Mechanisms of axonal dysfunction in diabetic and uraemic neuropathies

Clin Neurophysiol. 2013 Nov;124(11):2079-90. doi: 10.1016/j.clinph.2013.04.012. Epub 2013 May 15.

Abstract

The global burden imposed by metabolic diseases and associated complications continue to escalate. Neurological complications, most commonly peripheral neuropathy, represent a significant cause of morbidity and disability in patients with diabetes and chronic kidney disease. Furthermore, health care costs are substantially increased by the presence of complications making investigation into treatment a matter of high priority. Over the last decade nerve excitability techniques have entered the clinical realm and enabled in vivo assessment of biophysical properties and function of peripheral nerves in health and disease. Studies of excitability in diabetic neuropathy have demonstrated alteration in biophysical properties, including changes in Na(+) conductances and Na(+)/K(+) pump function, which may contribute to the development of neuropathic symptoms. Interventional studies have demonstrated that these changes are responsive to pharmacological agents. Excitability studies in patients with chronic kidney disease have demonstrated prominent changes that may contribute to the development of uraemic neuropathy. In particular, these studies have demonstrated strong correlation between hyperkalaemia and the development of nerve dysfunction. These studies have provided a basis for future work assessing the benefits of potassium restriction as a therapeutic strategy in this condition.

Keywords: Chronic kidney disease; Diabetes; Diabetic neuropathy; Dialysis; Nerve excitability; Uraemic neuropathy.

Publication types

  • Review

MeSH terms

  • Axons / metabolism*
  • Cell Membrane / metabolism
  • Diabetic Neuropathies / metabolism*
  • Electrical Synapses / metabolism
  • Humans
  • Hyperkalemia / complications*
  • Hyperkalemia / metabolism
  • Ion Pumps / metabolism
  • Neural Conduction
  • Peripheral Nervous System Diseases / etiology
  • Peripheral Nervous System Diseases / metabolism*
  • Potassium Channels / metabolism*
  • Renal Dialysis
  • Renal Insufficiency, Chronic / complications
  • Renal Insufficiency, Chronic / metabolism
  • Renal Insufficiency, Chronic / therapy
  • Sodium Channels / metabolism*
  • Uremia / complications*
  • Uremia / metabolism

Substances

  • Ion Pumps
  • Potassium Channels
  • Sodium Channels