| Title: |
Genotype–phenotype correlations and clinical outcomes of genetic TRPC6 podocytopathies |
| Authors: |
McAnallen, Susan M; Elhassan, Elhussein A E; Stoneman, Sinead; Pinto e Vairo, Filippo; Hogan, Marie C; Hoefele, Julia; Clince, Michelle; Mekraksakit, Poemlarp; Titan, Silvia M; Jorge, Sofia; Calado, Joaquim; Decramer, Stéphane; Colliou, Eloïse; Tellier, Stéphanie; Francisco, Telma; Servais, Aude; Cornet, Joséphine; de Fallois, Jonathan; Dossier, Claire; Fenoglio, Roberta; Renieri, Alessandra; Pinto, Anna Maria; Daga, Sergio; Loberti, Lorenzo; Fila, Marc; Quintana, Luis F; Becherucci, Francesca; Godefroid, Nathalie; Dubrasquet, Astrid; Kálmán, Tory; Dolan, Niamh; Alawi, Bushra Al; Sweeney, Clodagh; Riordan, Michael; Stack, Maria; Awan, Atif; Hui, Ng Kar; McCarthy, Hugh J; Biros, Erik; Harris, Trudie; Kidd, Kendrah; Haeberle, Stefanie; Bleyer, Anthony J; Mallett, Andrew J; Sayer, John A; Schafer, Franz; Benson, Katherine A; McCann, Emma; Conlon, Peter J |
| Contributors: |
UCL - SSS/IREC/NEFR - Pôle de Néphrologie; UCL - (SLuc) Service de néphrologie pédiatrique |
| Source: |
Nephrology Dialysis Transplantation, Vol. 41, no.1, p. 79-91 (2025) |
| Publisher Information: |
Oxford University Press (OUP) |
| Publication Year: |
2025 |
| Collection: |
DIAL@USL-B (Université Saint-Louis, Bruxelles) |
| Subject Terms: |
TRPC6; CKD; FSGS; podocytopathy; steroid-resistant nephrotic syndrome |
| Description: |
Background and hypothesis: Podocytopathy associated with likely pathogenic/pathogenic variants of Transient receptor potential cation channel subfamily C member 6 (TRPC6) (TRPC6-AP) has been recognized 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 characterized 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 (KF)]. 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 KF. Sporadic TRPC6-AP demonstrated an earlier progression to KF than familial cases (P = .001) and were more likely to present with nephrotic syndrome [odds ratio 4.34 (1.85-10.15); P = .001]. Gain-of-function TRPC6 variants were more frequent in familial than sporadic TRPC6-AP (70.8% vs 44.4%; P = .004). Compared with patients with other TRPC6 variants, patients with TRPC6 p.R175W and p.R895C variants progressed to KF earlier [median kidney survival of 21 years, hazard ratio 2.985 (95% confidence interval 1.40-5.79); and 38 years, hazard ratio 1.65 (95% confidence ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
boreal:310863; https://hdl.handle.net/2078.1/310863 |
| DOI: |
10.1093/ndt/gfaf086 |
| Availability: |
https://hdl.handle.net/2078.1/310863; https://doi.org/10.1093/ndt/gfaf086 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.7840378F |
| Database: |
BASE |