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The association of 5-year therapeutic responsiveness with long-term renal outcome in IgA nephropathy

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Abstract

Background

Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis. Since most patients have a relatively benign renal prognosis, long-term follow-up is required. During such a long course of disease, relapse of IgAN is occasionally observed after upper respiratory tract infection or without any trigger. However, little is known about the impact of relapse on long-term renal outcomes.

Methods

In this retrospective cohort study of biopsy-proven primary IgAN, we analyzed the association of 5-year therapeutic responsiveness (relapse) with the subsequent development of end-stage kidney disease (ESKD) using a 5-year landmark analysis (Cox model) and explored predictors of relapse from histological and clinical data at baseline.

Results

Among 563 patients from the exploratory cohort, most relapses (13.7%) occurred within 5 years after treatment. Using 5-year landmark analysis, among 470 patients, 79 developed ESKD during a median follow-up period of 155 months. Even after adjustment for clinicopathological relevant confounders, hazard ratios (95% confidence intervals) in the relapse and non-responder groups compared with the remission group were 2.86 (1.41–5.79) and 2.74 (1.48–5.11), respectively. Among 250 patients who achieved remission within 5 years, proteinuria, eGFR, mesangial hypercellularity, endocapillary hypercellularity, segmental sclerosis, and crescent, but not interstitial fibrosis/tubular atrophy, were independent predictors of 5-year relapse in multivariable logistic regression analysis,

Conclusions

Both relapsers and non-responders had similarly strong association with ESKD in patients with IgAN. We also confirmed the predictors of relapse 5 years after renal biopsy, which may guide the treatment strategies for patients with IgAN who occasionally relapse after remission.

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Acknowledgements

We thank Renee Mosi, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript

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Authors and Affiliations

  1. Department of Nephrology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara, 634-8521, Japan

    Hideo Tsushima, Ken-ichi Samejima, Masahiro Eriguchi, Takayuki Uemura, Hikari Tasaki, Fumihiro Fukata, Masatoshi Nishimoto, Takaaki Kosugi, Kaori Tanabe, Keisuke Okamoto, Masaru Matsui & Kazuhiko Tsuruya

  2. Department of Nephrology, Nara Prefecture General Medical Center, Nara, Japan

    Masaru Matsui

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  1. Hideo Tsushima
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Contributions

Research idea and study design: HidT, KS. Drafting the manuscript: HidT, ME. Revising the manuscript: ME, KazT. Data analysis/interpretation: HidT, KS, ME. Statistical analysis: HT, ME. Supervision or mentorship: KazT, TU, HikT, FF, MN, TK, KaoT, KO, MM. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Masahiro Eriguchi.

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The authors have declared that no conflict of interest exists.

Ethical approval

This study was approved by the Ethic Committee of Nara Medical University Hospital (Approval No. 2005-18) and registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000031121).

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Written informed consent was not required because of the retrospective observational study design. All patients gave their “opt-out” informed consent.

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Tsushima, H., Samejima, Ki., Eriguchi, M. et al. The association of 5-year therapeutic responsiveness with long-term renal outcome in IgA nephropathy. Clin Exp Nephrol 26, 797–807 (2022). https://doi.org/10.1007/s10157-022-02221-0

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