Mitochondrial DNA mutations in renal disease: an overview

Pediatr Nephrol. 2021 Jan;36(1):9-17. doi: 10.1007/s00467-019-04404-6. Epub 2020 Jan 10.

Abstract

Kidneys have a high energy demand to facilitate the reabsorption of the glomerular filtrate. For this reason, renal cells have a high density of mitochondria. Mitochondrial cytopathies can be the result of a mutation in both mitochondrial and nuclear DNA. Mitochondrial dysfunction can lead to a variety of renal manifestations. Examples of tubular manifestations are renal Fanconi Syndrome, which is often found in patients diagnosed with Kearns-Sayre and Pearson's marrow-pancreas syndrome, and distal tubulopathies, which result in electrolyte disturbances such as hypomagnesemia. Nephrotic syndrome can be a glomerular manifestation of mitochondrial dysfunction and is typically associated with focal segmental glomerular sclerosis on histology. Tubulointerstitial nephritis can also be seen in mitochondrial cytopathies and may lead to end-stage renal disease. The underlying mechanisms of these cytopathies remain incompletely understood; therefore, current therapies focus mainly on symptom relief. A better understanding of the molecular disease mechanisms is critical in order to improve treatments.

Keywords: Distal tubulopathies; Mitochondrial DNA; Nephrotic syndrome; Renal Fanconi syndrome; Renal disease; Tubulointerstitial nephritis.

Publication types

  • Review

MeSH terms

  • DNA, Mitochondrial / genetics
  • Humans
  • Kearns-Sayre Syndrome
  • Mitochondria / genetics
  • Mitochondrial Myopathies
  • Mutation*
  • Nephritis, Interstitial

Substances

  • DNA, Mitochondrial

Supplementary concepts

  • Mitochondrial cytopathy