Recent studies have clearly linked higher serum inorganic phosphate (Pi) concentrations and an imbalance of Pi-regulation by kidney-bone-parathyroid endocrine systems to cardiovascular events and mortality. This association has been identified in patients with chronic kidney disease, as well as in general population. The editorial discusses the available clinical and experimental data linking the pathophysiology of phosphate exchange disorders and cardiovascular events.

The lecture reviews molecular and cellular mechanisms, which are cornerstone of structural and functional  remodeling and kidney and heart fibrosis formation in chronic kidney disease. The key ways linking kidney and heart remodeling, including myofibroblast formation by epithelial-mesenchymal and endotelial-mesenchymal transdifferentiation, extracellular matrix production, are presented. The role of angiotensin II, transforming growth factor Я1, plasminogen activator inhibitor type I, vascular endothelial growth factor, matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in mechanisms of fibro- and angiofibrogenesis are discussed. Further research of the molecular and cellular mechanisms of tissue fibrosis broadens our understanding about nephro- and cardioprotective effects of traditional approaches (angiotensin converting enzyme inhibitors or angiotensin II receptor blockers) and gives an opportunity for therapy targeting common mediators of fibro- and angiofibrogenesis in kidneys and heart.

Resistant hypertension is defined as uncontrolled blood pressure on optimal doses of three antihypertensive agents, including a diuretic. According to the data from different studies, its prevalence achieves 10–15 %. The upto- date approaches to classification, diagnostic algorithms are discussed; the reasons of resistant hypertension are reviewed. Special attention is paid to the opportunities of ambulatory blood pressure monitoring in distinguishing particular forms of resistant hypertension and pseudoresistant hypertension; a specific diagnostic algorithm is presented. 

The article reviews in brief the main approaches to the hypertension management in kidney damage based on the recommendations by the leading worldwide experts (the Joint National Committee of the USA, European Society of Cardiology/European Society of Hypertension, American Society of Hypertension/International Society of Hypertension) and national guidelines. Treatment algorithm is particularly relevant due to the high prevalence of chronic kidney disease and association between renal damage and persistent blood pressure elevation. The paper concerns treatment approaches in hypertension associated with chronic kidney disease, microalbuminuria, glomerulonephritis, atherosclerotic renal artery lesions, end-stage renal disease, hemodialysis etc.

Objective. To find clinical predictors of long-term cardiovascular survival in patients with ischemic kidney  disease (IKD) caused by atherosclerotic renal arteries lesions.

Design and methods. In 1999–2012, 185 patients (118 males; aged 35–79 years) with the diagnosed significant atherosclerotic lesions of renal arteries (stenosis ≥ 50 %) were included in an open, single-center observation prospective study. Among them 123 subjects underwent renal revascularization (RR): open surgery in 61 cases, percutaneous angioplasty of renal arteries and stent implantation — in 62 patients. The mean follow-up was 33 months (95 % confidence interval 29–37 months). The estimated outcomes included hypertension dynamics, renal function and cardiovascular mortality. KaplanMeyer  curves and Cox proportional hazards regression model were used for survival analysis and associated factors assessment.

 Results. Cumulative cardiovascular survival in IKD patients after renal revascularization was significantly higher. Regression analysis showed that the independent predictors of long-term cardiovascular mortality included renal revascularization, cerebrovascular disease and lower limbs ischemia. Relative risks of cardiovascular death were 0,25 in case of renal revascularization; 4,0 and 3,7 in the presence of cerebrovascular disease and lower limb ischemia, respectively. Independent predictors of long-term cardiovascular mortality after RR were lack of hypertension improvement (OR 8,7); post-surgery estimated glomerular filtration rate ≤ 45 ml/min/1,73 m  (OR 5,6); baseline proteinuria ≥ 1 g/day (OR 8,7); and peripheral artery disease with the lower limb ischemia (OR 46).

 Conclusion. Renal revascularization is associated with the higher long-term cardiovascular survival. An improvement of cardiovascular prognosis in IKD patients after surgery should be expected when antihypertensive and renoprotective efficacy of RR is achieved and concomitant lower limb ischemia is cured.  

Objective. To evaluate the dynamics of arterial blood pressure and sympathetic activity in the male Wistar rats within 8 weeks after renal artery clamping (model «2 kidneys — 1 clamp»).

Design and methods. The sympathetic activity was examined by spectral analysis of the heart rate variability in the non-anaesthesized rats. The sympathetic vasomotor activity was examined by the registration of electric activity of the cervical spine cord in anaesthesized animals.

 Results. We found that sympathetic activity to the heart and blood vessels is comparable. Two weeks after renal artery clamping the activity of the sympathetic nervous system increases, and 4 weeks later it comes close to the reference values in the developed hypertension and then increases to maximum values by the end of the experiment. 

Objective. The study was aimed to test a hypothesis on possible connection between αKlotho and (or) fibroblast growth factor 23 (FGF23) and myocardial hypertrophy at early stages of the renal dysfunction (RD).

Design and methods. Experimental models of chronic kidney injury were 3/4 or 5/6 nephrectomy (NE) in SHR rats. Sham-operated SHR rats were used as control. The timing of experiments was one or two months to achieve an expected fall of glomerular filtration rate (GFR) corresponding to early stages of RD. αKlotho protein in tubular epithelium was detected by immunohistochemistry. Serum concentrations of FGF23 and intact parathyroid hormone (iPTH), serum and urine levels of inorganic phosphate (Pi), Na, creatinine and protein as well as myocardial mass index (MMI) were measured.

 Results. Implemented models of RD corresponded to 1C–3C stages of human chronic kidney disease. Renal excretion of Pi significantly increased in the groups of nephrectomized animals. No significant differences were observed in serum concentrations of FGF23 and iPTH whereas the renal αKlotho expression decreases along with an increasing degree of kidney injury and MMI. The significant negative association between MMI and the renal αKlotho expression was independent of other potential confounders as confirmed by a multivariate regression analysis.

Conclusions. The obtained experimental data suggest that αKlotho can participate in mechanisms of myocardial remodeling in persistent hypertension and RD.

Objective. To study associations between serum soluble Klotho level and vascular calcification in patients with chronic kidney disease (CKD) 1–5 stages.

Design and methods. We examined 70 patients with different stages of CKD, including 41 patients with chronic glomerulonephritis, among them 10 with systemic diseases, 22 with tubulo-interstitial nephritis (bacterial, gout and drug-induced) and 7 with hypertensive nephrosclerosis. All 70 patients with 1–5 stages of CRD underwent clinical examination and blood tests for serum Klotho levels by enzyme-linked immunosorbent assay. Vascular stiffness was assessed in 57 patients by applanation tonometry method (SphygmoCor, AtCor Medical, Australia).

 Results. Serum Klotho levels differed depending on the stage of CKD. When patients with different stages of CKD were compared, a reverse correlation between serum Klotho level and serum phosphorus level and intact parathormone was found in CKD progression. There is a correlation between serum Klotho level and an increase in left ventricular posterior wall thickness in patients with CKD and hypertension (n = 49). Also reduction in serum Klotho level is associated with a greater frequency of calcifications in heart and major arteries, increased vascular stiffness and reduced blood flow in the tibial arteries (ankle-brachial index).

Conclusions. Thus, circulating Klotho plays an important role in mineral metabolism in CKD and demonstrates pleiotropic effects that might modify cardiovascular risk through the impact on vascular calcification and cardiovascular remodeling. 

Objective. To determine the features of circadian blood pressure (BP) profile depending on renal function in patients with chronic heart failure (CHF).

Design and methods. We examined 211 patients with CHF (126 men and 85 women), including 125 (59,2 %) patients with cardiorenal syndrome and 86 (40,8 %) patients without chronic kidney disease (CKD). Mean age was 58,1 ± 10,8 years. CKD was diagnosed according to the Scientific Society of Russian Nephrologists guidelines 2012.

Results. An increase in time and area indices of arterial hypotension in patients with CHF, associated with CKD 3B stage was detected. Also, the nocturnal BP fall reduction was associated with increasing severity of CKD.

Conclusions. 1. The increase in nocturnal BP fall is associated with increasing in daytime area and time indices of arterial hypotension in patients with cardiorenal syndrome. 2. Twenty-four-hour ambulatory BP monitoring allows to obtain additional information on hemodynamic parameters in patients with CHF and should be recommended for this group of patients.

Objective. To investigate the doppler features of the blood flow in hypertensive patients.

 Design and methods. We examined 49 hypertensive patients (mean age 52,8 ± 12,9 years) and 20 healthy subjects (mean age 49,2 ± 17,6 years). The intrarenal blood flow was studied by the triplex scan. We also assessed creatinine levels, estimated glomerular filtration rate by MDRD formula and creatinine clearance by Cockroft-Gault formula, and albuminuria.

Results. A decreased blood flow velocity parameters and the increase of the proximal renal artery segment were found (peak systolic velocity in right and left renal arteries — 78,4 ± 21,4 and 59,3 ± 11,4 cm/s in hypertensive group and 100,8 ± 34,3 and 88,7 ± 18,2 сm/s in control group, p < 0,05; resistant index in right and left renal arteries — 0,66 ± 0,05 and 0,67 ±0,05 in hypertensives and 0,62 ± 0,06 and 0,63 ±0,06 in controls, p < 0,05). There was no difference of blood flow velocities in the distal segment of the renal arteries between the groups.

Conclusions. Different variants of the renal artery remodeling occur in proximal and distal segments of renal arteries in hypertensive patients. The most typical changes include the increase of the main renal artery trunk with the decreased blood flow velocity, while segment and interlobar renal arteries are characterized by narrowing that might result in nephroangiosclerosis.

Objective. To assess the impact of renal sympathetic denervation (RSD) in patients with resistant hypertension (RH) on the structural and functional changes (SFC) of the heart, and to determine predictors of the effectiveness of the procedure

Design and methods. Sixty patients (54.6 ± 9.5 years) with RH were included in the analysis. They signed an informed consent for both research and RSD. All of them received full-dose antihypertensive therapy (AHT) (4.1 drugs), including at least one diuretic. BP and heart rate (HR) measurement and cardiac diastolic function (DF) assessment by echocardiography were performed at baseline and after 24 weeks in all subjects. RSD was completed by endovascular radiofrequency ablation of renal arteries. AHT remained unchanged.

Results. There was a significant reduction of office BP, as well as a significant regression of myocardial mass in 36,7 % patients at 24 weeks after the procedure. DF was initially impaired in 58.6 %, and after the procedure it normalized in 31 %, and the diastolic dysfunction decreased in 14 % patients. Blood pressure, HR, ATH and left ventricular volume (LVV) were comparable in subgroups, and the dynamics of MM correlated only with the initial values of LV wall.

Conclusion. Significant positive changes of DF and the decrease of LV MM were registered 24 weeks after RSD. The initial values of LV wall thickness were the only predictor of MM regression.

Objective. The article presents the analysis of social, demographic and clinical risk factors, perioperative examination parameters, therapy and outcome data in patients with stable coronary artery coronary disease after coronary artery bypass grafting surgery (CABG) in three regions inRussian Federation during 2012 year in the context of Ricochet program. The other aim was to establish a correspondence of the findings to international myocardial revascularization guidelines.

 Design and methods. Altogether 300 patients (100 in each region) were chosen according to the inclusion/exclusion criteria, and all participants were given individual numbers. All data were registered in a special database “A registry of patients with stable coronary artery disease after coronary artery bypass grafting surgery”. Phone visits or office visits when necessary were scheduled in 12 months. Response rate was almost 100 %.

Results. It was shown that males dominated among patients. The female CABG rate was three times lower, though the most of them (90 %) had myocardial infarction in past in comparison with 73 % of patients among male group. The average patient age was 60–64 years and 43 % of them were invalids. Work-status analysis of pre- and postoperative periods showed no significant difference. Indications for surgery correspond to current guidelines, however, the preoperative stress test rate was only 36 %.

Conclusions. The majority of patients were treated with evidence-based medicine drugs. A significant number of patients with recurrent angina after CABG, including high functional class, was found. These data indicate the need for an out-patient follow-up system for patients undergoing CABG, including cardiac rehabilitation, therapy correction, and, if necessary, re-intervention.

Objective. To evaluate the relationship between endothelial dysfunction, proinflammatory activity of leucocytes and pleiotropics effects of hypolipidemic therapy by rozuvastatin vs. simvastatin (as monotherapy and in combination with ezetimibe) in patients with coronary artery disease undergoing coronary artery bypass surgery (CABG). Design and methods. Altogether 92 patients with coronary artery disease (study group) and 22 healthy individuals (a control group) were enrolled. Vascular endothelial function was evaluated by brachial artery response assessment (endothelium-dependent vasodilatation test, the method by D. Celermajer and co-authors, Vingmed CPM 800). Proinflammatory activity of leucocytes was measured by chemiluminescent microscopy, and the severity of atherosclerotic coronary lesions was assessed by invasive coronary angiography. Endothelial function, leucocytes activity and lipid levels were determined before CABG and 12 months after revascularization. Results. Patients with coronary artery disease showed more complex disorders involving endothelial dysfunction and higher levels of leucocytes activity. The clinical effect of CABG (absence of angina pectoris and negative result of stress-echo test during 1‑year of follow-up) was found in 80,6 %. Combination lipid lowering therapy (simvastatin 20 mg and ezetimibe 10 mg) and monotherapy by rosuvastatin 10 mg compared to monotherapy by simvastatin 20 mg demonstrated higher efficiency regarding target lipid levels achievement and improvement of endothelial function and stimulated oxidant activity of leucocytes.

In recent years, different advanced technologies for diagnosis and treatment of secondary endocrine and renovascular forms of arterial hypertension have been developed. However, rare causes of hypertension are still difficult for identification, especially when manifested with atypical clinical features. Two cases of atypical clinical manifestation of aorta coarctation at different level are discussed in this article. The article pays special attention to the causes and approaches to hypertension that usually manifests in childhood. At the same time in adult clinical practice young patients presenting with elevated blood pressure require careful examination and exclusion of secondary forms of hypertension even when the elevation of office blood pressure is mild-to-moderate.

Objective. Carotid-femoral pulse wave velocity (PWV) is a strong independent predictor of cardiovascular morbidity and mortality. The aim of the study was to evaluate treatment-induced changes in PWV in hypertensive subjects achieved target clinic blood pressure (BP). Design and methods. Patients with grade I–II hypertension were treated to achieve target clinic BP < 140/90 mmHg with combination of RAAS-inhibitors and amlodipine for 1 year. Baseline BP was 163,4 ± 8,1/100,9 ± 4,2 mmHg; achieved BP 123,7 ± 9,7/76,8 ± 6,7mmHg. Central BP and PWV were measured before treatment and after 8 months of target clinic BP was maintained. Results. In 47 patients (20 men, age 58,9 ± 9,0 years) target clinic BP was achieved and maintained for 8 months. In 11 (23 %) subjects PWV decreased by ≥ 1 m/s from baseline (G1), in 15 (32 %) patients it remained unchanged (G2), and in 21 (45 %) it increased by ≥ 1 m/s compared to baseline (G3). The groups were comparable by age, risk factors, baseline and achieved clinic BP. PWV differed between the groups at baseline (G1 15,9 ± 2,5 vs. G2 13,6 ± 1,9 vs. G3 10,9 ± 1,7 m/s, р < 0,05), but not at the end of the study (13,0 ± 2,1; 13,6 ± 1,9 and 13,4 ± 1,9 m/s, respectively, p > 0,05). Also 72,7 % of patients in G1 and 66,7 % in G2 received the highest recommended doses of RAAS-inhibitors and amlodipine 10 mg vs. 28,6 % in G3 (Pearson χ 2 = 9,0; р < 0,05). Correlation and multiple regression analysis revealed the association between PWV decrease and doses of RAAS-inhibitors and amlodipine (r = –0,5, β = –0,45, p < 0,05). Conclusions. There is a modulating effect of target BP achievement on PWV in hypertensive subjects. PWV reduction is associated with higher doses of RAAS inhibitors and amlodipine.