Abstract

Xerosis and pruritus are the most common skin disorders in patients with chronic kidney diseases (CKD). The prevalence and intensity of those skin changes are higher in patients undergoing dialysis, independent of its type, compared to patients treated conservatively. However, they can occur even in the early stages of CKD and be very bothersome for the sufferers. The problem of dry skin in CKD patients, its characteristics, reasons and relationship between xerosis and pruritus have been described. The current views on the pathogenesis of chronic kidney disease-associated pruritus (CKD-P), formerly known as uremic pruritus, have been discussed. This article summarizes the available treatment options for CKD-P, including both topical and systemic therapies. The authors direct attention to the need for skin lesions treatment in order to prevent their progression and to improve the quality of patients’ life.

References

• 1. Ada S., Seçkin D., Budakoğlu I., Ozdemir F.N.: Treatment of uremic pruritus with narrowband ultraviolet B phototherapy: an open pilot study. J. Am. Acad. Dermatol., 2005; 53: 149-151
  Google Scholar
• 2. Akiyama T., Carstens M.I., Carstens E.: Enhanced scratching evoked by PAR-2 agonist and 5-HT but not histamine in a mouse model of chronic dry skin itch. Pain, 2010; 151: 378-383
  Google Scholar
• 3. Amatya B., Agrawal S., Dhali T., Sharma S., Pandey S.S.: Pattern of skin and nail changes in chronic renal failure in Nepal: a hospital-based study. J. Dermatol., 2008; 35: 140-145
  Google Scholar
• 4. Anderson C.K.: Asteatotic egzema. E. Med. J., 2002; 538
  Google Scholar
• 5. Aperis G., Paliouras C., Zervos A., Arvanitis A., Alivanis P..: The use of pregabalin in the treatment of uraemic pruritus in haemodialysis patients. J. Ren. Care, 2010; 36: 180-185
  Google Scholar
• 6. Attia E.A., Hassan S.I., Youssef N.M.: Cutaneous disorders in uremic patients on hemodialysis: an Egyptian case-controlled study. Int. J. Dermatol., 2010; 49: 1024-1030
  Google Scholar
• 7. Balaskas E.V., Bamihas G., Karamouzis M., Voyiatzis G., Tourkantonis A.: Histamine and serotonin in uremic pruritus: effect of ondansetron in CAPD-pruritic patients. Nephron, 1998; 78: 395-402
  Google Scholar
• 8. Balaskas E., Chu M., Uldall R.P., Gupta A., Oreopoulos D.G.: Pruritus in continuous ambulatory peritoneal dialysis and hemodialysis patients. Perit. Dial. Int., 1993; 13 (Suppl. 2): S527-S532
  Google Scholar
• 9. Berger T.G., Steinhoff M.: Pruritus and renal failure. Semin. Cutan. Med. Surg., 2011; 30: 99-100
  Google Scholar
• 10. Biró T., Ko M.C., Bromm B., Wei E.T., Bigliardi P., Siebenhaar F., Hashizume H., Misery L., Bergasa N.V., Kamei C., Schouenborg J., Roostermann D., Szabó T., Maurer M., Bigliardi-Qi M. i wsp.: How best to fight that nasty itch – from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches. Exp. Dermatol., 2005; 14: 225-240
  Google Scholar
• 11. Carmichael A.J., Dickinson F., McHugh M.I., Martin A.M., Farrow M.: Magnesium free dialysis for uraemic pruritus. BMJ, 1988; 297: 1584-1585
  Google Scholar
• 12. Carmichael A.J., McHugh M.I., Martin A.M.: Renal itch as an indicator of poor outcome. Lancet, 1991; 337: 1225-1226
  Google Scholar
• 13. Carmichael A.J., McHugh M.I., Martin A.M.: Itch unrelated to adequacy of haemodialysis. Br. J. Dermatol., 1992; 126: 95
  Google Scholar
• 14. Carmichael A.J., McHugh M.M., Martin A.M., Farrow M.: Serological markers of renal itch in patients receiving long term haemodialysis. Br. Med. J., 1988; 296: 1575
  Google Scholar
• 15. Chen Y.C., Chiu W.T., Wu M.S.: Therapeutic effect of topical gamma-linolenic acid on refractory uremic pruritus. Am. J. Kidney Dis., 2006; 48: 69-76
  Google Scholar
• 16. Cho Y.L., Liu H.N., Huang T.P., Tarng D.C.: Uremic pruritus: Roles of parathyroid hormone and substance P. J. Am. Acad. Dermatol., 1997; 36: 538-543
  Google Scholar
• 17. Dar N.R., Akhter A.: Clinical characteristics of uremic pruritus in patients undergoing haemodialysis. J. Coll. Physicians Surg. Pak., 2006; 16: 94-96
  Google Scholar
• 18. Dugas-Breit S., Schöpf P., Dugas M., Schiffl H., Ruëff F., Przybilla B.: Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus. J. Dtsch. Dermatol. Ges., 2005; 3: 343-347
  Google Scholar
• 19. Duque M.I., Yosipovitch G., Fleischer A.B. Jr., Willard J., Freedman B.I.: 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: 519-521
  Google Scholar
• 20. Dyachenko P., Shustak A., Rozenman D.: Hemodialysis-related pruritus and associated cutaneous manifestations. Int. J. Dermatol., 2006; 45: 664-667
  Google Scholar
• 21. Feramisco J.D., Berger T.G., Steinhoff M.: Innovative management of pruritus. Dermatol. Clin., 2010; 28: 467-478
  Google Scholar
• 22. Gilchrest B.A., Rowe J.W., Mihm M.C. Jr.: Clinical and histological skin changes in chronic renal failure: evidence for a dialysis-resistant, transplant-responsive microangiopathy. Lancet, 1980; 2: 1271-1275
  Google Scholar
• 23. Goicoechea M., de Sequera P., Ochando A., Andrea C., Caramelo C.: Uremic pruritus: an unresolved problem in hemodialysis patients. Nephron, 1999; 82: 73-74
  Google Scholar
• 24. Graf H., Kovarik J., Stummvoll H.K., Wolf A.: Disappearance of uraemic pruritus after lowering dialysate magnesium concentration. Br. Med. J., 1979; 2: 1478-1479
  Google Scholar
• 25. Gunal A.I., Ozalp G., Yoldas T.K., Gunal S.Y., Kirciman E., Celiker H.: Gabapentin therapy for pruritus in haemodialysis patients: a randomized, placebo-controlled, double-blind trial. Nephrol. Dial. Transplant., 2004; 19: 3137-3139
  Google Scholar
• 26. Gupta A.K., Gupta M.A., Cardella C.J., Haberman H.F.: Cutaneous associations of chronic renal failure and dialysis. Int. J. Dermatol., 1986; 25: 498-504
  Google Scholar
• 27. Heisig M., Reich A., Szepietowski J.C.: Is uremic pruritus still an important clinical problem in maintenance hemodialysis patients? J. Eur. Acad. Dermatol. Venereol., 2016; 30: e198-e199
  Google Scholar
• 28. Hiroshige K., Kabashima N., Takasugi M., Kuroiwa A.: Optimal dialysis improves uremic pruritus. Am. J. Kidney Dis., 1995; 25: 413- 419
  Google Scholar
• 29. Hsu M.M., Yang C.C.: Uraemic pruritus responsive to broadband ultraviolet (UV) B therapy does not readily respond to narrowband UVB therapy. Br. J. Derm., 2003; 149: 888-889
  Google Scholar
• 30. Jamal A., Subramanian P.T.: Pruritus among end-stage renal failure patients on hemodialysis. Saudi J. Kidney Dis. Transpl., 2000; 11: 181-185
  Google Scholar
• 31. K/DOQI Clinical Practice Guidelines for Chronic Kidney Disease: Evaluation, classification and stratification. Am. J. Kidney Dis., 2002; 39 (Suppl. 1): S1-S266
  Google Scholar
• 32. Kato A., Hamada M., Maruyama T., Maruyama Y., Hishida A.: Pruritus and hydration state of stratum corneum in hemodialysis patients. Am. J. Nephrol., 2000; 20: 437-442
  Google Scholar
• 33. Kerr P.G., Argiles A., Mion C.: Whole blood serotonin levels are markedly elevated in patients on dialytic therapy. Am. J. Nephrol., 1992; 12: 14-18
  Google Scholar
• 34. Khanna D., Singal A., Kalra O.P.: Comparison of cutaneous manifestations in chronic kidney disease with or without dialysis. Postgrad. Med. J., 2010; 86: 641-647
  Google Scholar
• 35. Klein L.R., Klein J.B., Hanno R., Callen J.P.: Cutaneous mast cell quantity in pruritic and nonpruritic hemodialysis patients. Int. J. Dermatol., 1988; 27: 557-559
  Google Scholar
• 36. Kolla P.K., Desai M., Pathapati R.M., Mastan Valli B., Pentyala S., Madhusudhan Reddy G., Vijaya Mohan Rao A.: Cutaneous manifestations in patients with chronic kidney disease on maintenance hemodialysis. ISRN Dermatol., 2012; 2012: 679619
  Google Scholar
• 37. Kumagai H., Ebata T., Takamori K., Muramatsu T., Nakamoto H., Suzuki H.: Effect of a novel kappa-receptor agonist, nalfurafine hydrochloride, on severe itch in 337 haemodialysis patients: A phase III, randomized, double-blind, placebo-controlled study. Nephrol. Dial. Transplant., 2010; 25: 1251-1257
  Google Scholar
• 38. Matsumoto M., Ichimaru K., Horie A.: Pruritus and mast cell proliferation of the skin in end stage renal failure. Clin. Nephrol., 1985; 23: 285-288
  Google Scholar
• 39. Merkus M.P., Jager K.J., Dekker F.W., de Haan R.J., Boeschoten E.W., Krediet R.T.: Physical symptoms and quality of life in patients on chronic dialysis: results of The Netherlands Cooperative Study on Adequacy of Dialysis (NECOSAD). Nephrol. Dial. Transplant., 1999; 14: 1163-1170
  Google Scholar
• 40. Mettang M., Weisshaar E.: Pruritus: control of itch in patients undergoing dialysis. Skin Therapy Lett., 2010; 15: 1-5
  Google Scholar
• 41. Mettang T., Kremer A.E.: Uremic pruritus. Kidney Int., 2015; 87: 685-691
  Google Scholar
• 42. Mistik S., Utas S., Ferahbas A., Tokgoz B., Unsal G., Sahan H., Ozturk A., Utas C.: An epidemiology study of patients with uremic pruritus. J. Eur. Acad. Dermatol. Venereol., 2006; 20: 672-678
  Google Scholar
• 43. Momose A., Kudo S., Sato M., Saito H., Nagai K., Katabira Y., Funyu T.: Calcium ions are abnormally distributed in the skin of hemodialysis patients with uraemic pruritus. Nephrol. Dial. Transplant., 2004; 19: 2061-2066
  Google Scholar
• 44. Morton C.A., Lafferty M., Hau C., Henderson I., Jones M., Lowe J.G.: Pruritus and skin hydration during dialysis. Nephrol. Dial. Transplant., 1996; 11: 2031-2036
  Google Scholar
• 45. Myśliwiec H., Flisiak I., Myśliwiec P., Myśliwiec P., Myśliwiec M., Chodynicka B.: Obraz kliniczny świądu mocznicowego u chorych dializowanych. Dermatol. Klin., 2007; 9: 213-216
  Google Scholar
• 46. Myśliwiec H., Pawlak D.A., Flisiak I., Myśliwiec P., Myśliwiec M., Chodynicka B.: Wybrane metabolity kinureniny a świąd mocznicowy. Przegl. Dermatol., 2008; 95: 33-36
  Google Scholar
• 47. Naini A.E., Harandi A.A., Khanbabapour S., Shahidi S., Seirafiyan S., Mohseni M.: Gabapentin: a promising drug for the treatment of uremic pruritus. Saudi J. Kidney Dis. Transpl., 2007; 18: 378-381
  Google Scholar
• 48. Narita I., Alchi B., Omori K., Sato F., Ajiro J., Saga D., Kondo D., Skatsume M., Maruyama S., Kazama J.J., Akazawa K., Gejyo F.: Etiology and prognostic significance of severe uremic pruritus in chronic hemodialysis patients. Kidney Int., 2006; 69: 1626-1632
  Google Scholar
• 49. Onelmis H., Sener S., Sasmaz S., Ozer A.: Cutaneous changes in patients with chronic renal failure on hemodialysis. Cutan. Ocul. Toxicol., 2012; 31: 286-291
  Google Scholar
• 50. Ostlere L.S., Taylor C., Baillod R., Wright S.: Relationship between pruritus, transepidermal water loss, and biochemical markers of renal itch in haemodialysis patients. Nephrol. Dial. Transplant., 1994; 9: 1302-1304
  Google Scholar
• 51. Patel T.S., Freedman B.I., Yosipovitch G.: An update on pruritus associated with CKD. Am. J. Kidney Dis., 2007; 50: 11-20
  Google Scholar
• 52. Paus R., Schmelz M., Biró T., Steinhoff M.: Frontiers in pruritus research: scratching the brain for more effective itch therapy. J. Clin. Invest., 2006; 116: 1174-1186
  Google Scholar
• 53. Phan N.Q., Blome C., Fritz F., Gerss J., Reich A., Ebata T., Augustin M., Szepietowski J.C., Ständer S.: Assessment of pruritus intensity: prospective study on validity and reliability of the visual analogue scale, numerical rating scale and verbal rating scale in 471 patients with chronic pruritus. Acta Derm. Venereol., 2012; 92: 502-507
  Google Scholar
• 54. Pisoni R.L., Wikström B., Elder S.J., Akizawa T., Asano Y., Keen M.L., Saran R., Mendelssohn D.C., Young E.W., Port F.K.: Pruritus in haemodialysis patients: international results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrol. Dial. Transplant., 2006; 21: 3495–3505
  Google Scholar
• 55. Ponticelli C., Bencini P.L.: Uremic pruritus: a review. Nephron, 1992; 60: 1-5
  Google Scholar
• 56. Rayner H., Baharani J., Smith S., Suresh V., Dasgupta I.: Uraemic pruritus: relief of itching by gabapentin and pregabalin. Nephron Clin. Pract., 2012; 122: 75-79
  Google Scholar
• 57. Reich A., Heisig M., Phan N.Q., Taneda K., Takamori K., Takeuchi S., Furue M., Blome C., Augustin M., Ständer S., Szepietowski J.C.: Visual analogue scale: evaluation of the instrument for the assessment of pruritus. Acta Derm. Venereol., 2012; 92: 497-501
  Google Scholar
• 58. Reich A., Mędrek K., Szepietowski J.C.: Four-item itch questionnaire – validation of questionnaire. Przegl. Dermatol., 2012; 99: 600-604
  Google Scholar
• 59. Reich A., Szepietowski J.C.: Diagnostic procedures of itch. Curr. Probl. Dermatol., 2016; 50: 24-28
  Google Scholar
• 60. Sanada S., Kuze M., Yoshida O.: Beneficial effect of zinc supplementation on pruritus in hemodialysis patients with special reference to changes in serum histamine levels. Hinyokika Kiyo, 1987; 33: 1955-1960
  Google Scholar
• 61. Scherer J.S., Combs S.A., Brennan F.: Sleep disorders, restless legs syndrome, and uremic pruritus: diagnosis and treatment of common symptoms in dialysis patients. Am. J. Kidney Dis., 2017; 69: 117-128
  Google Scholar
• 62. Scholzen T., Armstrong C.A., Bunnett N.W., Luger T.A., Olerud J.E., Ansel J.C.: Neuropeptides in the skin: interactions between the neuroendocrine and the skin immune systems. Exp. Dermatol., 1998; 7: 81-96
  Google Scholar
• 63. Senturk N., Ozkaya O., Aytekin S., Bek K, Açikgöz Y., Aydin F., Bek Y., Turanli A.Y.: Characteristics of pruritus in children on peritoneal dialysis. Nephron Clin. Pract., 2008; 109: c168-c172
  Google Scholar
• 64. Shakiba M., Sanadgol H., Azmoude H.R., Mashhadi M.A., Sharifi H.: Effect of sertraline on uremic pruritus improvement in ESRD patients. Int. J. Nephrol., 2012; 2012: 363901
  Google Scholar
• 65. Stahle-Bäckdahl M.: Uremic pruritus. Clinical and experimental studies. Acta Derm. Venereol. Suppl., 1989; 145: 1-38
  Google Scholar
• 66. Ständer S., Böckenholt B., Schürmeyer-Horst F., Weishaupt C., Heuft G., Luger T.A., Schneider G.: Treatment of chronic pruritus with the selective serotonin re-uptake inhibitors paroxetine and fluvoxamine: results of an open-labelled, two-arm proof-of-concept study. Acta Derm. Venereol., 2009; 89: 45-51
  Google Scholar
• 67. Subach RA., Marx M.A.: Evaluation of uremic pruritus at an outpatient hemodialysis unit. Ren. Fail., 2002; 24: 609-614
  Google Scholar
• 68. Suseł J., Batycka-Baran A., Reich A., Szepietowski J.C.: Uraemic pruritus markedly affects the quality of life and depressive symptoms in haemodialysis patients with end-stage renal disease. Acta Derm. Venereol., 2014; 94: 276-281
  Google Scholar
• 69. Suthanthiran M., Strom T.B.: Renal transplantation. N. Engl. J. Med., 1994; 331: 365-376
  Google Scholar
• 70. Szepietowski J.: Selected elements of the pathogenesis of pruritus in haemodialysis patients. Med. Sci. Monit., 1996; 2: HY343-HY347
  Google Scholar
• 71. Szepietowski J., Reich A.: Świąd. Patomechanizm, klinika, leczenie. Termedia Wydawnictwa Medyczne, Poznań, 2010
  Google Scholar
• 72. Szepietowski J.C., Reich A., Schwartz R.: Uraemic xerosis. Nephrol. Dial. Transplant., 2004, 19: 2709-2712
  Google Scholar
• 73. Szepietowski J., Sikora M., Kusztal M., Salomon J., Magott M., Szepietowski T.: Uremic pruritus: a clinical study of maintenance hemodialysis patients. J. Dermatol., 2002; 29: 621-627
  Google Scholar
• 74. Tapia L.: Pruritus on hemodialysis. Int. J. Dermatol., 1979; 18: 217-218
  Google Scholar
• 75. Thomas E.A., Pawar B., Thomas A.: A prospective study of cutaneous abnormalities in patients with chronic kidney disease. Indian J. Nephrol., 2012; 22: 116-120
  Google Scholar
• 76. Udayakumar P., Balasubramanian S., Ramalingam K.S., Lakshmi C., Srinivas C.R., Mathew A.C.: Cutaneous manifestations in patients with chronic renal failure on hemodialysis. Indian J. Dermatol. Venereol. Leprol., 2006; 72: 119-125
  Google Scholar
• 77. Virga G., Visentin I., La Milia V., Bonadonna A.: Inflammation and pruritus in hemodialysis patients. Nephrol. Dial. Transplant., 2002; 17: 2164-2169
  Google Scholar
• 78. Weiss M., Mettang T., Tschulena U., Passlick-Deetjen J., Weisshaar E.: Prevalence of chronic itch and associated factors in haemodialysis patients: a representative cross-sectional study. Acta Derm. Venereol., 2015; 95: 816-821
  Google Scholar
• 79. Weisshaar E., Dalgard F.: Epidemiology of itch: adding to the burden of skin morbidity. Acta Derm. Venereol., 2009; 89: 339-350
  Google Scholar
• 80. Wikström B.: Itchy skin – a clinical problem for haemodialysis patients. Nephrol. Dial. Transplant., 2007; 22 (Suppl. 5): v3-v7
  Google Scholar
• 81. Wikström B., Gellert R., Ladefoged S.D., Danda Y., Akai M., Ide K., Ogasawara M., Kawashima Y., Ueno K., Mori A., Ueno Y.: κ-opioid system in uremic pruritus: multicenter, randomized, double-blind, placebo-controlled clinical studies. J. Am. Soc. Nephrol., 2005; 16: 3742-3747
  Google Scholar
• 82. Wojnowska D., Chodorowska G., Juszkiewicz-Borowiec M.: Sucha skóra – patogeneza, klinika i leczenie. Post. Dermatol. Alergol., 2003; 20: 98-105
  Google Scholar
• 83. Wojtowicz-Prus E., Kiliś-Pstrusińska K., Reich A., Zachwieja K., Miklaszewska M., Szczepańska M., Szepietowski J.C.: Disturbed skin barrier in children with chronic kidney disease. Pediatr. Nephrol., 2015; 30: 333-338
  Google Scholar
• 84. Wojtowicz-Prus E., Kilis-Pstrusinska K., Reich A., Zachwieja K., Miklaszewska M., Szczepanska M., Szepietowski J.C.: Chronic kidney disease-associated pruritus in children. Acta. Derm. Venereol., 2016; 96: 938-942
  Google Scholar
• 85. Yosipovitch G.: Dry skin and impairment of barrier function associated with itch – new insights. Int. J. Cosmet. Sci., 2004; 26: 1-7
  Google Scholar
• 86. Yosipovitch G., Duque M.I., Patel T.S., Ishiuji Y., Guzman-Sanchez D.A., Dawn A.G., Freedman B.I., Chan Y.H, Crumrine D., Elias P.M.: Skin barrier structure and function and their relationship to pruritus in end-stage renal disease. Nephrol. Dial. Transplant., 2007; 22: 3268-3272
  Google Scholar
• 87. Yosipovitch G., Reis J., Tur E., Sprecher E., Yarnitsky D., Boner G.: Sweat secretion, stratum corneum hydration, small nerve function and pruritus in patients with advanced chronic renal failure. Br. J. Dermatol., 1995; 133: 561-564
  Google Scholar
• 88. Yosipovitch G., Tur E., Morduchowicz G., Boner G.: Skin surface pH, moisture, and pruritus in haemodialysis patients. Nephrol. Dial. Transplant., 1993; 8: 1129-1132
  Google Scholar
• 89. Young A.W.Jr., Sweeney E.W., David D.S., Cheigh J., Hochgelerenl E.L., Sakai S., Stenzel K.H., Rubin A.L.: Dermatologic evaluation of pruritus in patients on hemodialysis. N.Y. State J. Med., 1973; 73: 2670-2674
  Google Scholar
• 90. Zucker I., Yosipovitch G., David M., Gafter U., Boner G.: 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: 842-846
  Google Scholar

Full text