C3 Staining, Serum IgA/C3 May Aid Treatment, Prediction of Renal Outcomes in IgAN

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Findings underscore the importance of considering both the serum IgA/C3 ratio and glomerular C3 staining in the management and treatment of IgAN.

Findings from a recent study are highlighting the importance of considering both the serum IgA/C3 ratio and glomerular C3 staining when predicting renal outcomes and guiding treatment decisions for adult patients with IgA nephropathy (IgAN).1

Results showed patients with serum IgA/C3 ≥ 2.806 and C3 staining ≥ 2 had worse outcomes, further identifying hypertension, serum creatinine, chronic kidney disease (CKD) stage, T1/2, and C3 staining as independent predictive factors of renal survival, all of which may inform an improved prognostic model for IgAN patients and allow for personalized treatment approaches.1

One of the leading causes of glomerulonephritis and renal failure, IgAN is an autoimmune disease causing antibody-mediated destruction of the glomerular basement membrane. Its pathophysiology is poorly understood, and although some patients experience a benign disease course, others progress to end-stage renal disease (ESRD). Stratification and treatment are difficult due to its broad clinical presentation, highlighting the need for a viable prognostic tool for predicting outcomes.2

“The serum IgA/C3 ratio and glomerular C3 staining may have a likely impact on adult IgAN patients, but no study has proven this,” Dandan Yang, of West China Hospital at Sichuan University in China, and colleagues wrote.1 “Thus, we speculated that this study could provide more exact evidence for the predictive outcomes of IgAN by using a combination of the serum IgA/C3 ratio and glomerular C3 staining.”

To assess the predictive value of the serum IgA/C3 ratio and glomerular C3 deposits in kidney biopsy in adult IgAN, investigators respectively enrolled adult patients with newly diagnosed, biopsy-proven IgAN at West China Hospital from December 2007 - February 2020. For inclusion, patients were required to have ≥ 12 months of follow-up data; predominance of IgA deposits in the glomerular mesangium by renal biopsy pathology; and complete serum IgA, serum C3, and pathological glomerular C3 staining data.1

A total of 718 eligible patients were included in the study. Among the cohort, the majority (57%) were female and the mean age was 34.04±11.09 years. Investigators divided patients into 2 groups based on their proteinuria range: proteinuria >3.5 g and proteinuria ≤3.5 g.1

Additionally, serum IgA and C3 were measured using the immunoturbidimetry method at baseline, and the serum IgA/C3 ratio was calculated to apply a receiver operating characteristic curve (ROC)-based cutoff ratio, 2.806, which had optimal sensitivity (63.9%) and specificity (58.7%) for both proteinuria groups. The composite endpoint was a renal function decline of >50% in estimated glomerular filtration rate (eGFR), ESRD, and/or death.1

Upon analysis, the difference in prognosis between the serum IgA/C3 ≥2.806 group and the serum IgA/C3 <2.806 group was not statistically significant (P = .656). Similar results were also found between the C3 staining ≥2 group and the C3 staining <2 group (P = .582), suggesting the serum IgA/C3 ratio or C3 staining is not an independent protective factor for the prognosis of IgAN.1

All 718 patients were classified into 4 groups according to serum IgA/C3 ratio and glomerular C3 staining in order to better understand the relationship between the risk factors C3 staining and serum IgA/C3 ratio: Group 1 (serum IgA/C3 ≥2.806 and C3 staining ≥2) (n = 250), Group 2 (serum IgA/C3 ≥2.806 and C3 staining <2) (n = 174), Group 3 (serum IgA/C3 <2.806 and C3 staining ≥2) (n = 128) and Group 4 (serum IgA/C3 <2.806 and C3 staining <2) (n = 166).1

Investigators noted when the serum IgA/C3 ratio was at the same level, patients with a glomerular C3 staining score ≥2 always had mesangial proliferation, segmental glomerulosclerosis, and tubular atrophy/interstitial fibrosis. When glomerular C3 staining was at the same level, proteinuria was significantly increased in patients with serum IgA/C3 <2.806. Investigators also pointed out serum creatinine was significantly lower and eGFR was higher in Group 4 compared to Group 1.1

Further analysis revealed patients with serum IgA/C3 ≥2.806 and C3 staining ≥2 seemed to have worse outcomes (Group 1 vs Group 2; P = .083). Additionally, male IgAN patients in Group 2 had statistically significantly better outcomes as opposed to females in Group 2, who had significantly poorer outcomes compared to Group 4 (P = .027). Investigators pointed out the renal survival rate also significantly differed between Group 2 and Group 3 in IgAN patients with CKD stage 1-2 and receiving support treatments.1

Further renal survival analysis indicated serum IgA/C3 ≥2.806 and glomerular C3 staining ≥2 (Group 1) may be correlated with a poorer prognosis, especially in different clinicopathological characteristics of IgAN patients. Multivariate Cox analysis revealed hypertension, serum creatinine, CKD stage, T1/2, and C3 staining were independent predictive factors of renal survival.1

“The combination of serum IgA/C3 and C3 staining may contribute to improved optimization of the prognostic model in IgAN patients, especially patients with different sexes and degrees of disease,” investigators concluded.1


  1. Yang D, Pei G, Wang S, Qin A, Tang Y, Qin W. Combined effects of the serum IgA/C3 ratio and glomerular C3 staining on the renal outcome in adult IgA nephropathy. Kidney Blood Press Res. Published online February 21, 2024. doi:10.1159/000536114
  2. Rawla P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease). StatPearls. July 7, 2023. Accessed March 20, 2024.