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Uremic pruritus

Author
Sidney M Kobrin, MD
Section Editor
Jeffrey S Berns, MD
Deputy Editor
Alice M Sheridan, MD

INTRODUCTION

Pruritus is a common and bothersome symptom among patients with end-stage-renal-disease (ESRD). The pathophysiology is incompletely understood, and it is often difficult to eradicate, although symptoms can usually be mitigated.

Uremic pruritus is discussed in this topic review. A general discussion of pruritus is presented separately. (See "Pruritus: Overview of management".)

EPIDEMIOLOGY

The reported prevalence of uremic pruritus in adult hemodialysis patients has varied over the years, and some studies suggest the prevalence may be decreasing with more effective dialysis [1]. Whereas the reported prevalence between 1980 and 1993 was 50 to 90 percent [2-4], subsequent surveys note a lower rate (22 to 57 percent) [5-8]. In one of the largest trials (the Dialysis Outcomes and Practice Patterns Study [DOPPS]), pruritus was experienced by 42 percent of hemodialysis patients [7]. The prevalence has not been as well studied in peritoneal dialysis patients and in children. Historically, small series suggested that the prevalence is lower in children (approximately 9 percent) and similar between hemodialysis and peritoneal dialysis patients [9-11]. However, two studies from Korea and Taiwan compared the prevalence of pruritus between hemodialysis and peritoneal dialysis patients and showed conflicting results. The Korean study showed a significantly higher rate of pruritus in peritoneal dialysis patients compared with hemodialysis patients (68.2 versus 48.3 percent, respectively), whereas the Taiwanese cohort showed no significant difference between hemodialysis and peritoneal dialysis patients [12,13].

PATHOPHYSIOLOGY

The pathophysiology of uremic pruritus is poorly understood. Hypotheses implicating immunologic and opioidergic systems have been proposed [14].

Immunohypothesis — The immunohypothesis proposes that uremic pruritus is the result of systemic inflammation rather than a local skin disorder [15,16]. Immunomodulating therapies such as ultraviolet B (UVB) phototherapy, thalidomide, and calcineurin inhibitors have been shown to decrease uremic pruritus in some studies [17-19].

                         

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Literature review current through: Nov 2016. | This topic last updated: Mon Nov 28 00:00:00 GMT+00:00 2016.
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References
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  1. Patel TS, Freedman BI, Yosipovitch G. An update on pruritus associated with CKD. Am J Kidney Dis 2007; 50:11.
  2. Nielsen T, Andersen KE, Kristiansen J. Pruritus and xerosis in patients with chronic renal failure. Dan Med Bull 1980; 27:269.
  3. Bencini PL, Montagnino G, Citterio A, et al. Cutaneous abnormalities in uremic patients. Nephron 1985; 40:316.
  4. Balaskas EV, Chu M, Uldall RP, et al. Pruritus in continuous ambulatory peritoneal dialysis and hemodialysis patients. Perit Dial Int 1993; 13 Suppl 2:S527.
  5. Wikström B. Itchy skin--a clinical problem for haemodialysis patients. Nephrol Dial Transplant 2007; 22 Suppl 5:v3.
  6. 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.
  7. Pisoni RL, Wikström B, Elder SJ, et al. Pruritus in haemodialysis patients: International results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol Dial Transplant 2006; 21:3495.
  8. Pauli-Magnus C, Mikus G, Alscher DM, et al. Naltrexone does not relieve uremic pruritus: results of a randomized, double-blind, placebo-controlled crossover study. J Am Soc Nephrol 2000; 11:514.
  9. 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.
  10. Tessari G, Dalle Vedove C, Loschiavo C, et al. The impact of pruritus on the quality of life of patients undergoing dialysis: a single centre cohort study. J Nephrol 2009; 22:241.
  11. Schwab M, Mikus G, Mettang T. Ura mischer pruritus im Kindes- und Jugendalter. Monatsschr Kinderheilkd 1999; 147:232.
  12. Min JW, Kim SH, Kim YO, et al. Comparison of uremic pruritus between patients undergoing hemodialysis and peritoneal dialysis. Kidney Res Clin Pract 2016; 35:107.
  13. Wu HY, Peng YS, Chen HY, et al. A Comparison of Uremic Pruritus in Patients Receiving Peritoneal Dialysis and Hemodialysis. Medicine (Baltimore) 2016; 95:e2935.
  14. Kuypers DR. Skin problems in chronic kidney disease. Nat Clin Pract Nephrol 2009; 5:157.
  15. Mettang T, Pauli-Magnus C, Alscher DM. Uraemic pruritus--new perspectives and insights from recent trials. Nephrol Dial Transplant 2002; 17:1558.
  16. Kimmel M, Alscher DM, Dunst R, et al. The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients. Nephrol Dial Transplant 2006; 21:749.
  17. Silva SR, Viana PC, Lugon NV, et al. Thalidomide for the treatment of uremic pruritus: a crossover randomized double-blind trial. Nephron 1994; 67:270.
  18. Gilchrest BA, Rowe JW, Brown RS, et al. Ultraviolet phototherapy of uremic pruritus. Long-term results and possible mechanism of action. Ann Intern Med 1979; 91:17.
  19. Kuypers DR, Claes K, Evenepoel P, et al. A prospective proof of concept study of the efficacy of tacrolimus ointment on uraemic pruritus (UP) in patients on chronic dialysis therapy. Nephrol Dial Transplant 2004; 19:1895.
  20. Fallahzadeh MK, Roozbeh J, Geramizadeh B, Namazi MR. Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications. Nephrol Dial Transplant 2011; 26:3338.
  21. Virga G, Visentin I, La Milia V, Bonadonna A. Inflammation and pruritus in haemodialysis patients. Nephrol Dial Transplant 2002; 17:2164.
  22. Yosipovitch G, Greaves MW, Schmelz M. Itch. Lancet 2003; 361:690.
  23. Umeuchi H, Togashi Y, Honda T, et al. Involvement of central mu-opioid system in the scratching behavior in mice, and the suppression of it by the activation of kappa-opioid system. Eur J Pharmacol 2003; 477:29.
  24. Ikoma A, Steinhoff M, Ständer S, et al. The neurobiology of itch. Nat Rev Neurosci 2006; 7:535.
  25. Kumagai H, Saruta T, Matsukawa S, et al. Prospects for a novel kappa-opioid receptor agonist, TRK-820 in uremic pruritus. In: Itch, Basic Mechanisms and Therapy, Yosipovitch G, Greaves MW, Fleischer JA, McGlone F (Eds), Dekker, New York 2004. p.286.
  26. Andrew D, Craig AD. Spinothalamic lamina I neurons selectively sensitive to histamine: a central neural pathway for itch. Nat Neurosci 2001; 4:72.
  27. Hori T, Oka T, Hosoi M, Aou S. Pain modulatory actions of cytokines and prostaglandin E2 in the brain. Ann N Y Acad Sci 1998; 840:269.
  28. Hiroshige K, Kabashima N, Takasugi M, Kuroiwa A. Optimal dialysis improves uremic pruritus. Am J Kidney Dis 1995; 25:413.
  29. Masi CM, Cohen EP. Dialysis efficacy and itching in renal failure. Nephron 1992; 62:257.
  30. Massry SG, Popovtzer MM, Coburn JW, et al. Intractable pruritus as a manifestation of secondary hyperparathyroidism in uremia. Disappearance of itching after subtotal parathyroidectomy. N Engl J Med 1968; 279:697.
  31. Chou FF, Ho JC, Huang SC, Sheen-Chen SM. A study on pruritus after parathyroidectomy for secondary hyperparathyroidism. J Am Coll Surg 2000; 190:65.
  32. Blachley JD, Blankenship DM, Menter A, et al. Uremic pruritus: skin divalent ion content and response to ultraviolet phototherapy. Am J Kidney Dis 1985; 5:237.
  33. 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.
  34. Rosenthal SR. Uremic dermatitis. Arch Dermatol Syphil 1931; 23:934.
  35. CAWLEY EP, HOCH-LIGHETI C, BOND GM. The eccrine sweat glands of patients in uremia. Arch Dermatol 1961; 84:889.
  36. Friga V, Linos A, Linos DA. Is aluminum toxicity responsible for uremic pruritus in chronic hemodialysis patients? Nephron 1997; 75:48.
  37. Navarro-González JF, Mora-Fernández C, García-Pérez J. Clinical implications of disordered magnesium homeostasis in chronic renal failure and dialysis. Semin Dial 2009; 22:37.
  38. Carmichael AJ, McHugh MM, Martin AM, Farrow M. Serological markers of renal itch in patients receiving long term haemodialysis. Br Med J (Clin Res Ed) 1988; 296:1575.
  39. 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.
  40. Berne B, Vahlquist A, Fischer T, et al. UV treatment of uraemic pruritus reduces the vitamin A content of the skin. Eur J Clin Invest 1984; 14:203.
  41. Charlesworth EN, Beltrani VS. Pruritic dermatoses: overview of etiology and therapy. Am J Med 2002; 113 Suppl 9A:25S.
  42. Mistik S, Utas S, Ferahbas A, et al. An epidemiology study of patients with uremic pruritus. J Eur Acad Dermatol Venereol 2006; 20:672.
  43. Young AW Jr, Sweeney EW, David DS, et al. Dermatologic evaluation of pruritus in patients on hemodialysis. N Y State J Med 1973; 73:2670.
  44. Yosipovitch G, Zucker I, Boner G, et al. A questionnaire for the assessment of pruritus: validation in uremic patients. Acta Derm Venereol 2001; 81:108.
  45. 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.
  46. Papa CM. Winter itch, dry skin. J Med Soc N J 1980; 77:817.
  47. Liakopoulos V, Krishnan M, Stefanidis I, et al. Improvement in uremic symptoms after increasing daily dialysate volume in patients on chronic peritoneal dialysis with declining renal function. Int Urol Nephrol 2004; 36:437.
  48. Ko MJ, Wu HY, Chen HY, et al. Uremic pruritus, dialysis adequacy, and metabolic profiles in hemodialysis patients: a prospective 5-year cohort study. PLoS One 2013; 8:e71404.
  49. Lin HH, Liu YL, Liu JH, et al. Uremic pruritus, cytokines, and polymethylmethacrylate artificial kidney. Artif Organs 2008; 32:468.
  50. Kato A, Takita T, Furuhashi M, et al. Polymethylmethacrylate efficacy in reduction of renal itching in hemodialysis patients: crossover study and role of tumor necrosis factor-alpha. Artif Organs 2001; 25:441.
  51. Aucella F, Vigilante M, Gesuete A, et al. Uraemic itching: do polymethylmethacrylate dialysis membranes play a role? Nephrol Dial Transplant 2007; 22 Suppl 5:v8.
  52. Carmichael AJ, Dickinson F, McHugh MI, et al. Magnesium free dialysis for uraemic pruritus. BMJ 1988; 297:1584.
  53. Morton CA, Lafferty M, Hau C, et al. Pruritus and skin hydration during dialysis. Nephrol Dial Transplant 1996; 11:2031.
  54. 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.
  55. Balaskas E, Szepietowski JC, Bessis D, et al. Randomized, double-blind study with glycerol and paraffin in uremic xerosis. Clin J Am Soc Nephrol 2011; 6:748.
  56. Young TA, Patel TS, Camacho F, et al. A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients. J Dermatolog Treat 2009; 20:76.
  57. Tarng DC, Cho YL, Liu HN, Huang TP. Hemodialysis-related pruritus: a double-blind, placebo-controlled, crossover study of capsaicin 0.025% cream. Nephron 1996; 72:617.
  58. Breneman DL, Cardone JS, Blumsack RF, et al. Topical capsaicin for treatment of hemodialysis-related pruritus. J Am Acad Dermatol 1992; 26:91.
  59. Cho YL, Liu HN, Huang TP, Tarng DC. Uremic pruritus: roles of parathyroid hormone and substance P. J Am Acad Dermatol 1997; 36:538.
  60. Gooding SM, Canter PH, Coelho HF, et al. Systematic review of topical capsaicin in the treatment of pruritus. Int J Dermatol 2010; 49:858.
  61. Rosner MH. Cromolyn sodium: a potential therapy for uremic pruritus? Hemodial Int 2006; 10:189.
  62. Feily A, Dormanesh B, Ghorbani AR, et al. Efficacy of topical cromolyn sodium 4% on pruritus in uremic nephrogenic patients: a randomized double-blind study in 60 patients. Int J Clin Pharmacol Ther 2012; 50:510.
  63. Pauli-Magnus C, Klumpp S, Alscher DM, et al. Short-term efficacy of tacrolimus ointment in severe uremic pruritus. Perit Dial Int 2000; 20:802.
  64. Duque MI, Yosipovitch G, Fleischer AB Jr, 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.
  65. www,fda.gov/medwatch/SAFETY/2005/safety05.htm#Elidel (Accessed on April 15, 2011).
  66. 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)]. Minerva Urol Nefrol 1986; 38:443.
  67. 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.
  68. 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.
  69. 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.
  70. Amirkhanlou S, Rashedi A, Taherian J, et al. Comparison of Gabapentin and Ketotifen in Treatment of Uremic Pruritus in Hemodialysis Patients. Pak J Med Sci 2016; 32:22.
  71. Nofal E, Farag F, Nofal A, et al. Gabapentin: A promising therapy for uremic pruritus in hemodialysis patients: A randomized-controlled trial and review of literature. J Dermatolog Treat 2016; :1.
  72. Shavit L, Grenader T, Lifschitz M, Slotki I. Use of pregabalin in the management of chronic uremic pruritus. J Pain Symptom Manage 2013; 45:776.
  73. Aperis G, Paliouras C, Zervos A, et al. The use of pregabalin in the treatment of uraemic pruritus in haemodialysis patients. J Ren Care 2010; 36:180.
  74. Yue J, Jiao S, Xiao Y, et al. Comparison of pregabalin with ondansetron in treatment of uraemic pruritus in dialysis patients: a prospective, randomized, double-blind study. Int Urol Nephrol 2015; 47:161.
  75. Foroutan N, Etminan A, Nikvarz N, Shojai Shahrokh Abadi M. Comparison of pregabalin with doxepin in the management of uremic pruritus: a randomized single blind clinical trial. Hemodial Int 2016.
  76. Solak Y, Biyik Z, Atalay H, et al. Pregabalin versus gabapentin in the treatment of neuropathic pruritus in maintenance haemodialysis patients: a prospective, crossover study. Nephrology (Carlton) 2012; 17:710.
  77. Rayner H, Baharani J, Smith S, et al. Uraemic pruritus: relief of itching by gabapentin and pregabalin. Nephron Clin Pract 2012; 122:75.
  78. Shakiba M, Sanadgol H, Azmoude HR, et al. Effect of sertraline on uremic pruritus improvement in ESRD patients. Int J Nephrol 2012; 2012:363901.
  79. Chan KY, Li CW, Wong H, et al. Use of sertraline for antihistamine-refractory uremic pruritus in renal palliative care patients. J Palliat Med 2013; 16:966.
  80. Altmeyer P, Kachel HG, Schäfer G, Fassbinder W. [Normalization of uremic skin changes following kidney transplantation]. Hautarzt 1986; 37:217.
  81. Szepietowski JC, Schwartz RA. Uremic pruritus. Int J Dermatol 1998; 37:247.
  82. Ada S, Seçkin D, Budakoğlu I, Ozdemir FN. Treatment of uremic pruritus with narrowband ultraviolet B phototherapy: an open pilot study. J Am Acad Dermatol 2005; 53:149.
  83. Szepietowski JC, Morita A, Tsuji T. Ultraviolet B induces mast cell apoptosis: a hypothetical mechanism of ultraviolet B treatment for uraemic pruritus. Med Hypotheses 2002; 58:167.
  84. Bernstein JE, Swift R. Relief of intractable pruritus with naloxone. Arch Dermatol 1979; 115:1366.
  85. Andersen LW, Friedberg M, Lokkegaard N. Naloxone in the treatment of uremic pruritus: a case history. Clin Nephrol 1984; 21:355.
  86. Peer G, Kivity S, Agami O, et al. Randomised crossover trial of naltrexone in uraemic pruritus. Lancet 1996; 348:1552.
  87. Legroux-Crespel E, Clèdes J, Misery L. A comparative study on the effects of naltrexone and loratadine on uremic pruritus. Dermatology 2004; 208:326.
  88. Dawn AG, Yosipovitch G. Butorphanol for treatment of intractable pruritus. J Am Acad Dermatol 2006; 54:527.
  89. Hawi A, Alcorn H Jr, Berg J, et al. Pharmacokinetics of nalbuphine hydrochloride extended release tablets in hemodialysis patients with exploratory effect on pruritus. BMC Nephrol 2015; 16:47.
  90. Study of nalbuphine HCl ER tables in hemodialysis patients with uremic pruritus. Last updated March 21, 2016. https://clinicaltrials.gov/ct2/show/NCT02143648 (Accessed on September 12, 2016).
  91. Yoshimoto-Furuie K, Yoshimoto K, Tanaka T, et al. Effects of oral supplementation with evening primrose oil for six weeks on plasma essential fatty acids and uremic skin symptoms in hemodialysis patients. Nephron 1999; 81:151.
  92. Ghanei E, Zeinali J, Borghei M, Homayouni M. Efficacy of omega-3 fatty acids supplementation in treatment of uremic pruritus in hemodialysis patients: a double-blind randomized controlled trial. Iran Red Crescent Med J 2012; 14:515.
  93. Pakfetrat M, Basiri F, Malekmakan L, Roozbeh J. Effects of turmeric on uremic pruritus in end stage renal disease patients: a double-blind randomized clinical trial. J Nephrol 2014; 27:203.
  94. Najafabadi MM, Faghihi G, Emami A, et al. Zinc sulfate for relief of pruritus in patients on maintenance hemodialysis. Ther Apher Dial 2012; 16:142.
  95. Pederson JA, Matter BJ, Czerwinski AW, Llach F. Relief of idiopathic generalized pruritus in dialysis patients treated with activated oral charcoal. Ann Intern Med 1980; 93:446.
  96. Giovannetti S, Barsotti G, Cupisti A, et al. Oral activated charcoal in patients with uremic pruritus. Nephron 1995; 70:193.
  97. Layegh P, Mojahedi MJ, Malekshah PE, et al. Effect of oral granisetron in uremic pruritus. Indian J Dermatol Venereol Leprol 2007; 73:231.
  98. Vessal G, Sagheb MM, Shilian S, et al. Effect of oral cromolyn sodium on CKD-associated pruritus and serum tryptase level: a double-blind placebo-controlled study. Nephrol Dial Transplant 2010; 25:1541.
  99. Silverberg DS, Iaina A, Reisin E, et al. Cholestyramine in uraemic pruritus. Br Med J 1977; 1:752.
  100. 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.
  101. Francos GC, Kauh YC, Gittlen SD, et al. Elevated plasma histamine in chronic uremia. Effects of ketotifen on pruritus. Int J Dermatol 1991; 30:884.
  102. Chen YC, Chiu WT, Wu MS. Therapeutic effect of topical gamma-linolenic acid on refractory uremic pruritus. Am J Kidney Dis 2006; 48:69.
  103. Aramwit P, Keongamaroon O, Siritientong T, et al. Sericin cream reduces pruritus in hemodialysis patients: a randomized, double-blind, placebo-controlled experimental study. BMC Nephrol 2012; 13:119.
  104. Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat 2005; 13:97.
  105. Jung KE, Woo YR, Lee JS, et al. Effect of topical vitamin D on chronic kidney disease-associated pruritus: An open-label pilot study. J Dermatol 2015; 42:800.