{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T01:28:00Z","timestamp":1792718880193,"version":"4.5.0"},"reference-count":38,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"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: Chronic kidney disease (CKD) is characterised by a disrupted gut\u2013kidney axis, wherein intestinal dysbiosis is associated with the accumulation of uraemic toxins and the potential depletion of beneficial short-chain fatty acids (SCFAs). Whilst acetate, propionate, and butyrate are known to modulate systemic inflammation and blood pressure, their precise circulating concentrations across different CKD stages and age groups remain poorly defined. This systematic review and meta-analysis aimed to quantify blood SCFA concentrations in CKD patients compared to healthy controls. Methods: We conducted a systematic search of Medline, EMBASE, and the Cochrane Library for clinical studies reporting blood SCFA concentrations in humans with CKD. Methodological quality was assessed using the NIH tool. Standardised mean differences (SMDs) were calculated for the quantitative meta-analysis, with subgroup analyses performed for age, CKD stage, and treatment modality (dialysis vs. transplantation). Results: Twenty-one studies encompassing 9661 participants were included. Quantitative synthesis revealed a significant and consistent systemic depletion of circulating acetate and propionate in adult CKD patients compared to healthy controls (p &lt; 0.05). This depletion followed a stage-dependent trajectory, worsening alongside declining glomerular filtration rates. Notably, a \u201cbutyrate paradox\u201d was identified in paediatric cohorts; whilst adults showed progressive butyrate depletion, children with CKD often maintained or exhibited elevated levels, particularly in the context of hypertension. Furthermore, whilst haemodialysis patients exhibited the most profound SCFA deficiencies, kidney transplantation appeared to partially restore these metabolites toward healthy baseline levels. Conclusions: CKD is associated with a profound systemic reduction in acetate and propionate, supporting the model of a compromised gut\u2013kidney axis based on converging evidence. The divergent results for butyrate in paediatric versus adult populations suggest that SCFA metabolism is influenced by age-related factors or compensatory mechanisms. These findings highlight the potential for SCFA monitoring as a candidate or emerging markers for detecting early renal damage and stratifying risk.<\/jats:p>","DOI":"10.3390\/nu18091440","type":"journal-article","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:35:53Z","timestamp":1777559753000},"page":"1440","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Circulating Short-Chain Fatty Acid Levels in Chronic Kidney Disease: A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0522-5431","authenticated-orcid":false,"given":"Devika","family":"Thakur","sequence":"first","affiliation":[{"name":"Department of Paediatrics, St Helier Hospital, Wrythe Ln, Carshalton SM5 1AA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2977-0263","authenticated-orcid":false,"given":"Matthew J.","family":"Harmer","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology, Southampton Children\u2019s Hospital, Tremona Rd, Southampton SO16 6YD, UK"},{"name":"School of Development and Health, Faculty of Medicine, University of Southampton, University Rd, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1002\/iub.572","article-title":"The Monocarboxylate Transporter Family\u2014Role and Regulation","volume":"64","author":"Halestrap","year":"2012","journal-title":"IUBMB Life"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2325","DOI":"10.1194\/jlr.R036012","article-title":"The Role of Short-Chain Fatty Acids in the Interplay between Diet, Gut Microbiota, and Host Energy Metabolism","volume":"54","author":"Groen","year":"2013","journal-title":"J. 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