Sirolimus versus mycophenolate mofetil (MMF) in primary combined pancreas and kidney transplantation. Results of a long-term prospective randomized study

American Journal of Transplantation. 2020;20(3):779-787
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Abstract

The study was aimed to compare pancreas graft survival rates in 2 groups of pancreas and kidney transplant recipients prospectively randomized to treatment either with sirolimus or MMF. From 2002 to 2013, 238 type 1 diabetic recipients with end-stage kidney disease were randomized 1:1 to sirolimus or MMF treatment. Non-censored pancreas survival at 5 years was 76.4 and 71.6 % for Sirolimus and MMF groups, respectively (p > 0.05). Death censored pancreas survival was better in the Sirolimus group (p=0.037). After removal of early graft losses pancreas survival did not differ between groups (MMF 83.1% vs Sirolimus 91.6%, p=0.11). Non-significantly more grafts were lost due to rejection in the MMF group (10 vs 5; p=0.19). Cumulative patient 5-year survival was 96 % in the MMF group and 91 % in the Sirolimus group (p>0.05). Five year cumulative non-censored kidney graft survival rates did not statistically differ (85.6% in Sirolimus group and 88.8% in MMF group) Recipients treated with MMF had significantly more episodes of gastrointestinal bleeding (7 vs 0, p=0.007). More recipients in the sirolimus group required corrective surgery due to incisional hernias (21 vs 12, p=0.019).

CET Conclusion

Reviewer: Mr John O'Callaghan, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
This was a single centre randomised controlled trial that was not blinded. There was a similar pancreas graft survival in both arms to 5 years, but out to 10 year follow up the sirolimus arm had a slight benefit when censored for death. 5-year rates of biopsy proven acute rejection were lower in the sirolimus arm. Incisional hernia rates were higher in the sirolimus arm (approximately 20% versus 12%) and rates of GI bleeding were significantly higher in the MMF arm. Given the early difficulties with wound healing, it may be more beneficial to convert to sirolimus after the first 3 months out from surgery. However, beyond this point there may be some slight benefits over MMF in terms of reduced acute rejection and improved death censored graft survival.

Methodological quality

Jadad score : 3
Allocation concealment : YES
Data analysis : STRICT INTENTION TO TREAT

Study details

Aims : The aim of this study was to compare 5‐year patient and graft survival outcomes in type 1 diabetic kidney and pancreas recipients prospectively randomized for treatment either with sirolimus or mycophenolate mofetil (MMF) in combination with tacrolimus and early steroid withdrawal.
Interventions : Patients were preoperatively randomized for prophylactic immunosuppressive treatment either with tacrolimus and sirolimus or tacrolimus and MMF. Methylprednisolone (250 mg) was administered before transplantation and following by 3 doses of 125 mg. Oral prednisone was initiated thereafter at 20 mg/day. The dose was gradually tapered before being completely withdrawn 6 weeks after transplantation.
Participants : 238 type 1 diabetic recipients with end‐stage kidney disease due to undergo first‐time simultaneous pancreas and kidney transplantation.
Outcomes : The primary outcome of the study was to compare 5‐year pancreas graft survival. Pancreas graft failure was defined as death, graftectomy, retransplantation, or resumption of regular insulin therapy lasting more than 30 days (at any dose). Secondary outcomes were to assess patient survival, kidney survival, and wound healing time. Kidney graft failure was defined as death, retransplantation, resumption of regular dialysis, or graftectomy.
Follow up : 5 years

Metadata

Publication type : Randomised Controlled Trial
Organ : Kidney ; Pancreas
Language : Engish