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Publications

Journal Article Review Epublish

PubMed: 42713026 DOI: 10.1016/j.ekir.2026.106999

Primary Mitochondrial-Disorders-Associated Nephropathy in Adulthood.

Kidney Int Rep 11(10):106999

Authors: Hugo Bakis, Aurélien Trimouille, Maximilian Schwarz, Christian Combe, Idris Boudhabhay, Marie-Laure Martin-Négrier, Claire Rigothier

Affiliations

  • Service de NĂ©phrologie, Transplantation, Dialyse et AphĂ©rèses, CHU de Bordeaux, Bordeaux, France.
  • Service de GĂ©nĂ©tique mĂ©dicale, CHU de Bordeaux, Bordeaux, France.
  • University of Bordeaux, INSERM U1211, Bordeaux, France.
  • Department of Nephrology and Kidney Transplantation, Necker Hospital, Assistance publique - HĂ´pitaux de Paris (AP-HP), Paris, France.
  • Tissue Bioengineering, U1026, INSERM, F-33000 Bordeaux, France.
  • Centre de rĂ©fĂ©rence pour les maladies mitochondriales de l'enfant Ă  l'adulte (CARAMMEL), CHU de Bordeaux, Bordeaux, France.

Abstract

Oxidative phosphorylation (OXPHOS) is the main source of cellular adenosine triphosphate (ATP) production and depends on proteins encoded by both mitochondrial and nuclear DNA (nDNA). Pathogenic variants affecting this dual genetic control cause primary mitochondrial disorders (MIDs), which follow either maternal inheritance when they affect mitochondrial DNA (mtDNA) or autosomal inheritance when they affect nuclear-encoded mitochondrial proteins. Once considered predominantly pediatric conditions, these disorders are increasingly recognized in adults where their clinical presentation is heterogeneous and frequently underdiagnosed, requiring the involvement of various medical specialties.Because of their high energy requirements, kidneys are particularly vulnerable to primary MIDs. Tubular epithelial cells rely on OXPHOS for solute transport, whereas podocytes require sustained ATP production to preserve the glomerular filtration barrier. Although kidney involvement in adult primary MIDs has long been regarded as rare, emerging data indicate that primary MIDs-associated nephropathy (MIDAN) is more common than previously appreciated, yet remains under-recognized, as a cause of adult kidney disease. Renal manifestations include a broad spectrum of glomerular disorders-predominantly focal segmental glomerulosclerosis (FSGS), often associated with diabetes mellitus and sensorineural hearing impairment-as well as tubulo-interstitial nephritis (TIN), which may present as an isolated renal phenotype or as part of a multisystemic disorder.Advances in next-generation sequencing, including mitochondrial genome sequencing and exome or whole-genome sequencing, are transforming the diagnostic approach to MIDAN. Improved recognition of mitochondrial etiologies in adults with unexplained glomerular or tubulo-interstitial kidney disease is essential to optimize diagnosis, management, and genetic counseling.

MeSH

Diabetes Mellitus, Kidney Diseases, Mitochondrial Diseases, Genome, Kidney, Dna, Mitochondrial