Twelve-Year Follow-up of a Family With CKD Caused by an mtDNA Variant

While a few studies have investigated renal manifestations associated with mitochondrial DNA (mtDNA) variants, detailed renal histopathological changes and long-term outcomes remain poorly characterized. This study reported a family in which all 5 siblings presented with hyperuricemia and chronic kidney disease (CKD); the proband died of end-stage kidney disease at 16 years of age, while both parents were unaffected. Renal histology from 3 siblings revealed multiple foci of sclerotic and atubular glomeruli, as well as focal tubular atrophy, making early pathologic diagnosis challenging. Ten years later, whole exome sequencing identified an m.616T>C variant in the MT-TF gene of mtDNA, confirming the diagnosis of mitochondrial tubulointerstitial kidney disease and demonstrating mitochondrial abnormalities in the distal tubules and collecting duct. Over a 12-year follow-up period, 1 patient died of end-stage kidney disease, 1 required dialysis, 2 progressed from CKD stage G2 to G4, and 1 remained stable at CKD stage G3. This 12-year study of a family with MT-TF m.616T>C-associated mitochondrial tubulointerstitial kidney disease highlights the relative homogeneity of renal pathology alongside marked heterogeneity in long-term outcomes, despite an identical genetic background.