Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy

Abstract IgA nephropathy (IgAN) is a common glomerular disease in adults with a smoldering course and high risk of progression to end-stage kidney disease (ESKD) in South Asians. We investigated serum IgA/C3 ratio as a potential biomarker for IgAN. We measured serum levels of IgA and C3 in 258 patie...

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Main Authors: Anitha Swamy, Abin Antony, Sudip Kumar Datta, Kalaivani Mani, Adarsh Barwad, Geetika Singh, Arunkumar Subbiah, Raj Kanwar Yadav, Sandeep Mahajan, Dipankar Bhowmik, Sanjay Kumar Agarwal, Soumita Bagchi
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Language:English
Published: Nature Portfolio 2025-08-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-10578-x
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author Anitha Swamy
Abin Antony
Sudip Kumar Datta
Kalaivani Mani
Adarsh Barwad
Geetika Singh
Arunkumar Subbiah
Raj Kanwar Yadav
Sandeep Mahajan
Dipankar Bhowmik
Sanjay Kumar Agarwal
Soumita Bagchi
author_facet Anitha Swamy
Abin Antony
Sudip Kumar Datta
Kalaivani Mani
Adarsh Barwad
Geetika Singh
Arunkumar Subbiah
Raj Kanwar Yadav
Sandeep Mahajan
Dipankar Bhowmik
Sanjay Kumar Agarwal
Soumita Bagchi
author_sort Anitha Swamy
collection DOAJ
description Abstract IgA nephropathy (IgAN) is a common glomerular disease in adults with a smoldering course and high risk of progression to end-stage kidney disease (ESKD) in South Asians. We investigated serum IgA/C3 ratio as a potential biomarker for IgAN. We measured serum levels of IgA and C3 in 258 patients with IgAN and 90 controls with non-IgAN primary glomerular disease and examined if serum IgA/C3 ratio differentiates IgAN from other glomerular diseases and if it predicts renal survival in IgAN. The primary outcome was lack of renal survival, defined as irreversible decline in eGFR > 50% from baseline or progression to ESKD. Median serum IgA/C3 ratio was higher in IgAN patients compared to controls (2.4, IQR: 1.9-3.0 vs. 1.8, IQR: 1.3–2.5, p < 0.001). The AUC for the receiver operating curve of IgA/C3 ratio was 0.6760 (95% CI: 0.6074–0.7446). The sensitivity and specificity of IgA/C3 ratio > 2.0 were 70.5% and 62.2% respectively, for differentiating IgAN from other non-IgAN glomerular diseases. With a median duration of follow-up of 35.0(IQR 16-56.8) months, 26.7% patients reached the primary outcome. Compared to patients with a low IgA/C3 ratio(≤ 2.0), those with a high ratio(> 2.0) were significantly older [median age 34 vs. 29 years, p = 0.003], more likely to have hypertension (70.6% vs. 50.5%, p = 0.001), had lower median eGFR [47.7 mL/min/1.73 m² vs. 77.7 mL/min/1.73 m², p < 0.001], lower urine protein creatinine ratio [2.0 g/g vs. 2.5 g/g, p = 0.015] and a significantly higher proportion of segmental glomerulosclerosis (S1 lesions) (80.4% vs. 62.1%, p = 0.005). Renal disease progression was comparable (26.3% vs. 27.0%, p = 0.906) between the low and high IgA/C3 ratio groups respectively. High IgA/C3 ratio (> 2.0) was not a significant predictor of primary outcome (HR = 1.32 95% CI: 0.80–2.2, p = 0.278). Serum IgA/C3 ratio is elevated in IgAN compared to other glomerular diseases but has limited diagnostic and prognostic utility in our patients.
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spelling doaj-art-85442fa441f24e3396ae3353d4b8fb1b2025-08-20T03:43:11ZengNature PortfolioScientific Reports2045-23222025-08-011511810.1038/s41598-025-10578-xSerum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathyAnitha Swamy0Abin Antony1Sudip Kumar Datta2Kalaivani Mani3Adarsh Barwad4Geetika Singh5Arunkumar Subbiah6Raj Kanwar Yadav7Sandeep Mahajan8Dipankar Bhowmik9Sanjay Kumar Agarwal10Soumita Bagchi11Department of Nephrology, All India Institute of Medical SciencesAll India Institute of Medical SciencesDepartment of Laboratory Medicine, All India Institute of Medical SciencesDepartment of Biostatistics, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesDepartment of Pathology, All India Institute of Medical SciencesDepartment of Nephrology, All India Institute of Medical SciencesDepartment of Nephrology, All India Institute of Medical SciencesDepartment of Nephrology, All India Institute of Medical SciencesDepartment of Nephrology, All India Institute of Medical SciencesDepartment of Nephrology, All India Institute of Medical SciencesDepartment of Nephrology, All India Institute of Medical SciencesAbstract IgA nephropathy (IgAN) is a common glomerular disease in adults with a smoldering course and high risk of progression to end-stage kidney disease (ESKD) in South Asians. We investigated serum IgA/C3 ratio as a potential biomarker for IgAN. We measured serum levels of IgA and C3 in 258 patients with IgAN and 90 controls with non-IgAN primary glomerular disease and examined if serum IgA/C3 ratio differentiates IgAN from other glomerular diseases and if it predicts renal survival in IgAN. The primary outcome was lack of renal survival, defined as irreversible decline in eGFR > 50% from baseline or progression to ESKD. Median serum IgA/C3 ratio was higher in IgAN patients compared to controls (2.4, IQR: 1.9-3.0 vs. 1.8, IQR: 1.3–2.5, p < 0.001). The AUC for the receiver operating curve of IgA/C3 ratio was 0.6760 (95% CI: 0.6074–0.7446). The sensitivity and specificity of IgA/C3 ratio > 2.0 were 70.5% and 62.2% respectively, for differentiating IgAN from other non-IgAN glomerular diseases. With a median duration of follow-up of 35.0(IQR 16-56.8) months, 26.7% patients reached the primary outcome. Compared to patients with a low IgA/C3 ratio(≤ 2.0), those with a high ratio(> 2.0) were significantly older [median age 34 vs. 29 years, p = 0.003], more likely to have hypertension (70.6% vs. 50.5%, p = 0.001), had lower median eGFR [47.7 mL/min/1.73 m² vs. 77.7 mL/min/1.73 m², p < 0.001], lower urine protein creatinine ratio [2.0 g/g vs. 2.5 g/g, p = 0.015] and a significantly higher proportion of segmental glomerulosclerosis (S1 lesions) (80.4% vs. 62.1%, p = 0.005). Renal disease progression was comparable (26.3% vs. 27.0%, p = 0.906) between the low and high IgA/C3 ratio groups respectively. High IgA/C3 ratio (> 2.0) was not a significant predictor of primary outcome (HR = 1.32 95% CI: 0.80–2.2, p = 0.278). Serum IgA/C3 ratio is elevated in IgAN compared to other glomerular diseases but has limited diagnostic and prognostic utility in our patients.https://doi.org/10.1038/s41598-025-10578-xIgA nephropathyIgA/C3 ratioBiomarkerOutcome
spellingShingle Anitha Swamy
Abin Antony
Sudip Kumar Datta
Kalaivani Mani
Adarsh Barwad
Geetika Singh
Arunkumar Subbiah
Raj Kanwar Yadav
Sandeep Mahajan
Dipankar Bhowmik
Sanjay Kumar Agarwal
Soumita Bagchi
Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy
Scientific Reports
IgA nephropathy
IgA/C3 ratio
Biomarker
Outcome
title Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy
title_full Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy
title_fullStr Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy
title_full_unstemmed Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy
title_short Serum IgA/C3 ratio as a diagnostic and prognostic biomarker for IgA nephropathy
title_sort serum iga c3 ratio as a diagnostic and prognostic biomarker for iga nephropathy
topic IgA nephropathy
IgA/C3 ratio
Biomarker
Outcome
url https://doi.org/10.1038/s41598-025-10578-x
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