Uremic Neuropathy Clinical Presentation

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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Presentation

History

Typical uremic neuropathy symptoms are insidious in onset and consist of a tingling and prickling sensation in the lower extremities. Paresthesia is the most common and usually the earliest symptom. Increased pain sensation is a prominent symptom. Weakness of lower extremities and atrophy follow the sensory symptoms. As disease progresses, symptoms move proximally and involve the upper extremities. Muscle cramps and restless legs syndrome were reported by 67% of uremic patients. These symptoms also can be seen in uremic patients without neuropathy. Patients report that crawling, prickling, and itching sensations in their lower extremities are relieved partially by movement of the affected limb. [22]

Autonomic dysfunction was revealed in 45–59% of uremic patients by autonomic nerve tests. Patients may complain of dizziness. It usually is associated with postural hypotension.

A Guillain-Barré type of presentation is rare, but a rapidly progressive course with respiratory failure has been reported. Generalized limb weakness develops over days or weeks with imbalance, numbness, and diminished reflexes. [23, 24]

Mononeuropathies in the form of compressive neuropathy can occur in the median nerve at the wrist, in the ulnar nerve at the elbow, or in the peroneal nerve at the fibular head. Already partially dysfunctional peripheral nerves may be more susceptible to local compression. Connective tissues and tendons are found to have amyloid deposits surrounding the carpal tunnel. [25] Multiple distal mononeuropathies present in an extremity following the construction of arteriovenous fistulas because of distal ischemia. [26]

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Physical

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  • Impaired vibratory perception and absent deep tendon reflexes are the most common clinical signs, noted in 93% of patients. Sixteen percent had sensory loss to pinprick in a glove and stocking distribution.

  • Paradoxical heat sensation was found in the feet of 42% of patients with chronic renal failure, as compared to less than 10% of healthy controls. [27]

  • Muscular weakness and wasting were observed in 14%.

  • Cranial nerve involvement is rare; transient nystagmus, miosis, impairment of extraocular movement, and facial asymmetry may be found rarely on physical examination. [18]

  • Focal weakness, sensory loss, and positive Tinel sign at compression sites can be observed in the median, ulnar, or peroneal nerve distribution if compressive mononeuropathy is present.

  • Abnormal Valsalva maneuver and orthostatic hypotension may be noted in patients with autonomic neuropathy.

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Causes

The nature of the toxic substances in uremia is unknown. Myoinositol, a precursor of phosphoinositide, is metabolized rapidly in neural membranes. It is elevated abnormally in chronic renal failure, poorly eliminated by hemodialysis, but excreted by the renal cortex of successfully transplanted kidneys. Substances of moderate molecular weight (ie, 300–2000 Daltons) can be toxic agents in uremia. Advanced glycosylated end products and parathyroid hormone generally are recognized as major uremic toxins. Possible uremic toxins are listed here but remain unproven. [28]

  • Small water-soluble compounds

    • Guanidines

    • Asymmetric dimethylarginine

    • Creatinine

    • Purines

    • Oxalate

    • Phosphorus

    • Urea

  • Middle, large molecules

    • Advanced glycosylated end products

    • Parathyroid hormone

    • Oxidation products

    • Peptides (beta-endorphin, methionine-enkephalin, beta-lipotropin, granulocyte inhibiting proteins I and II, degranulation-inhibiting protein, adrenomedullin)

    • Beta 2-microglobulin

    • Complement factor D

  • Protein-bound compounds

    • Indoles

    • 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid

    • Hippuric acid

    • Homocysteine

    • Indoxyl sulfate

    • P-cresol

    • Polyamines

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Physical Examination

Neurological examination frequently finds sensory deficits to temperature, pin prick, vibration in distal extremities, and diminished deep tendon reflex, loss of ankle jerks. Autonomic dysfunction, such as orthostatic hypotension, and distal muscle weakness and atrophy may be seen in severe cases.

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Complications

Individuals with uremic neuropathy can develop gait difficulty and are more likely to fall, which can result in severe fractures and subdural hematomas.

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