{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:18:00Z","timestamp":1793085480258,"version":"4.5.0"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017530","name":"Fresenius Kabi","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017530","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,26]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic kidney disease (CKD) is a global health concern with significant economic implications, particularly in the management of end-stage renal disease (ESRD), which often requires kidney replacement therapy such as dialysis or transplantation. The rising incidence of ESRD is expected to increase healthcare costs substantially by 2030. Dietary protein restriction is a cornerstone of managing CKD progression, and the use of ketoanalogues in very low-protein diets (VLPD) has shown promise in delaying dialysis initiation. This study evaluates the cost-effectiveness of a vegetarian ketoanalogue-supplemented VLPD (s-VLPD) compared with a low-protein diet (LPD) in patients with CKD stages 4 and 5 in Italy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A Markov model was developed to simulate the health outcomes and costs for patients with CKD stages 4 or 5, treated with either s-VLPD or LPD. The analysis was conducted from both the Italian National Healthcare Service (NHS) and societal perspectives. Healthcare costs considered were: ketoanalogue supplementation, dialysis and diet monitoring. Overall survival and quality-adjusted life years (QALYs) were used as effectiveness outcomes. Sensitivity analyses, including deterministic and probabilistic approaches, assessed the robustness of the results.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The s-VLPD strategy led to improved survival (+0.60 years) and increased QALYs (+0.49) compared with LPD, along with cost savings of approximately \u20ac34\u2009000 per patient from the NHS perspective. From the societal perspective, s-VLPD resulted in a cost saving of \u20ac59\u2009147 per patient. Sensitivity analyses confirmed that s-VLPD remains a dominant strategy, demonstrating both clinical and economic advantages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>s-VLPD is a cost-effective strategy for managing CKD stages 4 and 5, offering improved patient outcomes and significant cost savings. The findings support the integration of s-VLPD in routine clinical practice, helping delay dialysis initiation, reduce the financial burden on healthcare systems and improve patient quality of life.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ndt\/gfaf123","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T07:36:17Z","timestamp":1751960177000},"page":"2372-2378","source":"Crossref","is-referenced-by-count":2,"title":["Cost-effectiveness of a ketoanalogue-supplemented very low-protein diet in CKD"],"prefix":"10.1093","volume":"40","author":[{"given":"Massimiliano","family":"Povero","sequence":"first","affiliation":[{"name":"AdRes-Health Economics and Outcome Research , 10155 Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Simion","sequence":"additional","affiliation":[{"name":"AdRes-Health Economics and Outcome Research , 10155 Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Pradelli","sequence":"additional","affiliation":[{"name":"AdRes-Health Economics and Outcome Research , 10155 Turin ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"2025112604015646900_bib1","doi-asserted-by":"publisher","first-page":"2142","DOI":"10.12688\/f1000research.21374.1","article-title":"Humanistic burden and economic impact of chronic kidney disease: a systematic literature review","volume":"8","author":"Freeman","year":"2019","journal-title":"F1000Res"},{"key":"2025112604015646900_bib2","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1016\/S0140-6736(20)30045-3","article-title":"Global, regional, and national burden of chronic kidney disease, 1990\u20132017: a systematic analysis for the Global Burden of Disease Study 2017","volume":"395","author":"GBD Chronic Kidney Disease Collaboration","year":"2020","journal-title":"Lancet"},{"key":"2025112604015646900_bib3","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1016\/S0140-6736(14)61601-9","article-title":"Worldwide access to treatment for end-stage kidney disease: a systematic review","volume":"385","author":"Liyanage","year":"2015","journal-title":"Lancet"},{"key":"2025112604015646900_bib4","doi-asserted-by":"publisher","first-page":"e0230512","DOI":"10.1371\/journal.pone.0230512","article-title":"The impact of chronic kidney disease on developed countries from a health economics perspective: a systematic scoping review","volume":"15","author":"Elshahat","year":"2020","journal-title":"PLoS One"},{"key":"2025112604015646900_bib5","doi-asserted-by":"publisher","first-page":"S117","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","author":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group","year":"2024","journal-title":"Kidney Int"},{"key":"2025112604015646900_bib6","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1056\/NEJMra1700312","article-title":"Nutritional management of chronic kidney disease","volume":"377","author":"Kalantar-Zadeh","year":"2017","journal-title":"N Engl J Med"},{"key":"2025112604015646900_bib7","doi-asserted-by":"publisher","first-page":"710","DOI":"10.4103\/1319-2442.185227","article-title":"Comparative evaluation of efficacy and safety profile of rhubarb and \u03b1-keto analogs of essential amino acids supplementation in patients with diabetic nephropathy","volume":"27","author":"Khan","year":"2016","journal-title":"Saudi J Kidney Dis Transpl"},{"key":"2025112604015646900_bib8","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfz096.FO012","article-title":"Vegetarian severe hypoproteic diet supplemented with keto-analogues for predialysis chronic kidney disease patients: the influence on long term prognosis","volume":"34","author":"Garneata","year":"2019","journal-title":"Nephrol Dial Transpl"},{"key":"2025112604015646900_bib9","doi-asserted-by":"publisher","first-page":"2164","DOI":"10.1681\/ASN.2015040369","article-title":"Ketoanalogue-supplemented vegetarian very low-protein diet and CKD progression","volume":"27","author":"Garneata","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"2025112604015646900_bib10","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1053\/j.jrn.2013.01.030","article-title":"Effect of low-protein diet supplemented with keto acids on progression of chronic kidney disease","volume":"23","author":"Garneata","year":"2013","journal-title":"J Ren Nutr"},{"key":"2025112604015646900_bib11","article-title":"Linee guida per la compilazione del Dossier a supporto della domanda di rimborsabilit\u00e0 e prezzo di un medicinale. 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