Delayed initiation or reduced initial dose of calcineurin-inhibitors for kidney transplant recipients at high risk of delayed graft function.
A Cochrane review of 12 European randomised trials (2,230 recipients) found that neither delaying calcineurin inhibitors nor starting them at a reduced dose clearly changes delayed graft function, acute rejection, graft loss, death, infections or kidney function in recipients at high risk of delayed graft function; the evidence is mostly low certainty.
Background
Delayed graft function is more common with kidneys from donors after circulatory death, older donors, longer cold ischaemia and higher donor creatinine. Because calcineurin inhibitors are nephrotoxic, delaying their introduction or starting at a low dose has been proposed for recipients at high risk, but there is no agreement on the optimal approach.
Key findings
Twelve randomised or quasi-randomised trials (2,230 participants), all European, were included. Delayed versus early CNI: little or no difference in delayed graft function (6 studies, 905 recipients, RR 0.92, 95% CI 0.76 to 1.12; low certainty), acute rejection (RR 1.02, 95% CI 0.75 to 1.40; low certainty), eGFR (MD -0.81 mL/min; moderate certainty) or all infections (RR 1.10; moderate certainty), with very uncertain evidence on graft loss and death. Low versus standard initial CNI dose: similarly little or no difference in delayed graft function (RR 1.16, 95% CI 0.90 to 1.50; low certainty), acute rejection (RR 0.83; low certainty) or eGFR (MD 4.06 mL/min; low certainty).
Clinical implications
Current randomised evidence does not justify routinely delaying or reducing calcineurin inhibitors solely to prevent delayed graft function. Most trials were unblinded and judged at high risk of bias for dialysis-based DGF definitions and non-biopsy rejection diagnoses, so better-designed trials are needed before practice changes.
Category
Transplant
Source
Cochrane Database of Systematic Reviews
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