Risk Stratification to Predict Renal Survival in Anti-Glomerular Basement Membrane Disease.


Journal

Journal of the American Society of Nephrology : JASN
ISSN: 1533-3450
Titre abrégé: J Am Soc Nephrol
Pays: United States
ID NLM: 9013836

Informations de publication

Date de publication:
01 03 2023
Historique:
received: 17 05 2022
accepted: 29 10 2022
pmc-release: 01 03 2024
pubmed: 30 11 2022
medline: 4 3 2023
entrez: 29 11 2022
Statut: ppublish

Résumé

Most patients with anti-glomerular basement membrane (GBM) disease present with rapidly progressive glomerulonephritis, and more than half develop ESKD. Currently, no tools are available to aid in the prognostication or management of this rare disease. In one of the largest assembled cohorts of patients with anti-GBM disease (with 174 patients included in the final analysis), the authors demonstrated that the renal risk score for ANCA-associated vasculitis is transferable to anti-GBM disease and the renal histology is strongly predictive of renal survival and recovery. Stratifying patients according to the percentage of normal glomeruli in the kidney biopsy and the need for RRT at the time of diagnosis improves outcome prediction. Such stratification may assist in the management of anti-GBM disease. Prospective randomized trials investigating treatments and outcomes in anti-glomerular basement membrane (anti-GBM) disease are sparse, and validated tools to aid prognostication or management are lacking. In a retrospective, multicenter, international cohort study, we investigated clinical and histologic parameters predicting kidney outcome and sought to identify patients who benefit from rescue immunosuppressive therapy. We also explored applying the concept of the renal risk score (RRS), currently used to predict renal outcomes in ANCA-associated vasculitis, to anti-GBM disease. The final analysis included 174 patients (out of a total of 191). Using Cox and Kaplan-Meier methods, we found that the RRS was a strong predictor for ESKD. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-risk, moderate-risk, and high-risk groups, respectively. The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD. The best predictor for renal recovery was the percentage of normal glomeruli, with a cut point of 10% normal glomeruli providing good stratification. A model with the predictors RRT and normal glomeruli ( N ) achieved superior discrimination for significant differences in renal survival. Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N ≥10%), 74.0% (no RRT, N <10%), 42.3% (RRT, N ≥10%), and 14.1% (RRT, N <10%), respectively. These findings demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Such stratification may assist in the management of anti-GBM disease. This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Sections du résumé

SIGNIFICANCE STATEMENT
Most patients with anti-glomerular basement membrane (GBM) disease present with rapidly progressive glomerulonephritis, and more than half develop ESKD. Currently, no tools are available to aid in the prognostication or management of this rare disease. In one of the largest assembled cohorts of patients with anti-GBM disease (with 174 patients included in the final analysis), the authors demonstrated that the renal risk score for ANCA-associated vasculitis is transferable to anti-GBM disease and the renal histology is strongly predictive of renal survival and recovery. Stratifying patients according to the percentage of normal glomeruli in the kidney biopsy and the need for RRT at the time of diagnosis improves outcome prediction. Such stratification may assist in the management of anti-GBM disease.
BACKGROUND
Prospective randomized trials investigating treatments and outcomes in anti-glomerular basement membrane (anti-GBM) disease are sparse, and validated tools to aid prognostication or management are lacking.
METHODS
In a retrospective, multicenter, international cohort study, we investigated clinical and histologic parameters predicting kidney outcome and sought to identify patients who benefit from rescue immunosuppressive therapy. We also explored applying the concept of the renal risk score (RRS), currently used to predict renal outcomes in ANCA-associated vasculitis, to anti-GBM disease.
RESULTS
The final analysis included 174 patients (out of a total of 191). Using Cox and Kaplan-Meier methods, we found that the RRS was a strong predictor for ESKD. The 36-month renal survival was 100%, 62.4%, and 20.7% in the low-risk, moderate-risk, and high-risk groups, respectively. The need for renal replacement therapy (RRT) at diagnosis and the percentage of normal glomeruli in the biopsy were independent predictors of ESKD. The best predictor for renal recovery was the percentage of normal glomeruli, with a cut point of 10% normal glomeruli providing good stratification. A model with the predictors RRT and normal glomeruli ( N ) achieved superior discrimination for significant differences in renal survival. Dividing patients into four risk groups led to a 36-month renal survival of 96.4% (no RRT, N ≥10%), 74.0% (no RRT, N <10%), 42.3% (RRT, N ≥10%), and 14.1% (RRT, N <10%), respectively.
CONCLUSIONS
These findings demonstrate that the RRS concept is transferrable to anti-GBM disease. Stratifying patients according to the need for RRT at diagnosis and renal histology improves prediction, highlighting the importance of normal glomeruli. Such stratification may assist in the management of anti-GBM disease.
PODCAST
This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Identifiants

pubmed: 36446430
pii: 00001751-202303000-00016
doi: 10.1681/ASN.2022050581
pmc: PMC10103284
doi:

Types de publication

Multicenter Study Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

505-514

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2022 by the American Society of Nephrology.

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Auteurs

Lauren Floyd (L)

Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
Renal Department, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom.

Sebastian Bate (S)

Centre for Biostatistics, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, United Kingdom.
Manchester Academic Health Science Centre, Research and Innovation, Manchester University NHS Foundation Trust, Manchester, United Kingdom.

Abdul Hadi Kafagi (A)

Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.

Nina Brown (N)

Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
Renal Department, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom.

Jennifer Scott (J)

Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
Irish Centre for Vascular Biology, Dublin, Ireland.

Mukunthan Srikantharajah (M)

Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.

Marek Myslivecek (M)

First Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Nephrology, General University Hospital, Prague, Czech Republic.

Graeme Reid (G)

Renal Pathology, Adult Histopathology Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom.

Faten Aqeel (F)

Department of Medicine, John Hopkins University, Baltimore, Maryland.

Doubravka Frausova (D)

First Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Nephrology, General University Hospital, Prague, Czech Republic.

Marek Kollar (M)

Centre of Clinical and Transplant Pathology, Institute of Clinical and Experimental Medicine, Prague, Czech Republic.

Phuong Le Kieu (PL)

Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.

Bilal Khurshid (B)

Renal Department, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Salford, United Kingdom.

Charles D Pusey (CD)

Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.

Ajay Dhaygude (A)

Renal Department, Royal Preston Hospital, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom.

Vladimir Tesar (V)

First Faculty of Medicine, Charles University, Prague, Czech Republic.
Department of Nephrology, General University Hospital, Prague, Czech Republic.

Stephen McAdoo (S)

Department of Immunology and Inflammation, Imperial College London, London, United Kingdom.

Mark A Little (MA)

Trinity Health Kidney Centre, Trinity Translational Medicine Institute, Trinity College Dublin, Dublin, Ireland.
Irish Centre for Vascular Biology, Dublin, Ireland.

Duvuru Geetha (D)

Department of Medicine, John Hopkins University, Baltimore, Maryland.

Silke R Brix (SR)

Division of Cardiovascular Sciences, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.
Renal, Urology and Transplantation Unit, Manchester University NHS Foundation Trust, Manchester, United Kingdom.

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