α-Klotho is associated with cardiovascular and all-cause mortality in patients with stage 3b and 4 chronic kidney disease (CKD): a long-term prospective cohort study.

BACKGROUND: α-Klotho deficiency may increase cardiovascular risks and worsen survival. We evaluated the association of α-Klotho with cardiovascular and all-cause mortality in pre-dialysis chronic kidney disease (CKD) patients. METHODS: In this prospective study, 75 non-diabetic CKD stage 3b-4 patients were followed-up for a median of 8 years. Primary and secondary outcomes were all-cause and cardiovascular mortality, respectively. Human soluble α-Klotho ELISA Assay (IBL-Takara 27,998-96Well), Human Fibroblast Growth Factor-23 ELISA Assay (intact FGF23, Merck Millipore MILLENZ FGF23-32 K), and Human Sclerostin ELISA kits (Biomedica, Vienna, BI-20492) were used to measure serum α-Klotho, FGF23 and sclerostin levels in the certified laboratory at the Sechenov University according to the manufacturers' protocols. All patients underwent echocardiography to evaluate left ventricular mass index (LVMI), left ventricular ejection fraction by Simpson method, and cardiac (valve) calcification score by a semi-quantitative point scale. Lateral abdominal radiography by Kauppila method was used to estimate calcification of the abdominal aorta. Cox multivariate regression and receiver-operating characteristic curve (ROC)-analysis were used to evaluate risk factors for death and their cut-off values. RESULTS: Primary and secondary endpoints were reached in 15 (20%) and 9 (12%) patients, respectively. Median α-Klotho levels in deceased and surviving patients were 344 and 484 pg/ml, respectively (p = 0.002). In a multivariate Cox regression model, baseline α-Klotho levels (HR 0.99, 95% CI 0.98-1.00, p = 0.023), aortic calcification (HR 1.18, 95% CI 1.02-1.36, p = 0.029) and left ventricular mass index (LVMI) (HR 1.04, 95% CI 1.00-1.08, p = 0.033) were associated with the primary endpoint, whereas α-Klotho (HR 0.99, 95% CI 0.98-1.00, p = 0.029), aortic calcification (HR 1.23, 95% CI 1.07-1.42, p = 0.003) and LVMI (HR 1.04, 95% CI 1.00-1.08, p = 0.021) were associated with the secondary endpoint. α-Klotho levels had the highest area under the curve (AUC) by ROC analysis, that is, 0.766 (95% CI 0.70-0.82) for the primary endpoint and 0.842 (95% CI 0.79-0.90) for the secondary endpoint with cut-off values of 412 pg/ml (HR 3.06, 95% CI 1.36-6.89, p = 0.007) and 368 pg/ml (HR 4.84, 95% CI 1.59-14.73, p = 0.005), respectively. CONCLUSION: In pre-dialysis CKD patients, α-Klotho levels are associated with all-cause and cardiovascular mortality and may be considered an early prognostic marker.

Soy Protein as a Part of a Low-protein Diet is a New Direction in Cardio- and Nephroprotection in Patients With 3b-4 Stages of Chronic kidney Disease.

It has been established that the use of a low-protein diet (LPD) in combination with ketoanalogues of essential amino acids (KA) can contribute to cardio and nephroprotection in chronic kidney disease (CKD). Moreover, it has been shown that partial replacement of the animal protein with soy protein (SP) in the diet contributed to more pronounced nephro and cardioprotection in CKD, however, the data, available in the literature, are mainly represented by experimental studies. AIM OF THE STUDY: We conducted a prospective randomized controlled clinical study that compared the effects of 2 types of diets on the main parameters of nephro and cardioprotection in patients with CKD. MATERIALS AND METHODS: The study included 85 CKD 3b-4 stages G3b-4 patients, compliant to LPD (0.6 g of protein/kg of body weight) + KA (1 tablet/5 kg of body weight). 43 patients (Group 1) received LPD with substitution of animal protein with soy (60% SP + 40% of other vegetable proteins) + KA, and 42 patients (control group (Group 2) received conventional LPD (60% animal protein +40% of vegetable protein) + KA, within 12 months. RESULTS: Substitution of animal protein with SP in diet of patients with CKD to a greater extent delayed the decrease in eGFR (-5.9% vs -11.3%, P = .048), the increase in left ventricle hypertrophy (+4.7% vs +12.3%, P = .042), as well as the increase in central systolic blood pressure (+2.6% vs +13.0%, P = .021), augmentation index (+7.6% vs +23.3%, P = .010), slowed down the decrease in lean body mass in males (+0.9% vs -11.2%, P = .017) and females (-1.8% vs -10.3%, P = .024), increase in phosphorus (-10.3% vs +13.0%, P = .029), cholesterol (-10.7% vs -3.4% P = .047) and urea (+6.3% vs +19.6%, P = .035) serum levels. CONCLUSION: The use of LPD with substitution of animal protein with SP + KA provides more pronounced effect on nephro and cardioprotection as well as maintenance of nutritional status, than conventional LPD + KA in patients with CKD 3b-4 stages.

Cardiovascular remodeling as a result of fibroblast growth factor-23 (FGF-23)/Klotho imbalance in patients with CKD.

BACKGROUND: In chronic kidney disease (CKD) cardiovascular remodeling (CVR) is very frequent compared with general population and, as suppose, may be associated with «new¼ renal risk factors. The aim of study was to estimate association of new serum biomarkers (FGF-23, Klotho) and traditional biomarker of cardiac damage-serum Troponin I (sTr-I) with signs of CVR. METHODS: One hundred thirty CKD G1-5D patients without cardiovascular disease (CVD) clinical manifestation were included. We measured serum FGF-23, Klotho and sTr-I. The instrumental methods were: echocardiography, SphygmoCor test [Pulse Wave Velocity (PWV), Central (aortic) Blood Pressure (CBP), Subendocardial Blood Supply (SBS)]. RESULTS: FGF-23 level correlated with: sTr-I (r = 0.512; p < 0.01), eccentric left ventricular hypertrophy, LVH (r = 0.543; p < 0.01), SBS (r = - 0.499; p < 0.05). There were no differences of FGF-23 level in patients with normal and high CBP. Klotho correlated with concentric LVH (r = - 0.451; p < 0.01), PWV (r = - 0.667; p < 0.001), Cardiac Calcification Score, CCS (r = - 0.581; p < 0.01). Multivariate analysis revealed positive independent association of FGF-23 with eccentric LVH (OR = 1.036, 95% CI (1.004-1.068); p = 0.038). Klotho was a negative determinant for concentric LVH (OR = 0.990, 95% CI 0.987-0.994; p < 0.001), increased PWV (OR = 0.984, 95% CI (0.977-0.991); p < 0.001) and CCS (OR = 0.991, 95% CI (0.988-0.995); p < 0.001). In addition, multivariate analysis revealed a relationship between serum Klotho (OR = 0.980, 95% CI (0.964-0.996); p = 0.016), FGF-23 (OR = 3.145, 95% CI (1.020-9.695); p = 0.046) and troponin I level. CONCLUSION: In CKD patients without CVD clinical manifestation increased serum FGF-23 level and decreased Klotho are associated with CVR: FGF-23 with eccentric LVH (independently of CBP), Klotho determinate concentric LVH, PWV and CCS. Moderately elevated sTr-I levels may be a manifestation of FGF-23/Klotho imbalance in CKD.