A four-drug combination therapy consisting of low-dose tacrolimus, low-dose mycophenolate mofetil, corticosteroids, and mizoribine in living donor renal transplantation: A randomized study.
Yan T, Wu X, et al.SAGE Open Medicine 2016; 4: 2050312116643672.
Aims
To compare the effects of a three-drug, versus four-drug combination therapy in living donor renal transplantation.
Interventions
Participants were randomized to either a four-drug combination therapy (study group), versus a three-drug combination therapy (control group).
Participants
56 patients aged 17-60 years who had undergone an ABO-identical or compatible living donor renal transplantation.
Outcomes
The primary outcome measured was the incidence of gastrointestinal disorders , specifically diarrhoea. Secondary measured outcomes included acute rejection, patient and graft survival, serum creatinine levels, adverse effects and estimated glomerular filtration rate.
Follow-up
1 year
CET Conclusions
In this small pilot study from China recipients of ABO compatible living donor renal transplants were randomised to receive tacrolimus, mycophenolate and steroids at normal doses although the steroid dose would be considered to be high-dose steroids in this day and age. The study group received tacrolimus and MMF with dosage and trough levels reducing by 50% but did include the addition of Mizoribine plus the same steroid dosage. One major criticism is that the randomisation was based on allocation according to the hospital chart number which of course introduces potential bias and prevents allocation concealment. The number of patients assessed for eligibility was 60 of whom 56 were randomised to the study group or control group. The primary outcome was the incidence of diarrhoea for which sample size had been calculated, and secondary outcomes were acute rejection, renal function and graft survival. Twenty-three recipients in the study group were available for analysis and 28 in the control group. In terms of the primary outcome there was a marked decrease in the incidence of diarrhoea and there was no difference in the incidence of acute rejection. Renal function was a little bit better in the study group at 12 months and this difference was significant. The authors point out the limitations of the study to which I have added the question of randomisation but the results are suggestive and do perhaps lend weight to the suggestion of reducing mycophenolate or, indeed, I would suggest abolishing it altogether and adding Mizoribine in its place (or indeed azathioprine). Further large prospective randomised trials will be required to support the suggestions made in this paper.
Data analysis
Modified intention-to-treat analysis
Trial registration
Chinese Clinical Trial Registry - ChiCTR-ICQ-15007131