Association Between Surrogate Endpoints and Clinical Outcomes in Immunoglobulin A Nephropathy: A Systematic Literature Review

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-08-19 DOI:10.1007/s12325-025-03331-3

Maria Lorenzi, Sarah N. Ali, Sarah Cadarette, Stephen Ebohon, Vakaramoko Diaby, Mohit Mathur, Ancilla W. Fernandes

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引用次数: 0

Abstract

Introduction

At least 50% of patients with immunoglobulin A nephropathy (IgAN) reach kidney failure within 12 years of diagnosis. Delayed progression to kidney failure remains the gold standard treatment endpoint in IgAN, but the prolonged time course limits feasibility as a primary endpoint in clinical trials. Earlier measurable endpoints may serve as surrogate endpoints for clinically important long-term kidney outcomes. Regulatory bodies recognize surrogate endpoints like proteinuria reduction. However, other stakeholders, like payers, health technology assessment agencies, and policymakers, may require additional evidence. This literature review assessed data on associations between surrogate endpoints, including proteinuria and estimated glomerular filtration rate (eGFR), and long-term kidney outcomes in IgAN.

Methods

A systematic search of IgAN studies conducted in any country was performed in MEDLINE, Embase, and CENTRAL via Ovid (January 1, 2006–September 1, 2023), supplemented by conference abstracts (2019–2023) and relevant literature reviews and meta-analyses. Eligible studies evaluated the association of surrogate endpoints of kidney disease progression with long-term outcomes in IgAN.

Results

Among 1833 unique citations screened, 23 publications met inclusion criteria. Proteinuria was associated with progression to kidney failure (p < 0.001–0.021; n = 5 studies), reaching a composite kidney event (p < 0.001–0.02; n = 6), doubling of serum creatinine (p = 0.009; n = 1), and long-term eGFR decline (p < 0.001–0.910; n = 5); absolute eGFR at months 3 and 6 was associated with composite kidney events (p ≤ 0.001–0.03; n = 2); and eGFR slope was associated with kidney failure (p < 0.001; n = 1) and doubling of serum creatinine (p < 0.001–0.007; n = 1).

Conclusion

The literature supports associations of proteinuria and eGFR with long-term clinical outcomes in IgAN across multiple studies and geographic regions. Despite regional variability in standard of care, which introduces heterogeneity in the strength of associations, the consistency of findings across regions supports the utility of proteinuria and eGFR as surrogate endpoints for clinically important long-term kidney outcomes.

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免疫球蛋白A肾病的替代终点和临床结局之间的关联：系统文献综述。

至少50%的免疫球蛋白A肾病（IgAN）患者在诊断后12年内发生肾衰竭。延迟进展到肾衰竭仍然是IgAN的金标准治疗终点，但延长的时间过程限制了作为临床试验主要终点的可行性。早期可测量的终点可以作为临床重要的长期肾脏结局的替代终点。监管机构认可替代终点，如蛋白尿减少。然而，其他利益攸关方，如付款人、卫生技术评估机构和决策者，可能需要额外的证据。本文献综述评估了替代终点（包括蛋白尿和估计肾小球滤过率（eGFR））与IgAN患者长期肾脏预后之间的关联数据。方法：通过Ovid（2006年1月1日-2023年9月1日）在MEDLINE、Embase和CENTRAL中系统检索在任何国家进行的IgAN研究，并辅以会议摘要（2019-2023年）和相关文献综述和荟萃分析。符合条件的研究评估了IgAN患者肾脏疾病进展的替代终点与长期预后的关系。结果：在筛选的1833篇文献中，有23篇文献符合入选标准。结论：在多个研究和地理区域中，文献支持蛋白尿和eGFR与IgAN长期临床结果的关联。尽管标准治疗存在地区差异，这导致了关联强度的异质性，但各地区研究结果的一致性支持了蛋白尿和eGFR作为临床重要的长期肾脏结局的替代终点的效用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.