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Delivery of care for kidney failure (KF) globally has a significant disparity; even in some countries, it means end of life for the person. The International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) tries to address gaps in KF care and standardize global nephrology care. From the third iteration of the ISN-GKHA, we present data for countries in the ISN Eastern and Central Europe region. The median prevalences of chronic kidney disease (12.8%) and treated KF (873.5 pmp) were higher than the global rates, respectively. Hemodialysis was the most preferred modality for KF in adults, whereas kidney replacement therapy was more balanced in children. Although most of the countries in the region had lower-middle–income and upper-middle–income levels, health expenditures for kidney health care were almost generally covered publicly. Nephrologists were responsible for the medical kidney care of people with KF in all countries. There was adequate infrastructure to provide all kinds of treatment for kidney care in the region. Regional characteristics such as high levels of obesity, smoking, and Balkan nephropathy as an endemic disease coupled with a shortage of workforce and finance continued to affect kidney care in the region negatively. By making organizational and legislative arrangements, partnerships with national authorities and societies may accelerate the improvement of kidney health care in the region.

Background: The hydrogen ion (H+) mobilisation model has been previously shown to accurately describe blood bicarbonate (HCO3) kinetics during haemodialysis (HD) when the dialysate bicarbonate concentration ([HCO3]) is constant throughout the treatment. This study evaluated the ability of the H+mobilization model to describe blood HCO3kinetics during HD treatments with a time-dependent dialysate [HCO3].Methods: Data from a recent clinical study where blood [HCO3] was measured at the beginning of and every hour during 4-h treatments in 20 chronic, thrice-weekly HD patients with a constant (Treatment A), decreasing (Treatment B) and increasing (Treatment C) dialysate [HCO3] were evaluated. The H+mobilization model was used to determine the model parameter (Hm) that provided the best fit of the model to the clinical data using nonlinear regression. A total of 114 HD treatments provided individual estimates of Hm.Results: Mean ± standard deviation estimates of Hmduring Treatments A, B and C were 0.153 ± 0.069, 0.180 ± 0.109 and 0.205 ± 0.141 L/min (medians [interquartile ranges] were 0.145 [0.118,0.191], 0.159 [0.112,0.209], 0.169 [0.115,0.236] L/min), respectively; these estimates were not different from each other (p= 0.26). The sum of squared differences between the measured blood [HCO3] and that predicted by the model were not different during Treatments A, B and C (p= 0.50), suggesting a similar degree of model fit to the data.Conclusions: This study supports the validity of the H+mobilization model to describe intradialysis blood HCO3kinetics during HD with a constant Hmvalue when using a time-dependent dialysate [HCO3].

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Peritoneal dialysis (PD)-associated peritonitis is a serious complication of PD and prevention and treatment of such is important in reducing patient morbidity and mortality. The ISPD 2022 updated recommendations have revised and clarified definitions for refractory peritonitis, relapsing peritonitis, peritonitis-associated catheter removal, PD-associated haemodialysis transfer, peritonitis-associated death and peritonitis-associated hospitalisation. New peritonitis categories and outcomes including pre-PD peritonitis, enteric peritonitis, catheter-related peritonitis and medical cure are defined. The new targets recommended for overall peritonitis rate should be no more than 0.40 episodes per year at risk and the percentage of patients free of peritonitis per unit time should be targeted at >80% per year. Revised recommendations regarding management of contamination of PD systems, antibiotic prophylaxis for invasive procedures and PD training and reassessment are included. New recommendations regarding management of modifiable peritonitis risk factors like domestic pets, hypokalaemia and histamine-2 receptor antagonists are highlighted. Updated recommendations regarding empirical antibiotic selection and dosage of antibiotics and also treatment of peritonitis due to specific microorganisms are made with new recommendation regarding adjunctive oral N-acetylcysteine therapy for mitigating aminoglycoside ototoxicity. Areas for future research in prevention and treatment of PD-related peritonitis are suggested.

Introduction: The hydrogen ion (H+) mobilization model has been previously shown to provide a quantitative description of intradialytic changes in blood bicarbonate (HCO3) concentration during hemodialysis (HD). The current study evaluated the accuracy of different methods for estimating the H+mobilization parameter (Hm) from this model.Methods: The study compared estimates of the H+mobilization parameter using predialysis, hourly during the HD treatment, and postdialysis blood HCO3concentrations (Hm-full2) with those determined using only predialysis and postdialysis blood HCO3concentrations assuming steady state conditions (Hm-SS2) during the midweek treatment in 24 chronic HD patients treated thrice weekly.Results: Estimated Hm-full2 values (0.163 ± 0.079 L/min [mean ± standard deviation]) were higher than, but not statistically different (p= 0.067) from, those of Hm-SS2 (0.152 ± 0.065 L/min); the values of Hm-full2 and Hm-SS2 were highly correlated with a correlation coefficient of 0.948 and a mean difference that was small (0.011 L/min). Further, the H+mobilization parameter values calculated using only predialysis and postdialysis blood HCO3concentrations during the first and third HD treatments of the week were not different from those calculated during the midweek treatment.Conclusions: The H+mobilization model can be used to provide estimates of the H+mobilization parameter without the need to measure hourly intradialytic blood HCO3concentrations.

Cardiovascular disease (CVD) affects more than two-thirds of patients receiving hemodialysis and is the leading cause of death in this population, yet CVD outcomes are infrequently and inconsistently reported in trials in patients receiving hemodialysis. As part of the Standardised Outcomes in Nephrology-Haemodialysis (SONG-HD) initiative, we convened a consensus workshop to discuss the potential use of myocardial infarction and sudden cardiac death as core outcome measures for CVD for use in all trials in people receiving hemodialysis. Eight patients or caregivers and 46 health professionals from 15 countries discussed selection and implementation of the proposed core outcome measures. Five main themes were identified: capturing specific relevance to the hemodialysis population (acknowledging prevalence, risk, severity, unique symptomology, and pathophysiology), the dilemmas in using composite outcomes, addressing challenges in outcome definitions (establishing a common definition and addressing uncertainty in the utility of biomarkers in hemodialysis), selecting a meaningful metric for decision making (to facilitate comparison across trials), and enabling and incentivizing implementation (by ensuring that cardiologists are involved in the development and integration of the outcome measure into registries, trial design, and reporting guidelines). Based on these themes, participants supported the use of myocardial infarction and sudden cardiac death as core outcome measures of CVD to be reported in all hemodialysis trials.

Assessment of kidney function in oncology patients is a fundamental factor in profiling the survival risk, determining the appropriate dose of chemotherapeutic drugs, and defining a patient eligibility for clinical trials with novel agents. Both overestimation and underestimation of kidney function may affect the treatment efficacy and outcomes. Overestimation may lead to overdosing or inappropriate agent selection and the corresponding toxicity, whereas underestimation may be responsible for underdosing or inappropriate agent exclusion and subsequent treatment failure. This is of utmost importance in patients with cancer. Evaluation of kidney function is not only limited to the estimation of glomerular filtration rate or creatinine clearance. An accurate assessment of kidney function is advisable to reduce variability in decision making and ultimately the therapeutic outcomes of toxicity and clinical benefit. Therefore, additional studies are needed to investigate the validity of currently used formulas estimating kidney function in this population as well as their applicability to traditional chemotherapy, novel targeted therapies, and immunotherapies. Because of rapid discovery and development of new cancer agents, a reliable and comprehensive manner to screen for potential nephrotoxicity is critically important. As kidney function not only is limited to glomerular filtration rate changes but also involves tubular and even vascular dysfunction, urinalysis and kidney imaging studies should also be considered before therapeutic decisions are taken. However, several questions remain regarding these new technologies such as kidney-on-a-chip systems for the assessment of kidney function and injury, particularly in oncology, and it has yet to be implemented in clinical practice.

Onco-nephrology is an emerging field in medicine. Patients with cancer may suffer from kidney diseases because of the cancer itself and cancer-related therapy. It is critical for nephrologists to be knowledgeable of cancer biology and therapy in order to be fully integrated in the multidisciplinary team and optimally manage patients with cancer and kidney diseases. In a recent international meeting, the key issues in this challenging clinical interface were addressed, including many unresolved basic science questions, such as the high tumor incidence in kidney transplant recipients. To this end, 70 highly qualified faculty members were gathered from all over the world to discuss these issues in 8 plenary sessions, including 5 keynote lectures. In addition, 48 young nephrologists and oncologists were invited to present their original observations that were highlighted in 2 large poster sessions.

ABSTRACTIntroduction: Anemia is a common manifestation of chronic kidney disease (CKD). The pathogenesis of CKD-associated anemia is multifactorial. Our understanding of the molecular control of iron metabolism has improved dramatically because of the discovery of hepcidin and attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway have recently emerged.Areas covered: We examine the possible role of hepcidin in iron metabolism and regulation and the potential therapeutic options involving hepcidin and hepcidin-ferroportin axis in renal anemia treatment. We focus on therapeutic targeting of hepcidin, the hepcidin-ferroportin axis and key molecules such as anti-hepcidin antibodies, spigelmers, and anticalins. We also discuss compounds affecting the bone morphogenetic protein receptor [BMP/BMPR] complex and molecules that influence hepcidin, such as hypoxia-inducible factor 1 stabilizers.Expert opinion: Hepcidin is a key regulator of iron availability and is a potential future therapeutic target for managing anemia that is associated with CKD. There are potential risks and benefits associated with novel sophisticated therapies and there are several novel options on the horizon; however, clinical data are currently limited and need development. Inhibition of hepcidin via various pathways might be a viable adjunctive therapeutic option in other clinical situations.

There are an estimated 14,000 randomized trials published in chronic kidney disease. The most frequently reported outcomes are biochemical endpoints, rather than clinical and patient-reported outcomes including cardiovascular disease, mortality, and quality of life. While many trials have focused on optimizing kidney health, the heterogeneity and uncertain relevance of outcomes reported across trials may limit their policy and practice impact. The international Standardized Outcomes in Nephrology (SONG) Initiative was formed to identify core outcomes that are critically important to patients and health professionals, to be reported consistently across trials. We convened a SONG Implementation Workshop to discuss the implementation of core outcomes. Eighty-two patients/caregivers and health professionals participated in plenary and breakout discussions. In this report, we summarize the findings of the workshop in two main themes: socializing the concept of core outcomes, and demonstrating feasibility and usability. We outline implementation strategies and pathways to be established through partnership with stakeholders, which may bolster acceptance and reporting of core outcomes in trials, and encourage their use by end-users such as guideline producers and policymakers to help improve patient-important outcomes.

ABSTRACTThe 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.

Premature Ovarian Insufficiency (POI) is a fertility-related disorder affecting 1% of women. It is defined as the development of hypergonadotropic hypogonadism before the typical natural age of the menopause. The diagnosis of POI, previously described as premature ovarian failure, is one of unexpected, bad news for generally young, healthy and well-being women less than 40 years old. Despite iatrogenic and genetic pathogenesis approximately 90% of cases are diagnosed accidentally with unknown etiology. Sirtuins (SIRTs) are a class of nicotine adenine dinucleotide (NAD+)-dependent proteins which regulate various biochemical pathways and participate in a wide range of major cellular processes, such as aging, apoptosis, inflammation, stress resistance, genomic stability and energy metabolism. Some findings also suggest that sirtuins family proteins may be potential markers of ovarian aging. The present review evaluates some activities of sirtuins, especially sirtuin1 and its possible association with woman's metabolism, ovarian aging and premature ovarian insufficiency. This discussion gives the novel insight into the etiology of idiopathic premature ovarian insufficiency and offers new research directions in the field (Fig. 1).

Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has favourable effects on cardiorenal outcomes in patients with mild‐to‐severe chronic kidney disease with increased albuminuria and type 2 diabetes. Two large, randomized trials have evaluated the effects of finerenone on clinical outcomes. The first trial (FIDELIO‐DKD) investigated renal outcomes, and the second (FIGARO‐DKD) cardiovascular outcomes. Patients in the two studies had a high intrinsic risk of hyperkalemia due to type 2 diabetes, treatment with optimized doses of an inhibitor of the renin‐angiotensin system, and, in some patients, their advanced chronic kidney disease. This was reflected in the incidence of hyperkalemia in the placebo group during the trials. Patients on finerenone had a significantly higher incidence of hyperkalemia compared with patients on placebo, but treatment discontinuation due to hyperkalemia was low, and no patients experienced death attributable to hyperkalemia. Structured routine potassium monitoring with temporary treatment interruption and dose reduction, as used in the two trials, should ensure the safe use of finerenone to protect the kidneys and cardiovascular system of patients with albuminuric chronic kidney disease and type 2 diabetes. The aim of this document is to highlight the routine potassium management required when using finerenone and to provide practical recommendations. Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, has favorable effects on cardiorenal outcomes in patients with mild to severe chronic kidney disease with increased albuminuria and type 2 diabetes. This article highlights the routine potassium management required when using finerenone and provides furthermore practical recommendations.

Many chemotherapeutic drugs used to treat malignancies undergo renal clearance. Thus, accurate knowledge of kidney function is critical to ensure proper dosing, maximize efficacy, and minimize toxicity of drugs that often have a narrow therapeutic index. Making this issue more salient is the fact that impaired kidney function, as assessed by glomerular filtration rate (GFR), is encountered commonly in patients with cancer. Recent data and expert guidelines recommend the use of the Chronic Kidney Disease–Epidemiology Collaboration equation to guide the assessment of kidney function, except when directly measured GFR is clinically necessary. Controversies regarding the measurement of kidney function include the use of race in this equation, indexing to body surface area, and dosing of medications based on stages of chronic kidney disease versus more discrete values of estimated GFR. The development of accurate, real-time GFR measures may hold great promise in allowing for more accurate dosing of these important drugs.

ABSTRACTIntroduction: Anemia has been remained one of the most characteristic and visible manifestations of chronic renal failure. Correction of anemia requires two main treatment strategies: increased stimulation of erythropoiesis, and maintenance of an adequate iron supply to the bone marrow.Areas covered: Erythropoiesis activating agents became a mainstay in the treatment of renal anemia for more than 25 years. Recently, there have been several attempts to introduce new drugs to stimulate erythropoiesis or affect the hepcidin-ferroportin pathway. Orally available hypoxia-inducible factor (HIF) stabilizing compounds are attractive alternatives. They not only increase hemoglobin, but also suppress hepcidin production and improve iron availability. Novel iron preparations, may also help to ameliorate anemia, with acceptable safety profile and other beneficial properties such a phosphate binding.Expert opinion: One should be aware of potential risks and benefits of novel sophisticated therapies and their role in the management of renal anemia remain to be established. In particular HIF stabilizers needs to be proven safe, or even safer than ESAs, in large long-term safety studies testing hard end points, due its ubiquitous nature and the regulation of variety of biological processes potentially leading to unexpected side effects. Besides safety, cost-effectiveness appears the major issue in the modern world, including nephrology.

The association between chronic kidney disease (CKD) and cardiovascular disease (CVD) is well established, and there is mounting evidence of interorgan cross talk that may accelerate pathologic processes and the progression of organ dysfunction in both systems. This process, termed cardiorenal syndrome (CRS) by the Acute Dialysis Quality Initiative, is considered a major health problem: patients with CKD and CVD are at much higher risk of mortality than patients with either condition alone. To date, the majority of CRS research has focused on neurohormonal mechanisms and hemodynamic alterations. However, mounting evidence suggests that abnormalities in the normal pathophysiology of the bone-mineral axis, iron, and erythropoietin play a role in accelerating CKD and CVD. The goal of this article is to review the role and interrelated effects of the bone-mineral axis and anemia in the pathogenesis of chronic CRS.

Background: The most common complications of chronic kidney disease (CKD) are hypertension and cardiovascular (CV) disorders. Renalase is produced and released by the kidney and also cardiomyocytes. Renalase deficiency was claimed to be responsible for hypertension and CV complication in CKD. There are contradictory data about serum renalase because of low activity and high levels revealed in hypertensive patients with CKD. We assessed serum renalase concentration in objects with CKD after one-side and both-side nephrectomy (on haemodialysis [HD]), or hemodiafiltration (HDF), in urine and ultrafiltrate in hemodialysis objects. We also evaluated the influence of hemodialysis sessions on renalase concentrations. Methods: The concentration of renalase in plasma, ultrafiltrate and urine of 100 hemodialysis patients was assessed by commercially accessible test. We evaluated renalase in 17 HDF objects and 24 healthy controls. Western Blot test was also used to assess renalase concentration. Results: Ultrafiltrate in hemodialysis objects contained renalase and there was no impact of dialysers&apos type (high-flux and low-flux). Renalase concentration of urine in control group was higher than in hemodialysis objects (n=60). The anuric group had higher renalase concentration comparing to those with remaining diuresis (p<0.001). Univariate analysis revealed the correlation between renalase concentration in plasma and in urine (r=-0.28, p<0.05) and ultrafiltrate renalase in hemodialysis group and between renalase in urine in the control group (r=0.61, p<0.01). There was a correlation between urinary renalase and residual diuresis, hemodialysis sessions non-significantly lowered renalase, the type of heparin had no effect on serum renalase levels. HDF patients had significantly lower renalase than HD patients. In Western blot analysis we found that patients after bilateral nephrectomy had the highest renalase, followed by unilateral nephrectomy. Conclusion: Kidneys eliminate renalase and it is possible that the increased renalase has the impact on cardiovascular diseases in chronic kidney disease.

In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure established a definition of a new category of BP levels called ‘prehypertension’ (preHT) that included individuals with a systolic BP of 120–139 mm Hg or a diastolic BP of 80–89 mm Hg. Patients with preHT were considered to be at increased risk for progression to hypertension and in individuals with BP in the range 130/80 to 139/89 mmHg the risk of developing hypertension was twice as high as in subjects with lower values. Still then there has been a large debate whether the introduction of preHT was based on evidence and as a consequence, it was fully justified. It has been suggested that the term prehypertension may in many subjects create anxiety and a need for unnecessary medical visits and examinations. This group of patients is also very heterogeneous and it has been pointed out that subdividing preHT group into individuals with normal BP and high normal BP would much better correspond to the continuum of BP risk for CV disease. Finally, despite some data suggesting the potential benefits of antihypertensive therapy in patients with preHT (high normal BP), there are still no hard evidences on the outcome reduction by giving antihypertensive drugs in these individuals.

Screening is the systematic use of a test for a health problem or risk factor when no recognized signs or symptoms would indicate the presence of that problem or risk factor. Abnormal glucose metabolism can be documented years before the onset of overt diabetes. Nowadays, prediabetes can be subdivided into impaired fasting glucose or impaired glucose tolerance. Substantial number of subjects with either will progress to overt diabetes within years. Prediabetes bears also the increased risk of cardiovascular complications. Prehypertension is much newer term introduced by the seventh report of the Joint National Committee (JNC 7) published in 2003 as systolic blood pressure from 120 to 139 mmHg or diastolic blood pressure from 80 to 89 mmHg in adults (not receiving blood pressure-lowering treatment). Similarly prehypertension also increased the risk of cardiovascular complications and progression to hypertension. Chronic kidney disease is also highly prevalent mainly in the elderly. It is associated with important adverse outcomes such as cardiovascular mortality and morbidity. Factors associated with higher risk of chronic kidney disease include mainly hypertension, diabetes, obesity and older age. Early detection and diagnosis of chronic kidney disease may prevent the full blown disease and its end-stage requiring renal replacement therapy. The review focus on the problem of high risk population for development of diabetes, hypertension and whether time has come to focus also on the conditions predisposing to the development of chronic kidney disease.

Contrast-induced nephropathy, or contrast-induced acute kidney injury (AKI), is an acute impairment of renal function as manifested by an increase in serum creatinine. Different urinary and serum proteins have been intensively investigated as possible biomarkers for the early diagnosis of AKI. Promising candidate biomarkers have the ability to detect an early and graded increase in tubular epithelial cell injury and to distinguish prerenal causes of AKI from acute tubular necrosis. In this article new, emerging biomarkers of contrast-induced AKI are presented and described, of which serum neutrophil gelatinase-associated lipocalin appears to be the most promising.

Anemia has remained one of the most characteristic and visible manifestations of chronic renal failure for over 150 years. The pathogenesis of anemia of chronic kidney disease (CKD) is multifactorial with inadequate production of erythropoietin being the leading factor. The development of recombinant human erythropoietin (epoetin) in the late 1980s was a milestone in treatment of renal anemia. Despite new drugs, our ‘good old friend' erythropoietin-stimulating agents are our everyday life in nephrology practice. It seems that peginesatide would not become a new approach for treating anemia of CKD patients, but rather a falling star. Several new strategies for treating the anemia of CKD are currently being investigated in clinical trials, including prolyl hydroxylase inhibitors and modulators of hepcidin activity, but their role in the management of this condition remains to be established. As shown by the expert in this review, we have to take into account not only the safety and convenience of administration but also cost-effectiveness, while biosimilars are consequently knocking at the doors of dialysis units more and more, particularly in Europe.

The uremic syndrome is a complex mosaic of clinical alterations that may be attributable to one or more of these different solutes. Uremic symptoms in patients with chronic kidney disease are primarily a consequence of inadequate removal and subsequent accumulation of organic products normally metabolized or excreted by the kidney.

AbstractAnemia is more prevalent in renal transplant recipients than in GFR-matched chronic kidney disease patients. Hepcidin is a small defensin-like peptide whose production by hepatocytes is modulated in response to anemia, hypoxia or inflammation. Growth differentiation factor 15 (GDF15) was recently identified as a hepcidin-suppression factor that is expressed at high levels in patients with ineffective erythropoiesis. The aim of the study was to assess GDF15 levels with relation to iron parameters in 62 stable kidney allograft recipients maintained on triple immunosuppressive therapy. Methods:Complete blood count, urea, creatinine, and iron status were assessed by standard methods. We measured GDF15, hepcidin, hemojuvelin, IL-6 and NGAL with commercially available assays. Results:Mean levels of GDF15, NGAL, hepcidin and hemojuvelin were significantly higher in kidney allograft recipients when compared to the control group (p < 0.001 for all). GDF15 was significantly higher in patients with anemia according to the WHO definition when compared to their nonanemic counterparts (p < 0.05). GDF15 levels were not dependent on the type of immunosuppressive therapy. In univariate analysis GDF15 was related to kidney function (creatinine r = 0.39, p < 0.01, eGFR by MDRD r = -0.37, p < 0.01), urea (r = 0.39, p < 0.01), uric acid (r = 0.42, p < 0.01), hepcidin (r = -0.32, p < 0.01), IL-6 (r = 0.28, p < 0.05), hemoglobin (r = -0.32, p < 0.05), and NGAL (r = -0.35, p < 0.01). GDF15 was not related to serum iron, or ferritin. In multivariate analysis, hepcidin was found to be a predictor of GDF15. In conclusion, our preliminary data may suggest possible mutual relations between GDF15 and hepcidin in patients with kidney disease and that GDF15 might be involved in the pathogenesis of anemia in kidney allograft recipients. However, the role of inflammation should be also elucidated.Copyright © 2013 S. Karger AG, Basel

The aim of this study was to assess the value of the angiographically-derived Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score in predicting mortality and major adverse cardiac events (MACEs) during a 3-year follow-up of dialysis patients undergoing a percutaneous coronary intervention or coronary artery bypass graft operation. We compared the aforementioned results with the clinical Khan index.

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 renalasegene 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 andor 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.

Limited data exist in regard to the correlation between ST-segment resolution (STR) in patients treated with primary percutaneous coronary intervention (pPCI) and very late mortality. The aim of the study was to determine the correlation between STR and 6-year mortality in patients successfully treated with pPCI.

AbstractBackground:Neutrophil gelatinase-associated lipocalin (NGAL) binds small, iron-carrying molecules – siderophores. On the other hand, hepcidin is a small defensin-like peptide produced by hepatocytes, modulated in response to anaemia, hypoxia, or inflammation. We tested the hypothesis that NGAL may be related to hepcidin, not only to iron metabolism, in 182 prevalent haemodialysed patients. Methods:Iron status (iron, total iron-binding capacity, ferritin, total saturation of transferrin, TSAT), complete blood count, creatinine, albumin, serum lipids were assessed using standard laboratory methods. Soluble receptor of transferrin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, prohepcidin, hepcidin and NGAL were measured in serum using commercially available kits. Results:Serum NGAL, prohepcidin, hepcidin levels were significantly higher in haemodialysed patients over healthy volunteers (579.11 ± 213.95 vs. 78.43 ± 32.21 ng/ml, p < 0.001, 320.54 ± 182.65 vs. 98.65 ± 34.32 ng/ml, p < 0.01, 155.30 ± 94.05 vs. 23.65 ± 12.76 ng/ml, p < 0.001, respectively). Serum NGAL correlated strongly with residual renal function (r = –0.54, p < 0.001), Kt/V (r = 0.41, p < 0.001), hepcidin (r = –0.28, p < 0.01), serum creatinine (r = 0.63, p < 0.001), iron (r = 0.25, p < 0.01), TSAT (r = 0.30, p < 0.001), ferritin (r = 0.33, p < 0.001), hsCRP (r = 0.32, p < 0.001). In multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in haemodialysed patients. Conclusions:NGAL is highly induced in dialysed patients. NGAL could reflect both kidney function and iron metabolism. Taking into account the antimicrobial properties 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

Renal function affects the thyroid gland in many ways. Disturbances in hemostasis and inflammation are common complications of kidney diseases. Endothelial dysfunction may link these two processes.

Renal function affects thyroid function and adipocytokines in many ways. We aimed to assess the adipocytokines adiponectin and leptin in relation to thyroid function in patients with chronic renal failure treated conservatively, in haemodialysed patients and in kidney allograft recipients.

Cardiovascular disease (CVD) is the single best predictor of mortality in patients with chronic kidney disease and in kidney transplant recipients. These populations are considered to be at extraordinarily high risk for CVD and its complications. On the other hand, renal dysfunction should be considered as a CVD risk factor. The management of CVD in patients with chronic kidney disease is a special challenge for clinicians. In this article, major risk factors for CVD are presented, as well as diagnosis of coronary artery disease, acute coronary syndromes, its treatment modalities (pharmacological therapy and coronary revascularisation procedures), and outcomes in patients with chronic renal failure and kidney allograft recipients.

Background:The use of noncuffed nontunneled central venous catheters is a widely accepted method of gaining temporary vascular access for hemodialysis. Malfunction and bacteremia are the main factors limiting catheter survival. Methods:We followed up prospectively 73 hemodialysis catheters (HC) (40 internal jugular, 33 femoral) in order to establish factors influencing HC malfunction. HC malfunction was defined as a catheter that was unable to attain and maintain blood flows of at least 150 ml/min. 73 HC were used for a total 1,100 days. Results:HC malfunction occurred in 23 cases (31.51%) during the study period, giving an overall rate of 21 episodes per 1,000 catheter days at risk. An analysis revealed a higher risk of HC malfunction with the catheterization of the femoral vein compared to the internal jugular vein (hazard ratio (HR) 6.3; 95% confidence interval (CI) 5.3–7.3). After correction for confounding factors in multivariate Cox analysis, the site of the catheterization remained a statistically significant predictor of HC malfunction (HR 5.03, 95% CI 3.83–6.23). After the first week malfunction rate was 42 and 8% for femoral and internal jugular site, respectively (relative risk (RR) for malfunction 5.3 (95% CI, 2.5–8). After the second and third week, the incidence of malfunction was 51 and 14% for femoral and internal jugular vein, respectively (RR 3.6, 95% CI 2.2–5.1). Conclusions:Catheterization of the internal jugular vein is associated with longer catheter survival when compared to the femoral vein. Hemodialysis catheters should be placed, if possible, in internal jugular vein to prevent their premature malfunction.

← Background Patients on continuous ambulatory peritoneal dialysis (CAPD) are prone to dyslipidemia and have a high risk of cardiovascular death. Statins show beneficial effects on serum lipids and thrombogenesis in various groups of patients, but prospective studies have so far not been performed on CAPD patients.← Aim To determine the effects of 6 month's treatment with simvastatin on platelet function and some hemostatic parameters, markers of endothelial cell injury, in 14 CAPD patients with hypercholesterolemia.← Methods Simvastatin was given in a dose of 10 mg at bedtime. Commercially available kits were used for all determinations.← Results Cholesterol and low density lipoprotein fell significantly as early as after 1 month of the therapy (p< 0.001). Platelet aggregation in whole blood and plateletrich plasma was transiently decreased by simvastatin therapy. The fibrinolytic activity index increased significantly after 6 months of simvastatin administration (p< 0.05), reaching values observed in the control group, whereas euglobulin clot lysis time, which was also significantly shortened after 6 months (p< 0.05), did not reach values obtained in healthy volunteers. Vascular cell adhesion molecule, thrombomodulin, and protein Z decreased significantly after 3 months of the therapy (p< 0.05, p< 0.05, and p< 0.01, respectively), whereas intercellular adhesion molecule decreased after 6 months (p< 0.05). Vascular endothelial growth factor and its receptor, protein Z, total tissue factor pathway inhibitor (TFPI), TFPI/Xa complexes, and thrombin activatable fibrinolysis inhibitor concentration and activity fell significantly after 6 months of treatment with simvastatin (all p< 0.05). Tissue plasminogen activator concentration increased after 1 month (p< 0.01 after 1 month, p< 0.05 after 3 and 6 months), whereas total homocysteine fell after 6 months of simvastatin therapy (p< 0.05). Truncated TFPI decreased significantly as early as after 1 month of therapy (p< 0.05 after 1 month, p< 0.01 after 3 and 6 months).← Conclusion Simvastatin is an effective hypolipemic agent in CAPD patients. It favorably affects platelet aggregation and the extrinsic coagulation pathway, improves fibrinolysis, and ameliorates endothelial dysfunction. Simvastatin might reduce the risk of thrombotic complications in CAPD patients.

Abstract Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. Recently, attention has been drawn to the beneficical effects of statins on haemostasis in kidney patients prone to dyslipidaemia and with a high risk of cardiovascular death. The purpose of this study was to assess whether fluvastatin affects TAFI concentration in renal transplant recipients. We evaluated thrombin‐antithrombin (TAT) comlplexes, prothrombin fragments 1 + 2, thrombomodulin, plasmin‐antiplasmin (PAP) complexes, TAFI, P‐selectin, and lipoprotein (a), 1, 2, and 3 months before and after fluvastatin treatment and in normolipaemic kidney transplant recipients and healthy volunteers. Cholesterol and LDL fell significantly as soon as 1 month after treatment had soon as 1 month after treatment had begun and remained lowered during the therapy. TAFI and prothrombin fragments 1 + 2 decreased significantly after 3 months of fluvastatin administration, whereas P‐selectin decreased significantly after 2 months and remained significantly lower after 3 months of this therapy. We caxn conclude that fluvastatin is an effective hypolipaemic agent that favourable affects haemostasis.

Abstract Thrombin activatable fibrinolysis inhibitor (TAFI) is a glycoprotein, linking coagulation and fibrinolysis. Recently, attention has been drawn to the beneficial effects of statins on haemostasis in kidney patients prone to dyslipidaemia and with a high risk of cardiovascular death. The purpose of this study was to assess whether fluvastatin affects TAFI concentration in renal transplant recipients. We evaluated thrombin-antithrombin (TAT) complexes, prothrombin fragments 1+2, thrombomodulin, plasmin-antiplasmin (PAP) complexes, TAFI, P-selectin, and lipoprotein (a), 1, 2, and 3 months before and after fluvastatin treatment and in normolipaemic kidney transplant recipients and healthy volunteers. Cholesterol and LDL fell significantly as soon as 1 month after treatment had begun and remained lowered during the therapy. TAFI and prothrombin fragments 1+2 decreased significantly after 3 months of fluvastatin administration, whereas P-selectin decreased significantly after 2 months and remained significantly lower after 3 months of this therapy. We can conclude that fluvastatin is an effective hypolipaemic agent that favourably affects haemostasis.

Objective Bleeding diathesis and simultaneous thrombotic complications may be seen in dialyzed patients. Erythropoietin (EPO) may shift the precarious balance of the hemostatic system toward thrombosis. Platelets and tissue factor (TF) play a major role in plug formation. Tissue factor pathway inhibitor (TFPI) appears to play a primary role in regulating TF-induced coagulation. Thrombin activatable fibrinolysis inhibitor (TAFI) is a key protein linking coagulation and fibrinolysis. The aim of the study was to assess whether 6 months of EPO therapy affects platelet function, that is, platelet aggregation and P-selectin level; moieties of the extrinsic coagulation pathway: TF, TFPI, and TFPI/Xa complexes, and factors VII and X; markers of ongoing coagulation: thrombin–antithrombin complexes (TAT) and prothrombin fragments 1+2; a marker of ongoing fibrinolysis: plasmin–antiplasmin complexes (PAP); fibrinolytic activity: euglobulin clot lysis time (ECLT); and markers of endothelial cell injury: von Willebrand factor, thrombomodulin, E-selectin, and TAFI, in continuous ambulatory peritoneal dialysis (CAPD) patients.Patients and Methods 22 patients on CAPD were given EPO 6000 U/week. 12 patients with chronic renal failure and 12 healthy volunteers served as control groups. All parameters were studied before, and after 1, 3, and 6 months of EPO therapy.Setting Department of Nephrology and Internal Medicine, Medical Academy of Bialystok, Poland.Results Platelet aggregation in whole blood did not change significantly during EPO treatment. A significant rise in arachidonic acid-induced platelet aggregation in platelet-rich plasma was observed after 3 and 6 months, and in collagen-induced platelet aggregation after 6 months of EPO therapy, compared to the baseline values. The TFPI concentration decreased significantly after 6 months of EPO therapy. The activity of factor VII increased transiently after 1 month of EPO therapy, compared to the baseline values. The TAFI concentration and activity in the CAPD group were significantly higher than in the control group. Erythropoietin therapy resulted in a significant decrease in TAFI concentration and activity after 6 months of EPO treatment. The ECLT was shortened significantly as early as after 1 month of EPO therapy. Thrombomodulin, von Willebrand factor concentration and activity, PAP, TAT, TFPI/Xa complexes, prothrombin fragments 1+2, factor X activity, P-selectin, E-selectin, and lipoprotein(a) did not change significantly during EPO treatment.Conclusion Erythropoietin treatment has a minimal effect on hemostasis in CAPD patients. A tendency toward a decline in TAFI is of unknown clinical relevance so far, and awaits further research.

Background. Cardiovascular disease (CVD) is a major cause of death in renal transplant recipients (RTR). Suppression of fibrinolysis plays a role in the progression of atherosclerosis. Accelerated progression of atherosclerosis and fibrinolytic system suppression has been observed in RTR. Despite many years of intensive research, the reason for impaired fibrinolysis in this patient population is not fully understood. Thrombin‐activatable fibrinolysis inhibitor (TAFI) is a recently discovered glycoprotein combining coagulation and fibrinolysis. This study was conducted to evaluate concentrations of TAFI, markers of thrombin generation, endothelial injury, and some standard laboratory parameters in RTR receiving triple immunosuppressive drug regimen.Methods. The study was performed in 29 stable, non‐diabetic kidney transplant recipients treated with cyclosporin A, azathioprine, and prednisone and in 18 age‐ and sex‐matched healthy volunteers. Soluble thrombomodulin (sTM), prothrombin fragments F1+2 (F1+2), thrombin–antithrombin complexes (TAT), plasmin–antiplasmin complexes (PAP), and TAFI were measured with commercially available kits.Results. The RTR group had significantly higher plasma levels of TAT, F1+2, sTM and TAFI than the healthy volunteers. There were no differences in PAP concentrations between the two groups. Plasma sTM correlated inversely with creatinine clearance, body mass index, haemoglobin, and albumin. Plasma TAT level was positively associated with total cholesterol. TAFI antigen influenced negatively PAP antigen concentration.Conclusions. On the basis of our research, we concluded that elevated circulating TAFI antigen might be a new link in the pathogenesis of impaired fibrinolysis in RTR, and thus atherosclerosis progression. In the patient group there is also evidence of endothelial injury, followed by secondary activation of the coagulation cascade. Hypercholesterolaemia in RTR is associated with enhanced thrombin activity.

Objective Disturbances in hemostasis are common findings in uremic patients. Both bleeding diathesis and thrombosis are observed. The purpose of this study was to assess whether renal replacement therapy in the form of hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) affects coagulation and fibrinolysis in patients with end-stage renal failure.Design Comparison of hemostatic measures in patients on CAPD, HD, and matched healthy controls.Setting Department of Nephrology and Internal Medicine, Bialystok University School of Medicine.Patients and Methods Twenty-four HD patients and 23 CAPD patients were evaluated with respect to platelet aggregation, hemostatic parameters, serum lipids, lipoprotein(a), and cytokines [tumor necrosis factor alpha (TNFα) and interleukin-1 (IL-1)].Interventions Four exchanges of CAPD per day, using 2.0 L dialysate over a period of 25 ± 31 months; or 4 – 5 hours of HD 3 times per week for a period of 31 ± 22 months.Results Platelet aggregation in whole blood and platelet-rich plasma was significantly impaired in both groups of dialyzed patients compared to healthy volunteers. Markers of endothelial cell injury (thrombomodulin and von Willebrand factor) were significantly higher in HD and CAPD patients compared to the control group. A similar pattern of changes was observed for lipoprotein(a), fibrinogen, tissue factor pathway activity, and factor VII activity. Activity of factor X was significantly enhanced in CAPD compared to HD patients and controls. Euglobulin clot lysis time was significantly prolonged in HD and CAPD patients over controls, being more prolonged in CAPD patients. Markers of ongoing coagulation (thrombin–antithrombin complexes and prothrombin fragments 1+2) were higher in uremic patients, significantly higher in CAPD than in HD. A marker of ongoing fibrinolysis (plasmin–antiplasmin complexes) was higher in uremic patients but was lower in CAPD than in HD patients. Concentrations of TNFα and IL-1 were higher in HD than in CAPD patients.Conclusion Patients on CAPD showed evidence of a higher degree of hypercoagulation than HD patients. Thus, hemostatic abnormalities in end-stage renal failure may be affected to some extent by the choice of renal replacement therapy.