title: Insulin resistance and vascular dysfunction in chronic kidney disease: mechanisms and therapeutic interventions.
abstract: Insulin resistance (IR) is a novel cardiovascular risk factor that has been implicated in the pathogenesis of cardiovascular disease (CVD) in patients with chronic kidney disease (CKD). Beyond its metabolic effects, insulin can potentially mediate the increased risk for CVD through its vasoactive properties. This review examines key clinical data and potential mechanisms linking IR and cardiovascular risk in CKD. While lifestyle interventions and pharmacotherapies with known insulin-sensitizing properties are promising therapeutic targets to reduce the CVD burden in this population, clinical trial data on the effect of insulin sensitization on vascular function in CKD are either lacking or conflicting and are limited by small sample size and short duration of intervention. Affirming the role of IR in lowering CVD risk in CKD will require prospective randomized controlled studies with sufficient sample size and hard clinical outcomes. Future research efforts should be directed at assessing the efficacy, safety and mechanisms by which novel insulin sensitizers such as bile acid sequestrant, selective and dual peroxisome proliferator-activated receptor modulators and modulators of gut microbiota and uraemic toxins alter vascular function in patients with CKD.
authors.affiliation: Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
authors.forename: Doris T
authors.initials: DT
authors.lastname: Chan
authors.affiliation: Lipid Disorders Clinic, Cardiovascular Medicine, Royal Perth Hospital, Perth, WA, Australia.|School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia.
authors.forename: Gerald F
authors.initials: GF
authors.lastname: Watts
authors.affiliation: Department of Nephrology, Fiona Stanley Hospital, Murdoch, WA, Australia.
authors.forename: Ashley B
authors.initials: AB
authors.lastname: Irish
authors.affiliation: Department of Renal Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia.
authors.forename: Gursharan K
authors.initials: GK
authors.lastname: Dogra
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D006801:Humans; D007333:Insulin Resistance; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000503:physiopathology; D012307:Risk Factors
keywords: chronic kidney disease; insulin resistance; metabolic syndrome; vascular function