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Saudi Journal of Kidney Diseases and Transplantation
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LETTER TO THE EDITOR Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 2  |  Page : 291-292
Nicotinamide as a potential novel addition to the anti-uremic pruritus weaponry


1 Department of Dermatology, Medicinal and Natural Chemistry, Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
2 Department of Pediatric, Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3 Department of Nephrology, Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

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How to cite this article:
Namazi MR, Fallahzadeh MK, Roozbeh J. Nicotinamide as a potential novel addition to the anti-uremic pruritus weaponry. Saudi J Kidney Dis Transpl 2009;20:291-2

How to cite this URL:
Namazi MR, Fallahzadeh MK, Roozbeh J. Nicotinamide as a potential novel addition to the anti-uremic pruritus weaponry. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2014 Jul 24];20:291-2. Available from: http://www.sjkdt.org/text.asp?2009/20/2/291/45584
To the Editor,

Uremic pruritus (UP) remains one of the most frustrating, common, and potentially disabling symptoms in patients with end-stage renal di­sease. A number of factors may contribute to UP in individual patients but a specific general etiology has not been identified yet. [1] Included in this group is immune dysfunction. Based on several observations and results from various trials on UP, there is increasing evidence that UP is a systemic rather than an isolated skin disease and that an alteration of the immune system with an inflammatory pattern resulting in a dominant T helper1 (Th1) differentiation may be involved in the pathogenesis of UP. [2] In a Th1-dominant immune response, a more cytotoxic and inflammatory cytokine pattern is present. It is often associated with an infla­mmatory state, because the Th1 cytokines re­cruit and activate inflammatory leucocytes. In contrast, T helper 2 (Th2) cells secrete anti­inflammatory cytokines and in this subset the cytokine pattern is associated with antibody and allergic responses. [3] As mentioned, in pa­tients with UP Th1 predominance and gene­ralized inflammatory process exists. [2]

Regardless of the etiology, the symptom of pruritus is thought to be related to the release of histamine from skin mast cells and there are some treatment modalities that target this pro­cess such as ultraviolet B phototherapy that decreases mast cell numbers and antihista­mines that block histamine receptors. [4]

Dry skin is frequently observed in uremic pa­tients and a link with the common complaint of pruritus has been suggested, therefore emo­llients are one of the treatment modalities of UP. [5]

Nicotinamde, also known as niacinamide, is the pyridin-3-carboxylic acid amide of niacin, a component of the vitamin B complex. This agent has no effect on blood pressure, pulse, or body temperature. [6] This drug is an inhibitor of poly (ADP-ribose) polymerase-1 (PARP-1) which is a nuclear enzyme enhancing nuclear factor kappa B-mediated transcription. The latter plays a pivotal role in the expression of adhesion molecules and inflammatory mediators. [6]

There are three mechanisms that may explain its potential effectiveness in treatment of UP:

  1. Nicotinamide has been shown to be capa­ble of inhibition of the expression of MHC­II and the production of IL-12, TNF-α, and IL-1. It interacts with glycosylphosphatidyl­inositol-anchored ADP-ribosyl transferrases. These enzymes occur on the outer mem­brane of lymphocytes. The best known is CD38. Antibodies to CD38 potentiate many biological activities of lymphocytes, parti­cularly in promoting B cell differentiation. This effect, accompanying the inhibitory effect of nicotinamide on IFN-gamma­induced macrophage activation and IL-1, IL-12, and TNF-α- production, results in a mild TH2 bias. This explains why this agent is effective in preventing destructive insulitis, which is characterized by a Th1 bias. [6] As stated above one of the proposed etiologies of UP is Th1 overactivity and the ensuing generalized inflammation; there­fore, the anti-inflammatory effect and Th1 to Th2 shift induced by nicotinamide can alleviate UP. The successfulness of the treatment modalities of UP that suppress Th1 overactivity, such as topical tacroli­mus, supports this notion. [7]
  2. Nicotinamide has been shown to be a potent inhibitor of cAMP phosphodies­terase and to stabilize mast cells and leukocytes, hence exerting considerable histamine-release blocking activity. [6] The mast cell stabilization may be the second mechanism supporting our hypothesis.
  3. Nicotinamide increases the biosynthesis of ceramides by keratinocytes through incre­ment of the activity of serine palmitoyl­transferase, the rate-limiting enzyme in sphingolipid synthesis, by increasing its mRNA levels. [6] Therefore increased level of ceramides in skin, with the resultant alleviation of xerosis, may be another justification for treatment of UP by nicotinamide.


In conclusion, given the anti-inflammatory and Th1 to Th2 switching effects of nicotina­mide, and the anti-xerosis and mast-cell stabi­lizing effects of this agent, we theorize that niacinamide could be effective against UP. We invite our dermatologist and nephrologist colleagues to conduct clinical trials on oral or topical nicotinamide for treatment of UP.

 
   References Top

1.Ponticelli C, Bencini PL. Pruritus in dialysis patients: A neglected problem. Nephrol Dial Transplant 1995;10:2174.  Back to cited text no. 1  [PUBMED]  [FULLTEXT]
2.Mettang T, Pauli-Magnus C, Alscher DM. Uraemic pruritus new perspectives and insights from recent trials. Nephrol Dial Transplant 2002;17:1558-63.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
3.Abbas AK, Murphy KM, Sher A. Functional diversity of helper T lymphocytes. Nature 1996;383:787-93.  Back to cited text no. 3  [PUBMED]  [FULLTEXT]
4.De Marchi S, Cecchin E, Villalta D, Sepiacci G, Santini G, Bartoli E. Relief of pruritus and decreases in plasma histamine concentrations during erythropoietin therapy in patients with uremia. N Engl J Med 1992;326:969-74.  Back to cited text no. 4  [PUBMED]  
5.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.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Namazi MR. Nicotinamide: a potential addition to the anti-psoriatic weaponry. FASEB J 2003; 17(11):1377-9.  Back to cited text no. 6    
7.Pauli-Magnus C, Klumpp S, Alscher DM, Kuhlmann U, Mettang T. Short-term efficacy of tacrolimus ointment in severe uremic pruritus. Perit Dial Int 2000;20(6):802-3.  Back to cited text no. 7    

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Correspondence Address:
Mohammad K Fallahzadeh
Department of Pediatric, Research Center, Shiraz University of Medical Sciences, Shiraz
Iran
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PMID: 19237824

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