Recent Advances in Treatment for Uremic Pruritus


This review highlights recent advances in pathophysiology and treatment for uremic pruritus, especially focusing on various interventions. Pruritus in patients on hemodialysis (HD) and peritoneal dialysis (PD) still remains an unresolved issue. Recently, the efficacy and safety of nalfurafine hydrochloride have been reported in Japan, and at present, more than thirty thousand patients receive this new drug. In comparison with the efficacy of this new drug, acupuncture, a form of traditional Japanese therapy, has been validated for relief of symptoms of pruritus. In this review, various interventions for relief of symptoms of pruritus as well as recent studies on its pathophysiology will be introduced. This review will be helpful for treatment of pruritus in patients on dialyzed therapy in clinical practice.

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Suzuki, H. , Omata, H. and Kumagai, H. (2015) Recent Advances in Treatment for Uremic Pruritus. Open Journal of Nephrology, 5, 1-13. doi: 10.4236/ojneph.2015.51001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Stahle-Backdahl, M. (1989) Uremic Pruritus. Clinical and Experimental Studies. Acta Dermato-Venereologica. Supplementum, 145, 1-38.
[2] Stahle-Backdahl, M. (1992) Pruritus in Hemodialysis Patients. Skin Pharmacology and Physiology, 5, 14-20.
[3] Stahle-Backdahl, M. (1995) Uremic Pruritus. Seminars in Dermatology, 14, 297-301.
[4] Manenti, L., Tansinda, P. and Vaglio, A. (2009) Uraemic Pruritus: Clinical Characteristics, Pathophysiology and Treatment. Drugs, 69, 251-263.
[5] Yosipovitch, G., Greaves, M.W. and Schmelz, M. (2003) Itch. The Lancet, 361, 690-694.
[6] Lugon, J.R. (2005) Uremic Pruritus: A Review. Hemodialysis International, 9, 180-188.
[7] Kosmadakis, G.C. and Zerefos, N. (2006) Uremic Pruritus. The International Journal of Artificial Organs, 29, 938-943.
[8] Greaves, M.W. (2007) Recent Advances in Pathophysiology and Current Management of Itch. Annals Academy of Medicine Singapore, 36, 788-792.
[9] Patel, T.S., Freedman, B.I. and Yosipovitch, G. (2007) An Update on Pruritus Associated with CKD. American Journal of Kidney Diseases, 50, 11-20.
[10] Narita, I., Iguchi, S., Omori, K. and Gejyo, F. (2008) Uremic Pruritus in Chronic Hemodialysis Patients. Journal of Nephrology, 21, 161-165.
[11] Berger, T.G. and Steinhoff, M. (2011) Pruritus and Renal Failure. Seminars in Cutaneous Medicine and Surgery, 30, 99-100.
[12] Greaves, M.W. (2010) Pathogenesis and Treatment of Pruritus. Current Allergy and Asthma Reports, 10, 236-242.
[13] Kfoury, L.W. and Jurdi, M.A. (2012) Uremic Pruritus. Journal of Nephrology, 25, 644-652.
[14] Mettang, T. and Kremer, A.E. (2014) Uremic Pruritus. Kidney International. [Equib ahead of print]
[15] Pontremoli, R., Sofia, A., Ravera, M., Nicolella, C., Viazzi, F., Tirotta, A., et al. (1997) Prevalence and Clinical Correlates of Microalbuminuria in Essential Hypertension: The MAGIC Study. Hypertension, 30, 1135-1143.
[16] Narita, I., Alchi, B., Omori, K., Sato, F., Ajiro, J., Saga, D., et al. (2006) Etiology and Prognostic Significance of Severe Uremic Pruritus in Chronic Hemodialysis Patients. Kidney International, 69, 1626-1632.
[17] Pisoni, R.L., Wikstrom, B., Elder, S.J., Akizawa, T., Asano, Y., Keen, M.L., et al. (2006) Pruritus in Haemodialysis Patients: International Results from the Dialysis Outcomes and Practice Patterns Study (DOPPS). Nephrology Dialysis Transplantation, 21, 3495-3505.
[18] Gilchrest, B.A., Stern, R.S., Steinman, T.I., Brown, R.S., Arndt, K.A. and Anderson, W.W. (1982) Clinical Features of Pruritus among Patients Undergoing Maintenance Hemodialysis. JAMA Dermatology, 118, 154-156.
[19] Dar, N.R. and Akhter, A. (2006) Clinical Characteristics of Uremic Pruritus in Patients Undergoing Haemodialysis. Journal of the College of Physicians and Surgeons-Pakistan, 16, 94-96.
[20] Tominaga, M. and Takamori, K. (2014) Sensitization of Itch Signaling: Itch Sensitization—Nerve Growth Factor, Semaphorins.
[21] Kumagai, H., Matsukawa, S., Sasamura, H., Hayashi, M. and Saruta, T. (2004) Prospects for a Novel κ-Opioid Receptor Agonist, TRK-820, in Uremic Pruritus. In: Yoshipovitch, G., Ed., Itch Basic Mechanisms and Therapy, Marcel Dekker, New York, 279-286.
[22] Walter, B., Sadlo, M.N., Kupfer, J., Niemeier, V., Brosig, B., Stark, R., Vaitl, D. and Gieler, U. (2005) Brain Activation by Histamine Prick Test-Induced Itch. Journal of Investigative Dermatology, 125, 380-382.
[23] Schmelz, M., Hilliges, M., Schmidt, R., Orstavik, K., Vahlquist, C., Weidner, C., et al. (2003) Active “Itch Fibers” in Chronic Pruritus. Neurology, 61, 564-566.
[24] Liakopoulos, V., Krishnan, M., Stefanidis, I., Savaj, S., Ghareeb, S., Musso, C., et al. (2004) Improvement in Uremic Symptoms after Increasing Daily Dialysate Volume in Patients on Chronic Peritoneal Dialysis with Declining Renal Function. International Urology and Nephrology, 36, 437-443.
[25] Szepietowski, J.C., Reich, A. and Szepietowski, T. (2005) Emollients with Endocannabinoids in the Treatment of Uremic Pruritus: Discussion of the Therapeutic Options. Therapeutic Apheresis and Dialysis, 9, 277-279.
[26] Novak, M.J., Sheth, H., Bender, F.H., Fried, L. and Piraino, B. (2008) Improvement in Pittsburgh Symptom Score Index after Initiation of Peritoneal Dialysis. Advances in Peritoneal Dialysis, 24, 46-50.
[27] Hiroshige, K., Kabashima, N., Takasugi, M. and Kuroiwa, A. (1995) Optimal Dialysis Improves Uremic Pruritus. American Journal of Kidney Diseases, 25, 413-419.
[28] Graf, H., Kovarik, J., Stummvoll, H.K. and Wolf, A. (1979) Disappearance of Uraemic Pruritus after Lowering Dialysate Magnesium Concentration. British Medical Journal, 2, 1478-1479.
[29] Carmichael, A.J., Dickinson, F., McHugh, M.I., Martin, A.M. and Farrow, M. (1988) Magnesium Free Dialysis for Uraemic Pruritus. British Medical Journal, 297, 1584-1585.
[30] Kyriazis, J. and Glotsos, J. (2000) Dialysate Calcium Concentration of ≤1.25 mmol/l: Is It Effective in Suppressing Uremic Pruritus? Nephron, 84, 85-86.
[31] Kato, A., Takita, T., Furuhashi, M., Takahashi, T., Watanabe, T., Maruyama, Y. and Hishida, A. (2001) Polymethylmethacrylate Efficacy in Reduction of Renal Itching in Hemodialysis Patients: Crossover Study and Role of Tumor Necrosis Factor-Alpha. Artificial Organs, 25, 441-447.
[32] Morton, C.A., Lafferty, M., Hau, C., Henderson, I., Jones, M. and Lowe, J.G. (1996) Pruritus and Skin Hydration during Dialysis. Nephrology Dialysis Transplantation, 11, 2031-2036.
[33] Twycross, R., Greaves, M.W., Handwerker, H., Jones, E.A., Libretto, S.E., Szepietowski, J.C. and Zylicz, Z. (2003) Itch: Scratching More than the Surface. QJM: An International Journal of Medicine, 96, 7-26.
[34] Szepietowski, J.C., Szepietowski, T. and Reich, A. (2005) Efficacy and Tolerance of the Cream Containing Structured Physiological Lipids with Endocannabinoids in the Treatment of Uremic Pruritus: A Preliminary Study. Acta Dermatovenerologica Croatica, 13, 97-103.
[35] Okada, K. and Matsumoto, K. (2004) Effect of Skin Care with an Emollient Containing a High Water Content on Mild Uremic Pruritus. Therapeutic Apheresis and Dialysis, 8, 419-422.
[36] Itai, T., Amayasu, H., Kuribayashi, M., Kawamura, N., Okada, M., Momose, A., et al. (2000) Psychological Effects of Aromatherapy on Chronic Hemodialysis Patients. Psychiatry and Clinical Neurosciences, 54, 393-397.
[37] Dvorak, M., Watkinson, A., McGlone, F. and Rukwied, R. (2003) Histamine Induced Responses Are Attenuated by a Cannabinoid Receptor Agonist in Human Skin. Inflammation Research, 52, 238-245.
[38] Facci, L., Dal Toso, R., Romanello, S., Buriani, A., Skaper, S.D. and Leon, A. (1995) Mast Cells Express a Peripheral Cannabinoid Receptor with Differential Sensitivity to Anandamide and Palmitoylethanolamide. Proceedings of the National Academy of Sciences of the United States of America, 92, 3376-3380.
[39] Breneman, D.L., Cardone, J.S., Blumsack, R.F., Lather, R.M., Searle, E.A. and Pollack, V.E. (1992) Topical Capsaicin for Treatment of Hemodialysis-Related Pruritus. Journal of the American Academy of Dermatology, 26, 91-94.
[40] Tarng, D.C., Cho, Y.L., Liu, H.N. and Huang, T.P. (1996) Hemodialysis-Related Pruritus: A Double-Blind, Placebo-Controlled, Crossover Study of Capsaicin 0.025% Cream. Nephron, 72, 617-622.
[41] Weisshaar, E., Dunker, N. and Gollnick, H. (2003) Topical Capsaicin Therapy in Humans with Hemodialysis-Related Pruritus. Neuroscience Letters, 345, 192-194.
[42] Tamimi, N.A., Mikhail, A.I. and Stevens, P.E. (1999) Role of γ-Linolenic Acid in Uraemic Pruritus. Nephron, 83, 170-171.
[43] Chen, Y.C., Chiu, W.T. and Wu, M.S. (2006) Therapeutic Effect of Topical Gamma-Linolenic Acid on Refractory Uremic Pruritus. American Journal of Kidney Diseases, 48, 69-76.
[44] Miller, M.J.S., Vergnolle, N., McKnight, W., Musah, R.A., Davison, C.A., Trentacosti, A.M., et al. (2001) Inhibition of Neurogenic Inflammation by the Amazonian Herbal Medicine Sangre de Grado. Journal of Investigative Dermatology, 117, 725-730.
[45] Pauli-Magnus, C., Mikus, G., Alscher, D.M., Kirschner, T., Nagel, W., Gugeler, N., et al. (2000) Naltrexone Does Not Relieve Uremic Pruritus: Results of a Randomized, Double-Blind, Placebo-Controlled Crossover Study. Journal of the American Society of Nephrology, 11, 514-519.
[46] Duque, M.I., Thevarajah, S., Chan, Y.H., Tuttle, A.B., Freedman, B.I. and Yosipovitch, G. (2006) Uremic Pruritus Is Associated with Higher kt/V and Serum Calcium Concentration. Clinical Nephrology, 66, 184-191.
[47] Gilchrest, B.A., Rowe, J.W., Brown, R.S., Steinman, T.I. and Arndt, K.A. (1979) Ultraviolet Phototherapy of Uremic Pruritus: Long-Term Results and Possible Mechanism of Action. Annals of Internal Medicine, 91, 17-21.
[48] Shultz, B. and Roenigk, H. (1980) Uremic Pruritus Treated with Ultraviolet Light. Journal of American Medical Association, 243, 1836-1837.
[49] Imazu, L.E., Tachibana, T., Danno, K., Tanaka, M. and Imamura, S. (1993) Histamine-Releasing Factor(s) in Sera of Uraemic Pruritus Patients in a Possible Mechanism of UVB Therapy. Archives of Dermatological Research, 285, 423-427.
[50] Fjellner, B. and Hagermark, O. (1982) Influence of Ultraviolet Light on Itch and Flare Reactions in Human Skin Induced by Histamine and the Histamine Liberator Compound 48/80. Acta Dermato-Venereologica, 62, 137-140.
[51] Wallengren, J. and Sundler, F. (2004) Phototherapy Reduces the Number of Epidermal and CGRP-Positive Dermal Nerve Fibres. Acta Dermato-Venereologica, 84, 111-115.
[52] Blachley, J.D., Blankenship, D.M., Menter, A., Parker III, T.F. and Knochel, J.P. (1985) Uremic Pruritus: Skin Divalent Ion Content and Response to Ultraviolet Phototherapy. American Journal of Kidney Diseases, 5, 237-241.
[53] Kim, K.H., Lee, M.S., Choi, S.M. and Ernst, E. (2010) Acupuncture for Treating Uremic Pruritus in Patients with End-Stage Renal Disease: A Systematic Review. Journal of Pain and Symptom Management, 40, 117-125.
[54] Che-Yi, C., Wen, C.Y., Min-Tsung, K. and Chiu-Ching, H. (2005) Acupuncture in Haemodialysis Patients at the Quchi (LI11) Acupoint for Refractory Uraemic Pruritus. Nephrology Dialysis Transplantation, 20, 1912-1915.
[55] Gao, H., Zhang, W. and Wang, Y. (2002) Acupuncture Treatment for 34 Cases of Uremic Cutaneous Pruritus. Journal of Traditional Chinese Medicine, 22, 29-30.
[56] Sakuraba, H., Takeuchi, H., Takeuchi, M., Syoji, M. and Moriyama, T. (2007) Questionnaire Survey of Complaints and Accupuncutre Treatment in Maintenance Hemodialysis Patients. Nihon Toseki Igakkai Zasshi, 40, 513-516.
[57] Shapiro, R., Stockard, H. and Schank, A. (1986) Successful Treatment of Uremic Pruritus with Acupuncutre. American Journal of Acupuncture, 14, 235-242.
[58] Antoni, F. (1986) Hypothalamic Control of Adrenocorticotropin Secretion: Advances Since the Discovery of 41-Redue Corticotropin-Releasing Factor. Endocrine Reviews, 7, 351-378.
[59] Percival, S.L., Emanuel, C., Cutting, K.F. and Williams, D.W. (2012) Microbiology of the Skin and the Role of Biofilms in Infection. International Wound Journal, 9, 14-32.
[60] Tominaga, M. and Takamori, K. (2013) An Update on Peripheral Mechanisms and Treatments of Itch. Biological and Pharmaceutical Bulletin, 36, 1241-1247.
[61] Andersen, L.W., Friedberg, M. and Lokkegaard, N. (1984) Naloxone in the Treatment of Uremic Pruritus: A Case History. Clinical Nephrology, 21, 355-356.
[62] Peer, G., Kivity, S., Agami, O., Fireman, E., Silverberg, D., Blum, M. and Iaina, A. (1996) Randomised Crossover Trial of Naltrexone in Uraemic Pruritus. Lancet, 348, 1552-1554.
[63] Legroux-Crespel, E., Cledes, J. and Misery, L. (2004) A Comparative Study on the Effects of Naltrexone and Loratadine on Uremic Pruritus. Dermatology, 208, 326-330.
[64] Wikstrom, B., Gellert, R., Ladefoged, S.D., Danda, Y., Akai, M., Ide, K., et al. (2005) κ-Opioid System in Uremic Pruritus: Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Studies. Journal of the American Society of Nephrology, 16, 3742-3747.
[65] Seki, T., Awamura, S., Kimura, C., Ide, S., Sakano, K., Minami, M., et al. (1999) Pharmacological Properties of TRK-820 on Cloned μ-, δ-and κ-Opioid Receptors and Nociceptin Receptor. European Journal of Pharmacology, 376, 159-167.
[66] Nagase, H., Hayakawa, J., Kawamura, K., Kawai, K., Takezawa, Y., Matsuura, H., et al. (1998) Discovery of a Structurally Novel Opioid κ-Agonist Derived from 4,5-Epoxymorphinan. Chemical and Pharmaceutical Bulletin (Tokyo), 46, 366-369.
[67] Wakasa, Y., Fujiwara, A., Umeuchi, H., Endoh, T., Okano, K., Tanaka, T. and Nagase, H. (2004) Inhibitory Effects of TRK-820 on Systemic Skin Scratching Induced by Morphine in Rhesus Monkeys. Life Sciences, 75, 2947-2957.
[68] Togashi, Y., Umeuchi, H., Okano, K., Ando, N., Yoshizawa, Y., Honda, T., et al. (2002) Antipruritic Activity of the κ-Opioid Receptor Agonist, TRK-820. European Journal of Pharmacology, 435, 259-264.
[69] Kumagai, H., Ebata, T., Takamori, K., Muramatsu, T., Nakamoto, H. and Suzuki, H. (2010) Effect of a Novel κ-Receptor Agonist, Nalfurafine Hydrochloride, on Severe Itch in 337 Haemodialysis Patients: A Phase III, Randomized, Double-Blind, Placebo-Controlled Study. Nephrology Dialysis Transplantation, 25, 1251-1257.
[70] Wager, T.D., Rilling, J.K., Smith, E.E., Sokolik, A., Casey, K.L., Davidson, R.J., et al. (2004) Placebo-Induced Changes in FMRI in the Anticipation and Experience of Pain. Science, 303, 1162-1167.
[71] Kumagai, H., Ebata, T., Takamori, K., Miyasato, K., Muramatsu, T., Nakamoto, H., et al. (2012) Efficacy and Safety of a Novel κ-Agonist for Managing Intractable Pruritus in Dialysis Patients. American Journal of Nephrology, 36, 175-183.

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