Associations of renal complement deposition with oxford MEST-C pathological lesions and renal outcomes in Iga nephropathy: a meta-analysis
Abstract
BackgroundIgA nephropathy (IgAN) is a common primary glomerular disease with heterogeneous progression and prognosis. Current risk stratification relies on proteinuria, estimated glomerular filtration rate (eGFR), and the Oxford MEST-C score, but these factors do not fully explain differences in disease progression. Renal deposition of C3, C4d, and C1q may be associated with pathological lesions and prognosis, although previous findings are inconsistent. We systematically evaluated the associations of renal complement deposition with MEST-C lesions and composite renal outcomes in IgAN.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from inception to May 2026. Cohort and cross-sectional studies of biopsy-proven IgAN were included. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for MEST-C lesions, and hazard ratios (HRs) with 95% CIs for composite renal outcomes. Fixed- or random-effects models were used according to heterogeneity.ResultsThirty studies involving 10,656 patients were included. C4d, C3, and C1q deposition were associated with pathological lesions and composite renal outcomes. C4d deposition was associated with all MEST-C components, most strongly with T lesions (RR = 2.21, 95% CI: 1.92–2.54), and with increased risk of composite renal outcomes (HR = 2.02, 95% CI: 1.29–3.17). C3 deposition was associated with all MEST-C components and composite renal outcomes (HR = 1.59, 95% CI: 1.16–2.18). C1q deposition was associated with M, T, and C lesions and composite renal outcomes (HR = 1.99, 95% CI: 1.44–2.75). Subgroup analyses supported associations of C4d and C3 with composite renal outcomes in selected age, country, and detection-method subgroups. Meta-regression showed no significant effect of age.ConclusionRenal deposition of C3, C4d, and C1q was associated with pathological lesions and adverse renal prognosis in IgAN. C4d showed the strongest association with chronic tubulointerstitial injury and progression, C3 may reflect overall complement activation, and C1q may indicate a high-risk immunopathological phenotype. Renal complement deposition may serve as an adjunctive marker for risk stratification, although large multicenter prospective studies are needed for validation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251107357, identifier CRD420251107357.
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BibTeX
@article{bao2026associations,
title = {{Associations of renal complement deposition with oxford MEST-C pathological lesions and renal outcomes in Iga nephropathy: a meta-analysis}},
author = {Yali Bao and Jianing Xu and He Nan and Meixi Liu and Shoulin Zhang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1944021},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944021},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Associations of renal complement deposition with oxford MEST-C pathological lesions and renal outcomes in Iga nephropathy: a meta-analysis
AU - Yali Bao
AU - Jianing Xu
AU - He Nan
AU - Meixi Liu
AU - Shoulin Zhang
PY - 2026
DA - 2026/11/03
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1944021
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1944021
AB - BackgroundIgA nephropathy (IgAN) is a common primary glomerular disease with heterogeneous progression and prognosis. Current risk stratification relies on proteinuria, estimated glomerular filtration rate (eGFR), and the Oxford MEST-C score, but these factors do not fully explain differences in disease progression. Renal deposition of C3, C4d, and C1q may be associated with pathological lesions and prognosis, although previous findings are inconsistent. We systematically evaluated the associations of renal complement deposition with MEST-C lesions and composite renal outcomes in IgAN.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from inception to May 2026. Cohort and cross-sectional studies of biopsy-proven IgAN were included. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled for MEST-C lesions, and hazard ratios (HRs) with 95% CIs for composite renal outcomes. Fixed- or random-effects models were used according to heterogeneity.ResultsThirty studies involving 10,656 patients were included. C4d, C3, and C1q deposition were associated with pathological lesions and composite renal outcomes. C4d deposition was associated with all MEST-C components, most strongly with T lesions (RR = 2.21, 95% CI: 1.92–2.54), and with increased risk of composite renal outcomes (HR = 2.02, 95% CI: 1.29–3.17). C3 deposition was associated with all MEST-C components and composite renal outcomes (HR = 1.59, 95% CI: 1.16–2.18). C1q deposition was associated with M, T, and C lesions and composite renal outcomes (HR = 1.99, 95% CI: 1.44–2.75). Subgroup analyses supported associations of C4d and C3 with composite renal outcomes in selected age, country, and detection-method subgroups. Meta-regression showed no significant effect of age.ConclusionRenal deposition of C3, C4d, and C1q was associated with pathological lesions and adverse renal prognosis in IgAN. C4d showed the strongest association with chronic tubulointerstitial injury and progression, C3 may reflect overall complement activation, and C1q may indicate a high-risk immunopathological phenotype. Renal complement deposition may serve as an adjunctive marker for risk stratification, although large multicenter prospective studies are needed for validation.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420251107357, identifier CRD420251107357.
SN - 1664-3224
ER -