Table 3.

Summary of findings, comparison 1: Mammalian target of rapamycin inhibitor versus calcineurin inhibitor (all other cointerventions are identical)

OutcomesNo. of Participants (Studies) Follow-UpQuality of the Evidence (GRADE)Relative Effect (95% CI)Anticipated Absolute Effects
Risk with CNIRisk Difference with mTORi
CMV infection3914 (19 RCTs)⊕⊕⊕⊕ HighRR, 0.54 (0.41 to 0.72)110 per 100050 Fewer per 1000 (65–31 fewer)
BK virus infection1989 (12 RCTs)⊕⊕⊕◯ ModerateaRR, 0.71 (0.40 to 1.25)35 per 100010 Fewer per 1000 (21 fewer to 9 more)
Incidence of other viral, bacterial, or fungal infections2682 (12 RCTs)⊕⊕⊕⊕ HighRR, 1.08 (1.02 to 1.15)524 per 100042 More per 1000 (10–79 more)
Composite of incidence of acute cellular or antibody-mediated rejection or DSAs3921 (19 RCTs)⊕⊕⊕◯ ModeratebRR, 1.39 (1.09 to 1.77)194 per 100076 More per 1000 (17–150 more)
Graft loss3589 (17 RCTs)⊕⊕⊕◯ ModerateaRR, 1.10 (0.74 to 1.65)41 per 10004 More per 1000 (11 fewer to 27 more)
Serious adverse events2173 (7 RCTs)⊕⊕⊕◯ ModeratecRR, 1.26 (1.02 to 1.56)387 per 1000101 More per 1000 (8–217 more)
Proteinuria2844 (12 RCTs)⊕⊕⊕⊕ HighRR, 2.35 (1.52 to 3.64)41 per 100055 More per 1000 (21–107 more)
BK nephropathy defined by kidney biopsy561 (3 RCTs)⊕⊕◯◯ Lowa,dRR, 0.54 (0.20 to 1.49)35 per 100016 Fewer per 1000 (28 fewer to 17 more)
Wound-healing complications1826 (7 RCTs)⊕⊕⊕⊕ HighRR, 1.62 (1.22 to 2.15)82 per 100051 More per 1000 (18–94 more)
eGFR or creatinine clearance, ml/min per 1.73 m23768 (18 RCTs)⊕⊕⊕◯ ModerateeMD 4.07 higher (1.34–6.8 higher)
  • The risk in the intervention group (and its 95% CI) is on the basis of the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). GRADE Working Group grades of evidence were used. The approach classifies the quality of evidence into four categories: high, moderate, low, and very low. It takes into account the following factors: risk of bias, imprecision, inconsistency, indirectness, and publication bias. High quality: we are very confident that the true effect is close to that of the estimate of the effect. Moderate quality: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low quality: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low quality: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. GRADE, grading of recommendations assessment, development and evaluation; 95% CI, 95% confidence interval; CNI, calcineurin inhibitor; mTORi, mammalian target of rapamycin inhibitor; CMV, cytomegalovirus; RCT, randomized, controlled trial; RR, risk ratio; DSA, donor-specific antibody; —, risk ratio not applicable for continuous variables; MD, mean difference.

  • a 95% CI does not rule out or confirm difference between the intervention and control groups.

  • b Heterogeneity detected I2=67%.

  • c Heterogeneity detected I2=63%.

  • d Unclear risk of bias in some of the included trials.

  • e Heterogeneity detected I2=74%.