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Wong, L.S.; Cheng, A. The Clinical Features and Diagnosis of Uremic Pruritus. Encyclopedia. Available online: https://encyclopedia.pub/entry/23040 (accessed on 21 June 2024).
Wong LS, Cheng A. The Clinical Features and Diagnosis of Uremic Pruritus. Encyclopedia. Available at: https://encyclopedia.pub/entry/23040. Accessed June 21, 2024.
Wong, Lai San, An-Yu Cheng. "The Clinical Features and Diagnosis of Uremic Pruritus" Encyclopedia, https://encyclopedia.pub/entry/23040 (accessed June 21, 2024).
Wong, L.S., & Cheng, A. (2022, May 18). The Clinical Features and Diagnosis of Uremic Pruritus. In Encyclopedia. https://encyclopedia.pub/entry/23040
Wong, Lai San and An-Yu Cheng. "The Clinical Features and Diagnosis of Uremic Pruritus." Encyclopedia. Web. 18 May, 2022.
The Clinical Features and Diagnosis of Uremic Pruritus
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Uremic pruritus, or chronic kidney disease-associated pruritus, is common, bothersome, and sometimes debilitating in patients with chronic kidney disease or end-stage renal disease. Due to its variable clinical manifestations, the diagnosis of uremic pruritus requires exquisite evaluation. Excluding itch resulting from other dermatological causes as well as other systemic conditions is essential for a proper diagnosis. The pathophysiology of uremic pruritus remains uncertain. Hypotheses including toxin deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance are supposed.

uremic pruritus chronic kidney disease associated pruritus chronic pruritus

1. Introduction

Uremic pruritus, also known as chronic kidney disease-associated pruritus (CKD-aP), is a common, bothersome, and sometimes debilitating symptom in patients with chronic kidney disease (CKD) or end-stage renal disease (ESRD).
One large international cohort study of adult dialysis patients (Dialysis Outcomes and Practice Patterns Study (DOPPS)) reported that around 70% of hemodialysis patients suffered from pruritus and 40% of them were bothered by at least moderate pruritus. Notably, not only in patients with dialysis, the prevalence of moderate to severe pruritus in non-dialysis CKD patients was around 25% [1]. The prevalence of moderate to severe pruritus decreased from 46% in 1996 to 37% in 2015 [2][3], supposedly associated with the refinement of dialysis adequacy.
Risk factors of uremic pruritus in hemodialysis patients have been reported to be old age, gender, calcium–phosphate imbalance, longer duration of dialysis, and comorbidities such as concurrent cardiovascular disease, congestive cardiac failure, lung disease, liver disease, neurological disease, hepatitis C infection, and anemia [4]. However, some results were inconsistent in different studies [5][6][7][8]. Risk factors of developing pruritus in non-dialysis CKD patients include old age, female sex, advanced stage of CKD, lung disease, diabetes mellitus, and depression [1].
Pruritus in these patients dramatically affects their quality of life. Around half of them were bothered by pruritus all day long, and one-third were most bothered at night. The high percentage of night-time pruritus may lead to sleep disturbance. Sixty percent of patients with severe pruritus also frequently suffered from restless sleep [3]. Patients with pruritus also reported poor quality of life by appearance, mental distress, decreasing desire for social interaction, and ability to work. Notably, the bothersome symptoms not only decrease quality of life but also cause poorer medical outcomes. Pruritus in these patients was associated with significantly higher mortality, with a 13% higher risk in DOPPS phase I (1996–2001), a 21% higher risk in DOPPS phase II (2002–2004), and 37% higher risk in Japanese patients, and was suggested to be related to poor sleep quality [2][9]. One recent study using Taiwan’s national health insurance database revealed a higher risk of all-cause death and long-term morbidities including infection-associated hospitalization and major adverse cardiac and cerebrovascular events in patients with uremic pruritus [10][11].
Despite its high prevalence, disease burden, and even higher risk of mortality, pruritus is often underreported by patients and is underestimated by health care providers. Some 69% of medical facilities directors underestimated the prevalence of pruritus in their facilities, and 17% of patients who were frequently bothered by itchiness never reported their symptoms to any member of the medical facility. Among those who did report, they were more likely to report to nephrologists and staff of the dialysis facility, followed by dermatologists [3].

2. Clinical Features

The clinical manifestations of uremic pruritus are variable. The severity varies from somewhat uncomfortable to extremely disturbing and inducing restlessness. About 20% of patients experienced being very much and extremely itchy in the DOPPS study [3]. The distribution is usually generalized and symmetric, but may be localized and is more common on the back, face, and shunt arm [12]. However, there is no dermatomal distribution. Pruritus is aggravated by dryness, heat, cold, stress, and showering. The skin is often lacking prominent lesions in the affected patients. However, in addition to xerosis, there may be skin lesions secondary to repetitive scratching, such as excoriation, crusts, impetigo, and prurigo nodularis. Most patients (61%) reported that pruritus has no relation to the timing of dialysis, but some reported that the pruritus was more severe during dialysis (15%), or soon after dialysis (9%), or on non-dialysis days (14%) [3].
Chronic pruritus also developed in patients receiving peritoneal dialysis, although it is less studied compared to patients with hemodialysis. A meta-analysis study showed comparable prevalence of CKD-aP in patients with hemodialysis and peritoneal dialysis (55% vs. 56%) [13]. However, Min et al. reported a higher prevalence of pruritus in patients with peritoneal dialysis compared to patients with hemodialysis (62.6% vs. 48.3%) [14]. The intensity of pruritus was higher in patients undergoing peritoneal dialysis and was associated with lower total weekly Kt/V, longer duration of dialysis, higher dietary protein intake, higher parathyroid hormone, and higher high-sensitivity C-reactive protein [13][15].
Several observations have shown that the prevalence of pruritus declined after renal transplantation [16][17]. A recent large study revealed that pruritus resolved completely in 73.7% (56/76) of renal transplant recipients [18]. Furthermore, pruritus improved or totally resolved in 97.3% of patients (74/76) with renal transplantation. Intriguingly, new onset of pruritus was found in 18.2% (22/121) of patients with renal transplantation with undetermined reasons [18].

3. Diagnosis

Uremic pruritus is defined by itching directly resulting from CKD, without other explainable conditions [19]. Due to its variability and the lack of specific skin lesions, there are no well-established criteria nor laboratory tests for the diagnosis of uremic pruritus. Accurate diagnosis of uremic pruritus may be challenging. Diagnosis requires thorough consideration including dermatologic, renal, hepatobiliary, endocrine, rheumatologic, hematologic or oncologic, neuropathic, and psychogenic causes. The initial approach is to evaluate whether there is primary or inflamed skin lesions to exclude other dermatological causes of pruritus. Common dermatological causes of chronic pruritus include atopic dermatitis, psoriasis, chronic urticaria, dermatophytosis, scabies infestations, and bullous pemphigoid [20]. To be noted, skin lesions secondary to scratching and rubbing, such as crusts, erosions, ulcerations, and prurigo nodularis, should not be counted. Personal drug history should also be reviewed to exclude drug-induced pruritus without visible skin lesions. Angiotensin-converting enzyme inhibitors, clonidine, calcium antagonists, beta blockers, diuretics, and allopurinol may induce itch by activating mu-opioid receptors [21]. Whether patients have chronic pruritus before deteriorating renal function helps to clarify the diagnosis of uremic pruritus. Referring to dermatologists may help to reach an appropriate diagnosis of uremic pruritus.

References

  1. Sukul, N.; Speyer, E.; Tu, C.; Bieber, B.A.; Li, Y.; Lopes, A.A.; Asahi, K.; Mariani, L.; Laville, M.; Rayner, H.C.; et al. Pruritus and Patient Reported Outcomes in Non-Dialysis CKD. Clin. J. Am. Soc. Nephrol. 2019, 14, 673–681.
  2. 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. Transpl. 2006, 21, 3495–3505.
  3. Rayner, H.C.; Larkina, M.; Wang, M.; Graham-Brown, M.; van der Veer, S.N.; Ecder, T.; Hasegawa, T.; Kleophas, W.; Bieber, B.A.; Tentori, F.; et al. International Comparisons of Prevalence, Awareness, and Treatment of Pruritus in People on Hemodialysis. Clin. J. Am. Soc. Nephrol. 2017, 12, 2000–2007.
  4. Kim, D.; Pollock, C. Epidemiology and burden of chronic kidney disease-associated pruritus. Clin. Kidney J. 2021, 14, i1–i7.
  5. Ramakrishnan, K.; Bond, T.C.; Claxton, A.; Sood, V.C.; Kootsikas, M.; Agnese, W.; Sibbel, S. Clinical characteristics and outcomes of end-stage renal disease patients with self-reported pruritus symptoms. Int. J. Nephrol. Renovasc. Dis. 2013, 7, 1–12.
  6. 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.
  7. Weisshaar, E.; Weiss, M.; Passlick-Deetjen, J.; Tschulena, U.; Maleki, K.; Mettang, T. Laboratory and dialysis characteristics in hemodialysis patients suffering from chronic itch--results from a representative cross-sectional study. BMC Nephrol. 2015, 16, 184.
  8. Mathur, V.S.; Lindberg, J.; Germain, M.; Block, G.; Tumlin, J.; Smith, M.; Grewal, M.; McGuire, D. A longitudinal study of uremic pruritus in hemodialysis patients. Clin. J. Am. Soc. Nephrol. 2010, 5, 1410–1419.
  9. Kimata, N.; Fuller, D.S.; Saito, A.; Akizawa, T.; Fukuhara, S.; Pisoni, R.L.; Robinson, B.M.; Akiba, T. Pruritus in hemodialysis patients: Results from the Japanese Dialysis Outcomes and Practice Patterns Study (JDOPPS). Hemodial. Int. 2014, 18, 657–667.
  10. Ting, S.W.; Fan, P.C.; Lin, Y.S.; Lin, M.S.; Lee, C.C.; Kuo, G.; Chang, C.H. Uremic pruritus and long-term morbidities in the dialysis population. PLoS ONE 2020, 15, e0241088.
  11. Ting, S.W.; Fan, P.C.; Lin, Y.S.; Lin, M.S.; Lee, C.C.; Kuo, G.; Chang, C.H. Association between uremic pruritus and long-term outcomes in patients undergoing dialysis. J. Am. Acad. Dermatol. 2020, 83, 924–925.
  12. Mettang, T.; Kremer, A.E. Uremic pruritus. Kidney Int. 2015, 87, 685–691.
  13. Hu, X.; Sang, Y.; Yang, M.; Chen, X.; Tang, W. Prevalence of chronic kidney disease-associated pruritus among adult dialysis patients: A meta-analysis of cross-sectional studies. Medicine 2018, 97, e10633.
  14. Min, J.W.; Kim, S.H.; Kim, Y.O.; Jin, D.C.; Song, H.C.; Choi, E.J.; Kim, Y.L.; Kim, Y.S.; Kang, S.W.; Kim, N.H.; et al. Comparison of uremic pruritus between patients undergoing hemodialysis and peritoneal dialysis. Kidney Res. Clin. Pract. 2016, 35, 107–113.
  15. Wu, H.Y.; Huang, J.W.; Tsai, W.C.; Peng, Y.S.; Chen, H.Y.; Yang, J.Y.; Hsu, S.P.; Pai, M.F.; Ko, M.J.; Hung, K.Y.; et al. Prognostic importance and determinants of uremic pruritus in patients receiving peritoneal dialysis: A prospective cohort study. PLoS ONE 2018, 13, e0203474.
  16. Schricker, S.; Weisshaar, E.; Kupfer, J.; Mettang, T. Prevalence of Pruritus in a Single Cohort of Long-term Kidney Transplant Recipients. Acta Derm. Venereol. 2020, 100, adv00066.
  17. Krajewski, P.K.; Krajewska, M.; Szepietowski, J.C. Pruritus in renal transplant recipients: Current state of knowledge. Adv Clin Exp Med. 2020, 29, 769–772.
  18. Krajewski, P.K.; Olczyk, P.; Krajewska, M.; Krajewski, W.; Szepietowski, J.C. Clinical Characteristics of Itch in Renal Transplant Recipients. Front. Med. 2021, 7, 615334.
  19. Verduzco, H.A.; Shirazian, S. CKD-Associated Pruritus: New Insights into Diagnosis, Pathogenesis, and Management. Kidney Int. Rep. 2020, 5, 1387–1402.
  20. Roh, Y.S.; Choi, J.; Sutaria, N.; Kwatra, S.G. Itch: Epidemiology, clinical presentation, and diagnostic workup. J. Am. Acad Dermatol. 2022, 86, 1–14.
  21. Manenti, L.; Leuci, E. Do you feel itchy? A guide towards diagnosis and measurement of chronic kidney disease-associated pruritus in dialysis patients. Clin. Kidney J. 2021, 14, i8–i15.
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