12-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) mutations, detailed renal histopathological changes and long-term outcomes remain poorly characterized. This study reported a family in which all the five siblings presented with hyperuricemia and chronic kidney disease (CKD); the proband died of kidney failure at 16 years of age, while both parents were unaffected. Renal histology from three siblings revealed multiple foci of sclerotic and atubular glomeruli, as well as focal tubular atrophy, making early pathological diagnosis challenging. Ten years later, whole-exome sequencing identified an m.616T>C mutation 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, one patient died of kidney failure, one required dialysis, two progressed from CKD stage G2 to G4, and one 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.