Tacrolimus berbanding cyclosporin sebagai imunotindasan utama untuk penerima pemindahan buah pinggang
Abstract
Background
Kidney transplantation is the treatment of choice for most patients with end‐stage renal disease (ESRD). Standard protocols in use typically involve three drug groups each directed to a site in the T‐cell activation or proliferation cascade which are central to the rejection process: calcineurin inhibitors (e.g. cyclosporin, tacrolimus), anti‐proliferative agents (e.g. azathioprine, mycophenolate mofetil) and steroids (prednisolone). It remains unclear whether new regimens are more specific or simply more potent immunosuppressants.
Objectives
To compare the effects of tacrolimus with cyclosporin as primary therapy for kidney transplant recipients.
Search methods
MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Renal Group's specialist register and conference proceedings were searched to identify relevant reports of randomised controlled trials (RCTs). Two reviewers assessed studies for eligibility, quality and extracted data independently.
Selection criteria
All RCTs where tacrolimus was compared with cyclosporin for the initial treatment of kidney transplant recipients
Data collection and analysis
Data were synthesised (random effects model) and results expressed as risk ratio (RR), values <1 favouring tacrolimus, with 95% confidence intervals (CI). Subgroup analysis and meta‐regression were used to examine potential effect modification by differences in study design and immunosuppressive co‐interventions.
Main results
123 reports from 30 studies (4102 patients) were included. At six months graft loss was significantly reduced in tacrolimus‐treated recipients (RR 0.56, 95% CI 0.36 to 0.86), and this effect was persistent up to three years. Meta‐regression showed that this benefit diminished as higher trough levels of tacrolimus were targeted (P = 0.04), after allowing for differences in cyclosporin formulation (P = 0.97) and cyclosporin target trough level (P = 0.38). At one year, tacrolimus patients suffered less acute rejection (RR 0.69, 95% CI 0.60 to 0.79), and less steroid‐resistant rejection (RR 0.49, 95% CI 0.37 to 0.64), but more insulin‐requiring diabetes mellitus (RR 1.86, 1.11 to 3.09), tremor, headache, diarrhoea, dyspepsia and vomiting. Cyclosporin‐treated recipients experienced significantly more constipation and cosmetic side‐effects. We demonstrated no differences in infection or malignancy.
Authors' conclusions
Tacrolimus is superior to cyclosporin in improving graft survival and preventing acute rejection after kidney transplantation, but increases post‐transplant diabetes, neurological and gastrointestinal side effects. Treating 100 recipients with tacrolimus instead of cyclosporin would avoid 12 suffering acute rejection, two losing their graft but cause an extra five to become insulin‐requiring diabetics.
PICO
Plain language summary
Tacrolimus adalah lebih unggul daripada cyclosporin dalam memperbaiki kemandirian graft dan mencegah penolakan akut selepas pemindahan buah pinggang, tetapi meningkatkan diabetes lepas pemindahan dan kesan sampingan yang lain
Pemindahan buah pinggang adalah rawatan pilihan bagi kebanyakan pesakit dengan penyakit buah pinggang peringkat akhir (ESRD). Strategi untuk meningkatkan ketersediaan penderma organ dan untuk memanjangkan kemandirian buah pinggang telah menjadi keutamaan dalam pemindahan buah pinggang. Terapi piawai imunosupresif terdiri daripada rawatan awal dan rejim penyelenggaraan untuk mencegah penolakan dan terapi imunosupresif jangka pendek yang lebih intensif untuk merawat episod penolakan yang akut. Ulasan ini membandingkan tacrolimus dengan cyclosporin yang digunakan sebagai imunosupresi utama untuk penerima pemindahan buah pinggang. Tiga puluh kajian (4102 pesakit) disertakan. Tacrolimus adalah lebih unggul daripada cyclosporin dalam meningkatkan kemandirian graft dan mencegah penolakan akut selepas pemindahan buah pinggang, tetapi meningkatkan diabetes lepas pemindahan, kesan sampingan neurologi dan gastrousus. Tiada maklumat yang cukup untuk menilai kos tacrolimus berbanding dengan cyclosporin, dan terdapat kegagalan umum untuk mempertimbangkan kualiti hidup (QOL) global bagi penerima pemindahan yang boleh memaklumkan kefahaman kami tentang keutamaan pesakit dan komplians.
