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.