Kidney Week

Abstract: PUB301

Mitochondrial Nephropathy with m.5538G>A Mutation within the tRNA-Trp Region Treated with Imeglimin: A Case Report

Session Information

• Publication Only

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

• Ikeda, Mari, Kameda Medical Center, Kamogawa, Chiba, Japan

Mari Ikeda, MD

• Imasawa, Toshiyuki, Chiba-East National Hospital, Chiba, Chiba, Japan

Toshiyuki Imasawa, MD, PhD

• Inoue, Tomohiko, St. Marianna University School of Medicine Hospital, Kawasaki, Kanagawa, Japan

Tomohiko Inoue

• Ohara, Mamiko, Kameda Medical Center, Kamogawa, Chiba, Japan

Mamiko Ohara, MD, PhD, FASN

• Suzuki, Tomo, Kameda Medical Center, Kamogawa, Chiba, Japan

Tomo Suzuki, MD, PhD

Introduction

Mitochondrial nephropathy (MN) is a genetic disease characterized by a defect in oxidative phosphorylation, with a diverse clinical presentation, urinary protein in more than 90% of cases, and decreased kidney function reported in about 70% of cases. Although CoQ10 and taurine have been reported to be effective in improving kidney function in some cases, most cases are difficult to treat. We report the first case of mitochondrial nephropathy treated with imeglimin after genetic and mitochondrial function analysis.

Case Description

This case is a 25-year-old male with mild proteinuria who was diagnosed with minor glomerular abnormalities in his first kidney biopsy at age 15. Due to increased urinary protein (urine protein creatinine ratio 2.2 g/gCr) and decreased kidney function (serum creatine 1.24 mg/dL), we performed second kidney biopsy at age 22. Light microscopy showed segmental glomerulosclerosis lesions. Electron microscopy revealed many abnormal mitochondria in the podocytes. Serum lactate was 27.8 mg/dL and cerebrospinal fluid lactate was 35.5 mg/dL after admission. Therefore, we considered mitochondrial disease (MD). We further suspected MD when cultured dermal fibroblasts showed decreased oxygen consumption and decreased respiratory chain enzyme activity complex III and complex IV, leading us to perform genetic testing. Genetic analysis of frozen sections of kidney tissue confirmed with m.5538G>A mutation in the tRNA-Trp region. Similarly, we detected the same genetic mutations in blood, urine, and skin fibroblasts. The rate of urine, blood, and skin fibroblast of heteroplasmy were 64.0%, 32.4%, and 73.3%, respectively. We treated him on olmesartan and dapagliflozin for chronic kidney disease with severe persistent urinary protein. In addition, we added imeglimin in the hope of improving new-onset diabetes and reducing complex III activity. Approximately one year after the start of imeglimin treatment, renal function declined at a faster rate, but proteinuria and lactate/pyruvate ratio decreased, suggesting that mitochondrial function may have improved.

Discussion

Imeglimin may be effective in MN with reduced complex III activity, but the long-term effects need to be verified.