Mitochondrial Nephropathy With m.5538G>A Mutation Within the tRNA-Trp Region Assessed by Mitochondrial Function Analysis: A Case Report

Abstract

Mitochondrial nephropathy (MIT-N) presents with urinary protein in more than 90% of cases and reduced kidney function in approximately 70%. Coenzyme Q10 is effective only in a subset of patients. Herein, we report the first case of MIT-N treated with imeglimin, a drug known to improve mitochondrial function. A 25-year-old man had been diagnosed with minor glomerular abnormality at age 15. As his urinary protein increased (urine protein creatinine ratio 2.2 g/gCre) and decreased kidney function (serum creatinine 1.24 mg/dL), a kidney biopsy was performed. Light microscopy revealed focal segmental glomerulosclerosis, and electron microscopy demonstrated numerous abnormal mitochondria in podocytes. Serum and cerebrospinal fluid lactate levels were 27.8 and 35.5 mg/dL, respectively, raising suspicion of mitochondrial disease. Genetic analysis confirmed the m.5538G>A mutation in the tRNA-Trp region in the blood, urine and skin fibroblasts. Additionally, the enzymatic activity of mitochondrial respiratory chain complex (C) I–IV in dermal fibroblasts showed reduced activity of CIII and CIV. The patient was treated with olmesartan, dapagliflozin and imeglimin for chronic kidney disease with persistent urinary protein levels and new-onset diabetes, respectively. Approximately 1 year after starting treatment with imeglimin, the rate of kidney function decline accelerated, although proteinuria decreased. While it is difficult to attribute a renoprotective effect solely to imeglimin, further studies are needed to verify its long-term efficacy in MIT-N.