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. 2025 Aug 8;15(1):29007.
doi: 10.1038/s41598-025-10578-x.

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

Anitha Swamy #  1   2 , Abin Antony #  3 , Sudip Kumar Datta  4 , Kalaivani Mani  5 , Adarsh Barwad  6 , Geetika Singh  6 , Arunkumar Subbiah  1 , Raj Kanwar Yadav  1 , Sandeep Mahajan  1 , Dipankar Bhowmik  1 , Sanjay Kumar Agarwal  1   7 , Soumita Bagchi  8
Affiliations

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

Anitha Swamy et al. Sci Rep. .

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.

Keywords: Biomarker; IgA nephropathy; IgA/C3 ratio; Outcome.

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Conflict of interest statement

Declarations. Competing interests: Soumita Bagchi, Arunkumar Subbiah and Dipankar Bhowmik are site investigators/co-investigators for clinical trials in kidney diseases (all funding is received by All Institute of Medical Sciences, New Delhi with no personal financial involvement). The rest of the authors have no competing interests to declare. Remaining authors do not have any competing interests to disclose. Ethics and informed consent approval: The study was approved by the Institute Ethics Committee at All India Institute of Medical Sciences, New Delhi(IECPG-464/27.09.2018) and conducted according to the declaration of Helsinki. Informed consent was taken for patients recruited prospectively while waiver of consent had been granted for samples tested retrospectively from the biorepository. Informed consent: Informed consent was taken from patients recruited prospectively while waiver of consent was provided by the Institute Ethics Committee for patients included retrospectively.

Figures

Fig. 1
Fig. 1
Comparison of IgA/C3 ratio between IgAN (cases) and non-IgA glomerular diseases (controls).
Fig. 2
Fig. 2
Receiver Operating Characteristic (ROC) curve of the baseline IgA/C3 ratio for the cases and controls.
Fig. 3
Fig. 3
Kaplan Meier Analysis of Renal Survival in IgAN patients with high(> 2.0) and low(≤ 2.0) IgA C3 ratio.
See this image and copyright information in PMC

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