Calcineurin inhibitor withdrawal or tapering for kidney transplant recipients.
Karpe KM, Talaulikar GS, et al.Cochrane Database of Systematic Reviews 2017; 7: CD006750.
Aims
To conduct a systematic review to determine the benefits and harms of calcineurin inhibitor (CNI) tapering or withdrawal in kidney transplant recipients.
Interventions
The Cochrane Kidney and Transplant Specialised Register was searched up to 11th October 2016 for all randomised controlled trials where standard dose CNI regimens were compared with CNI withdrawal or tapering for kidney transplant recipients. Two authors independently screened titles and abstracts for inclusions and independently carried out the data extraction.
Participants
83 studies (583 records and 16,156 participants) were included in the analysis.
Outcomes
Measured outcomes included graft function and loss, all-cause mortality, acute rejection episodes, treatment-related side effects, rates of malignancy and the incidence of infections.
Follow-up
Variable across studies with the majority between 6 months - 3 years
CET Conclusions
This Cochrane systematic review and meta-analysis represents a large project investigating CNI withdrawal, avoidance or conversion to mTORi in renal transplant recipients. The authors identify 83 studies in over 16,000 recipients, although the quality of many included studies is poor. Given the large scope of the review, dissecting out the key findings is challenging but the authors provide a good summary. Both CNI withdrawal and avoidance most likely increase the risk of acute rejection, but may improve graft function and reduce graft loss. Conversion to mTORi also increases acute rejection, but use of low-dose CNI with an mTORi improves function without an increase in rejection. As one would expect from a Cochrane review, it is very comprehensive and the methodology is sound. What the authors perhaps don’t make clear is that many of the outcomes demonstrate significant heterogeneity (especially acute rejection and renal function) which probably reflects the very variable nature of the included studies such as concomitant immunosuppression, timing of withdrawal/conversion, patient population and baseline graft function. Coupled with the poor quality of much of the evidence, this makes interpretation difficult. There are also a lack of studies with longer-term follow-up.
Quality notes
Quality assessment not appropriate
Trial registration
None