IgA nephropathy and atypical hemolytic uremic syndrome: a case series and a literature review.
Acute renal failure
Complement
End-stage-kidney disease
Genetic
Hemolytic uremic syndrome
Hypertension
IgA nephropathy
Thrombotic microangiopathy
Journal
Journal of nephrology
ISSN: 1724-6059
Titre abrégé: J Nephrol
Pays: Italy
ID NLM: 9012268
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
14
06
2021
accepted:
22
10
2021
pubmed:
11
11
2021
medline:
18
5
2022
entrez:
10
11
2021
Statut:
ppublish
Résumé
IgA nephropathy (IgAN) has been anecdotally reported in association with atypical hemolytic uremic syndrome (aHUS). The association likely portends poor renal outcome, and the possible relationship with complement overactivation has yet to be elucidated. We evaluated a series of IgAN patients with aHUS and reviewed the available literature. Adult patients who received a diagnosis of IgAN and developed aHUS between January 2009 and December 2019 were included in this retrospective review. We identified six IgAN-aHUS patients, all of whom developed end-stage kidney disease. At aHUS presentation all patients had decreased serum C3 levels. Predisposing pathogenetic variants and risk haplotypes for aHUS in CFH gene heterozygosity were documented in four out of six patients. Anti-CFH antibodies were found to be negative in the five tested patients. In the literature we identified 21 case reports involving aHUS-IgAN and six retrospective studies evaluating the presence of TMA at the time of renal biopsy. Hypertension, severe proteinuria, reduced sC3 and a worse renal prognosis were the common features of most cases. Our case series and literature review show that the onset of either aHUS or renal TMA in the course of IgAN are associated with very poor renal outcome. Activation of the alternative pathway revealed by consumption of serum C3 seems to play a major role. Our hypothesis is that the presence of a predisposing factor (e.g. dysregualtion of complement alternative pathway and/or other intrarenal precipitating factors) might be at the heart of aHUS-IgAN pathophysiology.
Sections du résumé
BACKGROUND
IgA nephropathy (IgAN) has been anecdotally reported in association with atypical hemolytic uremic syndrome (aHUS). The association likely portends poor renal outcome, and the possible relationship with complement overactivation has yet to be elucidated. We evaluated a series of IgAN patients with aHUS and reviewed the available literature.
METHODS
Adult patients who received a diagnosis of IgAN and developed aHUS between January 2009 and December 2019 were included in this retrospective review.
RESULTS
We identified six IgAN-aHUS patients, all of whom developed end-stage kidney disease. At aHUS presentation all patients had decreased serum C3 levels. Predisposing pathogenetic variants and risk haplotypes for aHUS in CFH gene heterozygosity were documented in four out of six patients. Anti-CFH antibodies were found to be negative in the five tested patients. In the literature we identified 21 case reports involving aHUS-IgAN and six retrospective studies evaluating the presence of TMA at the time of renal biopsy. Hypertension, severe proteinuria, reduced sC3 and a worse renal prognosis were the common features of most cases.
CONCLUSION
Our case series and literature review show that the onset of either aHUS or renal TMA in the course of IgAN are associated with very poor renal outcome. Activation of the alternative pathway revealed by consumption of serum C3 seems to play a major role. Our hypothesis is that the presence of a predisposing factor (e.g. dysregualtion of complement alternative pathway and/or other intrarenal precipitating factors) might be at the heart of aHUS-IgAN pathophysiology.
Identifiants
pubmed: 34757577
doi: 10.1007/s40620-021-01189-6
pii: 10.1007/s40620-021-01189-6
doi:
Substances chimiques
Complement System Proteins
9007-36-7
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1091-1100Informations de copyright
© 2021. Italian Society of Nephrology.
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