Uremic pruritus explained

Uremic pruritus
Synonyms:Uraemic pruritus or Renal pruritus[1]

Uremic pruritus is caused by chronic kidney failure and is the most common internal systemic cause of itching.[2]

Nalfurafine, an orally administered, centrally acting κ-opioid receptor agonist, is approved to treat the condition in Japan.[3]

Signs and symptoms

The signs and symptoms of uremic pruritus can vary. The intensity ranges from mildly uncomfortable to highly upsetting and causing agitation.[4] The distribution is more prevalent on the back, face, and shunt arm and is typically symmetric and generalized, though it can also be localized.[5] Dryness, heat, cold, stress, and showering all exacerbate pruritus. Patients with this condition frequently have skin devoid of noticeable lesions. But in addition to xerosis, skin lesions like excoriation, crusts, impetigo, and prurigo nodularis may also develop as a result of repeated scratching.[4]

Causes

There are several potential causes of uremic pruritus, including immune dysregulation, uremic toxins, neuropathy, and opioid imbalance.[4]

Mechanism

Vitamin A,[6] parathyroid hormone,[7] calcium, phosphate, magnesium, histamine,[8] and phosphate[9]  are the most researched potential pruritogens in the pathophysiology of uremic pruritus.[4]

The etiology of uremic pruritus may involve the immune system as well. Research comparing hemodialysis patients with and without uremic pruritus revealed that those with the condition had noticeably higher levels of T helper 1 cells[10] as well as serum interleukin (IL)-6, IL-2,[11] and IL-31.[12] [13]

In uremic pruritus, both peripheral and central neuropathy are thought to be involved.[4]

Diagnosis

Uremic pruritus is defined as itching that is directly caused by chronic kidney disease, with no other explainable conditions.[14] Uremic pruritus cannot be diagnosed with laboratory tests or established criteria because of its variability and lack of specific skin lesions. Comprehensive consideration of the diagnosis is necessary, encompassing neuropathic, psychogenic, renal, dermatologic, endocrine, hepatobiliary, hematologic, rheumatologic, oncologic, and endocrine causes.[4]

Treatment

The pathophysiology of uremic pruritus is still poorly understood, which contributes to the difficulty of current treatments.[4] Prior to the approval of difelikefalin in the US in 2021, there was no FDA-approved treatment for uremic pruritus.[15] Emollients, topical medications, antihistamines, phototherapy, dialysis modification, and serotonin receptor antagonists are examples of conventional treatments. More data from recent studies indicates that biologics, gabapentin, pregabalin, and opioid receptor agonists and antagonists may be involved in treating uremic pruritus.[4]

Xerosis is a contributing factor to pruritus and is present in 50–85% of patients with uremic pruritus.[16] Many studies have shown that emollients such as glycerol and paraffin,[17] physiological lipids,[18] 10% urea and dexpanthenol,[19] and baby oil[20] can reduce xerosis and pruritus in patients with uremic pruritus. For patients with uremic pruritus, especially in cases of milder severity, emollient is recommended as the initial line of treatment.[14]

Pregabalin and gabapentin are analogues of gamma-aminobutyric acid that modulate neurotransmitters, possibly through reducing the release of neurotransmitters.[21] Numerous pruritic disorders, including brachioradial pruritus and pruritus in patients with diabetic neuropathic pain, have been linked to the neuropathic role in their pathogenesis.[22] Pregabalin and gabapentin have been shown in multiple clinical trials to be statistically significant in reducing the intensity of pruritus in patients with uremic pruritus.[23] [24]

It has been demonstrated that mast cell stabilizers, which stop mast cells from releasing inflammatory mediators, are useful in treating uremic pruritus. These stabilizers include zinc sulfate,[25] ketotifen,[26] oral cromolyn sodium,[27] and topical cromolyn sodium.[28]

See also

Further reading

External links

Notes and References

  1. Book: Rapini RP, Bolognia JL, Jorizzo JL . Dermatology: 2-Volume Set . Mosby . St. Louis . 2007 . 978-1-4160-2999-1 .
  2. Book: James WD, Berger T, Elston D . Andrews' Diseases of the Skin: Clinical Dermatology . 2006 . Saunders Elsevier . Philadelphia . 978-0-7216-2921-6 . 10th.
  3. Inui S . Nalfurafine hydrochloride to treat pruritus: a review . Clinical, Cosmetic and Investigational Dermatology . 8 . 249–255 . 2015 . 26005355 . 4433050 . 10.2147/CCID.S55942 . free .
  4. Cheng . An-Yu . Wong . Lai-San . Uremic Pruritus: From Diagnosis to Treatment . Diagnostics . MDPI AG . 12 . 5 . April 28, 2022 . 2075-4418 . 10.3390/diagnostics12051108 . free . 1108. 35626264 . 9140050 .
  5. Mettang . Thomas . Kremer . Andreas E. . Uremic pruritus . Kidney International . Elsevier BV . 87 . 4 . 2015 . 0085-2538 . 10.1038/ki.2013.454 . 685–691. 24402092 . free .
  6. Yatzidis . H . Digenis . P . Fountas . P . Hypervitaminosis A accompanying advanced chronic renal failure. . BMJ . 3 . 5979 . August 9, 1975 . 0959-8138 . 10.1136/bmj.3.5979.352 . 352–353. 1156752 . 1673813 .
  7. STÅHLE-BÅCKDAHL . M. . HÄGERMARK . Ö. . LINS . L.-E. . TÖRRING . O. . HILLIGES . M. . JOHANSSON . O. . Experimental and immunohistochemical studies on the possible role of parathyroid hormone in uraemic pruritus . Journal of Internal Medicine . Wiley . 225 . 6 . 1989 . 0954-6820 . 10.1111/j.1365-2796.1989.tb00104.x . 411–415. 2746157 . 44406280 .
  8. Dugas-Breit . Susanne . Schöpf . Pia . Dugas . Martin . Schiffl . Helmut . Ruëff . Franziska . Przybilla . Bernhard . Baseline serum levels of mast cell tryptase are raised in hemodialysis patients and associated with severity of pruritus . JDDG: Journal der Deutschen Dermatologischen Gesellschaft . Wiley . 3 . 5 . April 14, 2005 . 1610-0379 . 10.1111/j.1610-0387.2005.05706.x . 343–347. 16372800 . 22968227 .
  9. Blachley . Jon D. . Blankenship . D. Michael . Menter . Alan . Parker . Tom F. . Knochel . James P. . Uremic Pruritus: Skin Divalent Ion Content and Response to Ultraviolet Phototherapy . American Journal of Kidney Diseases . Elsevier BV . 5 . 5 . 1985 . 0272-6386 . 10.1016/s0272-6386(85)80115-3 . 237–241. 4003393 .
  10. Kimmel . Martin . Alscher . Dominik Mark . Dunst . Robert . Braun . Niko . Machleidt . Christoph . Kiefer . Thomas . Stülten . Christina . van der Kuip . Heiko . Pauli-Magnus . Christiane . Raub . Ulrich . Kuhlmann . Ulrich . Mettang . Thomas . The role of micro-inflammation in the pathogenesis of uraemic pruritus in haemodialysis patients . Nephrology Dialysis Transplantation . Oxford University Press (OUP) . 21 . 3 . October 25, 2005 . 1460-2385 . 10.1093/ndt/gfi204 . 749–755. 16249205 .
  11. Fallahzadeh . M. K. . Roozbeh . J. . Geramizadeh . B. . Namazi . M. R. . Interleukin-2 serum levels are elevated in patients with uremic pruritus: a novel finding with practical implications . Nephrology Dialysis Transplantation . Oxford University Press (OUP) . 26 . 10 . March 3, 2011 . 0931-0509 . 10.1093/ndt/gfr053 . 3338–3344. 21372257 .
  12. Oweis . Ashraf O. . AL-Qarqaz . Firas . Bodoor . Khaldon . Heis . Leen . Alfaqih . Mahmoud A. . Almomani . Rowida . Obeidat . Motaz A. . Alshelleh . Sameeha A. . Elevated interleukin 31 serum levels in hemodialysis patients are associated with uremic pruritus . Cytokine . Elsevier BV . 138 . 2021 . 1043-4666 . 10.1016/j.cyto.2020.155369 . 155369. 33221158 . 227132161 .
  13. Ko . Mei-Ju . Peng . Yu-Sen . Chen . Hung-Yuan . Hsu . Shih-Ping . Pai . Mei-Fen . Yang . Ju-Yeh . Wen . Su-Ying . Jee . Shiou-Hwa . Wu . Hon-Yen . Chiu . Hsien-Ching . Interleukin-31 is associated with uremic pruritus in patients receiving hemodialysis . Journal of the American Academy of Dermatology . Elsevier BV . 71 . 6 . 2014 . 0190-9622 . 10.1016/j.jaad.2014.08.004 . 1151–1159.e1. 25270263 .
  14. Verduzco . Hector Alvarado . Shirazian . Shayan . CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management . Kidney International Reports . Elsevier BV . 5 . 9 . 2020 . 2468-0249 . 10.1016/j.ekir.2020.04.027 . 1387–1402. 32954065 . 7486142 .
  15. Deeks . Emma D. . Difelikefalin: First Approval . Drugs . Springer Science and Business Media LLC . 81 . 16 . October 21, 2021 . 0012-6667 . 10.1007/s40265-021-01619-6 . 1937–1944. 34674115 . 239042330 .
  16. Szepietowski . J. C. . Uraemic xerosis . Nephrology Dialysis Transplantation . Oxford University Press (OUP) . 19 . 11 . September 22, 2004 . 1460-2385 . 10.1093/ndt/gfh480 . 2709–2712. 15328388 .
  17. Balaskas . Elias . Szepietowski . Jacek C. . Bessis . Didier . Ioannides . Dimitrios . Ponticelli . Claudio . Ghienne . Corinne . Taberly . Alain . Dupuy . Patrick . Randomized, Double-blind Study with Glycerol and Paraffin in Uremic Xerosis . Clinical Journal of the American Society of Nephrology . Ovid Technologies (Wolters Kluwer Health) . 6 . 4 . 2011 . 1555-9041 . 10.2215/cjn.05490610 . 748–752. 21258039 . 3069365 .
  18. Szepietowski . Jacek C . Szepietowski . Tomasz . Reich . Adam . Efficacy and tolerance of the cream containing structured physiological lipids with endocannabinoids in the treatment of uremic pruritus: a preliminary study . Acta Dermatovenerologica Croatica . 2005 . 13 . 2 . 97–103 . 16324422.
  19. Okada . Kazuyoshi . Matsumoto . Koichi . Effect of Skin Care With an Emollient Containing a High Water Content on Mild Uremic Pruritus . Therapeutic Apheresis and Dialysis . Wiley . 8 . 5 . 2004 . 1744-9979 . 10.1111/j.1526-0968.2004.00175.x . 419–422. 15663539 . 2690300 .
  20. Singh . VimalaSuryanarayan . Vinayadev . V . Effectiveness of Baby Oil Therapy for Uremic Pruritus in Hemodialysis Patients . Saudi Journal of Kidney Diseases and Transplantation . Medknow . 32 . 1 . 2021 . 163–169 . 1319-2442 . 10.4103/1319-2442.318518 . free . 34145126 .
  21. Robertson . Kelvin . Marshman . Laurence A. G. . Plummer . David . Downs . Elena . Effect of Gabapentin vs Pregabalin on Pain Intensity in Adults With Chronic Sciatica . JAMA Neurology . American Medical Association . 76 . 1 . January 1, 2019 . 28–34 . 2168-6149 . 10.1001/jamaneurol.2018.3077 . 30326006 . 6439871 .
  22. 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 . Nephrology Dialysis Transplantation . Oxford University Press (OUP) . 19 . 12 . December 1, 2004 . 0931-0509 . 10.1093/ndt/gfh496 . 3137–3139. 15575002 .
  23. Nofal . Eman . Farag . Fawzia . Nofal . Ahmad . Eldesouky . Fatma . Alkot . Reham . Abdelkhalik . Zeinab . Gabapentin: A promising therapy for uremic pruritus in hemodialysis patients: A randomized-controlled trial and review of literature . Journal of Dermatological Treatment . Informa UK Limited . 27 . 6 . April 4, 2016 . 0954-6634 . 10.3109/09546634.2016.1161161 . 515–519. 27043168 . 25857291 .
  24. SOLAK . YALCIN . BIYIK . ZEYNEP . ATALAY . HUSEYIN . GAIPOV . ABDUZHAPPAR . GUNEY . FIGEN . TURK . SULEYMAN . COVIC . ADRIAN . GOLDSMITH . DAVID . KANBAY . MEHMET . Pregabalin versus gabapentin in the treatment of neuropathic pruritus in maintenance haemodialysis patients: A prospective, crossover study . Nephrology . Wiley . 17 . 8 . October 29, 2012 . 1320-5358 . 10.1111/j.1440-1797.2012.01655.x . 710–717. 22909343 . 1870828 .
  25. Najafabadi . Mojgan Mortazavi . Faghihi . Gita . Emami . Afsoon . Monghad . Maryam . Moeenzadeh . Firoozeh . Sharif . Nima . Davarpanah Jazi . Amir Hosein . Zinc Sulfate for Relief of Pruritus in Patients on Maintenance Hemodialysis . Therapeutic Apheresis and Dialysis . Wiley . 16 . 2 . January 5, 2012 . 1744-9979 . 10.1111/j.1744-9987.2011.01032.x . 142–145. 22458392 . 205906092 .
  26. Amirkhanlou . Saeid . Rashedi . Anna . Taherian . Jalal . Hafezi . Ali Akbar . Parsaei . Sahar . Comparison of Gabapentin and Ketotifen in Treatment of Uremic Pruritus in Hemodialysis Patients . Pakistan Journal of Medical Sciences . 32 . 1 . December 31, 1969 . 22–26 . 1681-715X . 10.12669/pjms.321.8547 . 27022338 . 4795872 .
  27. ROSNER . Mitchell H. . Cromolyn sodium: A potential therapy for uremic pruritus? . Hemodialysis International . Wiley . 10 . 2 . March 28, 2006 . 1492-7535 . 10.1111/j.1542-4758.2006.00093.x . 189–192. 16623673 . 34803063 .
  28. Feily . Amir . Dormanesh . Benafshe . Ghorbani . Ali Reza . Moosavi . Zahra . Kouchak . Maryam . Cheraghian . Bahman . Mousavi . Seyed Seifollah Beladi . Mehrabian . Abolfath . Ranjbari . Nastaran . Efficacy of topical cromolyn sodium 4% on pruritus in uremic nephrogenic patients: A randomized double-blind study in 60 patients . Int. Journal of Clinical Pharmacology and Therapeutics . Dustri-Verlgag Dr. Karl Feistle . 50 . 7 . July 1, 2012 . 0946-1965 . 10.5414/cp201629 . 510–513. 22732382 .

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