Paediatric Nephrology, Necker Enfants Malades Hospital, MARHEA, APHP, Imagine Institute, Paris Cité University, 149 rue de Sèvres, 75015, Paris, France.
J Nephrol. 2023 Jun;36(5):1473-1476. doi: 10.1007/s40620-023-01611-1. Epub 2023 May 20.
Primary hyperoxaluria type 1 is a rare genetic disorder caused by bi-allelic pathogenic variants in the AGXT gene leading to an overproduction of oxalate which accumulates in the kidneys in the form of calcium oxalate crystals. Thus, patients may present with recurrent nephrocalcinosis and lithiasis, with progressive impairment of the renal function and eventually kidney failure. There is no specific treatment besides liver-kidney transplantation, and pre-transplantation management by 24 h-hyperhydration, crystallisation inhibitors and high-dose pyridoxine has a high negative impact on quality of life, especially because of the discomfort due to nocturnal hyperhydration. Since 2020, lumasiran, an RNA-interfering therapy, has been approved for the treatment of primary hyperoxaluria type 1 in adults and children. However, to date, there are no recommendations regarding the discontinuation of other supportive measures during RNAi therapy. In this report, we present two patients with primary hyperoxaluria type 1 who were treated with lumasiran and stopped nocturnal hyperhydration with positive outcomes, i.e. normal urinary oxalate, absence of crystalluria, stable kidney function and improved well-being. These data suggest that discontinuing nocturnal hydration may be safe in children responding to lumasiran, and may have a positive impact on their quality of life. Additional data are needed to update treatment recommendations.
原发性高草酸尿症 1 型是一种罕见的遗传性疾病，由 AGXT 基因的双等位基因致病性变异引起，导致草酸盐过度产生，在肾脏中以草酸钙晶体的形式积累。因此，患者可能会出现反复的肾钙质沉着症和结石形成，肾功能逐渐受损，最终导致肾衰竭。除了肝-肾移植外，目前尚无特异性治疗方法，肝移植前 24 小时水化、结晶抑制剂和大剂量吡哆醇的治疗方案对生活质量有很大的负面影响，特别是由于夜间水化引起的不适。自 2020 年以来，lumasiran（一种 RNA 干扰疗法）已被批准用于治疗成人和儿童的原发性高草酸尿症 1 型。然而，迄今为止，尚无关于在 RNAi 治疗期间停止其他支持措施的建议。在本报告中，我们介绍了 2 例接受 lumasiran 治疗并停止夜间水化的原发性高草酸尿症 1 型患者，其结果良好，即尿草酸盐正常、无结晶尿、肾功能稳定且生活质量改善。这些数据表明，对 lumasiran 有反应的儿童可能可以安全地停止夜间水化，并且可能对其生活质量产生积极影响。需要更多的数据来更新治疗建议。
