{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:03:49Z","timestamp":1790327029615,"version":"4.1.0"},"reference-count":63,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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>Protein restriction is an established nutritional intervention for selected adults with non-dialysis chronic kidney disease (CKD); a supplemented very-low-protein diet (sVLPD) combines marked protein restriction with essential amino acids and their nitrogen-free keto- and hydroxyanalogues (KAs). KAs may accept amino groups and regenerate essential amino acids while limiting exogenous nitrogen, but reversible transamination competes with irreversible oxidative decarboxylation. This narrative review integrates the biochemical pharmacology of KA\/EAA mixtures with the clinical conditions required for effectiveness. Controlled and pragmatic trials are contrasted to distinguish efficacy under selected, adherent conditions from effectiveness in routine care. Safe implementation requires achieved protein restriction, adequate non-protein energy intake, correction of persistent metabolic acidosis, metabolic stability, administration with meals, appropriate dosing and structured monitoring; however, the specific effects of these conditions on in vivo KA disposition have not been quantified in advanced CKD. KA\/EAA-supplemented VLPD may delay kidney replacement therapy in appropriately selected and supervised patients, but the supplement should be prescribed as part of a complete nutritional strategy rather than as an autonomous drug.<\/jats:p>","DOI":"10.3390\/nu18193157","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T08:09:02Z","timestamp":1790323742000},"page":"3157","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ketoanalogues of Essential Amino Acids in Chronic Kidney Disease: From Biochemical Rationale to Conditions for Clinical Effectiveness"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8995-936X","authenticated-orcid":false,"given":"Adamasco","family":"Cupisti","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2313-5461","authenticated-orcid":false,"given":"Claudia","family":"D\u2019Alessandro","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Panichi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1223-0167","authenticated-orcid":false,"given":"Diego","family":"Moriconi","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-9744","authenticated-orcid":false,"given":"Domenico","family":"Giannese","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/S0140-6736(64)91919-1","article-title":"A low nitrogen diet with proteins of high biological value for severe chronic uremia","volume":"1","author":"Giovannetti","year":"1964","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1093\/ndt\/gfu218","article-title":"Protein restriction: A revisited old strategy with new opportunities?","volume":"29","author":"Locatelli","year":"2014","journal-title":"Nephrol. 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