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

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.