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

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
• mesangial IgM deposition
• immunofluorecence
• end-stage kidney disease

Acknowledgments

The publication of this paper was supported by the University of Medicine and Pharmacy “Carol Davila,” through the institutional program “Publish not Perish.”

Authors’ contributions

G.T.B., G.S. responsible for conceptualization, methodology and original draft preparation. S.S. and A.Z. carried out data bibliographic research, data recording and coordinated the study. G.S. performed the statistical analysis. All authors contributed to clinical care of patients, commented on previous versions of the manuscript, and read and approved the final manuscript.

Disclosure 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.

Ethical approval

The study was conducted with the provisions of the Declaration of Helsinki and the protocol was approved by the local ethics committee (“Dr Carol Davila” Teaching Hospital of Nephrology, Bucharest, Romania, approval number 2021-012). Since all data were anonymized, informed consent was not obtained from individual patients.

Data availability statement

The data underlying this article will be shared on reasonable request to the corresponding author.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.