{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T09:03:27Z","timestamp":1790240607286,"version":"4.1.0"},"reference-count":144,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Chronic kidney disease (CKD) is associated with intestinal dysbiosis, barrier dysfunction, uremic toxin accumulation, and systemic inflammation. This narrative review critically evaluates the gut\u2013kidney axis, focusing on the distinction between NLRP3 [Nucleotide-binding Oligomerization Domain (NOD)-like receptor pyrin domain-containing protein 3] inflammasome priming and direct activation. It also examines the diagnostic and prognostic relevance of related biomarkers. Preclinical studies, clinical investigations, systematic reviews, meta-analyses, and relevant clinical trials within the past decade were considered. CKD-associated barrier dysfunction increases exposure to lipopolysaccharides and gut-derived metabolites. Lipopolysaccharide (LPS)-mediated TLR4\/NF-\u03baB (Toll-like receptor 4\/nuclear factor kappa B) signaling provides well-supported inflammasome priming. Indoxyl sulfate acts predominantly as a priming stimulus, although its effects vary among cell types. Direct NLRP3 activation by p-cresyl sulfate has not been demonstrated. Trimethylamine N-oxide has the strongest experimental evidence for inflammasome activation. Candidate biomarkers include these metabolites, microbial profiles, intestinal permeability markers, and inflammasome-related mediators. However, their interpretation is limited by dependence on renal clearance, assay heterogeneity, absent standardized thresholds, and uncertain added value beyond estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. Interventional studies remain small and predominantly use surrogate endpoints. The gut\u2013toxin\u2013inflammasome axis is mechanistically plausible, but evidence for priming is substantially stronger than that for direct activation. Its biomarkers remain research tools and require assay harmonization, prospective validation, and demonstration of independent clinical value before routine implementation.<\/jats:p>","DOI":"10.3390\/diagnostics16193084","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:03:26Z","timestamp":1790172206000},"page":"3084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut Dysbiosis, Uremic Toxins, and NLRP3 Signaling in Chronic Kidney Disease: From Mechanistic Evidence to Clinical Biomarker Evaluation"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-9542-0035","authenticated-orcid":false,"given":"Imola","family":"Donath-Miklos","sequence":"first","affiliation":[{"name":"Department of Biology and Life Science, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, B-dul Revolu\u021biei nr. 94-96, 310025 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8127-5131","authenticated-orcid":false,"given":"Oana","family":"\u0218tirbu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, B-dul Revolu\u021biei nr. 94-96, 310025 Arad, Romania"},{"name":"Hemodialysis Department, Arad County Emergency Clinical Hospital, Str. Andr\u00e9nyi K\u00e1roly nr 2-4, 310037 Arad, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1192-1452","authenticated-orcid":false,"given":"Romana Olivia","family":"Pope\u021biu","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine, \u201cVasile Goldi\u0219\u201d Western University of Arad, B-dul Revolu\u021biei nr. 94-96, 310025 Arad, Romania"},{"name":"Internal Medicine Clinic, Arad County Emergency Clinical Hospital, Str. 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