Hannah J Lomax-Browne1, Nicholas R Medjeral-Thomas1, Sean J Barbour2, Jack Gisby1, Heedeok Han3, Andrew S Bomback3, Fernando C Fervenza4, Thomas H Cairns5, Richard Szydlo6, Sven-Jean Tan7, Stephen D Marks8,9, Aoife M Waters8, Gerald B Appel3, Vivette D D'Agati10, Sanjeev Sethi11, Cynthia C Nast12, Ingeborg Bajema13, Charles E Alpers14, Agnes B Fogo15, Christoph Licht16, Fadi Fakhouri17, Daniel C Cattran18, James E Peters1, H Terence Cook1, Matthew C Pickering19. 1. Department for Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom. 2. Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada. 3. Department of Medicine, Division of Nephrology, Columbia University Irving Medical Center, New York, New York. 4. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota. 5. West London Renal and Transplant Centre, Imperial College Healthcare NHS Trust, London, United Kingdom. 6. Department for Immunology and Inflammation, Centre for Haematology, Imperial College London, London, United Kingdom. 7. Department of Nephrology, The Royal Melbourne Hospital, Parkville, Victoria, Australia. 8. Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom. 9. 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. 10. Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York. 11. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota. 12. Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California. 13. Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands. 14. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, Washington. 15. Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, Tennessee. 16. Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada. 17. Service of Nephrology and Hypertension, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. 18. Toronto General Research Institute, Division of Nephrology, University of Toronto, Toronto, Ontario, Canada. 19. Department for Immunology and Inflammation, Centre for Inflammatory Disease, Imperial College London, London, United Kingdom matthew.pickering@imperial.ac.uk.
Abstract
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.
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.
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Authors: Cristina Rabasco; Teresa Cavero; Elena Román; Jorge Rojas-Rivera; Teresa Olea; Mario Espinosa; Virginia Cabello; Gema Fernández-Juarez; Fayna González; Ana Ávila; José María Baltar; Montserrat Díaz; Raquel Alegre; Sandra Elías; Monserrat Antón; Miguel Angel Frutos; Alfonso Pobes; Miguel Blasco; Francisco Martín; Carmen Bernis; Manuel Macías; Sergio Barroso; Alberto de Lorenzo; Gema Ariceta; Manuel López-Mendoza; Begoña Rivas; Katia López-Revuelta; José María Campistol; Santiago Mendizábal; Santiago Rodríguez de Córdoba; Manuel Praga Journal: Kidney Int Date: 2015-07-29 Impact factor: 10.612
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