Uremic Neuropathy

Updated: Aug 27, 2018
  • Author: Yi Pan, MD, PhD; Chief Editor: Tarakad S Ramachandran, MBBS, MBA, MPH, FAAN, FACP, FAHA, FRCP, FRCPC, FRS, LRCP, MRCP, MRCS  more...
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Practice Essentials

Uremic neuropathy is a distal sensorimotor polyneuropathy caused by uremic toxins. Symptoms are insidious in onset. Paresthesia is usually the earliest symptom; weakness and atrophy will follow the sensory symptoms. The pathologic features are severe axonal degeneration in the most distal nerve trunks with secondary segmental demyelination. The occurrence of neuropathy is highly correlated with the severity and duration of renal failure. The diagnosis of a uremic peripheral neuropathy is established by medical history, neurologic examination, and electrophysiological studies. Chronic dialysis may prevent neuropathy in some patients, especially if begun early. Renal transplantation is generally the most successful method to prevent neuropathy.



Uremic neuropathy is a distal sensorimotor polyneuropathy caused by uremic toxins. The severity of neuropathy is correlated strongly with the severity of the renal insufficiency. Uremic neuropathy is considered a dying-back neuropathy or central-peripheral axonopathy associated with secondary demyelination. However, uremia and its treatment can also be associated with mononeuropathy at compression sites. [1]

Charcot suspected the existence of uremic neuropathy in 1880 [2] , and Osler suspected it in 1892. Since the introduction of hemodialysis and renal transplantation in the early 1960s, uremic neuropathy has been investigated thoroughly. Asbury, Victor, and Adams described the clinical and pathologic features in detail in 1962. [3]

In 1971, Dyck and colleagues established the current concept of uremic neuropathy based on their extensive nerve conduction studies in vivo and in vitro, as well as light and electron microscopy studies. [4] Using quantitative histology, they demonstrated axonal shrinkage. Myelin sheaths appeared to be affected out of proportion to axons. The dysfunction of the neuron, rather than the Schwann cell, resulted in a decrease in the diameter of the axon, rearrangement of myelin, and finally, complete degeneration of the axon.

Nielsen published numerous papers on clinical and electrophysiologic studies from 1970-1974. [5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16] He is a major contributor in uremic neuropathy. Bolton and Young summarized uremic neuropathy thoroughly in their 1990 book. [17]



The mechanism of uremic neuropathy remains unclear. Fraser and Arieff postulated that neurotoxic compounds deplete energy supplies in the axon by inhibiting nerve fiber enzymes required for maintenance of energy production. [18] Although all neuronal perikarya would be affected similarly by the toxic assault, the long axons would be the first to degenerate since the longer the axon, the greater the metabolic load that the perikaryon would bear. In toxic neuropathy, dying back of axons is more severe in the distal aspect of the neuron and may result from a metabolic failure of the perikaryon. Energy deprivation within the axon may be especially critical at nodes of Ranvier, since these nodes demand more energy for impulse conduction and axonal transport.

Nielsen theorized that peripheral nerve dysfunction was related to an interference with the nerve axon membrane function and inhibition of Na+/K+ -activated ATPase by toxic factors in uremic serum. Bolton postulated that membrane dysfunction was occurring at the perineurium, which functioned as a diffusion barrier between interstitial fluid and nerve, or within the endoneurium, which acted as a barrier between blood and nerve. As a result, uremic toxins may enter the endoneural space at either site and cause direct nerve damage and water and electrolyte shifts with expansion or retraction of the space.

Krishnan and colleagues investigated axonal membrane properties by measuring nerve excitability in chronic renal failure patients before, during and after hemodialysis. They suggested that motor and sensory axons in patients with uremic neuropathy were depolarized before dialysis, and hyperkalemia that was primarily responsible for uremic depolarization could contribute to the development of neuropathy. [19, 20, 21]




According to Bolton and Young, the incidence of clinical uremic neuropathy varies from 10–83% in patients with renal failure in the United States. [17]

According to Nielsen, of 109 patients in Denmark with chronic renal failure, 77% reported clinical symptoms, and 51% had clinical signs of a neuropathy. [5]


Hemodialysis has reduced the incidence of severe uremic neuropathy and the rate of mortality of renal failure. Although deaths associated with complications related to quadriplegia and respiratory failure have been reported, the death rate from uremic neuropathy is not known.


Uremic neuropathy is more common in males than in females. Nielsen reported the female-to-male ratio as 49:60 in his 109 patients. [5]

Uremic polyneuropathy may occur at any age once the degree of renal failure is sufficient.



With intermittent hemo- or peritoneal dialysis, the clinical manifestations of uremic neuropathy generally stabilize, and either improve slowly over time or progress, especially in the elderly. Renal transplantation can result in complete recovery from uremic neuropathy if the duration between the onset of neuropathy and transplantation is short.


Patient Education

Patients have a very important role in their treatment of chronic renal disease. It is important to educate patients, so that they understand the relationship between their kidney disease and symptoms of peripheral neuropathy. Patients should be educated that treatment of uremic neuropathy is not only symptomatic management, but with chronic dialysis may prevent, minimize, or stabilize their neuropathy and reduce complications.