipients.

Hricik DE, Formica RN, et al.

Journal of the American Society of Nephrology 2015; 26(12): 3114-3122.

To identify a specific subset of kidney transplant recipients capable of tolerating calcineurin inhibitor (CNI) withdrawal.

Participants received rabbit antithymocyte globulin, tacrolimus, mycophenolate mofetil, and prednisone. Those without de novo donor-specific antibodies (DSAs), acute rejection (AR) or inflammation at a protocol biopsy six months post-transplantation were randomized to wean off or remain on tacrolimus.

21 primary living donor recipients of a related or unrelated, HLA–mismatched kidney transplant, aged ≥18 years old.

The primary outcome measured was interstitial fiborisis/tubular atrophy. Secondary outcomes measured included incidence of AR, estimated glomerular filtration rate, allograft and subject survival rates, and percentage of subjects with de novo post-transplant DSAs.

24 months

CET Conclusions
It is unclear what the target enrolment was for this study, however it was stopped after the randomisation of only 21 patients by the DMSB. Eight of the 14 patients randomised to tacrolimus withdrawal developed acute rejection and/or de novo DSA. Although 6 subjects remained stable off tacrolimus for the duration of follow up (24 months), the attempt to identify recipients who could safely tolerate tacrolimus withdrawal using standard clinical/epidemiological factors indicative of low risk, failed. The transplant recipients involved were over 18 years old, recipients of related/unrelated live donor kidneys, PRA<30% with negative pre-transplant DSA. Patients recieved rATG induction followed by tacrolimus, mycophenolate and prednisolone. The prednisolone was tapered to <5mg by 3 months post-transplant and patients were then randomised to continue tacrolimus or have it withdrawn at 6 months post-transplant.

Jadad score

Data analysis
Per protocol analysis

Allocation concealment

Trial registration - NCT01517984

Funding source
Non-industry funded