Table 3.
Summary of findings, comparison 1: Mammalian target of rapamycin inhibitor versus calcineurin inhibitor (all other cointerventions are identical)
| Outcomes | No. of Participants (Studies) Follow-Up | Quality of the Evidence (GRADE) | Relative Effect (95% CI) | Anticipated Absolute Effects | |
|---|---|---|---|---|---|
| Risk with CNI | Risk Difference with mTORi | ||||
| CMV infection | 3914 (19 RCTs) | ⊕⊕⊕⊕ High | RR, 0.54 (0.41 to 0.72) | 110 per 1000 | 50 Fewer per 1000 (65–31 fewer) |
| BK virus infection | 1989 (12 RCTs) | ⊕⊕⊕◯ Moderatea | RR, 0.71 (0.40 to 1.25) | 35 per 1000 | 10 Fewer per 1000 (21 fewer to 9 more) |
| Incidence of other viral, bacterial, or fungal infections | 2682 (12 RCTs) | ⊕⊕⊕⊕ High | RR, 1.08 (1.02 to 1.15) | 524 per 1000 | 42 More per 1000 (10–79 more) |
| Composite of incidence of acute cellular or antibody-mediated rejection or DSAs | 3921 (19 RCTs) | ⊕⊕⊕◯ Moderateb | RR, 1.39 (1.09 to 1.77) | 194 per 1000 | 76 More per 1000 (17–150 more) |
| Graft loss | 3589 (17 RCTs) | ⊕⊕⊕◯ Moderatea | RR, 1.10 (0.74 to 1.65) | 41 per 1000 | 4 More per 1000 (11 fewer to 27 more) |
| Serious adverse events | 2173 (7 RCTs) | ⊕⊕⊕◯ Moderatec | RR, 1.26 (1.02 to 1.56) | 387 per 1000 | 101 More per 1000 (8–217 more) |
| Proteinuria | 2844 (12 RCTs) | ⊕⊕⊕⊕ High | RR, 2.35 (1.52 to 3.64) | 41 per 1000 | 55 More per 1000 (21–107 more) |
| BK nephropathy defined by kidney biopsy | 561 (3 RCTs) | ⊕⊕◯◯ Lowa,d | RR, 0.54 (0.20 to 1.49) | 35 per 1000 | 16 Fewer per 1000 (28 fewer to 17 more) |
| Wound-healing complications | 1826 (7 RCTs) | ⊕⊕⊕⊕ High | RR, 1.62 (1.22 to 2.15) | 82 per 1000 | 51 More per 1000 (18–94 more) |
| eGFR or creatinine clearance, ml/min per 1.73 m2 | 3768 (18 RCTs) | ⊕⊕⊕◯ Moderatee | — | MD 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.
95% CI does not rule out or confirm difference between the intervention and control groups.
Heterogeneity detected I2=67%.
Heterogeneity detected I2=63%.
Unclear risk of bias in some of the included trials.
Heterogeneity detected I2=74%.