{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T00:55:35Z","timestamp":1793753735940,"version":"4.6.1"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This systematic review examines chronic kidney disease-associated pruritus (CKD-aP) as a complex clinical manifestation in patients undergoing hemodialysis. Traditionally considered a secondary symptom of end-stage renal disease, emerging evidence now positions CKD-aP as a multidimensional disorder with substantial pathogenic influence on patient outcomes. Using the PRISMA 2020 methodology, we critically evaluated 54 peer-reviewed studies published between 2020 and 2025. Our synthesis highlights a convergence of five mechanistic frameworks underpinning CKD-aP: elevated levels of uremic toxins originating from gut microbial dysbiosis, immune activation driven by IL-31 and other pro-inflammatory cytokines, heightened peripheral and central neural sensitization, dysregulation of endogenous opioid receptor pathways favoring \u03bc-receptor activation, and xerosis-related epidermal barrier dysfunction. These mechanisms contribute to a systemic cycle of microinflammation, pruritogenic signaling, and neural hyperexcitability. We also identified and compared validated assessment tools\u2014including the NRS, VAS, Skindex-10, and the UP-Dial scale\u2014that facilitate standardized quantification of disease burden. While available treatments such as gabapentinoids and phototherapy offer partial relief, targeted therapies\u2014including \u03ba-opioid receptor agonists\u2014represent a major advancement, although long-term effectiveness and accessibility remain under investigation. Growing scientific consensus establishes CKD-aP as a priority therapeutic target in hemodialysis care, underscoring the need for integrated, mechanism-based management strategies to improve quality of life and clinical outcomes. This work represents a narrative systematic review, integrating evidence from mechanistic, translational, and clinical studies to critically examine the biological pathways underlying CKD-associated pruritus.<\/jats:p>","DOI":"10.3390\/ijms27020851","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:26:36Z","timestamp":1768465596000},"page":"851","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Chronic Kidney Disease-Associated Pruritus in Hemodialysis: Unraveling Mechanisms and Emerging Therapeutic Targets\u2014A Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"given":"Fasie","family":"Dragos","sequence":"first","affiliation":[{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suliman 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Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tudor","family":"Iuliana-Cezara","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitu Radu","family":"Adrian","sequence":"additional","affiliation":[{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"},{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4996-2484","authenticated-orcid":false,"given":"Chisnoiu","family":"Tatiana","sequence":"additional","affiliation":[{"name":"\u201cSfantul Apostol Andrei\u201d Emergency County Clinical Hospital, 900591 Constanta, Romania"},{"name":"Faculty of Medicine, \u201cOvidius\u201d University of Constanta, 900470 Constanta, 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Suppl."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"C\u00eerstea, \u0218., Orzan, O.A., and Zili\u0219teanu, D.S. (2025). Pruritus in Uremic Patients: Approaches to Alleviating a Common Symptom in Chronic Kidney Disease. Life, 15.","DOI":"10.3390\/life15071001"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"i23","DOI":"10.1093\/ckj\/sfab200","article-title":"Unravelling the pathophysiology of chronic kidney disease-associated pruritus","volume":"14","author":"Schricker","year":"2021","journal-title":"Clin. Kidney J."},{"key":"ref_4","first-page":"465","article-title":"Information and consensus document for the diagnostic and therapeutic management of pruritus associated with chronic kidney disease in patients on haemodialysis in Spain","volume":"44","author":"Goicoechea","year":"2024","journal-title":"Nefrol. (Engl. Ed.)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"adv00390","DOI":"10.2340\/00015555-3758","article-title":"Risk of Skin Cancer among Patients with Chronic Kidney Disease Treated with Ultraviolet B Phototherapy for Uraemic Pruritus: A Nationwide Cohort Study","volume":"101","author":"Ko","year":"2021","journal-title":"Acta Derm.-Venereol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1016\/j.ekir.2020.04.027","article-title":"CKD-Associated Pruritus: New Insights Into Diagnosis, Pathogenesis, and Management","volume":"5","author":"Verduzco","year":"2020","journal-title":"Kidney Int. Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1152\/physrev.00017.2019","article-title":"Physiology and Pathophysiology of Itch","volume":"100","author":"Cevikbas","year":"2020","journal-title":"Physiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.nephro.2022.05.002","article-title":"Hydration, barrier of skin and uremic pruritus in patients undergoing hemodialysis: A pilot investigation","volume":"18","author":"Chang","year":"2022","journal-title":"N\u00e9phrol. Th\u00e9r."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1007\/BF00374079","article-title":"Itch and inflammation induced by intradermally injected interleukin-2 in atopic dermatitis patients and healthy subjects","volume":"287","author":"Wahlgren","year":"1995","journal-title":"Arch. Dermatol. Res."},{"key":"ref_10","first-page":"CD011393","article-title":"Interventions for itch in people with advanced chronic kidney disease","volume":"12","author":"Hercz","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2175590","DOI":"10.1080\/0886022X.2023.2175590","article-title":"Randomized controlled trial of nalfurafine for refractory pruritus in hemodialysis patients","volume":"45","author":"Zhang","year":"2023","journal-title":"Ren. Fail."},{"key":"ref_12","first-page":"e65788","article-title":"Comparison Between Pregabalin and Sertraline in the Treatment of Uremic Pruritus in Patients with Maintenance Hemodialysis","volume":"16","author":"Ansari","year":"2024","journal-title":"Cureus"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1038\/ki.2013.454","article-title":"Uremic pruritus","volume":"87","author":"Mettang","year":"2015","journal-title":"Kidney Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"i447","DOI":"10.1093\/ndt\/gfy104.SP305","article-title":"SP305 Novel Oral Anticoagulants in Patients with Severe Chronic Kidney Disease, a Real Challenge","volume":"33","author":"Tuta","year":"2018","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Suliman, I.L., Panculescu, F.G., Cimpineanu, B., Popescu, S., Fasie, D., Cozaru, G.C., Gafar, N., Tuta, L.-A., and Alexandru, A. (2025). The Interplay of Cardiovascular Comorbidities and Anticoagulation Therapy in ESRD Patients on Haemodialysis\u2014The South-Eastern Romanian Experience. Biomedicines, 13.","DOI":"10.3390\/biomedicines13102387"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.23876\/j.krcp.21.189","article-title":"Uremic pruritus: Pathophysiology, clinical presentation, and treatments","volume":"42","author":"Ko","year":"2023","journal-title":"Kidney Res. Clin. Pract."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1001\/jama.2024.4899","article-title":"Chronic Pruritus: A Review","volume":"331","author":"Butler","year":"2024","journal-title":"JAMA"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1093\/ajhp\/53.18.2159","article-title":"Uremic pruritus","volume":"53","author":"Robertson","year":"1996","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1053\/j.ajkd.2016.07.031","article-title":"Sleep Disorders, Restless Legs Syndrome, and Uremic Pruritus: Diagnosis and Treatment of Common Symptoms in Dialysis Patients","volume":"69","author":"Scherer","year":"2017","journal-title":"Am. J. Kidney Dis."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1016\/j.jpainsymman.2022.08.017","article-title":"Acupuncture for Uremic Pruritus: A Systematic Review and Meta-Analysis","volume":"65","author":"Zhang","year":"2023","journal-title":"J. Pain Symptom Manag."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lu, P.H., Wang, J.Y., Chuo, H.E., and Lu, P.H. (2021). Effects of Uremic Clearance Granules in Uremic Pruritus: A Meta-Analysis. Toxins, 13.","DOI":"10.3390\/toxins13100702"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"644","DOI":"10.5301\/jn.5000039","article-title":"Uremic pruritus","volume":"25","author":"Kfoury","year":"2012","journal-title":"J. Nephrol."},{"key":"ref_23","unstructured":"Osakwe, N., and Rout, P. (2024). Uremic Pruritus Evaluation and Treatment. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1007\/s00403-024-03756-w","article-title":"Clinical efficacy and safety of sodium thiosulfate in the treatment of uremic pruritus: A meta-analysis of randomized controlled trials","volume":"317","author":"Xu","year":"2025","journal-title":"Arch. Dermatol. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113563","DOI":"10.1016\/j.intimp.2024.113563","article-title":"Serum untargeted metabolomics analysis of uremic pruritus in patients with various etiologies","volume":"143","author":"Tan","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_26","unstructured":"Rout, P., Foris, L.A., Katta, S., and Bashir, K. (2024). Uremia. StatPearls [Internet], StatPearls Publishing."},{"key":"ref_27","first-page":"e86058","article-title":"Metabolomic Analysis of Uremic Pruritus in Patients on Hemodialysis","volume":"17","author":"Mobushar","year":"2025","journal-title":"Cureus"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Wang, Q., Yang, G., Zhou, X., Zhong, X., Liu, J., and Zhang, L. (2025). Dupilumab relieves pruritus both in uremic pruritus and in atopic dermatitis with chronic kidney disease: A retrospective real-world study. Front. Med., 12.","DOI":"10.3389\/fmed.2025.1627955"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s00403-024-03637-2","article-title":"A review of the efficacy of complementary and alternative Medicines in managing Pruritus","volume":"317","author":"Ufomadu","year":"2024","journal-title":"Arch. Dermatol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.61882\/ijkd.19.1.1","article-title":"Effect of the Combination of Hemodialysis and Hemoperfusion on Clearing Interleukin-31: A Prospective, Randomized Crossover Trial in Patients under Maintenance Hemodialysis","volume":"19","author":"Zhang","year":"2025","journal-title":"Iran. J. Kidney Dis."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pan, M.M., Gao, M., Zhou, L., Xu, Y., Yao, L., Wu, C.Q., Mei, C.L., Zhao, Z.Z., Sun, D., and Guan, T.J. (2025). Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: A multicenter, randomized, double-blind, placebo-controlled trial. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1583515"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Chen, S., and Zhang, Y. (2025). Challenges and perspectives in traditional Chinese medicine intervention for uremic pruritus: Emphasis on blinding, mechanisms, and safety assessment. Int. Urol. Nephrol., ahead of print.","DOI":"10.1007\/s11255-025-04742-5"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rungkitwattanakul, D., Brooks, M., Adesina, S., Belrhiti, S., Chaijamorn, W., Charoensareerat, T., Nwaogwugwu, U., and Mere, C. (2025). Extemporaneous Preparation and Effectiveness of Low-Dose Naltrexone for the Treatment of Uremic Pruritus: A Literature Review and Case Report. Pharmacy, 13.","DOI":"10.3390\/pharmacy13060160"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"sfaf131","DOI":"10.1093\/ckj\/sfaf131","article-title":"The efficacy and safety of kappa opioid receptor (KOR) agonists in patients with uraemic pruritus: A systematic review and network meta-analysis","volume":"18","author":"Yang","year":"2025","journal-title":"Clin. Kidney J."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Y.C., Tsai, I.J., Hsieh, T.H., Wu, C.C., Lu, K.C., and Liao, M.T. (2025). Enhanced sleep quality and reduced indoxyl sulfate levels following probiotic supplementation were linked to gut microbiota modulation in hemodialysis patients. J. Formos. Med. Assoc., ahead of print.","DOI":"10.1016\/j.jfma.2025.08.036"},{"key":"ref_36","first-page":"1044","article-title":"Clinical Research Progress on Using \u03ba-Opioid Receptor Agonists to Treat Uremic Pruritus","volume":"55","author":"Yang","year":"2024","journal-title":"Sichuan Da Xue Xue Bao Yi Xue Ban"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"125","DOI":"10.4103\/1319-2442.391890","article-title":"Effects of Increased Blood Flow Rate and Oral Activated Charcoal on the Severity of Uremic Pruritus: A Randomized Crossover Clinical Trial","volume":"34","author":"Zanganeh","year":"2023","journal-title":"Saudi J. Kidney Dis. Transplant."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhao, J.H., Zhu, Q.S., Li, Y.W., and Wang, L.L. (2021). Determinants of the intensity of uremic pruritus in patients receiving maintenance hemodialysis: A cross-sectional study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0245370"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bolanos, C.G., Pham, N.M., Mair, R.D., Meyer, T.W., and Sirich, T.L. (2021). Metabolomic analysis of uremic pruritus in patients on hemodialysis. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0246765"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1684\/ndt.2024.60","article-title":"Diagnosis and management of pruritus associated with chronic kidney disease in hemodialyzed patients","volume":"20","author":"Lanot","year":"2024","journal-title":"Nephrol. Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1684\/ndt.2023.26","article-title":"Complications en h\u00e9modialyse: Focus sur le prurit et les calcifications vasculaires [Hemodialysis complications: Focus on pruritus and vascular calcifications]","volume":"19","author":"Lanot","year":"2023","journal-title":"Nephrol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Suliman, I.L., Panculescu, F.G., Fasie, D., Cimpineanu, B., Alexandru, A., Gafar, N., Popescu, S., Nitu, T.S., Enache, F.-D., and Chisnoiu, T. (2025). Gut Microbiome in Patients with Chronic Kidney Disease Stages 4 and 5: A Systematic Literature Review. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110706"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/851\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T08:34:39Z","timestamp":1768466079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/851"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,15]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020851"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020851","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,15]]}}}