Uremic neuropathy is a gradually progressive condition that presents in 60-100% of patients suffering from end-stage kidney disease.

Among the types of neuropathy associated with uremia, polyneuropathy is the most characteristic, but focal and shunt-related neuropathies also occur [1]. The neuropathy only develops in patients who have substantially decreased glomerular filtration rates (less than 12 ml/min) [2], and was found in early studies using nerve biopsies to progress from distal to proximal sites [3]. It affects the lower extremities to a larger extent than the upper, and males more than females. The primary defect is axonal degeneration, accompanied by secondary segmental demyelination [4].

The early symptoms show mainly sensory losses, but motor function is also affected. The earliest signs include the loss of the Achilles reflex [4]. This and other early signs, - such as paresthesias, reduction in vibration sense and deep tendon reflexes, perturbation of position sensation, and muscle weakness - indicate defects in large fibers. Damage to small fibers can also show up as allodynia, pain, changes in temperature sensation, and visceral pain.

Autonomic function impairment occurs in about half of the patients, with postural hypotension, dizziness, gastroparesis, and erectile dysfunction. Cranial nerve dysfunction is rare.

• Short Stature

  Stature Small Jaw Muscle Hypertrophy and Stiffness 609 Case 99 An Elderly Woman with Muscle Spasms 612 Case 100 A Woman with Proximal Muscle Weakness and Neuromuscular Irritability 616 Case 101 A Woman with Focal Spontaneous Muscle Movements 620 Index [books.google.com]

• Episodic Weakness

  Weakness 464 Case 73B An African American Man with Hyperthyroidism and Acute Paralysis 470 Case 74 A Boy with Large Muscles Leg Pain and Elevated Serum Creatine Kinase 472 Case 75 A Woman with Proximal Muscle Weakness Calf Hypertrophy Heel Contractures [books.google.com]

• Blurred Vision

  Case summary A 40-year-old male who was diagnosed with chronic renal failure and treated with peritoneal dialysis and hemodialysis for 17 years presented with blurred vision and a moving pain in his left eye for 2 days. [synapse.koreamed.org]

• Miosis

  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 [emedicine.medscape.com]

• Restless Legs Syndrome

  "Iron status and restless leg syndrome in the elderly." Age Ageing, 1994;23:200. Collado-Seidel, V, Kohnen, R, Samtleben, W, et al. "Clinical and biochemical findings in uremic patients with and without restless legs syndrome." [mywhatever.com]

  The most common symptoms were restless legs syndrome (47%) and cramps (51%). Sensory symptoms were less common in patients on long-term hemodialysis, most common of them being paresthesia (29%) and burning feet syndrome (28%). [ncbi.nlm.nih.gov]

  leg syndrome - persistent, extremely uncomfortable sensation in - persistent, extremely uncomfortable sensation in lower extremities lower extremities - only relieved by movement of legs - only relieved by movement of legs - more prominent at night and [slideplayer.com]

  Muscle cramps and restless legs syndrome were reported by 67% of uremic patients. These symptoms also can be seen in uremic patients without neuropathy. [emedicine.medscape.com]

  legs syndrome- 20% of patients with CKD suffer from this disorder, dialysis does not substantially improve uremic restless legs syndrome, improvement of restless legs symptoms have been shown after kidney transplantation. 35. 6. [slideshare.net]

• Tinel's Sign

  ’s sign - numbness and tingling sense by percussing median n. - numbness and tingling sense by percussing median n.  Electrophysiologic studies - prolonged conduction for both motor and sensory fibers - prolonged conduction for both motor and sensory [slideplayer.com]

  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 [emedicine.medscape.com]

• Motor Restlessness

  restlessness - motor restlessness - worning Sx at rest partial relief during activity - worning Sx at rest partial relief during activity - worsening of Sx in evening or at nignt - worsening of Sx in evening or at nignt 16  Medical treatment for symptom [slideplayer.com]

• Foot Deformity

  Deformities 510 Case 81 A Woman with Droopy Eyelids and Ophthalmoplegia 515 Case 82 A Man with Weakness and Swelling in the Neck 522 Case 83 A Woman with Muscle Pains and Dark Urine 526 Case 84 A Woman with Progressive Proximal Muscle Weakness 533 Case [books.google.com]

• Absent Deep Tendon Reflex

  deep tendon reflexes are the most common clinical signs, noted in 93% of patients. [emedicine.medscape.com]

• Foot Drop

  Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly [books.google.com]

• Cranial Nerve Involvement

  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 [emedicine.medscape.com]

Uremic neuropathy needs to be differentiated from other forms of peripheral neuropathy. Foremost among these is diabetic neuropathy, as diabetes is often the cause of chronic kidney disease [2] [4]; however, there are other metabolic and hormonal states, as well as vitamin deficiencies, toxins, and inflammatory conditions that can cause neuropathies. Blood tests can be used for the identification of vitamin deficiencies (for example B12) and diabetes. They can also be used to detect antinuclear antibodies, markers of inflammation, and hormone levels.

Some of the neuropathies that need to be ruled out are vasculitic neuropathy [5], chronic or acute demyelinating neuropathies, such as the Guillain-Barré syndrome, and inflammatory demyelinating neuropathies associated with membranous glomerulonephritis [6] [7].

After general and neurological examinations, which provide background information, electrodiagnostic tools – sensory and motor nerve conduction, F response, H reflex and needle electromyography - help in categorizing the deficit, and defining its extent. [8]. These methods can also distinguish between axonal degeneration and demyelination, and characterize the disease as polyneuropathy or mononeuropathy [8].

Early studies of uremic neuropathy measured nerve conduction velocities and found them to be decreased, even in patients without clinical symptoms. Subsequent studies also found general slowing and abnormalities in conductance, but in addition noted a decrease in the amplitude in sensory, but not motor responses [2]. In one recent study, the amplitude of the sural sensory nerve action potential was the parameter most commonly affected in patients with end-stage kidney disease [9]. Another recent study also found sural sensory action potential a sensitive predictor of neuropathy, but identified F wave latency as the most sensitive indicator, especially in subclinical polyneuropathy [10].

Nerve excitability measurements, which identify changes in axonal membrane potential in neuropathy [11], were also performed on patients with chronic kidney disease [9]. These studies showed a reduction in compound muscle action potential, and indicated that axonal membranes were depolarized [9]. The excitability markers showed noticeable improvement on dialysis, and thus may be a good indication regarding the adequacy of dialysis [9]. More than one study [9] [12] detected a correlation between potassium levels and excitability markers, and concluded that it may be important to maintain normal serum potassium concentration between courses of dialysis [9].

• Slow Nerve Conduction Velocities

  Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly [books.google.com]

• Slow Nerve Conduction Velocities

  Case 58A A Woman with Leg Numbness Pain Weakness and Slow Nerve Conduction Velocities 372 Case 58B A Boy with Leg Weakness 375 Case 59 A Man with Hand Weakness and Numbness After Skiing 383 Case 60 A Man with Recurrent Foot Drop 386 Case 61 An Elderly [books.google.com]

1. Al-Hayk K, Bertorini TE. Neuromuscular complications in uremics: a review. Neurologist. 2007;13(4):188-196.
2. Krishnan AV, Kiernan MC. Uremic neuropathy: clinical features and new pathophysiological insights. Muscle Nerve. 2007 Mar;35(3):273-290.
3. Asbury AK, Victor M, Adams RD. Uremic polyneuropathy. Arch Neurol. 1963 ;8:413-428.
4. Ramirez BV, Gomez PAB. Uraemic neuropathy: A review. Int J Genet Mol Biol. 2012;3(11):155-160.
5. Schaublin GA, Michet CJ, Dyck PJ, Burns TM. An update on the classification and treatment of vasculitic neuropathy. Lancet Neurol. 2005; 4(12):853-865.
6. Kohli A, Tandon P, Kher V. Chronic inflammatory demyelinating polyradiculoneuropathy with membranous glomerulonephritis: report of one case. Clin Neurol Neurosurg. 1992; 94(1):31-33.
7. Panjwani M, Truong LD, Eknoyan G. Membranous glomerulonephritis associated with inflammatory demyelinating peripheral neuropathies. Am J Kidney Dis. 1996;27(2):279-283.
8. Misra UK, Kalita J, Nair PP. Diagnostic approach to peripheral neuropathy. Ann Indian Acad Neurol. 2008 Apr-Jun;11(2):89–97.
9. Krishnan AV, Phoon RK, Pussell BA, et al. Altered motor nerve excitability in end-stage kidney disease. Brain. 2005;128:2164-2174.
10. Laaksonen S, Metsärinne K, Voipio-Pulkki LM, Falck B. Neurophysiologic parameters and symptoms in chronic renal failure. Muscle Nerve. 2002;25(6): 884-890.
11. Kiernan MC, Burke D, Andersen KV, Bostock H. Multiple measures of axonal excitability: a new approach in clinical testing. Muscle Nerve. 2000 Mar;23(3):399-409
12. Kiernan MC, Walters RJ, Andersen KV, Taube D, Murray NM, Bostock H. Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalaemia. Brain. 2002; 125(6):1366- 1378.