Korean J Transplant.  2023 Mar;37(1):41-48. 10.4285/kjt.23.0003.

A systematic review and meta-analysis comparing everolimus and calcineurin inhibitors (CNIs) to mycophenolate and CNIs in kidney transplant patients

• Vergara-Rejante L
• Tanhui KK
• Alolod MKL

• KMID: 2541311
• DOI: http://doi.org/10.4285/kjt.23.0003

Abstract

Background
This study compared everolimus and mycophenolate mofetil, each paired with calcineurin inhibitors (CNIs) and used with or without steroids, for maintaining immunosuppression in kidney transplant (KT) patients.
Methods
Relevant studies published before August 21, 2022 were retrieved from PubMed, the Cochrane Central Register of Controlled Trials, and the gray literature. The risk of bias was assessed independently using the revised Cochrane risk of bias assessment tool (RoB 2). RevMan ver. 5.4 was used to calculate the risk ratios (RRs) with corresponding 95% confidence intervals (CIs) for biopsy-proven acute rejection, death, and infection. The mean difference (MD) was used to compare the estimated glomerular filtration rate (eGFR) between the groups.
Results
Sixteen randomized controlled trials with a total of 5,403 patients were synthesized to compare everolimus (n=2,763) with mycophenolate (n=2,542) for maintaining post-KT immunosuppression. The meta-analysis showed no significant difference in the risk for biopsy-proven acute rejection (RR=1.12; 95% CI, 0.92–1.35; I²=29%) and death (RR=0.85; 95% CI, 0.63–1.16; I²=0%). The eGFR had no significant difference between the two groups (MD=0.93; 95% CI, −2.25 to 4.1; I²=84%). The risk for any infection was significantly higher in the mycophenolate group than in the everolimus group (RR=0.83; 95% CI, 0.73−0.93; I²=66%).
Conclusions
Our meta-analysis showed that when paired with a CNI, everolimus and mycophenolate had no difference in risk for biopsy-proven acute rejection, death, or increase in eGFR. However, the mycophenolate group exhibited a significantly higher risk of infection.

Keyword

Everolimus; Mycophenolate; Rejection; Kidney transplant; Immunosuppression

Figure

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  Fig. 1 PRISMA flowchart [5]. This flowchart illustrates the number of studies included in a stepwise process. a)A total of 951 records were excluded which did not meet screening process.

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  Fig. 2 Quality of the included studies. Green (+), yes (high quality); yellow (?), unclear; red (–), no (low quality).

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  Fig. 3 Forest plot of studies among kidney transplant patients using a random-effect model showed no significant difference in the risk for biopsy-proven acute rejection between everolimus and mycophenolate, with a risk ratio of 1.12 and low heterogeneity among the studies (95% CI, 0.92–1.35; P=0.13 for heterogeneity; I2=29%). EVR, everolimus; MPS, mycophenolate; M–H, Mantel-Haenszel method; CI, confidence interval.

• 

  Fig. 4 Forest plot of studies among kidney transplant patients using a random-effect model showed no significant difference in the risk for death between everolimus and mycophenolate, with a risk ratio of 0.85 and low heterogeneity among the studies (95% CI, 0.63–1.16; P=0.57 for heterogeneity; I2=0%). EVR, everolimus; MPS, mycophenolate; M–H, Mantel-Haenszel method; CI, confidence interval.

• 

  Fig. 5 Forest plot of studies among kidney transplant patients using a random-effects model showed no difference in the estimated glomerular filtration rate between the everolimus and mycophenolate groups with a mean difference of 0.93 (95% CI, –2.25 to 4.1; P<0.00001 for heterogeneity). However, studies showed significant heterogeneity, with an I2 of 84%. EVR, everolimus; MPS, mycophenolate; M–H, Mantel-Haenszel method; SD, standard deviation; IV, inverse-variance method; CI, confidence interval.

• 

  Fig. 6 Forest plot of studies among kidney transplant patients using a random-effect model showed a significantly higher risk for any infection in the mycophenolate group than in the everolimus group, with a risk ratio of 0.83 and moderate heterogeneity among the studies (95% CI, 0.73–0.93; P=0.0003 for heterogeneity; I2=66%). EVR, everolimus; MPS, mycophenolate; M–H, Mantel-Haenszel method; CI, confidence interval.

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