Reduction of Oxidative Stress in Chronic Kidney Disease Does Not Increase Circulating alpha-Klotho Concentrations

The CKD-associated decline in soluble alpha-Klotho levels is considered detrimental. Some in vitro and in vivo animal studies have shown that anti-oxidant therapy can upregulate the expression of alpha-Klotho in the kidney. We examined the effect of anti-oxidant therapy on alpha-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 (alpha-tocopherol acetate, 300 mg/d) while the placebo was not treated with anti-oxidants. alpha-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/1.72m(2), 34 were male and mean age was 53.0 +/- 12.5 years old. Anti-oxidative therapy did successfully reduce oxLDL and LDL concentrations (P