Clinicopathologic Features of Mitochondrial Nephropathy

Toshiyuki Imasawa; Daishi Hirano; Kandai Nozu; Hiroshi Kitamura; Motoshi Hattori; Hitoshi Sugiyama; Hiroshi Sato; Kei Murayama; J-SMiN Collaborators

doi:10.1016/j.ekir.2021.12.028

Clinicopathologic Features of Mitochondrial Nephropathy

Kidney Int Rep. 2022 Jan 11;7(3):580-590. doi: 10.1016/j.ekir.2021.12.028. eCollection 2022 Mar.

Authors

Toshiyuki Imasawa¹, Daishi Hirano², Kandai Nozu³, Hiroshi Kitamura⁴, Motoshi Hattori⁵, Hitoshi Sugiyama⁶, Hiroshi Sato⁷, Kei Murayama⁸; J-SMiN Collaborators

Affiliations

¹ Department of Nephrology, National Hospital Organization Chiba-Higashi National Hospital, Chiba, Japan.
² Department of Pediatrics, The Jikei University School of Medicine, Tokyo, Japan.
³ Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
⁴ Department of Clinical Pathology, National Hospital Organization Chiba-Higashi National Hospital, Chiba, Japan.
⁵ Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.
⁶ Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
⁷ Department of Internal Medicine, JR Sendai Hospital, Miyagi, Japan.
⁸ Center for Medical Genetics, Department of Metabolism, Chiba Children's Hospital, Chiba, Japan.

Abstract

Introduction: The clinicopathologic characteristics of nephropathy associated with mitochondrial disease (MD) remain unknown. We retrospectively analyzed a cohort of patients with proteinuria, decreased glomerular filtration rate, or Fanconi syndrome who had a genetic mutation confirmed as the cause of MD, defined as mitochondrial nephropathy.

Methods: This nationwide survey included 757 nephrology sections throughout Japan, and consequently, data on 81 cases of mitochondrial nephropathy were collected.

Results: The most common renal manifestation observed during the disease course was proteinuria. Hearing loss was the most common comorbidity; a renal-limited phenotype was observed only in mitochondrial DNA (mtDNA) point mutation and COQ8B mutation cases. We found a median time delay of 6.0 years from onset of renal manifestations to diagnosis. Focal segmental glomerular sclerosis (FSGS) was the most common pathologic diagnosis. We then focused on 63 cases with the m.3243A>G mutation. The rate of cases with diabetes was significantly higher among adult-onset cases than among childhood-onset cases. Pathologic diagnoses were more variable in adult-onset cases, including diabetic nephropathy, nephrosclerosis, tubulointerstitial nephropathy, and minor glomerular abnormalities. During the median observation period of 11.0 years from the first onset of renal manifestations in patients with m.3243A>G, renal replacement therapy (RRT) was initiated in 50.8% of patients. Death occurred in 25.4% of the patients during the median observation period of 12.0 years. The median estimated glomerular filtration rate (eGFR) decline was 5.4 ml/min per 1.73 m²/yr in the cases, especially 8.3 ml/min per 1.73 m²/yr in FSGS cases, with m.3243A>G.

Conclusion: Here, we described the clinicopathologic features and prognosis of mitochondrial nephropathy using large-scale data.

Keywords: clinicopathologic feature; m.3243A>G; mitochondria; mitochondrial nephropathy; national survey; prognosis.