title: Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating α-Klotho Concentrations.
abstract: The CKD-associated decline in soluble α-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti-oxidant therapy can upregulate the expression of α-Klotho in the kidney. We examined the effect of anti-oxidant therapy on α-Klotho concentrations in a clinical cohort with mild tot moderate chronic kidney disease (CKD). We performed a post-hoc analysis of a prospective randomized trial involving 62 patients with mild to moderate CKD (the ATIC study), all using an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) for 12 months. On top of that, the intervention group received anti-oxidative therapy consisting of the combination of pravastatin (40 mg/d) and vitamin E (α-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. α-Klotho concentrations were measured at baseline and after 12 months of anti-oxidant therapy. Data were analysed using T-tests and Generalized Estimating Equations, adjusting for potential confounders such as vitamin D, parathyroid hormone, fibroblast-growth-factor 23 (FGF23) and eGFR. The cohort existed of 62 patients with an eGFR (MDRD) of 35 ± 14 ml/min/1.72 m2, 34 were male and mean age was 53.0 ± 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P <0.001). α-Klotho concentrations did not change in patients receiving either anti-oxidative therapy (476.9 ± 124.3 to 492.7 ± 126.3 pg/mL, P = 0.23) nor in those receiving placebo 483.2 ± 142.5 to 489.6 ± 120.3 pg/mL, P = 0.62). Changes in α-Klotho concentrations were not different between both groups (p = 0.62). No evidence was found that anti-oxidative therapy affected α-Klotho concentrations in patients with mild-moderate CKD.
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Aaltje Y
authors.initials: AY
authors.lastname: Adema
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frans J
authors.initials: FJ
authors.lastname: van Ittersum
authors.affiliation: Department of Physiology, Radboud university medical center Nijmegen, The Netherlands.
authors.forename: Joost G
authors.initials: JG
authors.lastname: Hoenderop
authors.affiliation: Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Martin H
authors.initials: MH
authors.lastname: de Borst
authors.affiliation: Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Prabath W
authors.initials: PW
authors.lastname: Nanayakkara
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Piet M
authors.initials: PM
authors.lastname: Ter Wee
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Annemieke C
authors.initials: AC
authors.lastname: Heijboer
authors.affiliation: Department of Nephrology, VU University Medical Center, Amsterdam, The Netherlands.|Institute for Cardiovascular Research VU (ICaR-VU), Amsterdam. The Netherlands.
authors.forename: Marc G
authors.initials: MG
authors.lastname: Vervloet
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood; D005919:Glomerular Filtration Rate; D005966:Glucuronidase / Q000097:blood*; D006801:Humans; D000090265:Klotho Proteins; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D017035:Pravastatin / Q000494:pharmacology / Q000627:therapeutic use*; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000188:drug therapy; D012084:Renin-Angiotensin System / Q000187:drug effects; D014810:Vitamin E / Q000494:pharmacology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000975:Antioxidants; D015415:Biomarkers; C000717427:FGF23 protein, human; D014810:Vitamin E; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D005966:Glucuronidase; D000090265:Klotho Proteins; D017035:Pravastatin