APRIL-targeted and dual BAFF/APRIL blockade in primary IgA nephropathy: a systematic review and meta-analysis of...

APRIL-targeted and dual BAFF/APRIL blockade are upstream immune approaches for primary IgA nephropathy. We evaluated their efficacy and safety in adults with this disease.

PubMed/MEDLINE, Embase, Web of Science, CENTRAL, ClinicalTrials.gov, WHO ICTRP and other registries were searched from inception to 8 May 2026. Randomized placebo-controlled trials of APRIL-targeted or dual BAFF/APRIL blockade in adults with biopsy-confirmed primary IgA nephropathy were included. The primary outcome was relative change in proteinuria, analyzed as the log ratio of means and back-transformed to the ratio of means (RoM). Serious adverse events were pooled as odds ratios. Risk of bias and certainty of evidence were assessed using RoB 2 and GRADE.

Nine full-text reports representing six independent trials were included. Five trials with 768 participants contributed to the primary proteinuria analysis. Active treatment reduced proteinuria versus placebo, with a pooled RoM of 0.539 (95%CI 0.477-0.609; p < 0.0001), corresponding to 46.1% lower proteinuria. Heterogeneity was low (I² = 21.3%), and results were stable across sensitivity analyses. eGFR outcomes were summarized narratively because reporting was heterogeneous. Six trials with 1269 participants contributed to the safety analysis. Active treatment was not associated with a higher incidence of serious adverse events (OR 0.582, 95%CI 0.318-1.064).

APRIL-targeted and dual BAFF/APRIL blockade reduced short-to-medium-term proteinuria in adults with primary IgA nephropathy. Longer follow-up is needed to clarify durability, immune safety and kidney outcome benefits.