MP263IMPACT OF TRADITIONAL ANTIHYPERTENSIVE THERAPY ON CARDIOVASCULAR RISK MARKER - KLOTHO IN CHRONIC KIDNEY DISEASE PATIENTS

Abstract

Introduction and Aims: Chronic kidney disease is widespread in the population, and the results of epidemiological studies in recent years allow to consider it as an independent predictor of development and progression of cardiovascular events (CVE), risk of which, including young patients with CKD increased in 10-100 times. In the genesis of CVE in CKD many mechanisms work. Among them, in recent years, much attention is paid to morphogenetic protein - Klotho. Experimental damage of Klotho gene in mice causes vascular calcification, pathological fractures, premature aging syndrome. At the same time, it is found that the circulating form of Klotho protein can function as a humoral factor that protects cardiovascular system: Klotho overexpression experimentally provides both renal and cardiovascular protection. The aim of the study was to evaluate the impact of traditional antihypertensive therapy on serum Klotho levels in CKD 1- 4 stages patients. Method(s): The main group consisted of 110 CKD patients (1-4 stages) and the control group - of 30 age and sex matched healthy volunteers. Patients were divided into groups according to the type of received antihypertensive drugs: ACE inhibitors, angiotensin II receptor antagonists (ARA), calcium channel blockers, beta-blockers and other drugs. The groups were matched for age, sex, stage of CKD and the number of people in a group (n = 22, n = 24, n = 23, n = 21, n = 20, respectively). Patients receiving combined antihypertensive therapy were excluded. All patients signed a voluntary consent to participate in research. ELISA was used for serum Klotho study (Human alpha-Kl ELISA kit with using anti-Klotho antibodies). Blood pressure (BP) including brachial and central (aortic) pressure were measured to all the patients, as well as PulseWave Velocity (PWV) with a Sfigmokor device (Australia), ECG, EchoCG were performed. All patients were observed in dynamic within 1 year. The study was approved by the institute ethical committee. Result(s): When comparing the degree of blood pressure-BP (both brachial and central) and serum Klotho levels at the time of screening it turned out that Klotho was sensitive to the hypertension severity [r=-0,564; p<0,01 and r=-0,675;p<0,01 respectively]. In addition, a negative correlation between Klotho and PWV [r=-0,647;p<0,01] as well as with the heart calcification degree [r=-0,612;p<0,01] assessed by semiquantitative scale, were obtained. According to the ROC-analysis the values of serum Klotho levels below 347 pg/ml testified the myocardium calcification with 80% sensitivity and 75% specificity. In studied patients we evaluated the effects of antihypertensive drug groups on serum Klotho levels after 1 year therapy. To the end of the study the highest Klotho levels [673+/- 68 pg/ml] were observed in patients, whose target values of BP (120/ 80-130/80 mm Hg) were achieved and maintained predominantly with ARA compared to those who used other drug groups [p<0,01] or who unreached target BP levels [ p<0,01]. Conclusion(s): The study has demonstrated that the use of ARA among the other groups of antihypertensive drugs most preferably prevent the reducing of Klotho production as cardio-nephroprotective marker. However, further research are required to study the effects of drugs and their combinations to stimulate Klotho production in CKD.