Serum klotho is inversely associated with metabolic syndrome in chronic kidney disease: results from the KNOW-CKD study

Abstract

BackgroundMetabolic syndrome (MS) is prevalent in chronic kidney disease (CKD). Klotho, a protein linked to aging, is closely associated with CKD. Each component of MS and klotho has an association. However, little is known about the association between klotho and MS per se. We investigated the association between serum klotho levels and MS using baseline cross-sectional data obtained from a large Korean CKD cohort.MethodsOf the 2238 subjects recruited in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) between 2011 and 2016, 484 patients with missing data on serum klotho and extreme klotho values (values lower than the detectable range or\u2009>\u20096000\u2009pg/mL) or with autosomal dominant polycystic kidney disease patients were excluded. The data of the remaining 1754 subjects were included in the present study. MS was defined using the revised National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III criteria. Serum klotho levels were measured using an enzyme-linked immunosorbent assay.ResultsMean patient age was 54.9\u2009±\u200912.1\u2009years and 1110 (63.3%) were male. The prevalence of MS among all study subjects was 63.7% (n\u2009=\u20091118). The median serum klotho level was 527\u2009pg/mL (interquartile range [IQR]: 418–656\u2009pg/mL). Serum klotho level was significantly lower in MS patients than patients without MS (Median [IQR]; 521\u2009pg/mL [413, 651] vs. 541\u2009pg/mL [427, 676], respectively; P\u2009=\u20090.012). After adjusting for age, sex, estimated glomerular filtration rate, and overt proteinuria, serum klotho was independently associated with MS (adjusted odds ratio [OR], 0.44; 95% confidence interval, 0.23–0.82; P\u2009=\u20090.010). Furthermore, the adjusted OR for MS was found to be significantly increased at serum klotho levels of <\u2009518\u2009pg/mL (receiver operating characteristic curve cut-off value).ConclusionsSerum klotho was inversely associated with the presence of MS in patients with CKD.Trial registrationThis trial was registered on ClinicalTrials.gov on 26 June 2012 (https://clinicaltrials.gov;NCT01630486).