Summary of findings 4. Calcineurin inhibitors ± steroids versus alkylating agents ± steroids.
| Calcineurin inhibitors ± steroids versus alkylating agents ± steroids for primary membranous nephropathy in adults with nephrotic syndrome | |||||
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Patient or population: primary membranous nephropathy in adults with nephrotic syndrome
Setting: primary care Intervention: calcineurin inhibitors ± steroids Comparison: alkylating agents ± steroids | |||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | No. of participants (studies) | Certainty of the evidence (GRADE) | |
| Risk with alkylating agents ± steroids | Risk with CNI ± steroids | ||||
| Death at final follow‐up (range: 9 to 60 months) |
38 per 1000 | 34 per 1000 (13 to 89) | RR 0.90 (0.35 to 2.34) | 394 (7) | ⊕⊖⊖⊖ Verylow 1,2,3 |
| End‐stage kidney disease at final follow‐up (range: 9 to 60 months) |
15 per 1000 | 36 per 1000 (10 to 134) | RR 2.40 (0.64 to 9.01) | 293 (5) | ⊕⊖⊖⊖ Very low 1,2,3 |
| Total remission at final follow‐up (range: 9 to 60 months) |
784 per 1000 | 791 per 1000 (697 to 901) | RR 1.01 (0.89 to 1.15) | 529 (10) | ⊕⊕⊕⊖ Moderate 1 |
| Complete remission at final follow‐up (range: 9 to 60 months) |
429 per 1000 | 493 per 1000 (360 to 669) | RR 1.15 (0.84 to 1.56) | 533 (10) | ⊕⊕⊖⊖ Low 4,5 |
| Recurrence of disease (relapse) at final follow‐up (range: 9 to 18 months) |
61 per 1000 | 130 per 1000 (43 to 390) |
RR 2.13 (0.71 to 6.37) |
295 (6) | ⊕⊕⊖⊖ Low 1,2 |
| 100% increase in SCr at final follow‐up (range: 9 to 60 months) |
136 per 1000 | 95 per 1000 (41 to 226) |
RR 0.70 (0.30 to 1.67) |
132 (2) | ⊕⊖⊖⊖ Verylow 1,2,3 |
| Adverse events ‐ temporary or permanent discontinuation/hospitalisation at final follow‐up (range: 9 to 12 months) |
42 per 1000 | 60 per 1000 (13 to 278) |
RR 1.43 (0.31 to 6.67) | 151 (3) | ⊕⊖⊖⊖ VeryLow 1,6 |
| Adverse events ‐ infection (range: 9 to 30 months) |
223 per 1000 | 191 per 1000 (96 to 381) |
RR 0.86 (0.43 to 1.71) |
552 (9) | ⊕⊕⊖⊖ Low 1,2 |
| Adverse events ‐ malignancy (range 30 to 36 months |
33 per 1000 | 6 per 1000 (0 to 121) |
RR 0.18 (0.01 to 3.69) |
127 (2) | ⊕⊖⊖⊖ VeryLow1,6 |
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: Confidence interval; CNI: calcineurin inhibitors; RR: Risk ratio | |||||
| GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: 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 certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect | |||||
1 Study limitations (studies generally at unclear or high risk of bias for many domains)
2 Serious imprecision: estimate of effect includes negligible difference and considerable benefit and harm
3 Serious indirectness: Follow‐up less than 10 years
4 Serious study limitations: Unclear randomisation sequence generation and allocation concealment
5 Serious inconsistency: point estimates vary widely, and the magnitude of statistical heterogeneity was high, with I2 =53%
6 Very serious imprecision (2 grades): few events, and estimate of effect includes negligible difference and considerable benefit and harm