Gd-IgA1 level and long-term kidney outcomes in IgA nephropathy: A systematic review and meta-analysis

Abstract This systematic review (SR) aimed to evaluate the evidence on the association between galactose-deficient immunoglobulin A1 (Gd-IgA1) levels and long-term kidney outcomes in adults with IgA nephropathy (IgAN). Searches were conducted to identify English-language observational and interventional studies in MEDLINE, Embase, BIOSIS Citations Index, SCI EXPANDED, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from inception to November 2025. Risk of bias was assessed with standardized tools, findings were synthesized qualitatively and meta-analyses were conducted on proteinuria, estimated glomerular filtration rate (eGFR), and chronic kidney disease (CKD) progression. Of 2,598 records identified, 32 unique studies representing 5,351 patients were included. Relationships between Gd-IgA1 and kidney outcomes were measured longitudinally in 22 studies and cross-sectionally in 18 studies, with 8 studies measuring the relationships both ways. The strongest and most consistent signal emerged from the longitudinal analyses on CKD progression and proteinuria. For proteinuria, most studies reported a significant longitudinal association, with greater Gd-IgA1 reduction associated with greater proteinuria reduction over time. The meta-analysis was consistent with the qualitative synthesis and estimated a pooled correlation of 0.53 (95% CI: 0.29–0.70). For CKD progression, most studies reported a significant longitudinal association, with higher Gd-IgA1 linked to increased risk of CKD progression. The unadjusted meta-analysis estimated a pooled hazard ratio of 1.61 (95% CI: 1.31–1.99), and the meta-analysis adjusting for demographic, clinical, pathological, and treatment factors estimated a pooled hazard ratio of 1.25 (95% CI: 1.09–1.43). Regarding eGFR, most cross-sectional studies reported that higher Gd-IgA1 levels were associated with lower eGFR values, with weak to modest correlations observed across studies. The meta-analysis estimated a pooled correlation of -0.21 (95% CI: -0.33–-0.09). This SR found consistent evidence of association between Gd-IgA1 levels and kidney outcomes in IgAN, particularly proteinuria, eGFR and CKD progression. Although these findings should be considered in the context of heterogeneity across studies and the observational nature of most available evidence, they support the potential of Gd-IgA1 as a biomarker of disease activity and progression, with possible relevance for risk stratification and therapeutic monitoring.