Tacrolimus versus ciclosporin as primary immunosuppression for kidney transplant recipients: meta-analysis and meta-regression of randomised trial data

Abstract

Objective To compare the positive and negative effects of tacrolimus and ciclosporin as initial treatment for renal transplant recipients. Design Systematic review. Data sources and study selection Reports of comparative randomised trials of tacrolimus and ciclosporin identified by searches of Medline, Embase, the Cochrane Register of Controlled Trials, the Cochrane Renal Group Specialist Register, and conference proceedings. Data extraction and synthesis Two reviewers assessed trials for eligibility and quality and extracted data independently. Data were synthesised (random effects model) and results expressed as relative risk (RR), with values < 1 favouring tacrolimus. Subgroup analysis and meta-regression were used to examine potential effect modification by differences in trial design and immunosuppressive co-interventions. Results 123 reports from 30 trials (4102 patients) were included. At six months, graft loss was significantly reduced in tacrolimus treated recipients (RR = 0.56, 95% confidence interval 0.36 to 0.86), and this effect persisted up to three years. The relative reduction in graft loss with tacrolimus diminished with higher concentrations of tacrolimus (P = 0.04) but did not vary with ciclosporin formulation (P = 0.97) or ciclosporin concentration (P = 0.38). At one year, tacrolimus treated patients had less acute rejection (RR = 0.69, 0.60 to 0.79) and less steroid resistant rejection (RR = 0.49, 0.37 to 0.64) but more diabetes mellitus requiring insulin (RR = 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia, and vomiting. The relative excess of diabetes increased with higher concentrations of tacrolimus (P = 0.003). Ciclosporin treated recipients had significantly more constipation and cosmetic side effects. No differences were seen in infection or malignancy. Conclusions Treating 100 recipients with tacrolimus instead of ciclosporin for the first year after transplantation avoids 12 patients having acute rejection and two losing their graft but causes an extra five patients to develop insulin dependent diabetes. Optimal drug choice may vary between patients.

Calcineurin Inhibitor Nephrotoxicity

“…However, when tacrolimus and cyclosporine efficacy were at similar level in renal transplantation (similar incidence of acute rejection), tacrolimus therapy was associated with significantly lower serum creatinine levels or higher GFR compared with cyclosporine (216 -218), and even better graft survival (219). A change from cyclosporine to tacrolimus for renal allograft dysfunction was also associated with significant improvement in renal function (220,221).…”

How do I manage hyperglycemia/post-transplant diabetes mellitus after allogeneic HSCT

“…7 However, the risk of developing PTDM with tacrolimus was not increased as compared with cyclosporin when lower levels of tacrolimus were used, although the reduced dose of tacrolimus might increase the risk of GVHD. 8 The use of glucocorticoids impairs peripheral glucose uptake and increases hepatic gluconeogenesis and glycogenolysis. 9 The plasma concentrations of various corticosteroids peak at approximately 1 h and their average half-life is about 2.5 h. 9 Prednisone and methylprednisone demonstrate their peak effect on blood glucose levels at 4-8 h with duration of action up to 12-16 h but not typically for 24 h. 10,11 Dexamethasone has a more extended effect up to ⩾ 20 h. 9 Patients who receive glucocorticoids usually have normal fasting glucose levels and high postprandial levels.…”

Renal Transplantation: Experience at a Single Centre

“…With introduction of cyclosporine there was a significant decrease in number of grafts lost due to acute rejections and the incidence of acute rejections reduced to 30% [4,5]. Initially cyclosporine was used in very high dose with significant nephrotoxicity.…”