Parasyri Maria, Brandström Per, Uusimaa Johanna, Ostergaard Elsebet, Hikmat Omar, Isohanni Pirjo, Naess Karin, de Coo I F M, Nascimento Osorio Andrés, Nuutinen Matti, Lindberg Christopher, Bindoff Laurence A, Tulinius Már, Darin Niklas, Sofou Kalliopi
Department of Paediatrics, Region Västra Götaland, Sahlgrenska University Hospital, Gothenburg, Sweden.
Department of Paediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Kidney Dis (Basel). 2022 Jan 24;8(2):148-159. doi: 10.1159/000521148. eCollection 2022 Mar.
This study aimed to investigate associations between renal and extrarenal manifestations of mitochondrial diseases and their natural history as well as predictors of renal disease severity and overall disease outcome. The secondary aim was to generate a protocol of presymptomatic assessment and monitoring of renal function in patients with a defined mitochondrial disease.
A multicenter, retrospective cohort study was performed by the Mitochondrial Clinical and Research Network (MCRN). Patients of any age with renal manifestations associated with a genetically verified mitochondrial disease were included from 8 expert European centers specializing in mitochondrial diseases: Gothenburg, Oulu, Copenhagen, Bergen, Helsinki, Stockholm, Rotterdam, and Barcelona.
Of the 36 patients included, two-thirds had mitochondrial DNA-associated disease. Renal manifestations were the first sign of mitochondrial disease in 19%, and renal involvement was first identified by laboratory tests in 57% of patients. Acute kidney injury occurred in 19% of patients and was the first sign of renal disease in the majority of these. The most common renal manifestation was chronic kidney disease (75% with stage 2 or greater), followed by tubulopathy (44.4%), the latter seen mostly among patients with single large-scale mitochondrial DNA deletions. Acute kidney injury and tubulopathy correlated with worse survival outcome. The most common findings on renal imaging were increased echogenicity and renal dysplasia/hypoplasia. Renal histology revealed focal segmental glomerulosclerosis, nephrocalcinosis, and nephronophthisis.
Acute kidney injury is a distinct renal phenotype in patients with mitochondrial disease. Our results highlight the importance to recognize renal disease as a sign of an underlying mitochondrial disease. Acute kidney injury and tubulopathy are 2 distinct indicators of poor survival in patients with mitochondrial diseases.
本研究旨在调查线粒体疾病的肾脏和肾外表现之间的关联及其自然病史，以及肾脏疾病严重程度和总体疾病结局的预测因素。次要目的是制定一份针对明确线粒体疾病患者的肾功能症状前评估和监测方案。
线粒体临床与研究网络（MCRN）开展了一项多中心回顾性队列研究。纳入了来自欧洲8个线粒体疾病专家中心（哥德堡、奥卢、哥本哈根、卑尔根、赫尔辛基、斯德哥尔摩、鹿特丹和巴塞罗那）的任何年龄的、有经基因验证的线粒体疾病相关肾脏表现的患者。
纳入的36例患者中，三分之二患有线粒体DNA相关疾病。肾脏表现是19%的线粒体疾病患者的首发症状，57%的患者通过实验室检查首次发现肾脏受累。19%的患者发生急性肾损伤，且在大多数此类患者中是肾脏疾病的首发症状。最常见的肾脏表现是慢性肾脏病（75%为2期或更严重），其次是肾小管病（44.4%），后者大多见于单个大规模线粒体DNA缺失的患者。急性肾损伤和肾小管病与较差的生存结局相关。肾脏影像学最常见的表现是回声增强和肾发育异常/发育不全。肾脏组织学显示局灶节段性肾小球硬化、肾钙质沉着症和肾单位肾痨。
急性肾损伤是线粒体疾病患者一种独特的肾脏表型。我们的结果凸显了将肾脏疾病识别为潜在线粒体疾病体征的重要性。急性肾损伤和肾小管病是线粒体疾病患者生存不良的两个不同指标。
