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. 2024 Dec;46(1):2313179.
doi: 10.1080/0886022X.2024.2313179. Epub 2024 Feb 15.

Prognostic role of mesangial IgM deposition in IgA nephropathy: a long-term cohort study

Gabriel Stefan  1   2 , Simona Stancu  1   2 , Adrian Zugravu  1   2 , George Terinte-Balcan  1   3
Affiliations

Prognostic role of mesangial IgM deposition in IgA nephropathy: a long-term cohort study

Gabriel Stefan et al. Ren Fail. 2024 Dec.

Abstract

Background: The clinical significance of mesangial immunoglobulin (Ig) M deposition in IgA nephropathy (IgAN) has been less explored and remains a topic of debate. Therefore, our study aimed to investigate the prognostic value of mesangial IgM deposition in a long-term follow-up cohort of IgAN patients.

Methods: A unicentric retrospective study was conducted on 93 consecutive IgAN patients (median age 41 years, 68% male, eGFR 48.7 mL/min, proteinuria 1.1 g/g) from 2010 to 2015. They were followed until end-stage kidney disease (ESKD), death, or until the end of the study in January 2021, with a median follow-up of 7 years. An independent pathologist evaluated the IgM immunofluorescence pattern, Oxford MEST-C score, and transmission electron microscopy (TEM) lesions following a comprehensive protocol.

Results: In our cohort, 70% had mesangial IgM-positive deposits, while 30% were IgM-negative. Both groups were similar in age, sex, prevalence of arterial hypertension, Charlson comorbidity scores, kidney function (eGFR and proteinuria), pathology findings (Oxford MEST-C score, IgG and C3 immune deposition), and TEM analysis. Treatment with RASI and immunosuppression, and death rates were also comparable. However, 37% of IgM-positive patients progressed to ESKD, significantly higher than the 11% in the IgM-negative group. Univariate and multivariate Cox proportional hazards regression analyses identified lower eGFR, higher Oxford MEST-C score, and mesangial IgM deposits as independent factors associated with shorter kidney survival.

Conclusions: Our study highlights mesangial IgM deposition as a potential risk factor for ESKD in patients with advanced IgAN, laying a foundation for further research in this area.

Keywords: IgA nephropathy; end-stage kidney disease; immunofluorecence; mesangial IgM deposition.

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Conflict of interest statement

The authors declare no conflicts of interest or competing interests. The results presented in this paper have not been published previously in whole or part, except in abstract format.

Figures

Figure 1.
Figure 1.
Immunofluorescence findings in IgAN; A: Immunofluorescence microscopy image showing very bright (3+) granular deposits for IgA located in the mesangium of a glomerulus; B: Immunofluorescence microscopy image showing positive granular deposits (2+) for IgM predominantly located in the mesangium of a glomerulus.
Figure 2.
Figure 2.
Patients with mesangial IgM positivity at immunofluorescence had a shorter mean renal survival time: 90.3 (95%CI 78.8, 101.7) versus 116.1 (95%CI 103.3, 128.8) months.
See this image and copyright information in PMC

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