Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis,Clinical Journal of the American Society of Nephrology

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Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis
Clinical Journal of the American Society of Nephrology ( IF 8.5 ) Pub Date : 2022-07-01 , DOI: 10.2215/cjn.16801221
Hannah J Lomax-Browne ₁ , Nicholas R Medjeral-Thomas ₁ , Sean J Barbour ₂ , Jack Gisby ₁ , Heedeok Han ₃ , Andrew S Bomback ₃ , Fernando C Fervenza ₄ , Thomas H Cairns ₅ , Richard Szydlo ₆ , Sven-Jean Tan ₇ , Stephen D Marks _{8,

9} , Aoife M Waters ₈ , Gerald B Appel ₃ , Vivette D D'Agati ₁₀ , Sanjeev Sethi ₁₁ , Cynthia C Nast ₁₂ , Ingeborg Bajema ₁₃ , Charles E Alpers ₁₄ , Agnes B Fogo ₁₅ , Christoph Licht ₁₆ , Fadi Fakhouri ₁₇ , Daniel C Cattran ₁₈ , James E Peters ₁ , H Terence Cook ₁ , Matthew C Pickering ₁

Affiliation

Department for Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom.
Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada.
Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota.
West London Renal and Transplant Centre, Imperial College Healthcare NHS Trust, London, United Kingdom.
Department for Immunology and Inflammation, Centre for Haematology, Imperial College London, London, United Kingdom.
Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia.
Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.
National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London Great Ormond Street Institute of Child Health, London, United Kingdom.
Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota.
Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California.
Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington.
Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee.
Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada.
Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Toronto General Research Institute, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada.

Background and objectives

C3 glomerulopathy and idiopathic Ig-associated membranoproliferative GN are kidney diseases characterized by abnormal glomerular complement C3 deposition. These conditions are heterogeneous in outcome, but approximately 50% of patients develop kidney failure within 10 years.

Design, setting, participants, & measurements

To improve identification of patients with poor prognosis, we performed a detailed analysis of percutaneous kidney biopsies in a large cohort of patients. Using a validated histologic scoring system, we analyzed 156 native diagnostic kidney biopsies from a retrospective cohort of 123 patients with C3 glomerulopathy and 33 patients with Ig-associated membranoproliferative GN. We used linear regression, survival analysis, and Cox proportional hazards models to assess the relationship between histologic and clinical parameters with outcome.

Results

Frequent biopsy features were mesangial expansion and hypercellularity, glomerular basement membrane double contours, and endocapillary hypercellularity. Multivariable analysis showed negative associations between eGFR and crescents, interstitial inflammation, and interstitial fibrosis/tubular atrophy. Proteinuria positively associated with endocapillary hypercellularity and glomerular basement membrane double contours. Analysis of second native biopsies did not demonstrate associations between immunosuppression treatment and improvement in histology. Using a composite outcome, risk of progression to kidney failure associated with eGFR and proteinuria at the time of biopsy, cellular/fibrocellular crescents, segmental sclerosis, and interstitial fibrosis/tubular atrophy scores.

Conclusions

Our detailed assessment of kidney biopsy data indicated that cellular/fibrocellular crescents and interstitial fibrosis/tubular atrophy scores were significant determinants of deterioration in kidney function.

中文翻译：

组织学参数与 C3 肾小球病和特发性免疫球蛋白相关膜增殖性肾炎结果的关联

背景和目标

C3 肾小球病和特发性 Ig 相关膜增殖性 GN 是以肾小球补体 C3 沉积异常为特征的肾脏疾病。这些疾病的结果各不相同，但大约 50% 的患者在 10 年内出现肾衰竭。

设计、设置、参与者和测量

为了更好地识别预后不良的患者，我们对一大群患者的经皮肾活检进行了详细分析。使用经过验证的组织学评分系统，我们分析了来自 123 名 C3 肾小球病患者和 33 名 Ig 相关膜增殖性肾小球肾病患者的回顾性队列中的 156 份天然诊断肾活检样本。我们使用线性回归、生存分析和 Cox 比例风险模型来评估组织学和临床参数与结果之间的关系。

结果

常见的活检特征是系膜扩张和细胞增多、肾小球基底膜双轮廓和毛细血管内细胞增多。多变量分析显示 eGFR 与新月体、间质炎症和间质纤维化/肾小管萎缩之间呈负相关。蛋白尿与毛细血管内细胞增多和肾小球基底膜双轮廓呈正相关。对第二次天然活检的分析并未证明免疫抑制治疗与组织学改善之间的关联。使用复合结果，进展为肾衰竭的风险与活检时的 eGFR 和蛋白尿、细胞/纤维细胞新月体、节段性硬化和间质纤维化/肾小管萎缩评分相关。

结论

我们对肾活检数据的详细评估表明，细胞/纤维细胞新月体和间质纤维化/肾小管萎缩评分是肾功能恶化的重要决定因素。

更新日期：2022-07-01

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