Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients

Justine Solignac (1) , Emilien Delmont (2) , Etienne Fortanier (2) , Shahram Attarian (3) , Julien Mancini (4, 5) , Laurent Daniel (2) , Ioana Ion (6) , Jean-Etienne Ricci (6) , Thomas Robert (3) , Gilbert Habib (2) , Olivier Moranne (6, 7) , Noemie Jourde-Chiche (1)

1 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
2 TIMONE - Hôpital de la Timone [CHU - APHM]
3 MMG - Marseille medical genetics - Centre de génétique médicale de Marseille
4 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
5 SESSTIM - U1252 INSERM - AMU - UMR 259 IRD - “Cancer, Biomedicine & Society” group
6 CHU Nîmes - Centre Hospitalier Universitaire de Nîmes
7 IDESP - Institut Desbrest de santé publique

Background: hereditary transthyretin amyloidosis (ATTRv) is a disabling and life-threatening disease that primarily affects the nervous system and heart. Its kidney involvement has not been systematically studied, particularly in non-V30M mutations, and is not well known to nephrologists. Methods: we conducted a retrospective study describing the kidney phenotype of all prevalent patients with ATTR mutations, with neurological or cardiac involvement or presymptomatic carriers, followed up in two university hospitals from the South of France between June 2011 and June 2021. Results: a total of 103 patients were included, among whom 79 were symptomatic and 24 were presymptomatic carriers. Patients carried 21 different ATTR mutations and 54% carried the V30M mutation. After a mean follow-up of 7.9 ± 25.7 years, 30.4% of the symptomatic patients had developed chronic kidney disease (CKD) and 20.3% had a urinary protein:creatinine ratio ≥0.5 g/g. None of the presymptomatic carriers had CKD or proteinuria. In a multivariate analysis, late onset of symptoms (after 60 years), the V122I mutation and proteinuria were significantly associated with CKD. The median CKD-free survival in symptomatic patients was estimated at 81.0 years (interquartile range 77.1–84.9). It did not differ between V30M and non-V30M patients, but was lower in patients with the V122I mutation. The average age of the onset of CKD was 69.3 ± 13.0 years. In one 38-year-old V30M female who presented a kidney-predominant phenotype, treatment with patisiran resulted in remission of the nephrotic syndrome. Conclusion: CKD affects almost one-third of patients with symptomatic ATTRv. The role of ATTRv per se in the development of CKD in this population remains to be determined, but some patients may benefit from specific therapies.

Mots clés: ATTR; Chronic kidney disease; Hereditary transthyretin amyloidosis; Kidney amyloidosis; Proteinuria

Domaines: Génétique

Justine Solignac, Emilien Delmont, Etienne Fortanier, Shahram Attarian, Julien Mancini, et al.. Kidney involvement in hereditary transthyretin amyloidosis: a cohort study of 103 patients. Clinical Kidney Journal, 2022, 15 (9), pp.1747-1754. ⟨10.1093/ckj/sfac118⟩. ⟨hal-03780364⟩