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Background: Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients., Method: We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH., Results: The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (≥130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload., Conclusion: TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload.

Acute and chronic kidney disease encompasses a complex set of diseases that can both lead to, and result from, cancer. In particular, kidney disease can arise from the use of chemotherapeutic agents. Many of the current and newly developed cancer chemotherapeutic agents are nephrotoxic and can promote kidney dysfunction, which frequently manifests during the terminal stages of cancer. Given the link between kidney disease and cancer development and treatment, the aim of this Review is to highlight the importance of multidisciplinary collaboration between oncologists and nephrologists to predict and prevent chemotherapeutic-induced nephrotoxicity. As new therapies are introduced to treat cancer, new renal toxicities require proper diagnosis and management. We anticipate that multidisciplinary collaborations will lead to the development and implementation of guidelines for clinicians to improve the therapeutic management of patients with both cancer and renal impairment., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Most patients on dialysis are hypertensive and their blood pressure (BP) control is often poor. Renalase is preferentially expressed in proximal tubules, but it is also present in glomeruli and distant tubules, as well as in cardiomyocytes, liver, and skeletal muscle. It had been proposed that renalase had a flavin adenine dinucleotide (FAD)-binding domain and that FAD was an essential cofactor for its stability and monoamine oxidase activity. It was reported that renalase, secreted by the kidney and circulating in the blood, degraded catecholamines and might play a role in the regulation of sympathetic tone and BP. It has been also proposed that renalase-coding gene is a novel susceptibility gene for essential hypertension and its variations may influence BP. In addition, polymorphisms of the renalase gene in hemodialysed patients were associated with hypertension. However, several unresolved and controversial issues still remain such as how to measure renalase and its physiological activity. Furthermore, there are few data on possible activators and/or inhibitors of renalase. We are at the very beginning of solving the problem of whether renalase is a causative factor of hypertension in kidney disease or just an innocent bystander. Therefore, more research is needed to establish whether renalase can become a useful therapeutic target.

Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

Aim: Visfatin is an adipocytokine that has recently generated much interest. The aim of the study was to assess visfatin in correlation with markers of endothelial damage and inflammation in haemodialyzed and peritoneally dialyzed patients., Methods: Visfatin, leptin, apelin and adiponectin, markers of coagulation (thrombin-antithrombin complexes (TAT), prothrombin fragments 1+2 (F1+2)), fibrinolysis (tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1)), endothelial function/injury (Von Willebrand factor (vWF), thrombomodulin, intracellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), CD146) and inflammation (high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-alpha (TNF-alpha) and interleukin (IL)-6) were assessed., Results: Triglycerides, hsCRP, creatinine, IL-6, TNF-alpha, vWF, F1+2, TAT, thrombomodulin, ICAM, VCAM, CD146, PAI-1, leptin, adiponectin and visfatin were elevated in dialyzed patients over controls. Visfatin correlated significantly, in univariate analysis, in haemodialyzed patients with markers of endothelial damage/inflammation (CD146, ICAM, IL-6), other adipocytokines, Kt/V and dialysis vintage, and tended to correlate with hsCRP. In peritoneally dialyzed patients, visfatin correlated significantly with haemoglobin, and markers of endothelial damage. In the healthy volunteers visfatin correlated significantly with ICAM, creatinine and IL-6. In multiple regression analysis in HD patients visfatin was only independently related to Kt/V, dialysis vintage and IL-6., Conclusion: Elevated visfatin related to markers of inflammation might represent a novel link between inflammation and adipocytokines in dialyzed patients. Time on dialyses and dialysis adequacy may influence visfatin in dialyzed patients due to the decreased clearance of visfatin.

Chronic kidney disease developed after non renal solid organ transplantation in a significant issue. Evaluation of kidney function starting form a complete history and physical examination, then an accurate measurement of renal function and a urinalysis, followed by kidney imaging study should be performed prior to transplantation. Moreover, probability of reversibility of kidney dysfunction and the risk of progression to end stage renal disease should be assessed. During peri- and postoperative period hypotensive episodes should be avoided or at least minimized. Good blood pressure control (however, no guidelines for target blood pressure values for non solid organ transplants are available) as well as tight control of diabetes and hyperlipidemia should be implemented. Proteinuria, if present, should be attenuated by the use of therapeutic modalities (RAS blockade) to prevent or delay the progression of renal failure. The ability to identify CKD may allow early implementation of treatments that could arrest or delay the progression of renal damage, enable effective treatment of its complications, and reduce the risk of drug-induced nephrotoxicity. Kidney function should be monitored in nonrenal solid organ transplant recipients as an important risk factor comparable with diabetes for cardiovascular mortality and morbidity. In presence of existing nephron sparing immunosuppressive regimens, early detection of deteriorating kidney function gives the opportunity to tailor the treatment. A multidisciplinary approach for these patients including also a nephrologist should be considered.

Aim: Hypertension is one of the risk factors for cardiovascular diseases. The kidneys could be a victim and/or culprit of hypertension. Recently, the value of neutrophil gelatinase-associated lipocalin (NGAL) was highlighted as a novel marker for early detection of acute renal damage. Therefore, the aim of the study was to assess whether hypertension could affect NGAL and cystatin C levels in patients with normal serum creatinine (lower than 1.5 mg/dL in males and 1.2 mg/dL in females) and stable coronary artery disease., Methods: Serum, urinary NGAL, cystatin C and estimated glomerular filtration rate (eGFR; Modification of Diet in Renal Disease study (MDRD) and Cockcroft-Gault formulas) were evaluated in hypertensive, normotensive patients with stable coronary heart disease and healthy volunteers., Results: Normotensives had significantly lower NGAL than hypertensives. Serum cystatin C was significantly lower in normotensives than in hypertensives. Urinary NGAL did not differ significantly between these groups. Despite similar serum creatinine levels, eGFR (MDRD and Cockcroft-Gault formulas) was significantly higher in normotensives than in hypertensives. Serum NGAL was related, in univariate analysis, to serum creatinine, urea, urinary NGAL, haemoglobin, haematocrit, duration of hypertension, age, eGFR by MDRD and Cockcroft-Gault, and cystatin C., Conclusion: Hypertension is associated with kidney injury as reflected by elevated serum NGAL and cystatin C. It is noteworthy that despite normal serum creatinine, eGFR is relatively low suggesting impaired renal function. Therefore, NGAL needs to be investigated as a potential early marker for impaired kidney function/kidney injury, especially in patients with another risk factor for kidney damage, namely coronary artery disease.

Maintaining the correct iron balance is crucial for health. Our understanding of the molecular control of iron metabolism has increased dramatically over the past 5 years due to the discovery of hepcidin. This is a circulating antimicrobial peptide mainly synthesized in the liver, which has been recently proposed as a factor regulating the uptake of dietary iron and its mobilization from macrophages and hepatic stores. Inflammation causes an increase of production of hepcidin, which is a potent mediator of anemia of chronic diseases. Anemia in chronic kidney disease is mainly due to erythropoietin deficiency but these patients often have a chronic inflammatory state. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin in iron metabolism and its regulation, particularly in kidney disease. In addition, current methods of determination of hepcidin are reviewed., (Copyright 2007 S. Karger AG, Basel.)

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium–glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction. Most importantly, in contrast to all previous studies with anti-diabetic agents, a series of recent randomized, placebo-controlled outcome trials showed that SGLT-2 inhibitors and GLP-1 receptor agonists are able to reduce cardiovascular events and all-cause mortality, as well as progression of renal disease, in patients with type 2 DM. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM. [ABSTRACT FROM AUTHOR]

Background/Aims: Several studies have implicated atrial fibrillation (AF) as a contributing factor in chronic kidney disease (CKD) and cardiovascular events. The prevalence of coronary artery disease (CAD) in patients with AF varies substantially from 17% to 46.5%. There are only few studies concerning renal function in population with AF undergoing coronary angiography. The aim of the present study was to assess which type of AF is dominant in CKD population scheduled for coronary angiography and if it can influence patients' outcome, the association between renal impairment and the type of coronary procedures in AF patients and the influence of renal function on in-hospital mortality. Methods: We retrospectively studied 867 patients with AF hospitalized due to coronary angiography in two year time. The cut off value of CKD was eGFR ≤ 60 ml/min./1.73m2 evaluated by CKD-EPI formula. Results: A total of 867 patients with AF (44% women; mean age 72±10 years) were included in the analysis. The mean eGFR was 44±11ml/min./1.73m2 in patients with CKD and 89±18 ml/min./1.73m2 in patients with preserved renal function. Patients with CKD and AF were older (p< 0.001), had more often diabetes (p=0.009), heart failure (p< 0.001) and anaemia (p< 0.001). Patients with CKD and AF had more often permanent type of AF (p< 0.001). In CKD patients CHA2DS2VASc score was 4.3±1.5 and HAS-BLED score was 2.0±1.2 and it was significantly higher as compared to population with preserved renal function (p< 0.001, p=0.02, respectively). The use of oral anticoagulation was less frequent in CKD group (p< 0.001) although these patients had higher CHA2DS2VASc score. Patients with AF and CKD were more often admitted due to myocardial infarction (STEMI or NSTEMI) (p=0.02, p< 0.001, respectively) and more often underwent percutaneous coronary intervention (PCI) (p=0.01). Among coronary arteries the percutaneous coronary intervention (PCI) of left main artery was done more frequently in CKD patients (p=0.01). Among CKD population in-hospital mortality was significantly higher in patients with eGFR < 30 ml/min (p< 0.001). Conclusion: Patients with CKD had more often permanent type of AF. Percutaneous interventions of the left main coronary artery, the only elective procedures influencing patients' prognosis, were done more frequently in CKD patients with AF. In-hospital mortality was significantly higher in patients with severe renal impairment. Despite the higher risk of ischaemic stroke in CKD group the use of oral anticoagulation therapy was significantly less frequent and the patients were deprived of the confirmed benefits of such treatment. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia of high clinical importance, occurring in 2% of the general population and in 19–24% in patients with chronic kidney disease. It is a well-known risk factor for cardiovascular morbidity and mortality. Kidney transplant recipients with a history of AF were associated with significantly higher rate of ischaemic strokes, graft failure and post-transplant mortality. AF occurs in over 7% of kidney transplant recipients in the first 3 years after transplantation and is associated with reduced graft and patient survival. The incidence of stroke in patients after kidney transplantation (KTx) is higher than the general population, but markedly lower than those on dialysis. Oral anticoagulation (OAC) therapy is recommended in AF patients at high risk of stroke. There are no randomized studies assessing OAC in patients after KTx and there are no specific recommendations and guidelines on therapeutic strategies in these patients. KTx recipients are a vulnerable population, exposed to variations in renal function, being at higher risk of bleeding and thrombotic complications, with possible interactions with immunosuppression. Surely, there is a place for novel oral anticoagulants (NOACs) in this group of patients as long as the summary of product characteristics is followed, as they are a valuable anticoagulation therapy. On one hand, they are at least as effective as warfarin; on the other hand NOACs are safer, especially when it comes to intracranial haemorrhages. However, NOACs seem to be underused in this population as they are excreted via kidney, may interact with immunosuppressive therapy and physicians need more experience and confidence in their administration. Percutaneous left atrial appendage occlusion procedure may also be considered as an opportunity for this group of patients, in particular in the presence of contraindications to anticoagulation. [ABSTRACT FROM AUTHOR]

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]

Background: Neutrophil gelatinase-associated lipocalin (NGAL), a widely accepted diagnostic marker of acute renal injury (AKI) may be involved in the development of atherosclerosis. Purpose: To assess the prognostic significance of serum and urinary NGAL and serum cystatin C in patients with stable angina undergoing percutaneous coronary intervention (PCI) on a 3-year follow-up. Methods: We included patients with stable angina undergoing PCI. Serum NGAL and cystatin C were evaluated before and 4h, 8h after PCI. Urinary NGAL was evaluated before and 12h and 24h after the procedure. The primary end-point was all-cause mortality on a 3-year follow-up. Results: Among 132 patients there were 63% of males (mean age 64,5±9,8 years). Mean eGFR was 86.2±28.5 ml/min. During follow-up 8% of the patients died. All-cause mortality was significantly higher in patients with increased urinary NGAL concentration 12h after PCI (p=0.04). Urinary NGAL 12h after PCI correlated with eGFR (p<0.05), with serum NGAL evaluated before and 4h and 8h after PCI (p<0.05) and with increased serum cystatin C evaluated 4 hours after PCI (p<0.05). Conclusions: Increased urinary NGAL concentration is a strong predictor of mortality in patients with stable angina who undergo PCI and may be used for the risk stratification in this population. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

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]

Hypertension and cardiovascular complications are very common in chronic kidney disease (CKD). Overactivation of sympathetic nervous system is also widely recognized in CKD. Renalase may play an important role in the control of blood pressure (BP) by its regulatory function of catecholamine metabolism. Renalase could be synthesized not only by the kidney but also by cardiomyocytes, liver, and adipose tissue. It probably exerts a hypotensive action, at least in animal models. Whether it metabolizes catecholamines remains to be proved. Another issue that remains to be resolved is the relationship between renalase and renal natriuresis and phosphaturia. In this review, the updated experimental and clinical data on renalase are presented and possible interactions with the endothelium are discussed. Renalase is “a new postulated therapeutic target.” Proof of concept studies are needed to define the pathophysiological link between the kidney, sympathetic tone, BP, and cardiovascular complications. [ABSTRACT FROM PUBLISHER]

Renalase, secreted by the kidney, degrades catecholamines and may play a role in the regulation of sympathetic tone and blood pressure. The aim of this study was to assess serum renalase levels in hemodialysis patients and their relationship to blood pressure control, type of antihypertensive therapy and the presence of residual renal function. Results: The mean serum renalase in the study cohort was significantly higher than in the control group (27.53 ± 7.18 vs. 3.86 ± 0.73 p,g/ml,p< 0.001).The serum renalase concentration was significantly lower in patients with residual renal function when compared to the anuric patients. The type of hypotensive treatment ((3-blockers, ACE inhibitors or AT1 receptor blockers) did not affect renalase levels. There was a significant inverse correlation between the serum renalase and age (r = -0.28, p = 0.023) and residual renal function (r = -0.327, p = 0.001). Renalase was not related to blood pressure, heart rate or hemodialysis vintage. Conclusion: Elevated renalase levels in HD patients may be due to impaired kidney function. Further studies are needed to prove or disprove the possible role of renalase in the pathogenesis of hypertension in patients with kidney diseases. [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]

Cardiovascular deaths account for about 40% of all deaths of patients with chronic kidney disease (CKD), particularly those on dialysis, while sudden cardiac death (SCD) might be responsible for as many as 60% of SCD in patients undergoing dialysis. Studies have demonstrated a number of factors occurring in hemodialysis (HD) that could lead to cardiac arrhythmias. Patients with CKD undergoing HD are at high risk of ventricular arrhythmia and SCD since changes associated with renal failure and hemodialysis-related disorders overlap. Antiarrhythmic therapy is much more difficult in patients with CKD, but the general principles are similar to those in patients with normal renal function - at first, the cause of arrhythmias should be found and eliminated. Also the choice of therapy is narrowed due to the altered pharmacokinetics of many drugs resulting from renal failure, neurotoxicity of certain drugs and their complex interactions. Cardiac pacing in elderly patients is a common method of treatment. Assessment of patients' prognosis is important when deciding whether to implant complex devices. There are reports concerning greater risk of surgical complications, which depends also on the extent of the surgical site. The decision concerning implantation of a pacing system in patients with CKD should be made on the basis of individual assessment of the patient. [ABSTRACT FROM AUTHOR]

Background/Aims: To assess the impact of diabetes mellitus (DM) on clinical outcome in patients with end-stage renal disease (ESRD) on a 3-year follow-up. Methods: 58 ESRD patients were divided into 2 groups according to the presence of DM. We analyzed following end points: death, cardiac arrest, myocardial infarction, stroke, hospitalizations due to cardiovascular causes, revascularization, and combined end point. Results: Among diabetics, 14 (77.8%) had significant atherosclerotic changes, in the group without DM only 8 (38.1%), p = 0.01. In the group without DM, 14 (46.7%) patients reached combined end point, while in the group with DM 16 (53.3%) patients, p = 0.0013. There were no statistical differences in mortality (p = 0.423). Conclusion: Survival of hemodialyzed diabetic patients is not inferior to nondiabetics; however, morbidity is significantly higher due to adverse cardiac events. Copyright © 2011 S. Karger AG, Basel [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]

Abstract: Endothelium is the largest organ in the body strategically located between the wall of blood vessels and the blood stream. The human body contains approximately 1013 endothelial cells weighing approximately 1kg, and covering a surface area of 4000 to 7000m2 equivalent to the soccer playground. Hypertension and shear stress, inflammation, diabetes-associated factors such as advanced glycated end products, and uremic toxins are some of the prevalent risk factors of endothelial dysfunction in chronic kidney disease. In renal failure endothelial dysfunction and atherosclerosis are almost universal, as well as cardiovascular complications. Endothelial cell damage or injury is invariably associated with such clinical conditions as thrombosis, hypertension, renal failure and atherosclerosis and may be also responsible for accelerated atherosclerosis in patients with chronic renal failure. Traditional risk factor cannot explain the high prevalence and incidence of cardiovascular disease in chronic kidney disease, therefore other non-traditional risk factors such as endothelial dysfunction, oxidative stress or insulin resistance have increasingly been studied. In this review paper mechanism of endothelial dysfunction, including the role of nitric oxide pathway, adipocytokines and hemodialysis-induced endothelial dysfunction is discussed. [Copyright &y& Elsevier]

Iron is the fourth most common element in the Earth’s crust and is crucial for life. Over the last few years, our understanding of iron metabolism has dramatically increased due to the discovery of hepcidin, which is produced by hepatocytes and modulated in response to anemia, hypoxia and inflammation. It has been found that anemia upregulates lipocalin 2 (NGAL; neutrophil gelatinase-associated lipocalin) in the liver and serum. The aim of this review is to summarize the current knowledge dealing with a possible role of hepcidin and NGAL in iron metabolism and its regulation, particularly in kidney disease. Elevated NGAL a few days after insult is a possible preventive or protective mechanism limiting renal injury. NGAL is an innate antibacterial factor as well as hepcidin. NGAL binds siderophores, thereby preventing iron uptake by bacteria. Hepcidin, an antibacterial defensin, prevents iron absorption from the gut and iron release from macrophages, leading to hypoferremia and anemia. Both proteins sequester iron, but by different mechanisms. However, these proteins involved in iron metabolism do not seem to be independently related. Taking into account the antimicrobial moieties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Myocardial ischaemia in patients with end-stage renal disease (ESRD) develops both due to the epicardial coronary artery stenosis and to the microvascular injury. We aimed to evaluate coronary blood flow in ESRD patients by means of the thrombolysis in myocardial infarction (TIMI) frame count method (TFC). In patients with ESRD, implementation of the TFC as a marker of the coronary flow abnormalities have not been previously investigated. [ABSTRACT FROM PUBLISHER]

Hepcidin is the predominant negative regulator of iron absorption in the small intestine, iron transport across the placenta, and iron release from the macrophages. Iron supplementation is often introduced in dialyzed patients to replete or to maintain iron stores, particularly in patients treated with erythropoietin-stimulating agents. The aim of this study was to assess hepcidin levels in 12 hemodialyzed (HD) patients (6 females, 6 males, mean age 64 years, mean time on HD 36 months) before and after intravenous iron therapy. Prohepcidin and hepcidin were studied using commercially available kits from DRG Instruments GmbH, Marburg, Germany (ELISA method), and Bachem, St. Helens, UK (RIA method). Soluble receptor of transferrin was studied using a kit from R&D, Abington, UK. We found a significant rise in hemoglobin concentration, hematocrit, ferritin, serum iron, transferrin saturation and a fall in soluble receptor of transferrin. Serum hepcidin and prohepcidin as well as urinary prohepcidin increased significantly after the therapy. In conclusion, hepcidin levels are influenced by iron supplementation in HD patients. Further examinations of hepcidin as a marker of iron deficiency using new validated measurement techniques are required. It remains to be seen if assay of hepcidin will be of help in identifying patients unresponsive to oral iron or requiring intravenous iron supplementation. Copyright © 2009 S. Karger AG, Basel [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]

Hypothesis: The recent Dialysis Outcome Quality Initiative publication on the evaluation, classification and stratification of chronic kidney disease (CKD) states that individuals with a reduced glomerular filtration rate (GFR) is at greater risk for cardiovascular diseases and cardiac deaths. Aim: To determine the prevalence of kidney dysfunction in a cohort of 1390 patients with and without diabetes with normal serum creatinine undergoing percutaneous coronary intervention. Methods: Kidney function was estimated using simplified MDRD, Cockcroft-Gault and Jeliffe formulas. Results: Normal serum creatinine was observed in 93% patients. Mean estimated GFR in 1068 non-diabetic patients was significantly higher than in 322 diabetic patients (all formulas). Diabetic females had significantly lower creatinine and estimated GFR, higher high-density lipoprotein and platelet count than diabetic males. A very high prevalence of CKD up to 77% was found in studied diabetic patients. Clinically significant CKD (as defined by GFR < 60 mL/min) was found in 13.0–33.8% patients depending on the formula used to estimate GFR. Conclusion: The prevalence of CKD (stages 2–3) is high in diabetic patients undergoing percutaneous coronary intervention despite normal creatinine. The risk of contrast nephropathy with worse outcomes is enhanced in these patients, particularly in elderly and females. Evaluation of renal function is important in order to select the appropriate strategy to reduce the cardiovascular risk. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: The efficacy of statin treatment in chronic kidney disease (CKD) patients remains controversial. Therefore, we performed a meta-analysis to investigate whether statins modulate renal function in patients with CKD. Methods: Data from Scopus, PubMed, Web of Science, and the Cochrane Central Register of randomized controlled trials for years 1966–December 2012 were searched for appropriate studies. Results: Twenty trials with 6452 CKD subjects randomized to receive either statin or placebo were included. Statin therapy significantly influenced high sensitivity C-reactive protein levels in patients on or off dialysis [−0.28mg/dl, 95%CI: −0.93 to −0.37; p <0.05 and −0.46mg/dl, 95%CI: −0.87 to −0.05; p =0.03], respectively], urinary protein (−0.77g/24h, 95%CI: −1.24 to −0.29, p <0.02; this effect persisted for treatment ≤12months), and serum creatinine but only for long-term therapy (3years) (−0.65mg/dl, 95%CI: −1.00 to −0.30; p =0.0003). The summary for standardized effect size of mean differences of glomerular filtration rate was 0.29ml/min/1.73m2 (95%CI: 0.01 to 0.58; p =0.04), and depended on treatment duration — a significant increase was observed for between 1 and 3years of statin therapy (0.50ml/min/1.73m2, 95%CI: 0.40 to 0.60; p <0.0001), with no significant increase for both ≤1 and >3years of the therapy. Conclusion: Statins might exert significant renoprotective effects in CKD patients; however, benefit may depend on the duration of treatment. This is an issue that warrants more definitive investigation. More studies are necessary in dialysis patients to credibly evaluate the renal effects of statin therapy. [Copyright &y& Elsevier]

A letter to the editor is presented in response to the article "The growth of acute kidney injury: A rising tide or just closer attention to detail?" in a 2015 issue.