Uremic neuropathy: clinical features and new pathophysiological insights

Muscle Nerve. 2007 Mar;35(3):273-90. doi: 10.1002/mus.20713.


Neuropathy is a common complication of end-stage kidney disease (ESKD), typically presenting as a distal symmetrical process with greater lower-limb than upper-limb involvement. The condition is of insidious onset, progressing over months. and has been estimated to be present in 60%-100% of patients on dialysis. Neuropathy generally only develops at glomerular filtration rates of less than 12 ml/min. The most frequent clinical features reflect large-fiber involvement, with paresthesias, reduction in deep tendon reflexes, impaired vibration sense, muscle wasting, and weakness. Nerve conduction studies demonstrate findings consistent with a generalized neuropathy of the axonal type. Patients may also develop autonomic features, with postural hypotension, impaired sweating, diarrhea, constipation, or impotence. The development of uremic neuropathy has been related previously to the retention of neurotoxic molecules in the middle molecular range, although this hypothesis lacked formal proof. Studies utilizing novel axonal excitability techniques have recently shed further light on the pathophysiology of this condition. Nerves of uremic patients have been shown to exist in a chronically depolarized state prior to dialysis, with subsequent improvement and normalization of resting membrane potential after dialysis. The degree of depolarization correlates with serum K(+), suggesting that chronic hyperkalemic depolarization plays an important role in the development of nerve dysfunction in ESKD. These recent findings suggest that maintenance of serum K(+) within normal limits between periods of dialysis, rather than simple avoidance of hyperkalemia, is likely to reduce the incidence and severity of uremic neuropathy.

Publication types

  • Review

MeSH terms

  • Axons / metabolism*
  • Humans
  • Hyperkalemia / complications*
  • Hyperkalemia / physiopathology
  • Kidney Failure, Chronic / complications*
  • Kidney Failure, Chronic / physiopathology
  • Membrane Potentials / physiology
  • Neural Conduction / physiology
  • Peripheral Nerves / metabolism
  • Peripheral Nerves / physiopathology*
  • Peripheral Nervous System Diseases / etiology*
  • Peripheral Nervous System Diseases / physiopathology
  • Potassium / blood
  • Uremia / complications*
  • Uremia / physiopathology


  • Potassium