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Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients




Karpe, Krishna
Talaulikar, Girish
Walters, Giles

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The Cochrane Library


What is the issue? Calcineurin inhibitors (CNI, cyclosporin and tacrolimus) are an important part of treatment to suppress the immune system to prevent rejection of transplanted kidneys. However, CNI can cause high blood pressure and kidney scarring which contribute to worsening of risk factors for heart attack, stroke, and loss of the transplanted organ over time. There are conflicting data on the results of withdrawing these drugs from kidney transplant recipients; some studies suggest improved kidney function but others report a moderate risk of developing rejection. Because of this uncertainty, we assessed the benefits and harms of CNI withdrawal or tapering in kidney transplant recipients to identify which approach was more beneficial. What did we do? We included 83 studies that involved more than 16,000 people in our review. Studies which compared standard dose CNI regimens with withdrawal, tapering or low dose CNI in the post-transplant period were analysed. What did we find? Although withdrawing CNI treatment resulted in more rejections in the short term, there was no clear change in transplanted organ failure, death, development of cancer, or infections. Replacing CNI with another group of drugs - the mTOR inhibitors - did not significantly change outcomes, except for fewer cytomegalovirus (CMV) infections. Lower CNI dose was associated with fewer episodes of kidney transplant rejection and loss, but only in the first year to up to five years after the transplant. Conclusions We found that the long-term outcomes for stopping or gradually reducing CNI therapy were not clear, and that mTOR inhibitors can reduce CMV infections with a higher risk of acute rejection. There were insufficient studies with long term follow-up to clearly determine which treatment is better for people who receive kidney transplants.



Keywords: azathioprine; calcineurin inhibitor; cyclosporin; mycophenolic acid 2 morpholinoethyl ester; tacrolimus; acute graft rejection; clinical trial; controlled clinical trial; creatinine clearance; drug dose comparison; drug dose reduction; drug withdrawal; hu



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