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The prevalence of chronic kidney disease (CKD) has increased markedly over past decades due to the aging of the worldwide population. Despite the progress in the prevention and treatment, the cardiovascular (CV) morbidity and mortality remain high among patients with CKD. Although CKD is a progressive and irreversible condition, it is possible to slow decreasing kidney function, as well as the development and progression of associated with kidney disease comorbidities. Diabetes mellitus has become major cause of CKD worldwide. It is estimated that the prevalence of diabetes will increase from 425 million worldwide in 2017 to 629 million by 2045, substantially the percentage of diabetic nephropathy among CKD patients is set to rise markedly. The results of multicenter trials concerning novel antidiabetic drugs suggest that efficacy in reducing CV risk is independent of the improvement in glycemic control. This review discusses underlying causes of high CV risk and strategies reducing individual burden among CKD patients. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is one of the primary modifiable risk factor for cardiac and renal diseases with the prevalence around 30–45% of the general population, with a steep increase with ageing. The administration of blood pressure-lowering drugs is to reduce the risk of major clinical cardiovascular outcomes. Hypertension guidelines recommend combination therapy in patients with high cardiovascular risk and with subclinical organ damage as well as when monotherapy fails. Areas covered: As the etiology of essential hypertension is multifactorial, combination therapy using different classes of antihypertensive agents have greater effect than each on its own (synergistic effect), may have better tolerability (two components minimizing each other’s side effects) and lead to improved patient compliance. Several studies assess the hypotensive efficacy on drug combination; there are also studies on triple drug combination. Expert commentary: At present, dual and triple combination therapy is available to hypertensive patients with good clinical outcomes, compliance and low profile of side effects. It is critical as patients’ adherence to the pharmacological therapy significantly decreases the risk of long-term adverse events including mortality. It appears that combinations not only of hypotensive drugs but also with statins (as well as antidiabetics) will be widely used. [ABSTRACT FROM PUBLISHER]

Background: hRenalase may degrade catecholamines and regulate sympathetic tone and blood pressure (BP). The aim of the study was to assess dopamine (DA), norepinephrine (NE), and renalase in 75 hemodialysis (HD) and 26 peritoneal dialysis (PD) patients and their correlations with heart rate (HR), BP, a type of hypotensive therapy, and residual renal function. Methods: Renalase, DA, NE were studied using commercially available assays. Results: Renalase and NE were higher and DA was lower in dialyzed groups comparing to healthy volunteers. Hemodialysis patients had lower NE and higher renalase level. Norepinephrine was higher in anuric patients in HD group. Renalase correlated with dialysis vintage and inversely with residual diuresis. Dopamine correlated with residual diuresis in the whole study cohort, with HR in PD patients, with renalase in HD patients. Norepinephrine correlated with aortic diameter in PD patients. Norepinephrine was significantly higher in patients with coronary artery disease (CAD) in HD group. Hemodialysis population with CAD had lower NE and higher DA and renalase level than their PD counterparts. In the follow up, 27% of HD group died. Cardiac death was diagnosed in 17% and there was higher renalase level than in noncardiac death. Conclusions: Elevated level of circulating renalase in dialysis patients is rather related to kidney function and the sympathetic nervous system hyperactivity found in this population. The real excess of renalase in the pathogenesis of cardiovascular disorders in patients with chronic kidney disease still remains to be proven. If confirmed, it may give a new way for pathophysiological therapy. [ABSTRACT FROM AUTHOR]

Aim: The aim was to assess if the pharmacological treatment due to cardiovascular causes in dialysis patients is compliant with the European Guidelines. Methods: In total, 110 consecutive end-stage renal disease (ESRD) patients on regular dialysis were enrolled into the study. We divided the population into subgroups with coronary artery disease (CAD), chronic heart failure (CHF) and diabetes mellitus (DM). Results: We gathered information about drugs from 99 patients. The mean age was 61.8 ± 12.9 years (70% of males). There were 37 patients with CAD. Acetylsalicylic acid (ASA) was taken by 89% of the patients with CAD, clopidogrel by 25%, beta-blockers by 70%, angiotensin converting enzyme inhibitors (ACEIs) by 50%, angiotensin receptor blockers (ARBs) by 8%, and statins by 41%. Dual antiplatelet therapy was used after stent implantation (35%). There were 24 patients with CHF. Beta-blockers were taken by 71% of the patients, ACEIs by 45%, statins by 54%, and diuretics by 21% with CHF. There were 36 patients with DM. ASA was taken by 89% of the patients, clopidogrel and ticlopidine by 34%, beta-blockers were taken by 67%, ACE-inhibitors by 55%, and statins by 38% of the population with DM. The patients with DM were taking more ACEIs than those without DM ( p = 0.033). DM was associated with a statistically 21% higher odds of ACEI/ARB use, but CHF was associated with no increase in the odds of beta-blocker use and no increase in ACEI/ARB use. Conclusions: Dialysis patients with cardiovascular diseases are given less cardioprotective drugs such as ASA, beta-blockers, ACEIs, ARBs, and statins than they should be given according to the guidelines. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension and kidney disease have been associated with increased incidence of stroke. Renalase, a newly discovered hormone, is secreted by the kidney and circulates in blood. The aim of this study was to assess possible correlations between renalase, blood pressure, stroke, and cardiovascular status in prevalent hemodialyzed patients. Methods: Renalase was assessed using commercially available assay. Echocardiography was performed in each patient. Results: Serum renalase was significantly lower in patients with a history of stroke (21%) than in patients without it. Similarly, renalase was significantly lower in hypertensive patients (82%) when compared with normotensives. Serum renalase correlated with creatinine, residual renal function, and transferrin saturation. The only predictor of renalase in multiple regression analysis was the presence of hypertension explaining 90% of the renalase variations. Conclusions: Our preliminary results suggest that renalase, probably due to the sympathetic nervous system hyperactivity, could be associated with hypertension and cardiovascular complications, including stroke in hemodialyzed patients. However, further studies are needed to establish the possible role of renalase in these complications. Renalase is 'a new postulated therapeutic target.' [ABSTRACT FROM AUTHOR]

Copeptin is cosynthesized with vasopressin, also known as anti-diuretic hormone, with similar plasma levels. In the past 2 years, copeptin has been studied as a diagnostic and prognostic marker in infections and other diseases. In patients with decompensated heart failure, copeptin was an accurate prognostic marker for mortality. Cardiovascular disease is a major contributor to the mortality and morbidity in chronic kidney disease. Creation of an arteriovenous fistula (AVF) might contribute to the development or worsening of congestive heart failure (CHF). The aim of the study was to assess associations between copeptin, New York Heart Association (NYHA) class, and the location of the AVF in hemodialysis (HD) patients. The cross-sectional study was performed on a cohort of 93 clinically stable HD patients. Patients with proximal AVF tend to be older, with decreased renal residual function and increased NYHA functional class. These patients were also highly anemic, had more acidosis, and had increased high-sensitivity C-reactive protein along with increased copeptin and NT-proBNP levels. These changes were also associated with significant changes in all intra-cardiac dimensions, including right ventricle, both atria, and intraventricular septum and increase in end-systolic and end-diastolic left ventricular intra-cardiac dimensions. In multiple logistic regression analysis, the only associate of copeptin was NYHA functional class. Copeptin level in HD patients depends on cardiac function and it might be involved in the pathophysiology of cardiovascular disease in these patients. Proximal AVF creation might contribute to the development or worsening of CHF in HD patients. [ABSTRACT FROM AUTHOR]

Background/aims: The aim of this study was to determine the correlation between renal function and 6-year mortality in patients with acute myocardial infarction (AMI), treated successfully with primary percutaneous coronary intervention (PCI), and to examine whether Cockcroft-Gault (C-G) formula or Modification of Diet in Renal Disease (MDRD) study equation or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation is the best predictor of very late mortality. Methods: A prospective cohort study with 6-year follow-up of a homogenous group of 193 patients, with ST-segment elevation AMI treated with successful primary PCI. Glomerular filtration rate (GFR) estimated by C-G formula, MDRD, and CKD-EPI equation were analyzed. Results: The patients with chronic kidney disease (CKD) had a much lower cumulative survival rate than those without it ( p < 0.05). A larger area under the receiver-operating characteristic curve for death with respect to GFR for C-G formula was observed. In the multivariate analysis, only GFR ≥ 55 mL/min according to C-G formula was independently associated with lower mortality. Conclusion: CKD is associated with higher mortality after a successful primary PCI during a 6-year follow-up. C-G formula is better than MDRD and CKD-EPI equations at predicting mortality after AMI. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to assess the prognostic significance of myocardial contrast echocardiography (MCE) in patients with end-stage renal disease (ESRD) on a 3-year follow-up and to compare the value of MCE with demographic, clinical, and laboratory parameters. Methods: Fifty-eight ESRD patients on regular dialysis were prospectively screened for coronary artery disease (CAD) using perfusion assessment on real-time MCE. We analyzed the following end points during the 3-year follow-up: death, cardiovascular complications, and combined end point, which consisted of adverse cardiac events mentioned above. All features were compared between the two groups with and without perfusion disturbances on MCE. Results: No adverse events related to MCE administration have been observed. Twenty-seven (47%) patients with ESRD demonstrated perfusion defects on MCE. The patients with perfusion defects on MCE comparison with those without perfusion disturbances were older ( p = 0.008) and had lower ejection fraction (EF) ( p = 0.0001) and higher wall motion index (WMSI) ( p = 0.0001). After the 3-year follow-up, the incidence of death ( p = 0.00018), cardiovascular end points, revascularizations [both percutaneous coronary intervention (PCI) and coronary artery bypass grafts (CABG) p = 0.0016 and p = 0.004, respectively], and composite end point ( p = 0.0015) was significantly higher in patients with perfusion defect on MCE. Conclusions: In patients with ESRD, MCE appears to be a safe and useful tool for risk stratification. MCE facilitates decision for coronary angiography. [ABSTRACT FROM AUTHOR]

Hepcidin is a small defensin-like peptide, the production of which by hepatocytes is modulated in response to anemia, hypoxia, or inflammation. Kidneys are involved in not only the synthesis of hepcidin, but they also may be involved in its elimination. A cross-sectional study was performed to assess prohepcidin and hepcidin in serum, urine, and ultrafiltrate/peritoneal effluent in relation to type of renal replacement therapy and prohepcidin and hepcidin correlations with renal function, iron status, and markers of inflammation. Methods. Prohepcidin and hepcidin high-sensitivity CRP, TNF alpha, and IL-6 were measured using commercially available kits in 102 patients on hemodialyses, 17 on hemodiafiltration, 44 on peritoneal dialyses, and 22 healthy volunteers. Results. In hemodialyzed and peritoneally dialyzed patients with residual renal function, serum prohepcidin (264.21 ± 95.84 vs. 341.84 ± 90.45 ng/mL, p < 0.01; 142.76 ± 57.87 vs. 238.42 ± 84.32 ng/mL, p < 0.01, respectively) and hepcidin (178.89 ± 89.87 vs. 295.76 ± 129.65 ng/mL, p < 0.01; 108.43 ± 75.49 vs. 186.53 ± 119.62 ng/mL, p < 0.01, respectively) were significantly lower than in anuric patients. In peritoneal effluent, prohepcidin level was significantly higher than in ultrafiltrate of HD/HDF patients. In multiple regression analysis, residual renal function, ferritin, and hsCRP were predictors of hepcidin in hemodialyzed patients, while residual renal function and ferritin were predictors of hepcidin in peritoneally dialyzed patients. Conclusions. Residual renal function seems to play a pivotal role in hepcidin levels in dialyzed patients. In addition, the presence of low-grade inflammation, more pronounced in anuric patients, and functional iron deficiency may also contribute to the elevated hepcidin. The removal of prohepcidin with ultrafiltrate/peritoneal effluent may partially explain its lower concentration in peritoneal dialysis and hemodiafiltration. [ABSTRACT FROM AUTHOR]

Background/Aims. Different serum and urinary biomarkers have been recently proposed to serve as markers of acute kidney injury. We tested the hypothesis whether NGAL and other biomarkers could represent an early biomarker of contrast nephropathy (CIN) in diabetic patients with normal serum creatinine undergoing cardiac catheterization in comparison with non-diabetic patients. Methods. Serum, urinary NGAL, cystatin C, urinary kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and liver-type fatty acid binding protein (L-FABP) were evaluated before and 2, 4, 8, 24, and 48 hours after cardiac catheterization using commercially available kits. Results. In both groups we found a significant rise in serum NGAL after 2, 4, and 8 hours, and in urinary NGAL and IL-18 after 4, 8, and 24 hours after cardiac catheterization. Serum cystatin C increased significantly 8 hours, reaching peak 24 hours after cardiac catheterization in both groups, and then decreased after 48 hours. L-FABP and KIM-1 increase significantly after 24 and 48 hours after cardiac catheterization. Conclusions. CIN was similarly prevalent in both diabetic and non-diabetic patients undergoing cardiac catheterization. NGAL seems to be a potential early marker for nephrotoxicity and predictor of contrast nephropathy. It is particularly important in the upcoming setting of short-time hospitalizations for cardiac catheterization. [ABSTRACT FROM AUTHOR]

Hepcidin is the key regulator of iron metabolism. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietic-stimulating agents. The present study was aimed to assess possible relation between hepcidin and erythropoietin therapy, with particular attention being paid to erythropoietin-hyporesponsiveness in hemodialyzed patients. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Germany (ELISA method) and Bachem, UK (RIA method). TNFα and IL-6 were studied using kits from and R&D (Abington, UK), and hsCRP was studied using kits from American Diagnostica, USA. Hyporesponsive patients to erythropoietin therapy had significantly lower serum albumin, cholesterol, LDL, hemoglobin, hematocrit, and residual renal function, and significantly higher serum ferritin, hsCRP, IL-6, TNFα, and erythropoietin dose. The difference in serum prohepcidin and hepcidin did not reach statistical significance; however, there was a tendency toward higher values of both prohepcidin and hepcidin in hyporesponsive patients. In conclusion, though hyporesponsiveness to erythropoietin therapy occur in dialyzed patients, it is mainly associated with subclinical inflammation than with hepcidin excess. Further studies are needed to develop a reliable and reproducible assay to elucidate the potential contribution of hepcidin to hyporesponsiveness during erythropoietin therapy. [ABSTRACT FROM AUTHOR]

The current Kidney Disease Outcomes Quality Initiative (K/DOQI) guidelines advocate creatinine-based equations for estimating GFR to identify patients with potential kidney disease and classify them into different stages due to the fact that serum creatinine is very insensitive to changes in the glomerular filtration rate. Very few biomarkers exist for monitoring chronic kidney disease. The aim of the study was to assess whether NGAL could represent a novel, sensitive marker of kidney function in adult patients with CKD. The study was performed on 92 non-diabetic patients with CKD stages 2-4. Serum and urinary NGAL as well as serum cystatin C were measured using commercially available kits. Serum NGAL was related, in univariate analysis, to serum creatinine, urinary NGAL, hemoglobin, hematocrit, leukocyte count, eGFR, and cystatin C. Urinary NGAL correlated with age, hemoglobin, hematocrit, serum creatinine, and eGFR. In multiple regression analysis, predictors of serum NGAL were creatinine (beta value = 0.97, p = 0.005), cystatin C (beta = 0.34, p = 0.01), and eGFR (beta value = 1.77, p = 0.001). In the healthy volunteers, serum NGAL correlated with age, serum creatinine, eGFR, leukocyte count, and cystatin C. Taking into consideration the fact that the recent DOQI (Dialysis Outcomes Quality Initiative) states that individuals with reduced GRF (glomerular filtration rate) are at greater risk for CVD and cardiac deaths, precise evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. NGAL should be investigated as a potential early and sensitive marker of kidney impairment/injury. [ABSTRACT FROM AUTHOR]