Epidemiology, Outcomes, and Complement Gene Variants in Secondary Thrombotic Microangiopathies.
Journal
Clinical journal of the American Society of Nephrology : CJASN
ISSN: 1555-905X
Titre abrégé: Clin J Am Soc Nephrol
Pays: United States
ID NLM: 101271570
Informations de publication
Date de publication:
21 Apr 2023
21 Apr 2023
Historique:
received:
25
10
2022
accepted:
13
04
2023
pmc-release:
01
07
2024
pubmed:
24
4
2023
medline:
24
4
2023
entrez:
24
04
2023
Statut:
aheadofprint
Résumé
The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA. In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers. During the study period, 336 patients were hospitalized with a first episode of TMA. Etiologies included atypical HUS in 49 patients (15%), thrombotic thrombocytopenic purpura (TTP) in 29 (9%), shigatoxin-associated HUS in 70 (21%), and secondary TMA in 188 (56%). The main causes of secondary TMA were hematopoietic stem-cell transplantation ( n =56, 30%), solid-organ transplantation ( n =44, 23%), and malignant hypertension ( n =25, 13%). Rare variants in complement genes were identified in 32 of 49 patients (65%) with atypical HUS and eight of 64 patients (13%) with secondary TMA; pathogenic or likely pathogenic variants were found in 24 of 49 (49%) and two of 64 (3%) of them, respectively ( P < 0.001). After a median follow-up of 1157 days, death or kidney failure occurred in 14 (29%), eight (28%), five (7%), and 121 (64%) patients with atypical HUS, TTP, shigatoxin-associated HUS, and secondary TMA, respectively. Unadjusted and adjusted Cox regressions showed that patients with secondary TMA had the highest risk of death or kidney failure (unadjusted hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.85 to 6.07; P < 0.001; adjusted HR, 4.11; 95% CI, 2.00 to 8.46; P < 0.001; considering atypical HUS as reference). Secondary TMAs represent the main cause of TMA and are independently associated with a high risk of death and progression to kidney failure.
Sections du résumé
BACKGROUND
BACKGROUND
The identification of complement defects as major drivers of primary atypical hemolytic uremic syndrome (HUS) has transformed the landscape of thrombotic microangiopathies (TMAs), leading to the development of targeted therapies and better patient outcomes. By contrast, little is known about the presentation, genetics, and outcomes of TMA associated with specific diseases or conditions, also referred to as secondary TMA.
METHODS
METHODS
In this study, we assessed the relative incidence, clinical and genetic spectra, and long-term outcomes of secondary TMA versus other TMAs in consecutive patients hospitalized with a first episode of TMA from 2009 to 2019 at two European reference centers.
RESULTS
RESULTS
During the study period, 336 patients were hospitalized with a first episode of TMA. Etiologies included atypical HUS in 49 patients (15%), thrombotic thrombocytopenic purpura (TTP) in 29 (9%), shigatoxin-associated HUS in 70 (21%), and secondary TMA in 188 (56%). The main causes of secondary TMA were hematopoietic stem-cell transplantation ( n =56, 30%), solid-organ transplantation ( n =44, 23%), and malignant hypertension ( n =25, 13%). Rare variants in complement genes were identified in 32 of 49 patients (65%) with atypical HUS and eight of 64 patients (13%) with secondary TMA; pathogenic or likely pathogenic variants were found in 24 of 49 (49%) and two of 64 (3%) of them, respectively ( P < 0.001). After a median follow-up of 1157 days, death or kidney failure occurred in 14 (29%), eight (28%), five (7%), and 121 (64%) patients with atypical HUS, TTP, shigatoxin-associated HUS, and secondary TMA, respectively. Unadjusted and adjusted Cox regressions showed that patients with secondary TMA had the highest risk of death or kidney failure (unadjusted hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.85 to 6.07; P < 0.001; adjusted HR, 4.11; 95% CI, 2.00 to 8.46; P < 0.001; considering atypical HUS as reference).
CONCLUSIONS
CONCLUSIONS
Secondary TMAs represent the main cause of TMA and are independently associated with a high risk of death and progression to kidney failure.
Identifiants
pubmed: 37094330
doi: 10.2215/CJN.0000000000000182
pii: 01277230-990000000-00134
pmc: PMC10356144
doi:
Banques de données
ClinicalTrials.gov
['NCT04743804']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Investigateurs
Selda Aydin
(S)
Charles Cuvelier
(C)
Pierre-Yves Decleire
(PY)
Nathalie Demoulin
(N)
Arnaud Devresse
(A)
Ludovic Gérard
(L)
Gaëlle Gillerot
(G)
Valentine Gillion
(V)
Eric Goffin
(E)
Philippe Hantson
(P)
Michel Jadoul
(M)
Jean Jamez
(J)
Nada Kanaan
(N)
Laura Labriola
(L)
Jean-Philippe Lengelé
(JP)
Lionel Mazzoleni
(L)
Yves Pirson
(Y)
Jean-Michel Pochet
(JM)
Nadejda Ranguelov
(N)
Marie-Astrid van Dievoet
(MA)
Elliott van Regemorter
(E)
Xavier Wittebole
(X)
Bert Bammens
(B)
Greet de Vlieger
(G)
Koenraad Devriendt
(K)
Katrien de Vusser
(K)
Pieter Evenepoel
(P)
Laurent Godinas
(L)
Priyanka Koshy
(P)
Dirk Kuypers
(D)
Evelyne Lerut
(E)
Björn Meijers
(B)
Maartens Naesens
(M)
Patrick Schöffski
(P)
Ben Sprangers
(B)
Dirk Timmerman
(D)
Amaryllis van Craenenbroeck
(A)
Alexander Wilmer
(A)
Informations de copyright
Copyright © 2023 by the American Society of Nephrology.
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