Supportive Evidence of Surrogate End Points Based on Treatment Effect of Corticosteroid in IgA Nephropathy - clinical research

Q: What surrogate end points were evaluated in IgA nephropathy?

The study evaluated estimated glomerular filtration rate (eGFR) slope and proteinuria reduction as surrogate end points for kidney outcomes in IgA nephropathy.

Q: How were patients grouped for corticosteroid exposure?

Patients with biopsy-proven IgA were categorized based on corticosteroid exposure within 12 months of diagnosis, and overlap weighting was used to balance baseline characteristics.

Q: What were the main findings regarding corticosteroid therapy?

Corticosteroid therapy showed a lower incidence of the composite kidney outcome, slower decline in eGFR, and greater reduction in proteinuria compared with non-corticosteroid therapy.

Sep 29, 2026

Uploaded by Olivia Brown

Supportive evidence evaluates surrogate end points in IgA nephropathy by analyzing corticosteroid treatment effects within a large Japanese cohort. Estimated GFR slope and proteinuria reduction are assessed for their ability to reflect kidney outcomes. Post hoc cohort analysis stratifies patients by corticosteroid exposure within 12 months and uses overlap weighting to reduce confounding. Corticosteroids associate with lower composite kidney events, slower eGFR decline, and greater proteinuria reduction.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages9

Reading Time23 min

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Introduction

Methods

Study Design and Population

Results

Conclusion

CLINICAL RESEARCH Supportive Evidence of Surrogate End Points Based on Treatment Effect of Corticosteroid in IgA Nephropathy Takaya Sasaki 1, Nobuo Tsuboi 1, Kentaro Koike 1, Hiroyuki Ueda 1, Masahiro Okabe 1, Shinya Yokote 1, Akihiro Shimizu 1, Keita Hirano 1, Tetsuya Kawamura 1, Takashi Yokoo 1 and Yusuke Suzuki2; on behalf of the J-IGACS Working Group3 1Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan; and 2Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan Introduction: Estimated glomerular filtration rate (eGFR) slope and proteinuria reduction have been proposed as surrogate end points for kidney outcomes in IgA nephropathy (IgAN), but their validity remains under debate. We aimed to evaluate the surrogate potential of these markers in the context of corticosteroid therapy within a large Japanese cohort. Methods: Patients with biopsy-proven IgAN from the Japan IgA Nephropathy Cohort Study were analyzed. Patients were categorized based on corticosteroid exposure within 12 months of diagnosis. To minimize confounding, overlap weighting was used to balance baseline characteristics. The primary outcome was a composite kidney end point defined as a $ 40 decline in eGFR or the initiation of kidney replacement therapy. Secondary outcomes included 2-year eGFR slope and proteinuria reduction at 1-year. Results: Corticosteroid therapy was associated with a lower incidence of the composite kidney outcome (5 .3 vs. 13. 1%, P = 0.0485), slower decline in eGFR ( − 0.32 vs. − 2.95 ml/min per 1.73 m2/yr, P = 0.01), and greater proteinuria reduction ( − 76.5% vs. − 48.0%, P < 0.001) . Conclusion: Both the eGFR slope and proteinuria reduction demonstrated strong and consistent associations with kidney outcomes in the context of corticosteroid therapy. These findings support their effectiveness as surrogate end points for clinical trials and suggest their usefulness for risk stratification and therapeutic monitoring in routine nephrology practice. Kidney Int Rep (2026) 11, 103588; [https://doi.org/10.1016/j.ekir.2025.09.002](https://doi.org/10.1016/j.ekir.2025.09.002) [KEYWORDS: corticosteroid](KEYWORDS: corticosteroid); eGFR slope; IgA nephropathy; kidney outcome; proteinuria © 2025 International Society of Nephrology. Published by Elsevier Inc. This is an open access article under the CC BYNC-ND license ([http://creativecommons.org/licenses/by-nc-nd/4.0/](http://creativecommons.org/licenses/by-nc-nd/4.0/)). I gAN is the most prevalent form of primary glomer ulonephritis globally and a major cause of chronic kidney disease and kidney failure. 1,2 Because IgAN progresses slowly over many years,3-5 establishing reliable surrogate end points that can be evaluated over a short period is crucial for improving the efficiency of clinical trials and guiding personalized treatment strategies as new therapies emerge. Among candidate surrogate markers, the trajectory of the Correspondence: Nobuo Tsuboi, Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan. E-mail: [tsuboi-n@jikei.ac.jp](tsuboi-n@jikei.ac.jp) 3Members of the J-IGACS Working Group are listed in the Appendix Received 26 June 2025; revised 5 August 2025; accepted 1 September 2025; published online 9 September 2025 eGFR slope and reduction in proteinuria have been proposed.6-9 However, their validity remains a topic of active discussion, particularly when applied to therapeutic interventions. Corticosteroid therapy has long been a cornerstone of treatment for IgAN, particularly in patients with persistent proteinuria despite supportive care. Importantly, randomized controlled trials 10 and meta-analysis 11 studies have consistently demonstrated that corticosteroids significantly reduce proteinuria and slow disease progression, establishing

FAQs

What surrogate end points were evaluated in IgA nephropathy?

The study evaluated estimated glomerular filtration rate (eGFR) slope and proteinuria reduction as surrogate end points for kidney outcomes in IgA nephropathy.

How were patients grouped for corticosteroid exposure?

Patients with biopsy-proven IgA were categorized based on corticosteroid exposure within 12 months of diagnosis, and overlap weighting was used to balance baseline characteristics.

What were the main findings regarding corticosteroid therapy?

Corticosteroid therapy showed a lower incidence of the composite kidney outcome, slower decline in eGFR, and greater reduction in proteinuria compared with non-corticosteroid therapy.

Sep 29, 2026

Uploaded by Olivia Brown