Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Hannah J Lomax-Browne; Nicholas R Medjeral-Thomas; Sean J Barbour; Jack Gisby; Heedeok Han; Andrew S Bomback; Fernando C Fervenza; Thomas H Cairns; Richard Szydlo; Sven-Jean Tan; Stephen D Marks; Aoife M Waters; Gerald B Appel; Vivette D D'Agati; Sanjeev Sethi; Cynthia C Nast; Ingeborg Bajema; Charles E Alpers; Agnes B Fogo; Christoph Licht; Fadi Fakhouri; Daniel C Cattran; James E Peters; H Terence Cook; Matthew C Pickering

doi:10.2215/CJN.16801221

Association of Histologic Parameters with Outcome in C3 Glomerulopathy and Idiopathic Immunoglobulin-Associated Membranoproliferative Glomerulonephritis

Clin J Am Soc Nephrol. 2022 Jul;17(7):994-1007. doi: 10.2215/CJN.16801221.

Authors

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 Marks^{8

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 Pickering¹

Affiliations

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.

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.

Keywords: complement; glomerulonephritis; kidney biopsy; membranoproliferative glomerulonephritis (MPGN).

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Atrophy
Biopsy
Fibrosis
Glomerulonephritis* / diagnosis
Glomerulonephritis, Membranoproliferative* / pathology
Humans
Immunoglobulins
Proteinuria / etiology
Renal Insufficiency* / complications
Retrospective Studies

Substances

Immunoglobulins

Abstract

Publication types

MeSH terms

Substances

Grants and funding