Logo do repositório
 
Publicação

Genotype-Phenotype Correlations and Clinical Outcomes of Genetic TRPC6 Podocytopathies

2026-01Artigo científico Acesso aberto
Ver registo simples
dc.contributor.authorMcAnallen, Susan M
dc.contributor.authorElhassan, Elhussein A E
dc.contributor.authorStoneman, Sinead
dc.contributor.authorPinto E Vairo, Filippo
dc.contributor.authorHogan, Marie C
dc.contributor.authorHoefele, Julia
dc.contributor.authorClince, Michelle
dc.contributor.authorMekraksakit, Poemlarp
dc.contributor.authorTitan, Silvia M
dc.contributor.authorJorge, Sofia
dc.contributor.authorCalado, Joaquim
dc.contributor.authorDecramer, Stéphane
dc.contributor.authorColliou, Eloïse
dc.contributor.authorTellier, Stéphanie
dc.contributor.authorFrancisco, Telma
dc.contributor.authorServais, Aude
dc.contributor.authorCornet, Joséphine
dc.contributor.authorde Fallois, Jonathan
dc.contributor.authorDossier, Claire
dc.contributor.authorFenoglio, Roberta
dc.contributor.authorRenieri, Alessandra
dc.contributor.authorPinto, Anna Maria
dc.contributor.authorDaga, Sergio
dc.contributor.authorLoberti, Lorenzo
dc.contributor.authorFila, Marc
dc.contributor.authorQuintana, Luis F
dc.contributor.authorBecherucci, Francesca
dc.contributor.authorNathalie, Godefroid
dc.contributor.authorAstrid, Dubrasquet
dc.contributor.authorToryDolan, KálmánNiamh
dc.contributor.authorAlawi, Bushra Al
dc.contributor.authorSweeney, Clodagh
dc.contributor.authorRiordan, Michael
dc.contributor.authorStack, Maria
dc.contributor.authorAwan, Atif
dc.contributor.authorHui, Ng Kar
dc.contributor.authorMcCarthy, Hugh
dc.contributor.authorBiros, Erik
dc.contributor.authorHarris, Trudie
dc.contributor.authorKidd, Kendrah
dc.contributor.authorHaeberle, Stefanie
dc.contributor.authorBleyer, Anthony J
dc.contributor.authorMallett, Andrew J
dc.contributor.authorSayer, John A
dc.contributor.authorSchafer, Franz
dc.contributor.authorBenson, Katherine A
dc.contributor.authorMcCann, Emma
dc.contributor.authorConlon, Peter J
dc.contributor.authorCalado, Joaquim
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblEuropean Renal Association - European Dialysis and Transplant Association (ERA-EDTA) | Oxford University Press
dc.date.accessioned2025-09-30T22:35:20Z
dc.date.available2025-09-30T22:35:20Z
dc.date.issued2026-01
dc.description© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.
dc.description.abstractBACKGROUND AND HYPOTHESIS: Podocytopathy associated with likely pathogenic/pathogenic variants of TRPC6 (TRPC6-AP) has been recognised for about 20 years. As a result of its rarity however, the spectrum of clinical phenotypes and genotype-phenotype correlation of TRPC6-AP remains poorly understood. Here, we characterised clinical, histological, and genetic correlates of familial and sporadic patients with TRPC6-AP. METHODS: In this multicentre observational study, an online questionnaire followed by a systematic literature review was performed to create a cohort with comprehensive data on genetic and clinical outcomes (age of onset, clinical presentation, treatment response, kidney biopsy findings, and progression to kidney failure). Logistic regression, Cox proportional hazards model and Kaplan-Meier analyses investigated the associations between genetic variants and disease progression. RESULTS: Among 87 families (96 familial and 45 sporadic cases), 31 distinct missense TRPC6 variants (including 2 novel) were identified, with c.2683C > T p.(Arg895Cys) and c.523C > T p.(Arg175Trp) the commonest variants. Proteinuric kidney disease/nephrotic syndrome was the most common clinical presentation (83.7%), while focal segmental glomerulosclerosis was the most common histological finding (89.4%). By 33 (interquartile range: 17-40) years, 48.9% (69/141) of patients had progressed to kidney failure. Sporadic TRPC6-AP demonstrated an earlier progression to kidney failure than familial cases (P = 0.001) and were more likely to present with nephrotic syndrome (odds ratio: 4.34 (1.85-10.15); P = 0.001). Gain-of-function TRPC6 variants were more frequent in familial than sporadic TRPC6-AP (70.8% vs. 44.4%; P = 0.004). Compared to patients with other TRPC6 variants, patients with TRPC6 p.R175W and p.R895C variants progressed to kidney failure earlier (median kidney survival of 21 years; Hazard ratios (HR): 2.985 [95% CI: 1.40-5.79] and 38 years; HR: 1.65 [95% CI: 1.01-2.81], respectively, log-rank P = 0.005). CONCLUSION: Our study shows unique clinical and genetic correlations of TRPC6-AP, which may enable personalised care and promising novel therapies.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent1371336
dc.identifier.doi10.1093/ndt/gfaf086
dc.identifier.issn0931-0509
dc.identifier.otherPURE: 130622446
dc.identifier.otherPURE UUID: b067ee6b-6db1-4e94-ba57-cae0e48dd171
dc.identifier.otherPubMed: 40388293
dc.identifier.otherORCID: /0000-0002-1194-3392/work/193189226
dc.identifier.otherScopus: 105025696329
dc.identifier.urihttp://hdl.handle.net/10362/188819
dc.language.isoeng
dc.peerreviewedyes
dc.titleGenotype-Phenotype Correlations and Clinical Outcomes of Genetic TRPC6 Podocytopathiesen
dc.typejournal article
degois.publication.firstPage
degois.publication.issue1
degois.publication.lastPage
degois.publication.titleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
degois.publication.volume41
dspace.entity.typePublication
person.familyNameCalado
person.givenNameJoaquim
person.identifier.orcid0000-0002-1194-3392
person.identifier.scopus-author-id7006897273
rcaap.rightsopenAccess
relation.isAuthorOfPublicationa272bd58-da86-4b61-a84c-3955ad4c5803
relation.isAuthorOfPublication.latestForDiscoverya272bd58-da86-4b61-a84c-3955ad4c5803

Ficheiros

Principais
A mostrar 1 - 1 de 1
Miniatura
Nome:
gfaf086.pdf
Tamanho:
1.31 MB
Formato:
Adobe Portable Document Format
Ver/Abrir

Coleções

NMS - Artigos em revista internacional com arbitragem científica