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)
| Outcomes | No. of Participants (Studies) Follow-Up | Quality of the Evidence (GRADE) | Relative Effect (95% CI) | Anticipated Absolute Effects | |
|---|---|---|---|---|---|
| Risk with Regular-Dose CNI + MMF/AZA | Risk Difference with mTORi + Reduced-Dose CNI | ||||
| CMV infection | 1547 (5 RCTs) | ⊕⊕⊕◯ Moderatea | RR, 0.43 (0.24 to 0.80) | 231 per 1000 | 132 Fewer per 1000 (176–46 fewer) |
| BK virus infection | 1320 (3 RCTs) | ⊕⊕◯◯ Lowb,c | RR, 0.57 (0.12 to 2.72) | 32 per 1000 | 14 Fewer per 1000 (28 fewer to 56 more) |
| Incidence of other viral, bacterial, or fungal infections | 1028 (2 RCTs) | ⊕⊕◯◯ Lowc,d | RR, 1.08 (0.87 to 1.34) | 505 per 1000 | 40 More per 1000 66 fewer to 172 more) |
| Acute cellular or antibody-mediated rejection | 1553 (5 RCTs) | ⊕⊕⊕◯ Moderatec | RR, 0.88 (0.70 to 1.09) | 192 per 1000 | 23 Fewer per 1000 (57 fewer to 17 more) |
| Graft loss | 1547 (5 RCTs) | ⊕⊕⊕◯ Moderate | RR, 1.03 (0.64 to 1.65) | 105 per 1000 | 3 More per 1000 (38 fewer to 68 more) |
| Serious adverse events | 1150 (3 RCTs) | ⊕⊕◯◯ Lowc,e | RR, 0.87 (0.62 to 1.20) | 632 per 1000 | 82 Fewer per 1000 (240 fewer to 126 more) |
| CMV disease | 1441 (4 RCTs) | ⊕⊕⊕◯ Moderatef | RR, 0.42 (0.21 to 0.82) | 119 per 1000 | 69 Fewer per 1000 (94–22 fewer) |
| Proteinuria | 1150 (3 RCTs) | ⊕⊕⊕⊕ High | RR, 1.47 (1.04 to 2.06) | 99 per 1000 | 46 More per 1000 (4–105 more) |
| Wound-healing complications | 1150 (3 RCTs) | ⊕⊕⊕◯ Moderateg | RR, 1.71 (1.16 to 2.50) | 230 per 1000 | 163 More per 1000 (37–345 more) |
| eGFR or creatinine clearance, ml/min per 1.73 m2 | 1543 (5 RCTs) | ⊕⊕◯◯ Lowc,h | — | MD 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.
Heterogeneity detected I2=81%.
Heterogeneity detected I2=71%.
95% CI does not rule out or confirm difference between the intervention and control groups.
Heterogeneity detected I2=53%.
Heterogeneity detected I2=85%.
Heterogeneity detected I2=58%.
Heterogeneity detected I2=56%.
Heterogeneity detected I2=84%.