Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neurological complications of chronic kidney disease

Nature Reviews Neurology volume 5, pages 542–551 (2009)Cite this article

Abstract

Chronic kidney disease (CKD) is a critical and rapidly growing global health problem. Neurological complications occur in almost all patients with severe CKD, potentially affecting all levels of the nervous system, from the CNS through to the PNS. Cognitive impairment, manifesting typically as a vascular dementia, develops in a considerable proportion of patients on dialysis, and improves with renal transplantation. Patients on dialysis are generally weaker, less active and have reduced exercise capacity compared with healthy individuals. Peripheral neuropathy manifests in almost all such patients, leading to weakness and disability. Better dialysis strategies and dietary modification could improve outcomes of transplantation if implemented before surgery. For patients with autonomic neuropathy, specific treatments, including sildenafil for impotence and midodrine for intradialytic hypotension, are effective and well tolerated. Exercise training programs and carnitine supplementation might be beneficial for neuromuscular complications, and restless legs syndrome in CKD responds to dopaminergic agonists and levadopa treatment. The present Review dissects the pathophysiology of neurological complications related to CKD and highlights the spectrum of therapies currently available.

Key Points

  • Chronic kidney disease (CKD) has a prevalence of approximately 15% in developed nations and causes neurological complications in the majority of patients

  • Cognitive impairment is common in patients on dialysis, typically manifesting as a vascular-type dementia with prominent deficits in executive function

  • Hyperkalemia disturbs resting axonal membrane potential and contributes to the development of length-dependent neuropathy in CKD

  • The onset of restless legs syndrome in CKD could reflect hyperphosphatemia or iron deficiency; therapy with intravenous iron and dopaminergic agonists might prove beneficial

  • Renal transplantation improves cognitive function, peripheral neuropathy and autonomic neuropathy

  • Exercise programs, adequate nutritional intake and treatment with erythropoietin improve muscle function and performance in patients with CKD

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The spectrum of neurological complications in chronic kidney disease.
Figure 2: Nerve excitability over the course of a dialysis session.
Figure 3: Uremic neuropathy.

Similar content being viewed by others

References

  1. Chadban, S. J. et al. Prevalence of kidney damage in Australian adults: the AusDiab kidney study. J. Am. Soc. Nephrol. 14, S131–S138 (2003).

    Article  PubMed  Google Scholar 

  2. Fox, C. S. et al. Cross-sectional association of kidney function with valvular and annular calcification: the Framingham heart study. J. Am. Soc. Nephrol. 17, 521–527 (2006).

    Article  PubMed  Google Scholar 

  3. Nitsch, D. et al. Prevalence of renal impairment and its association with cardiovascular risk factors in a general population: results of the Swiss SAPALDIA study. Nephrol. Dial. Transplant. 21, 935–944 (2006).

    Article  PubMed  Google Scholar 

  4. Ninomiya, T. et al. Chronic kidney disease and cardiovascular disease in a general Japanese population: the Hisayama Study. Kidney Int. 68, 228–236 (2005).

    Article  PubMed  Google Scholar 

  5. DuBose, T. D. Jr., American Society of Nephrology Presidential Address 2006: chronic kidney disease as a public health threat—new strategy for a growing problem. J. Am. Soc. Nephrol. 18, 1038–1045 (2007).

    Article  PubMed  Google Scholar 

  6. ANZDATA. 31st Annual Report. http://www.anzdata.org.au/v1/report_2008.html (2008).

  7. Barsoum, R. S. Chronic kidney disease in the developing world. N. Engl. J. Med. 354, 997–999 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Mallick, N. P. & Gokal, R. Haemodialysis. Lancet 353, 737–742 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Meyer, T. W. & Hostetter, T. H. Uremia. N. Engl. J. Med. 357, 1316–1325 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am. J. Kidney Dis. 39, S1–S266 (2002).

  11. Johansen, K. L. et al. Muscle atrophy in patients receiving hemodialysis: effects on muscle strength, muscle quality, and physical function. Kidney Int. 63, 291–297 (2003).

    Article  PubMed  Google Scholar 

  12. Painter, P., Messer-Rehak, D., Hanson, P., Zimmerman, S. W. & Glass, N. R. Exercise capacity in hemodialysis, CAPD, and renal transplant patients. Nephron 42, 47–51 (1986).

    Article  CAS  PubMed  Google Scholar 

  13. Krishnan, A. V. & Kiernan, M. C. Uremic neuropathy: clinical features and new pathophysiological insights. Muscle Nerve 35, 273–290 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Murray, A. M. Cognitive impairment in the aging dialysis and chronic kidney disease populations: an occult burden. Adv. Chronic Kidney Dis. 15, 123–132 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Campistol, J. M. Uremic myopathy. Kidney Int. 62, 1901–1913 (2002).

    Article  PubMed  Google Scholar 

  16. Krishnan, A. V., Pussell, B. A. & Kiernan, M. C. Neuromuscular disease in the dialysis patient: an update for the nephrologist. Semin. Dial. 22, 267–278 (2009).

    Article  PubMed  Google Scholar 

  17. Oh, S. J., Clements, R. S. Jr, Lee, Y. W. & Diethelm, A. G. Rapid improvement in nerve conduction velocity following renal transplantation. Ann. Neurol. 4, 369–373 (1978).

    Article  CAS  PubMed  Google Scholar 

  18. Nielsen, V. K. The peripheral nerve function in chronic renal failure. VI. The relationship between sensory and motor nerve conduction and kidney function, azotemia, age, sex, and clinical neuropathy. Acta Med. Scand. 194, 455–462 (1973).

    Article  CAS  PubMed  Google Scholar 

  19. Nielsen, V. K. The peripheral nerve function in chronic renal failure. 8. Recovery after renal transplantation. Clinical aspects. Acta Med. Scand. 195, 163–170 (1974).

    Article  CAS  PubMed  Google Scholar 

  20. Babb, A. L., Ahmad, S., Bergstrom, J. & Scribner, B. H. The middle molecule hypothesis in perspective. Am. J. Kidney Dis. 1, 46–50 (1981).

    Article  CAS  PubMed  Google Scholar 

  21. Vanholder, R., De Smet, R., Hsu, C., Vogeleere, P. & Ringoir, S. Uremic toxicity: the middle molecule hypothesis revisited. Semin. Nephrol. 14, 205–218 (1994).

    CAS  PubMed  Google Scholar 

  22. Bostock, H. et al. Has potassium been prematurely discarded as a contributing factor to the development of uraemic neuropathy? Nephrol. Dial. Transplant. 19, 1054–1057 (2004).

    Article  PubMed  Google Scholar 

  23. Bolton, C. F. & Young, G. B. Neurological Complications of Renal Disease (Butterworths, Boston, 1990).

    Google Scholar 

  24. Kiernan, M. C. et al. Nerve excitability changes in chronic renal failure indicate membrane depolarization due to hyperkalaemia. Brain 125, 1366–1378 (2002).

    Article  PubMed  Google Scholar 

  25. Krishnan, A. V. et al. Ischaemia induces paradoxical changes in axonal excitability in end-stage kidney disease. Brain 129, 1585–1592 (2006).

    Article  PubMed  Google Scholar 

  26. Krishnan, A. V., Phoon, R. K., Pussell, B. A., Charlesworth, J. A. & Kiernan, M. C. Sensory nerve excitability and neuropathy in end-stage kidney disease. J. Neurol. Neurosurg. Psychiatry 77, 548–551 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Friedland, J. & Paterson, D. Potassium and fatigue. Lancet 2, 961–962 (1988).

    Article  CAS  PubMed  Google Scholar 

  28. Sangkabutra, T. et al. Impaired K+ regulation contributes to exercise limitation in end-stage renal failure. Kidney Int. 63, 283–290 (2003).

    Article  CAS  PubMed  Google Scholar 

  29. Kurella, M. et al. Chronic kidney disease and cognitive impairment in the elderly: the health, aging, and body composition study. J. Am. Soc. Nephrol. 16, 2127–2133 (2005).

    Article  PubMed  Google Scholar 

  30. Kurella, M., Chertow, G. M., Luan, J. & Yaffe, K. Cognitive impairment in chronic kidney disease. J. Am. Geriatr. Soc. 52, 1863–1869 (2004).

    Article  PubMed  Google Scholar 

  31. Hailpern, S. M., Melamed, M. L., Cohen, H. W. & Hostetter, T. H. Moderate chronic kidney disease and cognitive function in adults 20 to 59 years of age: Third National Health and Nutrition Examination Survey (NHANES III). J. Am. Soc. Nephrol. 18, 2205–2213 (2007).

    Article  PubMed  Google Scholar 

  32. Fazekas, G. et al. Brain MRI findings and cognitive impairment in patients undergoing chronic hemodialysis treatment. J. Neurol. Sci. 134, 83–88 (1995).

    Article  CAS  PubMed  Google Scholar 

  33. Kurella, M., Mapes, D. L., Port, F. K. & Chertow, G. M. Correlates and outcomes of dementia among dialysis patients: the Dialysis Outcomes and Practice Patterns Study. Nephrol. Dial. Transplant. 21, 2543–2548 (2006).

    Article  PubMed  Google Scholar 

  34. Rakowski, D. A., Caillard, S., Agodoa, L. Y. & Abbott, K. C. Dementia as a predictor of mortality in dialysis patients. Clin. J. Am. Soc. Nephrol. 1, 1000–1005 (2006).

    Article  Google Scholar 

  35. Pereira, A. A., Weiner, D. E., Scott, T. & Sarnak, M. J. Cognitive function in dialysis patients. Am. J. Kidney Dis. 45, 448–462 (2005).

    Article  PubMed  Google Scholar 

  36. Arieff, A. I. Dialysis disequilibrium syndrome: current concepts on pathogenesis and prevention. Kidney Int. 45, 629–635 (1994).

    Article  CAS  PubMed  Google Scholar 

  37. Israni, R. K., Kasbekar, N., Haynes, K. & Berns, J. S. Use of antiepileptic drugs in patients with kidney disease. Semin. Dial. 19, 408–416 (2006).

    Article  PubMed  Google Scholar 

  38. Lacerda, G., Krummel, T., Sabourdy, C., Ryvlin, P. & Hirsch, E. Optimizing therapy of seizures in patients with renal or hepatic dysfunction. Neurology 67, S28–S33 (2006).

    Article  CAS  PubMed  Google Scholar 

  39. Frenchie, D. & Bastani, B. Significant removal of phenytoin during high flux dialysis with cellulose triacetate dialyzer. Nephrol. Dial. Transplant. 13, 817–818 (1998).

    Article  CAS  PubMed  Google Scholar 

  40. Murray, A. M. et al. Acute variation in cognitive function in hemodialysis patients: a cohort study with repeated measures. Am. J. Kidney Dis. 50, 270–278 (2007).

    Article  PubMed  Google Scholar 

  41. Seliger, S. L. et al. Moderate renal impairment and risk of dementia among older adults: the Cardiovascular Health Cognition Study. J. Am. Soc. Nephrol. 15, 1904–1911 (2004).

    Article  PubMed  Google Scholar 

  42. O'Brien, J. T. et al. Vascular cognitive impairment. Lancet Neurol. 2, 89–98 (2003).

    Article  PubMed  Google Scholar 

  43. Naganuma, T. et al. Silent cerebral infarction predicts vascular events in hemodialysis patients. Kidney Int. 67, 2434–2439 (2005).

    Article  PubMed  Google Scholar 

  44. Kim, C. D. et al. High prevalence of leukoaraiosis in cerebral magnetic resonance images of patients on peritoneal dialysis. Am. J. Kidney Dis. 50, 98–107 (2007).

    Article  PubMed  Google Scholar 

  45. Suzuki, M. et al. Cerebral magnetic resonance T2 high intensities in end-stage renal disease. Stroke 28, 2528–2531 (1997).

    Article  CAS  PubMed  Google Scholar 

  46. Seliger, S. L. et al. Cystatin C and subclinical brain infarction. J. Am. Soc. Nephrol. 16, 3721–3727 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Vermeer, S. E. et al. Silent brain infarcts and the risk of dementia and cognitive decline. N. Engl. J. Med. 348, 1215–1222 (2003).

    Article  PubMed  Google Scholar 

  48. Nakatani, T. et al. Silent cerebral infarction in hemodialysis patients. Am. J. Nephrol. 23, 86–90 (2003).

    Article  PubMed  Google Scholar 

  49. Martinez-Vea, A. et al. Silent cerebral white matter lesions and their relationship with vascular risk factors in middle-aged predialysis patients with CKD. Am. J. Kidney Dis. 47, 241–250 (2006).

    Article  PubMed  Google Scholar 

  50. Sehgal, A. R., Grey, S. F., DeOreo, P. B. & Whitehouse, P. J. Prevalence, recognition, and implications of mental impairment among hemodialysis patients. Am. J. Kidney Dis. 30, 41–49 (1997).

    Article  CAS  PubMed  Google Scholar 

  51. Koren-Morag, N., Goldbourt, U. & Tanne, D. Renal dysfunction and risk of ischemic stroke or TIA in patients with cardiovascular disease. Neurology 67, 224–228 (2006).

    Article  CAS  PubMed  Google Scholar 

  52. Wannamethee, S. G., Shaper, A. G. & Perry, I. J. Serum creatinine concentration and risk of cardiovascular disease: a possible marker for increased risk of stroke. Stroke 28, 557–563 (1997).

    Article  CAS  PubMed  Google Scholar 

  53. Guarnieri, G., Grassi, G., Barazzoni, R., Zanetti, M. & Biolo, G. The impact of inflammation on metabolic regulation in chronic kidney disease: a review. J. Ren. Nutr. 15, 121–124 (2005).

    Article  PubMed  Google Scholar 

  54. Schmidt, R. et al. Early inflammation and dementia: a 25-year follow-up of the Honolulu-Asia Aging Study. Ann. Neurol. 52, 168–174 (2002).

    Article  PubMed  Google Scholar 

  55. Teunissen, C. E. et al. Inflammation markers in relation to cognition in a healthy aging population. J. Neuroimmunol. 134, 142–150 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Madero, M., Gul, A. & Sarnak, M. J. Cognitive function in chronic kidney disease. Semin. Dial. 21, 29–37 (2008).

    Article  PubMed  Google Scholar 

  57. Dunea, G. Dialysis dementia: an epidemic that came and went. ASAIO J. 47, 192–194 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Alfrey, A. C., LeGendre, G. R. & Kaehny, W. D. The dialysis encephalopathy syndrome. Possible aluminum intoxication. N. Engl. J. Med. 294, 184–188 (1976).

    Article  CAS  PubMed  Google Scholar 

  59. Mahoney, C. A. & Arieff, A. I. Central and peripheral nervous system effects of chronic renal failure. Kidney Int. 24, 170–177 (1983).

    Article  CAS  PubMed  Google Scholar 

  60. Cooper, J. D., Lazarowitz, V. C. & Arieff, A. I. Neurodiagnostic abnormalities in patients with acute renal failure. J. Clin. Invest. 61, 1448–1455 (1978).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Marsh, J. T. et al. rHuEPO treatment improves brain and cognitive function of anemic dialysis patients. Kidney Int. 39, 155–163 (1991).

    Article  CAS  PubMed  Google Scholar 

  62. Griva, K. et al. Cognitive functioning pre- to post-kidney transplantation—a prospective study. Nephrol. Dial. Transplant. 21, 3275–3282 (2006).

    Article  PubMed  Google Scholar 

  63. Kramer, L. et al. Beneficial effect of renal transplantation on cognitive brain function. Kidney Int. 49, 833–838 (1996).

    Article  CAS  PubMed  Google Scholar 

  64. Mendley, S. R. & Zelko, F. A. Improvement in specific aspects of neurocognitive performance in children after renal transplantation. Kidney Int. 56, 318–323 (1999).

    Article  CAS  PubMed  Google Scholar 

  65. Teschan, P. E., Ginn, H. E., Bourne, J. R. & Ward, J. W. Neurobehavioral responses to “middle molecule” dialysis and transplantation. Trans. Am. Soc. Artif. Intern. Organs 22, 190–194 (1976).

    CAS  PubMed  Google Scholar 

  66. Montplaisir, J. et al. Clinical, polysomnographic, and genetic characteristics of restless legs syndrome: a study of 133 patients diagnosed with new standard criteria. Mov. Disord. 12, 61–65 (1997).

    Article  CAS  PubMed  Google Scholar 

  67. Mucsi, I. et al. Restless legs syndrome, insomnia and quality of life in patients on maintenance dialysis. Nephrol. Dial. Transplant. 20, 571–577 (2005).

    Article  PubMed  Google Scholar 

  68. Lauria, G. Small fibre neuropathies. Curr. Opin. Neurol. 18, 591–597 (2005).

    Article  PubMed  Google Scholar 

  69. Angus-Leppan, H. & Burke, D. The function of large and small nerve fibers in renal failure. Muscle Nerve 15, 288–294 (1992).

    Article  CAS  PubMed  Google Scholar 

  70. Hattan, E., Chalk, C. & Postuma, R. B. Is there a higher risk of restless legs syndrome in peripheral neuropathy? Neurology 72, 955–960 (2009).

    Article  PubMed  Google Scholar 

  71. Benes, H., Walters, A. S., Allen, R. P., Hening, W. A. & Kohnen, R. Definition of restless legs syndrome, how to diagnose it, and how to differentiate it from RLS mimics. Mov. Disord. 22 (Suppl. 18), S401–S408 (2007).

    Article  PubMed  Google Scholar 

  72. Enomoto, M., Inoue, Y., Namba, K., Munezawa, T. & Matsuura, M. Clinical characteristics of restless legs syndrome in end-stage renal failure and idiopathic RLS patients. Mov. Disord. 23, 811–816 (2008).

    Article  PubMed  Google Scholar 

  73. Novak, M., Mendelssohn, D., Shapiro, C. M. & Mucsi, I. Diagnosis and management of sleep apnea syndrome and restless legs syndrome in dialysis patients. Semin. Dial. 19, 210–216 (2006).

    Article  PubMed  Google Scholar 

  74. Turjanski, N., Lees, A. J. & Brooks, D. J. Striatal dopaminergic function in restless legs syndrome: 18F-dopa and 11C-raclopride PET studies. Neurology 52, 932–937 (1999).

    Article  CAS  PubMed  Google Scholar 

  75. Trenkwalder, C. et al. L-dopa therapy of uremic and idiopathic restless legs syndrome: a double-blind, crossover trial. Sleep 18, 681–688 (1995).

    Article  CAS  PubMed  Google Scholar 

  76. Takaki, J. et al. Clinical and psychological aspects of restless legs syndrome in uremic patients on hemodialysis. Am. J. Kidney Dis. 41, 833–839 (2003).

    Article  PubMed  Google Scholar 

  77. Winkelmann, J., Stautner, A., Samtleben, W. & Trenkwalder, C. Long-term course of restless legs syndrome in dialysis patients after kidney transplantation. Mov. Disord. 17, 1072–1076 (2002).

    Article  PubMed  Google Scholar 

  78. Sloand, J. A., Shelly, M. A., Feigin, A., Bernstein, P. & Monk, R. D. A double-blind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am. J. Kidney Dis. 43, 663–670 (2004).

    Article  CAS  PubMed  Google Scholar 

  79. Azar, S. A., Hatefi, R. & Talebi, M. Evaluation of effect of renal transplantation in treatment of restless legs syndrome. Transplant. Proc. 39, 1132–1133 (2007).

    Article  CAS  PubMed  Google Scholar 

  80. Novak, M. et al. Chronic insomnia in kidney transplant recipients. Am. J. Kidney Dis. 47, 655–665 (2006).

    Article  PubMed  Google Scholar 

  81. Trenkwalder, C. et al. Treatment of restless legs syndrome: an evidence-based review and implications for clinical practice. Mov. Disord. 23, 2267–2302 (2008).

    Article  PubMed  Google Scholar 

  82. Krishnan, A. V. et al. Altered motor nerve excitability in end-stage kidney disease. Brain 128, 2164–2174 (2005).

    Article  PubMed  Google Scholar 

  83. Laaksonen, S., Metsarinne, K., Voipio-Pulkki, L. M. & Falck, B. Neurophysiologic parameters and symptoms in chronic renal failure. Muscle Nerve 25, 884–890 (2002).

    Article  PubMed  Google Scholar 

  84. Panjwani, M., Truong, L. D. & Eknoyan, G. Membranous glomerulonephritis associated with inflammatory demyelinating peripheral neuropathies. Am. J. Kidney Dis. 27, 279–283 (1996).

    Article  CAS  PubMed  Google Scholar 

  85. Kohli, A., Tandon, P. & Kher, V. Chronic inflammatory demyelinating polyradiculoneuropathy with membranous glomerulonephritis: report of one case. Clin. Neurol. Neurosurg. 94, 31–33 (1992).

    Article  CAS  PubMed  Google Scholar 

  86. Mitz, M., Di Benedetto, M., Klingbeil, G. E., Melvin, J. L. & Piering, W. Neuropathy in end-stage renal disease secondary to primary renal disease and diabetes. Arch. Phys. Med. Rehabil. 65, 235–238 (1984).

    CAS  PubMed  Google Scholar 

  87. Ropper, A. H. Accelerated neuropathy of renal failure. Arch. Neurol. 50, 536–539 (1993).

    Article  CAS  PubMed  Google Scholar 

  88. Bolton, C. F., McKeown, M. J., Chen, R., Toth, B. & Remtulla, H. Subacute uremic and diabetic polyneuropathy. Muscle Nerve 20, 59–64 (1997).

    Article  CAS  PubMed  Google Scholar 

  89. Bolton, C. F. et al. Distinctive electrophysiological features of denervated muscle in uremic patients. J. Clin. Neurophysiol. 14, 539–542 (1997).

    Article  CAS  PubMed  Google Scholar 

  90. Schaublin, G. A., Michet, C. J. Jr, Dyck, P. J. B. & Burns, T. M. An update on the classification and treatment of vasculitic neuropathy. Lancet Neurol. 4, 853–865 (2005).

    Article  PubMed  Google Scholar 

  91. Bolton, C. F., Baltzan, M. A. & Baltzan, R. B. Effects of renal transplantation on uremic neuropathy. A clinical and electrophysiologic study. N. Engl. J. Med. 284, 1170–1175 (1971).

    Article  CAS  PubMed  Google Scholar 

  92. Nielsen, V. K. The peripheral nerve function in chronic renal failure. V. Sensory and motor conduction velocity. Acta Med. Scand. 194, 445–454 (1973).

    Article  CAS  PubMed  Google Scholar 

  93. Bolton, C. F. Electrophysiologic changes in uremic neuropathy after successful renal transplantation. Neurology 26, 152–161 (1976).

    Article  CAS  PubMed  Google Scholar 

  94. Solders, G. et al. Effects of combined pancreatic and renal transplantation on diabetic neuropathy: a two-year follow-up study. Lancet 2, 1232–1235 (1987).

    Article  CAS  PubMed  Google Scholar 

  95. Muller-Felber, W. et al. Diabetic neuropathy 3 years after successful pancreas and kidney transplantation. Diabetes 42, 1482–1486 (1993).

    Article  CAS  PubMed  Google Scholar 

  96. National Kidney Foundation. NKF-DOQI clinical practice guidelines for hemodialysis adequacy. Am. J. Kidney Dis. 30 (Suppl. 2), S15–S66 (1997).

  97. Orbach, H., Tishler, M. & Shoenfeld, Y. Intravenous immunoglobulin and the kidney—a two-edged sword. Semin. Arthritis Rheum. 34, 593–601 (2004).

    Article  CAS  PubMed  Google Scholar 

  98. Okada, H. et al. Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin. Nephrol. Dial. Transplant. 15, 1410–1413 (2000).

    Article  CAS  PubMed  Google Scholar 

  99. Kuwabara, S. et al. Intravenous methylcobalamin treatment for uremic and diabetic neuropathy in chronic hemodialysis patients. Intern. Med. 38, 472–475 (1999).

    Article  CAS  PubMed  Google Scholar 

  100. Kouidi, E. J. Central and peripheral adaptations to physical training in patients with end-stage renal disease. Sports Med. 31, 651–665 (2001).

    Article  CAS  PubMed  Google Scholar 

  101. Krishnan, A. V. et al. Neuropathy, axonal Na+/K+ pump function and activity-dependent excitability changes in end-stage kidney disease. Clin. Neurophysiol. 117, 992–997 (2006).

    Article  CAS  PubMed  Google Scholar 

  102. Jassal, S. V., Coulshed, S. J., Douglas, J. F. & Stout, R. W. Autonomic neuropathy predisposing to arrhythmias in hemodialysis patients. Am. J. Kidney Dis. 30, 219–223 (1997).

    Article  CAS  PubMed  Google Scholar 

  103. Vita, G. et al. Uremic autonomic neuropathy studied by spectral analysis of heart rate. Kidney Int. 56, 232–237 (1999).

    Article  CAS  PubMed  Google Scholar 

  104. Heidbreder, E., Schafferhans, K. & Heidland, A. Disturbances of peripheral and autonomic nervous system in chronic renal failure: effects of hemodialysis and transplantation. Clin. Nephrol. 23, 222–228 (1985).

    CAS  PubMed  Google Scholar 

  105. Chesterton, L. J., Sigrist, M. K., Bennett, T., Taal, M. W. & McIntyre, C. W. Reduced baroreflex sensitivity is associated with increased vascular calcification and arterial stiffness. Nephrol. Dial. Transplant. 20, 1140–1147 (2005).

    Article  PubMed  Google Scholar 

  106. McIntyre, C. W. The functional cardiovascular consequences of vascular calcification. Semin. Dial. 20, 122–128 (2007).

    Article  PubMed  Google Scholar 

  107. Kersh, E. S. et al. Autonomic insufficiency in uremia as a cause of hemodialysis-induced hypotension. N. Engl. J. Med. 290, 650–653 (1974).

    Article  CAS  PubMed  Google Scholar 

  108. Sato, M. et al. Autonomic insufficiency as a factor contributing to dialysis-induced hypotension. Nephrol. Dial. Transplant. 16, 1657–1662 (2001).

    Article  CAS  PubMed  Google Scholar 

  109. Henderson, L. W. Symptomatic hypotension during hemodialysis. Kidney Int. 17, 571–576 (1980).

    Article  CAS  PubMed  Google Scholar 

  110. Lilley, J. J., Golden, J. & Stone, R. A. Adrenergic regulation of blood pressure in chronic renal failure. J. Clin. Invest. 57, 1190–1200 (1976).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Shoji, T., Tsubakihara, Y., Fujii, M. & Imai, E. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int. 66, 1212–1220 (2004).

    Article  PubMed  Google Scholar 

  112. Mallamaci, F., Zoccali, C., Ciccarelli, M. & Briggs, J. D. Autonomic function in uremic patients treated by hemodialysis or CAPD and in transplant patients. Clin. Nephrol. 25, 175–180 (1986).

    CAS  PubMed  Google Scholar 

  113. Rockel, A., Hennemann, H., Sternagel-Haase, A. & Heidland, A. Uraemic sympathetic neuropathy after haemodialysis and transplantation. Eur. J. Clin. Invest. 9, 23–27 (1979).

    Article  CAS  PubMed  Google Scholar 

  114. Wilson, J. A., Yahya, T. M., Giles, G. R. & Davison, A. M. The effect of haemodialysis and transplantation on autonomic neuropathy. Proc. Eur. Dial. Transplant. 16, 261–265 (1979).

    CAS  Google Scholar 

  115. Rosas, S. E., Wasserstein, A., Kobrin, S. & Feldman, H. I. Preliminary observations of sildenafil treatment for erectile dysfunction in dialysis patients. Am. J. Kidney Dis. 37, 134–137 (2001).

    Article  CAS  PubMed  Google Scholar 

  116. Prakash, S., Garg, A. X., Heidenheim, A. P. & House, A. A. Midodrine appears to be safe and effective for dialysis-induced hypotension: a systematic review. Nephrol. Dial. Transplant. 19, 2553–2558 (2004).

    Article  CAS  PubMed  Google Scholar 

  117. Spertini, F., Wauters, J. P. & Poulenas, I. Carpal tunnel syndrome: a frequent, invalidating, long-term complication of chronic hemodialysis. Clin. Nephrol. 21, 98–101 (1984).

    CAS  PubMed  Google Scholar 

  118. Gousheh, J. & Iranpour, A. Association between carpel tunnel syndrome and arteriovenous fistula in hemodialysis patients. Plast. Reconstr. Surg. 116, 508–513 (2005).

    Article  CAS  PubMed  Google Scholar 

  119. Munoz-Gomez, J. et al. Amyloid arthropathy in patients undergoing periodical haemodialysis for chronic renal failure: a new complication. Ann. Rheum. Dis. 44, 729–733 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Drueke, T. B. β2-microglobulin and amyloidosis. Nephrol. Dial. Transplant. 15 (Suppl. 1), 17–24 (2000).

    Article  CAS  PubMed  Google Scholar 

  121. Wilson, S. W., Pollard, R. E. & Lees, V. C. Management of carpal tunnel syndrome in renal dialysis patients using an extended carpal tunnel release procedure. J. Plast. Reconstr. Aesthet. Surg. 61, 1090–1094 (2008).

    Article  CAS  PubMed  Google Scholar 

  122. Chary-Valckenaere, I. et al. Amyloid and non-amyloid carpal tunnel syndrome in patients receiving chronic renal dialysis. J. Rheumatol. 25, 1164–1170 (1998).

    CAS  PubMed  Google Scholar 

  123. Wilbourn, A. J., Furlan, A. J., Hulley, W. & Ruschhaupt, W. Ischemic monomelic neuropathy. Neurology 33, 447–451 (1983).

    Article  CAS  PubMed  Google Scholar 

  124. Berman, S. S. et al. Distal revascularization-interval ligation for limb salvage and maintenance of dialysis access in ischemic steal syndrome. J. Vasc. Surg. 26, 393–402 (1997).

    Article  CAS  PubMed  Google Scholar 

  125. Miles, A. M. Vascular steal syndrome and ischaemic monomelic neuropathy: two variants of upper limb ischaemia after haemodialysis vascular access surgery. Nephrol. Dial. Transplant. 14, 297–300 (1999).

    Article  CAS  PubMed  Google Scholar 

  126. Moore, G. E. et al. Uremic myopathy limits aerobic capacity in hemodialysis patients. Am. J. Kidney Dis. 22, 277–287 (1993).

    Article  CAS  PubMed  Google Scholar 

  127. Diesel, W. et al. Morphologic features of the myopathy associated with chronic renal failure. Am. J. Kidney Dis. 22, 677–684 (1993).

    Article  CAS  PubMed  Google Scholar 

  128. Mak, R. H. & DeFronzo, R. A. Glucose and insulin metabolism in uremia. Nephron 61, 377–382 (1992).

    Article  CAS  PubMed  Google Scholar 

  129. Massry, S. G. Parathyroid hormone and uremic myocardiopathy. Contrib. Nephrol. 41, 231–239 (1984).

    Article  CAS  PubMed  Google Scholar 

  130. Thompson, C. H. et al. Effect of chronic uraemia on skeletal muscle metabolism in man. Nephrol. Dial. Transplant. 8, 218–222 (1993).

    CAS  PubMed  Google Scholar 

  131. Savica, V. et al. Plasma and muscle carnitine levels in haemodialysis patients with morphological–ultrastructural examination of muscle samples. Nephron 35, 232–236 (1983).

    Article  CAS  PubMed  Google Scholar 

  132. Floyd, M., Ayyar, D. R., Barwick, D. D., Hudgson, P. & Weightman, D. Myopathy in chronic renal failure. Q. J. Med. 43, 509–524 (1974).

    CAS  PubMed  Google Scholar 

  133. Canepa, A. et al. Nutritional status and muscle amino acids in children with end-stage renal failure. Kidney Int. 41, 1016–1022 (1992).

    Article  CAS  PubMed  Google Scholar 

  134. Guarnieri, G. et al. Muscle biopsy studies in chronically uremic patients: evidence for malnutrition. Kidney Int. Suppl. 16, S187–S193 (1983).

    CAS  PubMed  Google Scholar 

  135. Robertson, H. T. et al. Recombinant erythropoietin improves exercise capacity in anemic hemodialysis patients. Am. J. Kidney Dis. 15, 325–332 (1990).

    Article  CAS  PubMed  Google Scholar 

  136. Fahal, I. H., Bell, G. M., Bone, J. M. & Edwards, R. H. Physiological abnormalities of skeletal muscle in dialysis patients. Nephrol. Dial. Transplant. 12, 119–127 (1997).

    Article  CAS  PubMed  Google Scholar 

  137. Kouidi, E. et al. The effects of exercise training on muscle atrophy in haemodialysis patients. Nephrol. Dial. Transplant. 13, 685–699 (1998).

    Article  CAS  PubMed  Google Scholar 

  138. Golper, T. A. et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients. I. Carnitine concentrations and lipid effects. Kidney Int. 38, 904–911 (1990).

    Article  CAS  PubMed  Google Scholar 

  139. Ahmad, S. et al. Multicenter trial of L-carnitine in maintenance hemodialysis patients. II. Clinical and biochemical effects. Kidney Int. 38, 912–918 (1990).

    Article  CAS  PubMed  Google Scholar 

  140. Semeniuk, J., Shalansky, K. F., Taylor, N., Jastrzebski, J. & Cameron, E. C. Evaluation of the effect of intravenous L-carnitine on quality of life in chronic hemodialysis patients. Clin. Nephrol. 54, 470–477 (2000).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

A. V. Krishnan was supported by a Career Development Award (Grant number 568680) of the National Health and Medical Research Council. Grant funding from the Brain Foundation and Pfizer Neuroscience Grants Scheme is gratefully acknowledged. Charles P. Vega, University of California, Irvine, CA is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. Translational Neuroscience Facility, School of Medical Sciences, University of New South Wales, Sydney, NSW, Australia

    Arun V. Krishnan

  2. Prince of Wales Medical Research Institute, University of New South Wales, Sydney, NSW, Australia

    Matthew C. Kiernan

Authors
  1. Arun V. Krishnan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew C. Kiernan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arun V. Krishnan.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Krishnan, A., Kiernan, M. Neurological complications of chronic kidney disease. Nat Rev Neurol 5, 542–551 (2009). https://doi.org/10.1038/nrneurol.2009.138

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrneurol.2009.138

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing