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

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

Fibroblast Growth Factor 23 and Cardiovascular Mortality after Kidney Transplantation

<p>Background and objectivesCirculating fibroblast growth factor 23 (FGF23) is associated with adverse cardiovascular outcomes in CKD. Whether FGF23 predicts cardiovascular mortality after kidney transplantation, independent of measures of mineral metabolism and cardiovascular risk factors, is unknown.Design, setting, participants, & measurementsThe association between plasma C-terminal FGF23 and cardiovascular mortality was analyzed in a single-center prospective cohort of 593 stable kidney transplant recipients (mean age SD, 5212 years; 54% male; estimated GFR, 47 +/- 16 ml/min per 1.73 m(2)), at a median of 6.1 (interquartile range, 2.7-11.7) years after transplantation. Multivariate Cox regression models were built, adjusting for measures of renal function and mineral metabolism; Framingham risk factors; the left ventricular wall strain markers midregional fragment of pro-A-type natriuretic peptide (MR-proANP) and N-terminal-pro brain natriuretic peptide (NT-proBNP); and copeptin, the stable C-terminal portion of the precursor of vasopressin.ResultsIn multivariate linear regression analysis, MR-proANP (=0.20, P</p>

Membrane-bound Klotho is not expressed endogenously in healthy or uraemic human vascular tissue

Perioperative Medicine: Efficacy, Safety and Outcom

Influence of exogenous growth hormone administration on circulating concentrations of α-klotho in healthy and chronic kidney disease subjects: a prospective, single-center open case-control pilot study

Abstract Background The CKD-associated decline in soluble α-Klotho (α-Klotho) levels is considered detrimental. Some studies suggest a direct induction of α-Klotho concentrations by growth hormone (GH). In the present study, the effect of exogenous GH administration on α-Klotho concentrations in a clinical cohort with mild chronic kidney disease (CKD) and healthy subjects was studied. Methods A prospective, single-center open case-control pilot study was performed involving 8 patients with mild CKD and 8 healthy controls matched for age and sex. All participants received subcutaneous GH injections (Genotropin®, 20 mcg/kg/day) for 7 consecutive days. α-Klotho concentrations were measured at baseline, after 7 days of therapy and 1 week after the intervention was stopped. Results α-Klotho concentrations were not different between CKD-patients and healthy controls at baseline (554 (388–659) vs. 547 (421–711) pg/mL, P = 0.38). Overall, GH therapy increased α-Klotho concentrations from 554 (405–659) to 645 (516–754) pg/mL, P < 0.05). This was accompanied by an increase of IGF-1 concentrations from 26.8 ± 5.0 nmol/L to 61.7 ± 17.7 nmol/L (P < 0.05). GH therapy induced a trend toward increased α-Klotho concentrations both in the CKD group (554 (388–659) to 591 (358–742) pg/mL (P = 0.19)) and the healthy controls (547 (421–711) pg/mL to 654 (538–754) pg/mL (P = 0.13)). The change in α-Klotho concentration was not different for both groups (P for interaction = 0.71). α-Klotho concentrations returned to baseline levels within one week after the treatment (P < 0.05). Conclusions GH therapy increases α-Klotho concentrations in subjects with normal renal function or stage 3 CKD. A larger follow-up study is needed to determine whether the effect size is different between both groups or in patients with more severe CKD. Trial registration This trial is registered in EudraCT (2013–003354-24)

Fish and omega-3 fatty acid intake in relation to circulating fibroblast growth factor 23 levels in renal transplant recipients

Background and aims: A high circulating fibroblast growth factor 23 (FGF23) level is an independent risk factor for cardiovascular mortality in renal transplant recipients and the general population. N-3 fatty acids eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) may contribute to cardiovascular risk reduction. We investigated whether fish and EPA-DHA intake are related to FGF23 levels in renal transplant recipients.Methods and results: We performed a cross-sectional analysis in 619 stable renal transplant recipients (mean age 53 years, 57% male, estimated glomerular filtration rate [eGFR] 53 +/- 20 mL/min/1.73 m(2)). Dietary intake was assessed by a 177-item food frequency questionnaire. Serum intact FGF23 was measured by ELISA. We examined differences in FGF23 levels across categories of fish and EPA-DHA intake using analysis of variance models adjusted for age, sex, dietary and lifestyle factors and key determinants of FGF23. Patients consumed on average 15 g of fish and 139 mg EPA-DHA/day. Median FGF23 was 62 pg/mL (IQR 43-98 pg/mL). Higher dietary EPA-DHA and fish intake were associated with lower serum FGF23 levels. Subgroup analyses revealed that particularly in patients with reduced renal function (eGFR <60 mL/min/1.73 m(2)), adjusted FGF23 levels (114, 79, 75 pg/mL, P = 0.0001) were inversely associated with tertiles of EPA-DHA intake. Similarly, we observed an inverse association between fish consumption and serum FGF23 levels in adjusted analyses.Conclusion: A higher intake of fish and dietary n-3 fatty acids (EPA-DHA) is related to lower circulating FGF23 levels in renal transplant recipients. Further research is needed to assess the causality of this association and the clinical implications. (C) 2014 Elsevier B.V. All rights reserved.Dutch Kidney Foundation (NIGRAM consortium)Dutch Kidney foundation (MHdB)University Medical Center Groningen (MHdB)Netherlands Organization for Scientific Research (Veni grant)Top Institute Food and Nutrition (EvdB)Royal Netherlands Academy of Arts and SciencesUniv Groningen, Univ Med Ctr Groningen, Dept Nephrol, NL-9700 RB Groningen, NetherlandsUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilVU Univ Med Ctr Amsterdam, Dept Nephrol, Amsterdam, NetherlandsWageningen Univ, Div Human Nutr, NL-6700 AP Wageningen, NetherlandsUniversidade Federal de São Paulo, Dept Nephrol, São Paulo, BrazilDutch Kidney Foundation (NIGRAM consortium): CP10.11Top Institute Food and Nutrition (EvdB): TIFN A1003Web of Scienc