Table 4.

Summary of findings, comparison 2: Mammalian target of rapamycin inhibitor plus reduced-dose calcineurin inhibitor versus regular-dose calcineurin inhibitor plus mycophenolic acid/azathioprine (all other cointerventions are identical)

OutcomesNo. of Participants (Studies) Follow-UpQuality of the Evidence (GRADE)Relative Effect (95% CI)Anticipated Absolute Effects
Risk with Regular-Dose CNI + MMF/AZARisk Difference with mTORi + Reduced-Dose CNI
CMV infection1547 (5 RCTs)⊕⊕⊕◯ ModerateaRR, 0.43 (0.24 to 0.80)231 per 1000132 Fewer per 1000 (176–46 fewer)
BK virus infection1320 (3 RCTs)⊕⊕◯◯ Lowb,cRR, 0.57 (0.12 to 2.72)32 per 100014 Fewer per 1000 (28 fewer to 56 more)
Incidence of other viral, bacterial, or fungal infections1028 (2 RCTs)⊕⊕◯◯ Lowc,dRR, 1.08 (0.87 to 1.34)505 per 100040 More per 1000 66 fewer to 172 more)
Acute cellular or antibody-mediated rejection1553 (5 RCTs)⊕⊕⊕◯ ModeratecRR, 0.88 (0.70 to 1.09)192 per 100023 Fewer per 1000 (57 fewer to 17 more)
Graft loss1547 (5 RCTs)⊕⊕⊕◯ ModerateRR, 1.03 (0.64 to 1.65)105 per 10003 More per 1000 (38 fewer to 68 more)
Serious adverse events1150 (3 RCTs)⊕⊕◯◯ Lowc,eRR, 0.87 (0.62 to 1.20)632 per 100082 Fewer per 1000 (240 fewer to 126 more)
CMV disease1441 (4 RCTs)⊕⊕⊕◯ ModeratefRR, 0.42 (0.21 to 0.82)119 per 100069 Fewer per 1000 (94–22 fewer)
Proteinuria1150 (3 RCTs)⊕⊕⊕⊕ HighRR, 1.47 (1.04 to 2.06)99 per 100046 More per 1000 (4–105 more)
Wound-healing complications1150 (3 RCTs)⊕⊕⊕◯ ModerategRR, 1.71 (1.16 to 2.50)230 per 1000163 More per 1000 (37–345 more)
eGFR or creatinine clearance, ml/min per 1.73 m21543 (5 RCTs)⊕⊕◯◯ Lowc,hMD 3.36 higher (4.31 lower to 11.02 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; mTORi, mammalian target of rapamycin inhibitor; CNI, calcineurin inhibitor; MPA, mycophenolic acid; AZA, azathioprine; CMV, cytomegalovirus; RCT, randomized, controlled trial; RR, risk ratio; —, risk ratio not applicable for continuous variables; MD, mean difference.

  • a Heterogeneity detected I2=81%.

  • b Heterogeneity detected I2=71%.

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

  • d Heterogeneity detected I2=53%.

  • e Heterogeneity detected I2=85%.

  • f Heterogeneity detected I2=58%.

  • g Heterogeneity detected I2=56%.

  • h Heterogeneity detected I2=84%.