Solignac Justine, Delmont Emilien, Fortanier Etienne, Attarian Shahram, Mancini Julien, Daniel Laurent, Ion Ioana, Ricci Jean-Etienne, Robert Thomas, Habib Gilbert, Moranne Olivier, Jourde-Chiche Noémie
Centre de Néphrologie et Transplantation Rénale, Hôpital de la Conception, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
Centre de Référence des Maladies Neuromusculaires et SLA, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille, France.
Clin Kidney J. 2022 May 5;15(9):1747-1754. doi: 10.1093/ckj/sfac118. eCollection 2022 Sep.
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.
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.
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.
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.
遗传性转甲状腺素蛋白淀粉样变性（ATTRv）是一种致残且危及生命的疾病，主要影响神经系统和心脏。其肾脏受累情况尚未得到系统研究，尤其是在非V30M突变患者中，并且肾脏病学家对此并不十分了解。
我们进行了一项回顾性研究，描述了2011年6月至2021年6月期间在法国南部两家大学医院接受随访的所有患有ATTR突变、有神经或心脏受累的现患患者或症状前携带者的肾脏表型。
共纳入103例患者，其中79例有症状，24例为症状前携带者。患者携带21种不同的ATTR突变，54%携带V30M突变。平均随访7.9±25.7年后，30.4%的有症状患者发生了慢性肾脏病（CKD），20.3%的患者尿蛋白：肌酐比值≥0.5 g/g。无症状前携带者发生CKD或蛋白尿。在多变量分析中，症状出现较晚（60岁以后）、V122I突变和蛋白尿与CKD显著相关。有症状患者的无CKD生存期中位数估计为81.0岁（四分位间距77.1 - 84.9）。V30M和非V30M患者之间无差异，但V122I突变患者的生存期较短。CKD发病的平均年龄为69.3±13.0岁。在一名表现为以肾脏为主的表型的38岁V30M女性患者中，使用帕替沙兰治疗导致肾病综合征缓解。
CKD影响近三分之一有症状的ATTRv患者。ATTRv本身在该人群CKD发生中的作用仍有待确定，但一些患者可能从特定治疗中获益。
