eMedicine Specialties > Neurology > Neurotoxicology

Uremic Neuropathy: Differential Diagnoses & Workup

Author: Yi Pan, MD, PhD, Assistant Professor, Department of Neurology, Saint Louis University Hospital
Contributor Information and Disclosures

Updated: Oct 11, 2006

Differential Diagnoses

Acute Inflammatory Demyelinating Polyradiculoneuropathy
Nutritional Neuropathy
Alcohol (Ethanol) Related Neuropathy
Paraneoplastic Autonomic Neuropathy
Chronic Inflammatory Demyelinating Polyradiculoneuropathy
Polyarteritis Nodosa
Diabetic Neuropathy
Restless Legs Syndrome
HIV-1 Associated Acute/Chronic Inflammatory Demyelinating Polyneuropathy
Systemic Lupus Erythematosus
HIV-1 Associated Distal Painful Sensorimotor Polyneuropathy
Toxic Neuropathy
HIV-1 Associated Multiple Mononeuropathies
Metabolic Neuropathy
Neuropathy of Leprosy

Workup

Laboratory Studies

  • Uremia is only one of the possible causes of neuropathy in chronic renal failure. Other metabolic disorders, neurotoxins, or inflammatory disorders may occur in association with chronic renal failure. Other causes of neuropathies, including diabetes, vitamin deficiencies, thyroid dysfunction, inflammatory disorders, and toxins should be excluded by blood tests for hemoglobin A1C, B-12, folate, thyroid-stimulating hormone, erythrocyte sedimentation rate, antinuclear antigen, serum protein electrophoresis/immunofixation electrophoresis, and urine heavy metal screen.
  • Patients with uremic neuropathy have creatinine clearance less than 10 mL/min.
  • Cerebrospinal fluid protein often is elevated; cell count and glucose are normal.

Imaging Studies

  • Imaging is not useful in making the diagnosis of uremic neuropathy.

Other Tests

  • Nerve conduction study is a sensitive test for diagnosis of neuropathy in patients with uremia. Both sensory and motor nerve conduction velocities are reduced.
    • Prolonged distal latencies are due to involvement of distal nerve segments; reduced compound action potential amplitudes are due mainly to reduced densities of large myelinated motor and sensory fibers.
    • In compressive mononeuropathy, slow conduction velocity is found across the compression site.
    • A Guillain-Barré type of neuropathy in chronic renal failure has moderate-to-severe conduction slowing; conduction block may occur.
    • Prolonged F wave latencies of tibial and peroneal nerves and prolonged H reflexes are the profound and reproducible abnormalities in patients with chronic renal failure.
  • Bolton found that needle electromyography revealed minimal or absent fibrillation or positive sharp wave. Only more advanced cases of uremic neuropathy lead to predominantly distal muscle denervation.
  • Autonomic nerve tests reveal dysautonomia by reduced R-R interval variation and delayed or absent sympathetic skin response. Esophageal manometry has been used to study subclinical manifestations of autonomic neuropathy in uremia. Abnormal motility in the lower two thirds of the esophageal body was reported in 11 of 16 patients.

Histologic Findings

In uremic neuropathy, the pathologic features are striking axonal degeneration in the most distal nerve trunks with secondary segmental demyelination (see Images 1-2). Dyck et al found that the number of myelinated fibers was approximately one half of normal at the mid calf level and only one third of normal at ankle level in their patients. In transverse electron microscope sections, most of the myelinated fibers of the uremic nerve had a normal appearance except for irregularities of the myelin sheath, such as splitting of the myelin lamellae and separation of axolemma from compact myelin.

Muscle biopsy revealed fiber type grouping from chronic denervation and reinnervation (see Image 3). Muscle was denervated severely in Guillain-Barré–type neuropathy. In advanced neuropathy, necrosis of myofibers, streaming of Z line, which anchors actin, and aggregation of glycogen also were found by electron microscope.

More on Uremic Neuropathy

Overview: Uremic Neuropathy
Differential Diagnoses & Workup: Uremic Neuropathy
Treatment & Medication: Uremic Neuropathy
Follow-up: Uremic Neuropathy
Multimedia: Uremic Neuropathy
References
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Further Reading

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Keywords

kidney failure, renal insufficiency, renal failure, uremia, distal sensorimotor polyneuropathy, uremic toxins, dying-back neuropathy, central-peripheral axonopathy associated with secondary demyelination

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Contributor Information and Disclosures

Author

Yi Pan, MD, PhD, Assistant Professor, Department of Neurology, Saint Louis University Hospital
Yi Pan, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Clinical Neurophysiology Society, American Physiological Society, and Society for Neuroscience
Disclosure: Nothing to disclose.

Medical Editor

J Stephen Huff, MD, Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia Health Sciences Center
J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Florian P Thomas, MD, MA, PhD, Drmed, Director, Spinal Cord Injury Unit, St Louis Veterans Affairs Medical Center; Director, National MS Society Multiple Sclerosis Center; Associate Program Director, Professor, Department of Neurology and Psychiatry, Associate Professor, Institute for Molecular Virology, and Department of Molecular Microbiology and Immunology, St Louis University
Florian P Thomas, MD, MA, PhD, Drmed is a member of the following medical societies: American Academy of Neurology, American Paraplegia Society, and National Multiple Sclerosis Society
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Y Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Y Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

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