title: Indoxyl sulphate and kidney disease: Causes, consequences and interventions.
abstract: In the last decade, chronic kidney disease (CKD), defined as reduced renal function (glomerular filtration rate (GFR) < 60 mL/min per 1.73 m(2) ) and/or evidence of kidney damage (typically manifested as albuminuria) for at least 3 months, has become one of the fastest-growing public health concerns worldwide. CKD is characterized by reduced clearance and increased serum accumulation of metabolic waste products (uremic retention solutes). At least 152 uremic retention solutes have been reported. This review focuses on indoxyl sulphate (IS), a protein-bound, tryptophan-derived metabolite that is generated by intestinal micro-organisms (microbiota). Animal studies have demonstrated an association between IS accumulation and increased fibrosis, and oxidative stress. This has been mirrored by in vitro studies, many of which report cytotoxic effects in kidney proximal tubular cells following IS exposure. Clinical studies have associated IS accumulation with deleterious effects, such as kidney functional decline and adverse cardiovascular events, although causality has not been conclusively established. The aims of this review are to: (i) establish factors associated with increased serum accumulation of IS; (ii) report effects of IS accumulation in clinical studies; (iii) critique the reported effects of IS in the kidney, when administered both in vivo and in vitro; and (iv) summarize both established and hypothetical therapeutic options for reducing serum IS or antagonizing its reported downstream effects in the kidney.
authors.affiliation: Centre for Kidney Disease Research, Translational Research Institute, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ellis
authors.affiliation: Centre for Kidney Disease Research, Translational Research Institute, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Small
authors.affiliation: Centre for Kidney Disease Research, Translational Research Institute, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: David A
authors.initials: DA
authors.lastname: Vesey
authors.affiliation: Centre for Kidney Disease Research, Translational Research Institute, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.|Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: David W
authors.initials: DW
authors.lastname: Johnson
authors.affiliation: Department of Renal Medicine, University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia.
authors.forename: Ross
authors.initials: R
authors.lastname: Francis
authors.affiliation: Sydney Medical School - Medical Sciences, Medlab, Sydney, New South Wales, Australia.|Medlab Clinical Ltd., Medlab, Sydney, New South Wales, Australia.
authors.forename: Luis
authors.initials: L
authors.lastname: Vitetta
authors.affiliation: Centre for Kidney Disease Research, Translational Research Institute, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Glenda C
authors.initials: GC
authors.lastname: Gobe
authors.affiliation: Centre for Kidney Disease Research, Translational Research Institute, School of Medicine, University of Queensland, Brisbane, Queensland, Australia.
authors.forename: Christudas
authors.initials: C
authors.lastname: Morais
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D018753:Diet, Protein-Restricted; D004043:Dietary Fiber / Q000008:administration & dosage; D064806:Dysbiosis; D000069196:Gastrointestinal Microbiome; D005919:Glomerular Filtration Rate; D006801:Humans; D007200:Indican / Q000097:blood*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019936:Probiotics; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D015854:Up-Regulation; D064804:Urological Agents / Q000627:therapeutic use
chemical_list: D004043:Dietary Fiber; D064804:Urological Agents; D007200:Indican
keywords: GFR; end-stage kidney disease; indoxyl sulphate; oxidative stress; uremic toxin