Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN.
Department of Clinical Genomics, Mayo Clinic College of Medicine, Rochester, MN; Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN.
Am J Kidney Dis. 2019 Feb;73(2):273-277. doi: 10.1053/j.ajkd.2018.06.032. Epub 2018 Oct 8.
In human kidney disease, mitochondrial ultrastructural damage has long been recognized. Although the extent to which such mitochondrial changes contribute to human kidney disease is uncertain, experimental studies clearly demonstrate that mitochondrial damage can instigate pathogenetic processes that drive ongoing kidney disease. Clinical credence for this experimentally based hypothesis is provided by the development of kidney disease in patients with primary mitochondrial disorders. In this regard, substantial interest surrounds the occurrence of kidney disease in primary mitochondrial cytopathies, a heterogeneous group of conditions in which mutations in mitochondrial DNA (mtDNA) or nuclear DNA impair the functionality of components of the mitochondrial respiratory chain. We describe a novel mtDNA mutation in a patient who developed chronic kidney disease. The patient exhibited mitochondrial abnormalities in both muscle and kidney, chronic tubulointerstitial changes, and recurrent episodes of rhabdomyolysis. We outline mechanisms that may underlie the occurrence of chronic kidney disease in the setting of this novel mtDNA mutation. We also underscore the need to consider in relevant kidney diseases the presence of an underlying mitochondrial cytopathy because the latter more commonly exists than is generally recognized.
在人类肾脏疾病中,线粒体超微结构损伤早已为人所知。尽管这种线粒体变化对人类肾脏疾病的影响程度尚不确定,但实验研究清楚地表明,线粒体损伤可以引发导致持续肾脏疾病的发病机制。这种基于实验的假设在临床上得到了证实,即原发性线粒体疾病患者会出现肾脏疾病。在这方面,人们对原发性线粒体细胞病变中肾脏疾病的发生产生了浓厚的兴趣,原发性线粒体细胞病变是一组异质性疾病,其中线粒体 DNA(mtDNA)或核 DNA 的突变会损害线粒体呼吸链组件的功能。我们描述了一位发生慢性肾脏病的患者中出现的一种新型 mtDNA 突变。该患者的肌肉和肾脏均存在线粒体异常、慢性肾小管间质变化和反复发作的横纹肌溶解症。我们概述了可能导致该新型 mtDNA 突变患者发生慢性肾脏病的机制。我们还强调了在相关肾脏疾病中需要考虑潜在的线粒体细胞病变的存在,因为后者比普遍认为的更为常见。