{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T13:10:39Z","timestamp":1780319439265,"version":"3.54.1"},"reference-count":27,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Arteriovenous fistula (AVF) maturation is a critical determinant for successful hemodialysis in patients with end-stage renal disease (ESRD). Endothelial dysfunction and arterial stiffness, which are highly prevalent in advanced chronic kidney disease (CKD), frequently impair AVF maturation. Emerging evidence suggests that a very-low-protein diet (VLPD) supplemented with ketoacid analogues (KA) mitigates nitrogenous waste accumulation and positively influences vascular health by reducing inflammation and improving endothelial function. This prospective observational study evaluates the effect of VLPD+KA on AVF maturation, endothelial function, inflammatory markers, nutritional status, and the timing of dialysis initiation. We enrolled 20 patients with advanced CKD (stage V) scheduled for AVF creation. Participants adhered to a strict VLPD protocol (0.3\u20130.4 g\/kg\/day) with KA supplementation (1 tablet\/5 kg\/day). We assessed biochemical parameters, inflammatory markers (CRP, ESR), uremic toxins (indoxyl sulfate [IS], p-cresyl sulfate [PCS]), endothelial function via flow-mediated dilation (FMD), and vascular imaging metrics. AVF maturation, central venous catheter (CVC) requirement, dialysis initiation, and nutritional parameters were monitored over a three-month follow-up period. Statistical analyses included paired t-tests or Wilcoxon signed-rank tests for within-group comparisons, Fisher\u2019s exact test for categorical variables, and Kaplan\u2013Meier analysis for time-to-event endpoints, performed using SPSS version 27.0. Results: The intervention led to significant improvements in endothelial function (FMD +1.7%, p &lt; 0.01), substantial reductions in the uremic toxins IS (\u221238%, p &lt; 0.001) and PCS (\u221243%, p &lt; 0.001), and a marked decrease in CRP levels (from 3.2 to 1.1 mg\/L, p &lt; 0.01). Nutritional status, assessed by BMI, BIA-derived phase angle, and handgrip strength, remained stable throughout the intervention period, confirming the metabolic safety of the VLPD+KA regimen. Notably, AVF maturation was achieved in 95% of patients, with zero CVC dependency among those who initiated dialysis. Conclusions: These findings strongly support the hypothesis that VLPD+KA therapy enhances vascular integrity, reduces uremic endotheliotoxicity, and facilitates successful AVF maturation. This nutritional intervention warrants further investigation in larger, randomized controlled trials as a standard pre-dialysis care strategy.<\/jats:p>","DOI":"10.3390\/nu18111777","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:19:42Z","timestamp":1780316382000},"page":"1777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of a Very-Low-Protein Diet Supplemented with Ketoacid Analogues on Arteriovenous Fistula Maturation and Endothelial Function: A Prospective Observational Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Silvia","family":"Barbarini","sequence":"first","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Protopapa","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Font\u00f2","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3964-5135","authenticated-orcid":false,"given":"Paolo","family":"Ria","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Pesino","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1377-6137","authenticated-orcid":false,"given":"Anna","family":"Zito","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Scardia","sequence":"additional","affiliation":[{"name":"Clinical Nutrition Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8969-2697","authenticated-orcid":false,"given":"Stefania Maria Pia","family":"Doronzo","sequence":"additional","affiliation":[{"name":"INSPIRE Lab, Department of Biological and Environmental Sciences and Technologies, University of Salento, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4535-4182","authenticated-orcid":false,"given":"Marcello","family":"Napoli","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1685-7263","authenticated-orcid":false,"given":"Antonio","family":"De Pascalis","sequence":"additional","affiliation":[{"name":"Nephrology Department, Vito Fazzi Hospital, ASL Lecce, 73100 Lecce, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1053\/j.ajkd.2019.12.001","article-title":"KDOQI Vascular Access Guideline Work Group. KDOQI Clinical Practice Guideline for Vascular Access: 2019 Update","volume":"75","author":"Lok","year":"2020","journal-title":"Am. J. Kidney Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/S0735-1097(01)01746-6","article-title":"Guidelines for the Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery","volume":"39","author":"Corretti","year":"2002","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1053\/j.ajkd.2013.08.023","article-title":"Patency Rates of the Arteriovenous Fistula for Hemodialysis: A Systematic Review and Meta-analysis","volume":"63","author":"Thomas","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Marrone, G., Cornali, K., Di Lauro, M., Ceravolo, M.J., Di Marco, L., Manca di Villahermosa, S., Mitterhofer, A.P., and Noce, A. (2024). Innovative Treatments to Counteract Endothelial Dysfunction in Chronic Kidney Disease Patients. Biomedicines, 12.","DOI":"10.3390\/biomedicines12051085"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.diabres.2008.09.053","article-title":"Serum indoxyl sulfate levels in patients with diabetic nephropathy: Relation to renal function","volume":"83","author":"Keita","year":"2009","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1111\/j.1523-1755.2004.00399.x","article-title":"The uremic solutes p-cresol and indoxyl sulfate inhibit endothelial proliferation and wound repair","volume":"65","author":"Dou","year":"2004","journal-title":"Kidney Int."},{"key":"ref_7","first-page":"2057","article-title":"Link between gut microbiota dysbiosis and chronic kidney disease","volume":"26","author":"Noce","year":"2022","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mertowska, P., Mertowski, S., Wojnicka, J., Korona-G\u0142owniak, I., Grywalska, E., B\u0142a\u017cewicz, A., and Za\u0142uska, W. (2021). A Link between Chronic Kidney Disease and Gut Microbiota in Immunological and Nutritional Aspects. Nutrients, 13.","DOI":"10.3390\/nu13103637"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Kadatane, S.P., Satariano, M., Massey, M., Mongan, K., and Raina, R. (2023). The Role of Inflammation in CKD. Cells, 12.","DOI":"10.3390\/cells12121581"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"38869","DOI":"10.1074\/jbc.M110.166686","article-title":"Indoxyl sulfate induces leukocyte-endothelial interactions through up-regulation of E-selectin","volume":"285","author":"Ito","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","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":"ref_12","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1053\/j.ajkd.2007.02.278","article-title":"Efficacy and safety of a very-low-protein diet when postponing dialysis in the elderly","volume":"49","author":"Brunori","year":"2007","journal-title":"Am. J. Kidney Dis."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Albert, L., Hsiang-Yen, L., and Yen-Chung, L. (2019). The effect of Ketoanalogues on Chronic Kidney Disease Deterioration: A Meta-analysis. Nutrients, 11.","DOI":"10.3390\/nu11050957"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"David, C., Peride, I., Niculae, A., Constantin, A.M., and Checherita, I.A. (2016). Very low protein diets supplemented with keto-analogues in ESRD predialysis patients and its effect on vascular stiffness and AVF Maturation. BMC Nephrol., 17.","DOI":"10.1186\/s12882-016-0347-y"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"11288","DOI":"10.3390\/ijms130911288","article-title":"Asymmetric dimethylarginine, endothelial dysfunction and renal disease","volume":"13","author":"Andrade","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s11658-023-00423-2","article-title":"Endothelial dysfunction due to eNOS uncoupling","volume":"28","author":"Dobrucki","year":"2023","journal-title":"Cell Mol. Biol. Lett."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1007\/s00508-008-0987-4","article-title":"Reduction of plasma asymmetric dimethylarginine in obese patients with chronic kidney disease after three years of a low-protein diet supplemented with keto-amino acids: A randomized controlled trial","volume":"120","author":"Teplan","year":"2008","journal-title":"Wien. Klin. Wochenschr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s41581-018-0098-z","article-title":"Endothelium structure and function in kidney health and disease","volume":"15","author":"Fakhouri","year":"2019","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1681\/ASN.2008101106","article-title":"Dietary phosphorus acutely impairs endothelial function","volume":"20","author":"Shuto","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cozzolino, M., Ciceri, P., Galassi, A., Mangano, M., Carugo, S., Capelli, I., and Cianciolo, G. (2019). The Key Role of Phosphate on Vascular Calcification. Toxins, 11.","DOI":"10.3390\/toxins11040213"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"E629","DOI":"10.1152\/ajpendo.00247.2020","article-title":"Endothelial dysfunction due to selective insulin resistance in vascular endothelium","volume":"319","author":"Muniyappa","year":"2020","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2219","DOI":"10.1056\/NEJMoa2025845","article-title":"Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes","volume":"383","author":"Bakris","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Marrone, G., Urciuoli, S., Di Lauro, M., Ruzzolini, J., Ieri, F., Vignolini, P., Di Daniele, F., Guerriero, C., Nediani, C., and Di Daniele, N. (2022). Extra Virgin Olive Oil and cardiovascular protection in Chronic kidney disease. Nutrients, 14.","DOI":"10.3390\/nu14204265"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kalantar-Zadeh, K., Joshi, S., Schlueter, R., Cooke, J., Brown-Tortorici, A., Donnelly, M., Schulman, S., Lau, W.-L., Rhee, C.M., and Streja, E. (2020). Plant-dominant low-protein diet for conservative management of chronic kidney disease. Nutrients, 12.","DOI":"10.20944\/preprints202005.0516.v1"},{"key":"ref_25","first-page":"3733","article-title":"The possible role of physical activity in the modulation of gut microbiota in chronic kidney disease and its impact on cardiovascular risk","volume":"27","author":"Noce","year":"2023","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Carmona, A., Guerrero, F., Buendia, P., Obrero, T., Aljama, P., and Carracedo, J. (2017). Microvesicles derived from indoxyl sulfate treated endothelial cells induce endothelial progenitor cells dysfunction. Front. Physiol., 8.","DOI":"10.3389\/fphys.2017.00666"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1038\/ki.2010.471","article-title":"Prevention and management of catheter-related infection in hemodialysis patient","volume":"79","author":"Charmaine","year":"2011","journal-title":"Kidney Int."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/11\/1777\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:33:34Z","timestamp":1780317214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/18\/11\/1777"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,31]]},"references-count":27,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2026,6]]}},"alternative-id":["nu18111777"],"URL":"https:\/\/doi.org\/10.3390\/nu18111777","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,31]]}}}