**5. Future perspectives**

made with cotton. These towels were cleansed with water and then dried under sunlight. After drying, the subjects gently rubbed their whole body with these towels, and if possible, this procedure was carried out in direct sunlight. The results are shown in Fig.4. The mechanism by which this traditional Japanese alternative medical procedure aids in symptom relief may be because skin-rubbing produces secretion of corticosteroid hormone through stimulation of the thalamus [53]. Further, skin-rubbing eliminates the bacterial flora on the surface of the skin [54]. In combination with ultraviolet rays, skin-rubbing may prevent intrusion of c-fiber from

**Figure 4.** Effect of rubdown with Japanese dry towels on change in visual analog scale for itching. Manipulation by rubdown with Japanese dry towels produced a marked reduction in pruritus using the visual analog scale. \*\* indicates

The use of opioid antagonists in uremic pruritus was first brought to our attention by Andersen et al. [57] when they published a case report about a terminally ill uremic patient successfully treated by naloxone for persistent itching. However, few studies were published, and these had conflicting findings. While Peer et al. [58] showed in a small placebo-controlled clinical trial that naltrexone, which is a µ-receptor antagonist, is effective, Pauli-Magnus et al. [40] failed to demonstrate any efficacy of naltrexone in the treatment of uremic pruritus. Later, Legroux-Crespel et al. [59] conducted a comparative study between naltrexone and loratadine, and concluded that naltrexone is not effective and not well-tolerated because of frequent side effects, except in a small subset of patients. More recently, another perspective was elaborated

P<0.01.

50 Updates in Hemodialysis

**4.6. Opioid antagonists**

the dermis into the epidermis which is one of the causes of itch [55, 56]

As stated in this review, recent advances in pathophysiology of itch and treatment for CKDassociated pruritus have improved this condition remarkably, however, there are still a lot of obstacles to overcome in order to achieve satisfactory comfort and relief from unpleasant symptoms stemming from pruritus. It is therefore of the utmost importance for investigators and physicians to study and research in this area.

### **Author details**

Hiromichi Suzuki1\*, Hiroshi Omata 2 and Hiroo Kumagai3

\*Address all correspondence to: iromichi@saitama-med.ac.jp


#### **References**


[15] Pontremoli R, Sofia A, Ravera M, Nicolella C, Viazzi F, Tirotta A, et al. Prevalence and clinical correlates of microalbuminuria in essential hypertension The MAGIC Study. Hypertension. 1997;30:1135-43.

**Author details**

52 Updates in Hemodialysis

**References**

Hiromichi Suzuki1\*, Hiroshi Omata 2

\*Address all correspondence to: iromichi@saitama-med.ac.jp

Venereol Suppl [Stockh]. 1989;145:1-38.

physiology and treatment. Drugs. 2009;69:251-63.

Ann Acad Med Singapore. 2007;36:788-92.

Am J Kidney Dis. 2007;50:11-20.

tients. J Nephrol. 2008;21:161-5.

2011;30:99-100.

2010;10:236-42.

January 2014;doi:10.1038

1 Department of Nephrology, Saitama Medical University, Japan

2 Department of Oriental Medicine, Saitama Medical University, Japan

and Hiroo Kumagai3

3 Department of Nephrology and Endocrinology National Defense Medical College, Japan

[1] Stahle-Backdahl M. Uremic pruritus. Clinical and experimental studies. Acta Derm

[2] Stahle-Backdahl M. Pruritus in hemodialysis patients. Skin Pharmacol. 1992;5:14-20.

[4] Manenti L, Tansinda P, Vaglio A. Uraemic pruritus: clinical characteristics, patho‐

[3] Stahle-Backdahl M. Uremic pruritus. Semin Dermatol. 1995;14:297-301.

[5] Yosipovitch G, Greaves MW, Schmelz M. Itch. The Lancet. 2003;361:690-4.

[7] Kosmadakis GC, Zerefos N. Uremic pruritus. Int J Artif Organs. 2006;29:938-43.

[8] Greaves MW. Recent advances in pathophysiology and current management of itch.

[9] Patel TS, Freedman BI, Yosipovitch G. An update on pruritus associated with CKD.

[10] Narita I, Iguchi S, Omori K, Gejyo F. Uremic pruritus in chronic hemodialysis pa‐

[11] Berger TG, Steinhoff M. Pruritus and renal failure. Semin Cutan Med Surg.

[12] Greaves MW. Pathogenesis and treatment of pruritus. Curr Allergy Asthma Rep.

[14] Mettang T, Kremer AE. Uremic pruritus. Kidney Int. advance online publication, 8

[6] Lugon JR. Uremic pruritus: a review. Hemodial Int. 2005;9:180-8.

[13] Kfoury LW, Jurdi MA. Uremic pruritus. J Nephrol. 2012;25:644-52.


[43] Shultz B, Roenigk H. Uremic pruritus treated with ultraviolet light. JAMA. 1980;243:1836-7.

[29] Twycross R, Greaves MW, Handwerker H, Jones EA, Libretto SE, Szepietowski JC, et

[30] Szepietowski JC, Szepietowski T, Reich A. Efficacy and tolerance of the cream con‐ taining structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study. Acta Dermatovenerol Croat. 2005;13:97-103. [31] Okada K, Matsumoto K. Effect of skin care with an emollient containing a high water

[32] Itai T, Amayasu H, Kuribayashi M, Kawamura N, Okada M, Momose A, et al. Psy‐ chological effects of aromatherapy on chronic hemodialysis patients. Psychiatry Clin

[33] Dvorak M, Watkinson A, McGlone F, Rukwied R. Histamine induced responses are attenuated by a cannabinoid receptor agonist in human skin. Inflamm Res.

[34] Breneman DL, Cardone JS, Blumsack RF, Lather RM, Searle EA, Pollack VE. Topical capsaicin for treatment of hemodialysis-related pruritus. J Am Acad Dermatol.

[35] Tarng DC, Cho YL, Liu HN, Huang TP. Hemodialysis-related pruritus: a doubleblind, placebo-controlled, crossover study of capsaicin 0.025% cream. Nephron.

[36] Weisshaar E, Dunker N, Gollnick H. Topical capsaicin therapy in humans with he‐

[37] Tamimi NA, Mikhail AI, Stevens PE. Role of gamma-linolenic acid in uraemic pruri‐

[38] Chen YC, Chiu WT, Wu MS. Therapeutic effect of topical gamma-linolenic acid on

[39] Miller MJS, Vergnolle N, McKnight W, Musah RA, Davison CA, Trentacosti AM, et al. Inhibition of Neurogenic Inflammation by the Amazonian Herbal Medicine San‐

[40] Pauli-Magnus C, Mikus G, Alscher DM, Kirschner T, Nagel W, Gugeler N, et al. Nal‐ trexone does not relieve uremic pruritus: results of a randomized, double-blind, pla‐

[41] Duque MI, Thevarajah S, Chan YH, Tuttle AB, Freedman BI, Yosipovitch G. Uremic pruritus is associated with higher kt/V and serum calcium concentration. Clin Neph‐

[42] Gilchrest BA, Rowe JW, Brown RS, Steinman TI, Arndt KA. Ultraviolet phototherapy of uremic pruritus. Long-term results and possible mechanism of action. Ann Intern

modialysis-related pruritus. Neurosci Lett. 2003;345:192-4.

refractory uremic pruritus. Am J Kidney Dis. 2006;48:69-76.

cebo-controlled crossover study. J Am Soc Nephrol. 2000;11:514-9.

al. Itch: scratching more than the surface. QJM. 2003;96:7-26.

content on mild uremic pruritus. Ther Apher Dial. 2004;8:419-22.

Neurosci. 2000;54:393-7.

2003;52:238-45.

54 Updates in Hemodialysis

1992;26:91-4.

1996;72:617-22.

tus. Nephron. 1999;83:170-1.

gre de Grado. 2001;117:725-30.

rol. 2006;66:184-91.

Med. 1979;91:17-21.

