Analysis of Clinicopathological Characteristics of Malignancy Patients with Membranous Nephropathy and Literature Review

Abstract

Purpose

In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.

Patients and Methods

A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.

Results

19 patients in our center’s MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).

Conclusion

The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.

Keywords:

• malignancy
• membranous nephropathy
• PLA2R
• THSD7A
• NELL-1

Data Sharing Statement

All data generated during this study are included in this article and its online supplementary material files. Further inquiries can be directed to the corresponding author.

Statement of Ethics

This study conformed to the Declaration of Helsinki and was approved by the ethics committee of Beijing Anzhen Hospital, Capital Medical University, approval number 2023154X. Written informed consent was obtained from the individuals for the publication of any potentially identifiable images or data included in this article.

Acknowledgments

We appreciate three participating hospitals for their contributions to this study, including Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, China; Division of Nephrology, Qinghai University Affiliated Hospital; Division of Nephrology, Beijing Jishuitan Hospital. The abstract of this paper was presented at the World Congress of Nephrology (WCN) 2024 and the European Renal Association (ERA) Congress 2024 as a poster presentation with interim findings. The poster’s abstract was published in ‘Poster Abstracts’ in Kidney International Reports and Nephrology Dialysis Transplantation: [https://www.kireports.org/article/S2468-02492400476-5/fulltext;https://academic.oup.com/ndt/article/39/Supplement_1/gfae069-1251-1305/7678468.]

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This work was supported by the National Natural Science Foundation of Beijing Grant 7192050 and Capital’s Funds for Health Improvement and Research (2022-2-2066).