Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Uraemic Pruritus

Clinical Characteristics, Pathophysiology and Treatment

Abstract

Pruritus is a common complication of end-stage renal disease (ESRD), affecting about one-third of dialysis patients. It is a chronic, unpleasant symptom with a strong negative impact on patients’ quality of life, often inducing sleeplessness and mood disorders. Recent data show that it is also associated with increased mortality.

The pathogenesis of uraemic pruritus (UP) is multifactorial. Triggering factors may include uraemia-related abnormalities (particularly involving calcium, phosphorus and parathyroid hormone metabolism), accumulation of uraemic toxins, systemic inflammation, cutaneous xerosis, and common co-morbidities such as diabetes mellitus and viral hepatitis. Recent findings suggest that the neurophysiology of itch is similar to that of pain; this has led to the hypothesis that the two phenomena also closely interact in ESRD patients, who often also experience uraemic neuropathy.

The management of UP needs to address several different issues, such as optimization of dialysis efficacy and skin hydration, and correction of calcium-phosphorus metabolism abnormalities. A wide range of antipruritic drugs have been suggested for the treatment of UP, although most of them have only been tested in small, uncontrolled trials, which have yielded conflicting results. Antihistamines are now known to have little or no efficacy, although they are still often prescribed. Novel neurotropic drugs such as gabapentin, along with opioid receptor modulators such as nalfur-afine, appear to be effective and well tolerated, but their efficacy has not yet been directly compared. Finally, physical therapies, including UV radiation, may also have a role in patients with refractory symptoms.

This is a preview of subscription content, log in to check access.

Fig. 1
Table I
Table II
Fig. 2

References

  1. 1.

    Masi CM, Cohen EP. Dialysis efficacy and itching in renal failure. Nephron 1992; 62: 257–61

  2. 2.

    Pisoni RL, Wikstrom B, Elder SJ, et al. Pruritus in haemo-dialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2006; 21: 3495–505

  3. 3.

    Mistik S, Utas S, Ferahbas A, et al. An epidemiology study of patients with uremic pruritus. J Eur Acad Dermatol Venereol 2006; 20: 672–8

  4. 4.

    Murphy M, Carmichael AJ. Renal itch. Clin Exp Dermatol 2000; 25: 103–6

  5. 5.

    Zucker I, Yosipovitch G, David M, et al. Prevalence and characterization of uremic pruritus in patients undergoing hemodialysis: uremic pruritus is still a major problem for patients with end-stage renal disease. J Am Acad Dermatol 2003; 49: 842–6

  6. 6.

    Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface. QJ Med 2003; 96: 7–26

  7. 7.

    Zakrzewska-Pniewska B, Jedras M. Is pruritus in chronic uremic patients related to peripheral somatic and autonomic neuropathy? Neurophysiol Clin 2001; 31: 181–93

  8. 8.

    Stahle-Backdal M. Pruritus in haemodialysis patients. Skin Pharmacol 1992; 5: 14–20

  9. 9.

    Stockenhuber F, Kurz RW, Setl K, et al. Increased plasma histamine in uremic pruritus. Clin Sci 1990; 79: 477–82

  10. 10.

    Mettang T, Fritz P, Weber J, et al. Uremic pruritus in patients on hemodialysis or continuous ambulatory peritoneal dialysis (CAPD): the role of plasma histamine and skin mast cells. Clin Nephrol 1990; 34: 136–41

  11. 11.

    Hiroshige K, Kabashima N, Takasugi M, et al. Optimal dialysis improves uremic pruritus. Am J Kidney Dis 1995; 25: 413–9

  12. 12.

    Dimkovic N, Djukanovic L, Radmilovic A, et al. Uremic pruritus and skin mast cells. Nephron 1992; 61: 5–9

  13. 13.

    Shim WS, Oh U. Histamine-induced itch and its relationship with pain. Mol Pain 2008 Jul 31; 4: 29

  14. 14.

    Massry SG, Popovtzer MM, Coburn JW, et al. Intractable pruritus as a manifestation of secondary hyperparathir-oidism in uremia: disappearance of itching after subtotal parathyroidectomy. N Engl J Med 1968; 279: 697–700

  15. 15.

    Keithy-Reddy SR, Patel TV, Armstrong AW, et al. Uremic pruritus. Kidney Int 2007; 72: 373–7

  16. 16.

    Momose A, Kudo S, Sato M, et al. Calcium ions are abnormally distributed in the skin of haemodialysis patients with uremic pruritus. Nephrol Dial Transplant 2004; 19: 2061–6

  17. 17.

    Akhyani M, Ganmji MR, Samadi N, et al. Pruritus in haemodialysis patients. BMC Dermatol 2005; 5: 7

  18. 18.

    Subach RA, Marx MA. Evaluation of uremic pruritus at an outpatient hemodialysis unit. Ren Fail 2002; 24: 609–14

  19. 19.

    Cho YL, Liu HN, Huang TP, et al. Uremic pruritus: roles of parathiroid hormone and substance P. J Am Acad Dermatol 1998; 38: 503–4

  20. 20.

    Daugirdas JT. Second generation logarithmic estimates of single-pool variable volume Kt/V: an analysis of error. J Am Soc Nephrol 1993; 4: 1205–13

  21. 21.

    Narita I, Alchi B, Omori K, et al. Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients. Kidney Int 2006; 69: 1626–32

  22. 22.

    Duque MI, Thevarajah S, Chan YH, et al. Uremic pruritus is associated with higher kt/V and serum calcium concentration. Clin Nephrol 2006; 66: 184–91

  23. 23.

    Kimmel M, Alscher DM, Dunst R, et al. The role of microinflammation in the pathogenesis of uraemic pruritus in haemodialysis patients. Nephrol Dial Transplant 2006; 21: 749–55

  24. 24.

    Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, placebo-controlled crossover-study. J Am Soc Nephrol 2000; 11: 514–9

  25. 25.

    Bosch-Krakenhaus R. Uremic pruritus is not related to b-endorphin serum levels in haemodialysis patients. Nephrol Dial Transplant 1998; 13: 231–2

  26. 26.

    Wikstrom B, Gellert R, Ladefoged SD, et al. k-Opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. J Am Soc Nephrol 2005; 16: 3742–7

  27. 27.

    Weisshaar E, Dunker N, Rohl FW, et al. Antipruritc effects of two different 5-HT3 receptor antagonists and an anti-histamine in haemodialysis patients. Exp Dermatol 2004; 13: 298–304

  28. 28.

    Tremont-Lukats IW, Megeff C, Backonja MM. Anti-convulsants for neuropathic pain syndromes. Drugs 2000; 60(S): 1029–52

  29. 29.

    Schmelz M. Itch and pain. Dermatol Ther 2005; 18: 304–7

  30. 30.

    Kidd BL, Urban LA. Mechanism of inflammatory pain. Br J Anaesth 2001; 87: 3–11

  31. 31.

    Yosipovitch G, Zucker I, Boner G, et al. A questionnaire for the assessment of pruritus: validation in urenic patients. Acta Dermatol Venereol 2001; 81: 108–11

  32. 32.

    Carruthers SG, Larochelle P, Haynes RB, et al. Report of the Canadian Hypertension Society Consensus Conference. I. Introduction. CMAJ 1993; 149: 289–93

  33. 33.

    Kato A, Takita T, Furuhashi M, et al. Polymethyl-methacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor-alpha. Artif Organs 2001; 25: 441–7

  34. 34.

    Lin HH, Liu YL, Liu JH, et al. Uremic pruritus, cytokines and polymethylmethacrilate artificial kidney. Artif Organs 2008; 32: 468–72

  35. 35.

    Aoike I. Clinical significance of protein adsorbable membranes: long-term clinical effects and analysis using a proteomic technique. Nephrol Dial Transplant 2007; 22 Suppl. 5: 13–9

  36. 36.

    Morton CA, Lafferty M, Hau C, et al. Pruritus and skin hydration during dialysis. Nephrol Dial Transplant 1996; 11: 2031–6

  37. 37.

    Okada K, Matsumoto K. Effect of skin care with an emollient containing a high water content on mild uremic pruritus. Ther Apher Dial 2004; 8: 419–22

  38. 38.

    Szepietowski JC, Reich A, Szepietowski T. Emollients with endocannabinoids in the treatment of uremic pruritus: discussion of the therapeutic options. Ther Apher Dial 2005; 9: 277–9

  39. 39.

    Chen YC, Chiu WT, Wu MS. Therapeutic effect of topical gamma-linolenic acid on refractory uremic pruritus. Am J Kidney Dis 2006; 48: 69–76

  40. 40.

    Breneman DL, Cardone S, Blumsack RF, et al. Topical capsaicin for treatment of hemodialysis-related pruritus. J Am Acad Dermatol 1992; 26: 91–4

  41. 41.

    Tarng DC, Cho YL, Liu HN, et al. Hemodialysis-related pruritus: a double-blind. Placebo-controlled, crossover study of capsaicin 0.025% cream. Nephron 1996; 72: 617–22

  42. 42.

    Weisshaar E, Dunker N, Gollnick H. Topical capsaicin therapy in humans with hemodialysis-related pruritus. Neurosci Lett 2003; 345: 192–4

  43. 43.

    Kuypers DR, Claes K, Evenepoel P, et al. A prospective proof of concept study of the efficacy of tacrolimus ointment on uremic pruritus (UP) in patients on chronic dialysis therapy. Nephrol Dial Transplant 2004; 19: 1895–901

  44. 44.

    Duque MI, Yosipovitch G, Fleischer AB, et al. Lack of efficacy of tacrolimus ointment 0,1% for treatment of hemodialysis-related pruritus: a randomized, double blind, vehicle-controlled study. J Am Acad Dermatol 2005; 52: 519–21

  45. 45.

    Gilchrest BA, Rowe JW, Brown RS, et al. Relief of uremic pruritus with ultraviolet phototherapy. N Engl J Med 1977; 297: 136–8

  46. 46.

    Schultz BC, Roenigk HH. Uremic pruritus treated with ultraviolet light. JAMA 1980; 243: 1836–7

  47. 47.

    Seckin D, Demircay Z, Akin O. Generalized pruritus treated with narrowband UVB. Int J Dermatol 2007; 46: 367–70

  48. 48.

    Gao H, Zhang W, Wang Y. Acupuncture treatment for 34 cases of uremic cutaneous pruritus. J Tradit Chin Med 2002; 22: 29–30

  49. 49.

    Che-yi C, Wen CY, Min-Tsung K, et al. Acupuncture in haemodialysis patients at the Quchi (LI11) acupoint for refractory uraemic pruritus. Nephrol Dial Transplant 2005; 20: 1912–5

  50. 50.

    Russo GE, Spaziani M, Guidotti C, et al. Pruritus in chronic uremic patients in periodic hemodialysis: treatment with terfenadine (an antagonist of histamine H1 receptors) [in Italian]. Minerva Urol Nephrol 1986; 38: 443–7

  51. 51.

    Balaskas EV, Bamihas GI, Karamouzis M, et al. Histamine and serotonine in uremic pruritus: effect of ondasetron in CAPD-pruritc patients. Nephron 1998; 78: 395–402

  52. 52.

    Ashmore SD, Jones CH, Newstead CG, et al. Ondasetron therapy for uremic pruritus in hemodialysis patients. Am J Kidney Dis 2000; 35: 827–31

  53. 53.

    Murphy M, Realch D, Pai P, et al. A randomized, placebo-controlled, double blind trial of ondasetron in renal itch. Br J Dermatol 2003; 148: 314–7

  54. 54.

    Layegh P, Mojahedi MJ, Malekshah PET, et al. Effect of oral granisetron in uremic pruritus. Indian J Dermatol Venereol Leprol 2007; 73: 231–4

  55. 55.

    Peer G, Kivity S, Agami O. Randomized crossover trial of naltrexone in uremic pruritus. Lancet 1996; 348: 1552–4

  56. 56.

    Legroux-Crespel E, Cledes J, Misery L. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology 2004; 208: 326–30

  57. 57.

    Manenti L, Vaglio A, Costantino E, et al. Gabapentin in the treatment of uremic itch: an index case and a pilot evaluation. J Nephrol 2005; 18: 86–91

  58. 58.

    Gunal AI, Ozalp G, Yoldas TK, et al. Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial. Nephrol Dial Transplant 2004; 19: 3137–9

  59. 59.

    Naini AE, Harandi AA, Khanbabapour S, et al. Gabapentin: a promising drug for the treatment of uremic pruritus. Saudi J Kidney Dis Transpl 2007; 18: 378–81

  60. 60.

    Silva SR, Viana PC, Lugon NV, et al. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron 1994; 67: 2011–2

  61. 61.

    De Marchi S, Cecchin E, Villalta D, et al. Relief of pruritus and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia. N Engl J Med 1992; 326: 969–74

  62. 62.

    Giovannetti S, Bersotti G, Cupisti A, et al. Oral activated charcoal in patients with uremic pruritus. Nephron 1995; 70: 193–6

  63. 63.

    Pederson JA, Matter BJ, Czerwinski AW, et al. Relief of idiopathic generalized pruritus in dialysis patients treated with activated oral charcoal. Ann Intern Med 1980; 93: 446–8

  64. 64.

    Bousquet J, Rivory JP, Maheut M, et al. Double-blind placebo-controlled study of nicergoline in the treatment of pruritus in patients receiving maintenance hemodialysis. J Allergy Clin Immunol 1989; 83: 825–8

  65. 65.

    Ro YJ, Ha HC, Kim CG, et al. The effects of aromatherapy on pruritus in patients undergoing hemodialysis. Dermatol Nurs 2002; 14: 231–8

  66. 66.

    Stahle-Backdahl M. Stratum corneum hydration in patients undergoing maintenence haemodialysis. Acta Dermatol Venereol 1988; 68: 531–4

  67. 67.

    Garssen J, Vandebriel RJ, De Gruiji FR, et al. UVB exposure-induced systemic modulation of Th1- and Th2-mediated immune responses. Immunology 1999; 97: 506–14

  68. 68.

    Melzack R, Wall PD. Pain mechanism: a new theory. Science 1965; 150: 971–9

  69. 69.

    Albares MP, Betloch I, Guijarro J, et al. Severe pruritus in a hemodialysed patient: dramatic improtvement with granisetron. Br J Dermatol 2003; 148: 376–7

  70. 70.

    Andersen LW, Friedberg M, Lokkegaard N. Naloxone in treatment of uremic pruritus: a case history. Clin Nephrol 1984; 21: 355–6

  71. 71.

    Kaku H, Fujita Y, Yago H, et al. Study on pruritus in hemodialysis patients and the antipruritic effect of neurotropin: plasma levels of substance P, somatostatin, IgE, PTH and histamine. Nippon Jinzo Gakkai Shi 1990; 32: 319–26

  72. 72.

    Balaskas EV, Uldall RP. Erythropoietin treatment does not improve uremic pruritus. Perit Dial Int 1992; 12: 330–1

  73. 73.

    Tapia L, Cheigh JS, David DS, et al. Pruritus in dialysis patients treated with parenteral lidocaine. N Engl J Med 1977; 296: 261–2

  74. 74.

    Mettang T, Krumme B, Bohler J, et al. Pentoxifylline as treatment for uraemic pruritus: an addition to the weak armentarium for a common clinical symptom? Neph Dial Transpl 2007; 22: 2727–8

  75. 75.

    Cavalcanti AM, Rocha LM, Carillo R, et al. Effect of homeopathic treatment on pruritus of haemodialysis patients: a randomised placebo-controlled double-blind trial. Homeopathy 2003; 92: 177–81

  76. 76.

    Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol 2006; 54: 527–31

  77. 77.

    Patel TS, Freedman BI, Yosipovitch G. An update on pruritus associated with CKD. Am J Kidney Dis 2007; 50: 11–20

Download references

Acknowledgements

No sources of funding were used to assist in the preparation of this article. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Correspondence to Dr Lucio Manenti.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Manenti, L., Tansinda, P. & Vaglio, A. Uraemic Pruritus. Drugs 69, 251–263 (2009). https://doi.org/10.2165/00003495-200969030-00002

Download citation

Keywords

  • Capsaicin
  • Gabapentin
  • Haemodialysis Patient
  • Naltrexone
  • ESRD Patient