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There is growing evidence that chronic kidney disease (CKD) is an independent risk factor for cognitive impairment, especially due to vascular damage, blood–brain barrier disruption and uremic toxins. Given the presence of multiple comorbidities, the medication regimen of CKD patients often becomes very complex. Several medications such as psychotropic agents, drugs with anticholinergic properties, GABAergic drugs, opioids, corticosteroids, antibiotics and others have been linked to negative effects on cognition. These drugs are frequently included in the treatment regimen of CKD patients. The first review of this series described how CKD could represent a risk factor for adverse drug reactions affecting the central nervous system. This second review will describe some of the most common medications associated with cognitive impairment (in the general population and in CKD) and describe their effects. [ABSTRACT FROM AUTHOR]

Transplantation offers cure for some haematological cancers, end-stage organ failure, but at the cost of long-term complications. Renal transplantation is the best-known kidney replacement therapy and it can prolong end-stage renal disease patient lives for decades. However, patients after renal transplantation are at a higher risk of developing different complications connected not only with surgical procedure but also with immunosuppressive treatment, chronic kidney disease progression and rejection processes. Various blood disorders can develop in post-transplant patients ranging from relatively benign anaemia through cytopenias to therapy-related myelodysplasia and acute myeloid leukaemia (AML) and post-transplant lymphoproliferative disorders followed by a rare and fatal condition of thrombotic microangiopathy and haemophagocytic syndrome. So far literature mainly focused on the post-transplant lymphoproliferative disease. In this review, a variety of haematological problems after transplantation ranging from rare disorders such as myelodysplasia and AML to relatively common conditions such as anaemia and iron deficiency are presented with up-to-date diagnosis and management. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY) is a 36-amino-acid peptide member of a family also including peptide YY and pancreatic polypeptide, which are all ligands to Gi/Go coupled receptors. NPY regulates several fundamental biologic functions including appetite/satiety, sex and reproduction, learning and memory, cardiovascular and renal function and immune functions. The mesenteric circulation is a major source of NPY in the blood in man and this peptide is considered a key regulator of gut–brain cross talk. A progressive increase in circulating NPY accompanies the progression of chronic kidney disease (CKD) toward kidney failure and NPY robustly predicts cardiovascular events in this population. Furthermore, NPY is suspected as a possible player in accelerated cognitive function decline and dementia in patients with CKD and in dialysis patients. In theory, interfering with the NPY system has relevant potential for the treatment of diverse diseases from cardiovascular and renal diseases to diseases of the central nervous system. Pharmaceutical formulations for effective drug delivery and cost, as well as the complexity of diseases potentially addressable by NPY/NPY antagonists, have been a problem until now. This in part explains the slow progress of knowledge about the NPY system in the clinical arena. There is now renewed research interest in the NPY system in psychopharmacology and in pharmacology in general and new studies and a new breed of clinical trials may eventually bring the expected benefits in human health with drugs interfering with this system. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins' putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care. [ABSTRACT FROM AUTHOR]

Anaemia is a common complication of chronic kidney disease (CKD). In this setting, iron deficiency is frequent because of the combination of increased iron needs to sustain erythropoiesis with increased iron losses. Over the years, evidence has accumulated on the involvement of iron in influencing pulmonary vascular resistance, endothelial function, atherosclerosis progression and infection risk. For decades, iron therapy has been the mainstay of therapy for renal anaemia together with erythropoiesis-stimulating agents (ESAs). Despite its long-standing use, grey areas still surround the use of iron therapy in CKD. In particular, the right balance between either iron repletion with adequate therapy and the avoidance of iron overload and its possible negative effects is still a matter of debate. This is particularly true in patients having functional iron deficiency. The recent Proactive IV Iron Therapy in Haemodialysis Patients trial supports the use of intravenous (IV) iron therapy until a ferritin upper limit of 700 ng/mL is reached in haemodialysis patients on ESA therapy, with short dialysis vintage and minimal signs of inflammation. IV iron therapy has also been proven to be effective in the setting of heart failure (HF), where it improves exercise capacity and quality of life and possibly reduces the risk of HF hospitalizations and cardiovascular deaths. In this review we discuss the risks of functional iron deficiency and the possible benefits and risks of iron therapy for the cardiovascular system in the light of old and new evidence. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is common in patients with chronic kidney disease (CKD), affecting 10–25% of patients requiring dialysis. Compared with the general population, patients requiring dialysis are also at increased risk of stroke, the major thromboembolic complication of AF. The evidence base for management strategies of AF specific to patients with advanced CKD is limited and not informed by randomized controlled trials. These gaps in evidence encompass rate and rhythm control strategies as well as a paucity of data informing which patients should receive anticoagulation. The European Renal Association–European Dialysis and Transplant Association and European Heart Rhythm Association undertook a survey of nephrologists and cardiologists exploring management strategies in patients with AF and CKD. We review the results of this survey, highlighting the differences in clinical approaches from cardiologists and nephrologists to these conditions. Closer collaboration between these specialties should lead to improved outcomes for patients with advanced CKD and AF. Specific issues that will need to be addressed may include healthcare burden to patients, location of clinics compared with dialysis sites and awareness of complications of treatments specific to CKD, such as calciphylaxis associated with vitamin K antagonism. [ABSTRACT FROM AUTHOR]

Background Cardiovascular disease (CVD) is a major contributor to morbidity and mortality in people on hemodialysis (HD). Cardiovascular outcomes are reported infrequently and inconsistently across trials in HD. This study aimed to identify the priorities of patients/caregivers and health professionals (HPs) for CVD outcomes to be incorporated into a core outcome set reported in all HD trials. Methods In an international online survey, participants rated the absolute importance of 10 cardiovascular outcomes (derived from a systematic review) on a 9-point Likert scale, with 7–9 being critically important. The relative importance was determined using a best–worst scale. Likert means, medians and proportions and best–worst preference scores were calculated for each outcome. Comments were thematically analyzed. Results Participants included 127 (19%) patients/caregivers and 549 (81%) HPs from 53 countries, of whom 530 (78%) completed the survey in English and 146 (22%) in Chinese. All but one cardiovascular outcome ('valve replacement') was rated as critically important (Likert 7–9) by all participants; 'sudden cardiac death', 'heart attack', 'stroke' and 'heart failure' were all rated at the top by patients/caregivers (median Likert score 9). Patients/caregivers ranked the same four outcomes as the most important outcomes with mean preference scores of 6.2 (95% confidence interval 4.8–7.5), 5.9 (4.6–7.2), 5.3 (4.0–6.6) and 4.9 (3.6–6.3), respectively. The same four outcomes were ranked most highly by HPs. We identified five themes underpinning the prioritization of outcomes: 'clinical equipoise and potential for intervention', 'specific or attributable to HD', 'severity or impact on the quality of life', 'strengthen knowledge and education', and 'inextricably linked burden and risk'. Conclusions Patients and HPs believe that all cardiovascular outcomes are of critical importance but consistently identify sudden cardiac death, myocardial infarction, stroke and heart failure as the most important outcomes to be measured in all HD trials. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of renal significance (MGRS) has introduced a new perspective to several well-known disease entities impacting nephrology, haematology and pathology. Given the constantly changing disease spectrum of these entities, it is clinically imperative to establish diagnostic and treatment pathways supported by evidence-based medicine. MGRS is a disease of the kidney, secondary to plasma cell clonal proliferation or immune dysfunction, requiring therapeutic intervention to eradicate the offending clone. To fully understand the disease(s), it is prerequisite to determine the significance of the findings. The diagnostic work up should be extensive due to the wide heterogeneity of clinical presentation, ultimately necessitating kidney biopsy. Particular patient profiles such as AL amyloidosis, which may be diagnosed through biopsies of other tissues/organs, may be an exception. Treatment decisions should be formulated by multi-disciplinary consensus: nephrologists, haematologists and pathologists. The ultimate goal in managing MGRS is eradication of the offending plasma cell clone which requires targeted chemotherapy and, in eligible cases, haematopoietic stem cell transplantation. We present a review of diagnostic procedures, treatment options and advances in the last few years in the management of MGRS in an effort to acquaint specialists with this new face of several older diseases. [ABSTRACT FROM AUTHOR]

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]

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]

Scientific societies are increasingly seen as central to the advancement of information sharing and collaboration among scientists and clinical investigators for the progress of medical research and the promotion of education, professional competence, integrity and quality studies. To more effectively serve the practicing nephrologists and investigators dedicated to renal science, the Council of the European Renal Association and European Dialysis and Transplantation Association (ERA-EDTA) reorganized and integrated the various activities of the society into two branches, the Clinical Nephrology Governance branch and the Renal Science branch. New affordable initiatives to promote research, education and professional development and to advocate for the recognition of chronic kidney disease as a major public health issue at the European level will be put in place and/or potentiated in the new organizational frame. Educational initiatives will be espoused to Continuous Professional Development and, starting from 2019, 14 Education & Continuous Professional Development courses will be held covering the full range of knowledge areas of modern nephrology. Consolidation and development is the short- and medium-term mantra of the ERA-EDTA. The society has a rich portfolio of successful activities and brilliant, creative scientists among its members. Integrating the various activities of the ERA-EDTA and treasuring the expertise and wisdom of its most accomplished members will facilitate collaborative research, education and its public impact at large. [ABSTRACT FROM AUTHOR]

Iron deficiency anaemia is a global health problem that manifests as fatigue and poor physical endurance. Anaemia can be caused by dietary iron deficiency, blood loss or a combination of poor iron absorption and ineffective iron mobilization in patients with chronic disease. Nephrologists caring for patients with impaired renal function understand that iron treatment is necessary to provide adequate iron for erythropoiesis during the treatment of overt anaemia. However, a less wellunderstood health problemis iron deficiency, which creates symptoms that overlap with those of anaemia and often occurs in concert with chronic disease. Recently, several randomized controlled clinical trials have been conducted to investigate the effects of treatment with intravenous iron in heart failure patients with iron deficiency who may or may not also have anaemia. Given that heart and kidney disease are often comorbid, these clinical trials may have implications for the way nephrologists view their patients with iron deficiency. In this article, we review several clinical studies of intravenous iron therapy for patients with iron deficiency and heart failure and discuss possible implications for the treatment of patients with kidney disease. [ABSTRACT FROM AUTHOR]

In 2011, Nephrology Dialysis and Transplantation (NDT) established a more restrictive selection process for manuscripts submitted to the journal, reducing the acceptance rate from 25% (2008-2009) to currently about 12-15%. To achieve this goal, we decided to score the priority of manuscripts submitted to NDT and to reject more papers at triage than in the past. This new scoring system allows a rapid decision for the authors without external review. However, the risk of such a restrictive policy may be that the journal might fail to capture important studies that are eventually published in higher-ranked journals. To look into this problem, we analysed random samples of papers (~10%) rejected by NDT in 2012. Of the papers rejected at triage and those rejected after regular peer review, 59 and 61%, respectively, were accepted in other journals. A detailed analysis of these papers showed that only 4 out of 104 and 7 out of 93 of the triaged and rejected papers, respectively, were published in journals with an impact factor higher than that of NDT. Furthermore, for all these papers, independent assessors confirmed the evaluation made by the original reviewers. The number of citations of these papers was similar to that typically obtained by publications in the corresponding journals. Even though the analyses seem reassuring, previous observations made by leading journals warn that the risk of 'big misses', resulting from selective editorial policies, remains a real possibility. We will therefore continue to maintain a high degree of alertness and will periodically track the history of manuscripts rejected by NDT, particularly papers that are rejected at triage by our journal. [ABSTRACT FROM AUTHOR]

Aims The changes in iron status occurring during the course of heart failure (HF) and the underlying pathomechanisms are largely unknown. Hepcidin, the major regulatory protein for iron metabolism, may play a causative role. We investigated iron status in a broad spectrum of patients with systolic HF in order to determine the changes in iron status in parallel with disease progression, and to associate iron status with long-term prognosis. Methods and results Serum concentrations of ferritin, transferrin saturation (Tsat), soluble transferrin receptor (sTfR), and hepcidin were assessed as the biomarkers of iron status in 321 patients with chronic systolic HF [age: 61 ± 11 years, men: 84%, left ventricular ejection fraction: 31 ± 9%, New York Heart Association (NYHA) class: 72/144/87/18] at a tertiary cardiology centre and 66 age- and gender-matched healthy subjects. Compared with healthy subjects, asymptomatic HF patients had similar haematological status, but increased iron stores (evidenced by higher serum ferritin without distinct inflammation, P < 0.01) with markedly elevated serum hepcidin (P < 0.001). With increasing HF severity, patients in advanced NYHA classes had iron deficiency (ID) (reduced serum ferritin, low Tsat, high sTfR), iron-restricted erythropoiesis (reduced haemoglobin, high red cell distribution width), and inflammation (high serum high-sensitivity-C-reactive protein and interleukin 6), which was accompanied by decreased circulating hepcidin (all P < 0.001). In multivariable Cox models, low hepcidin was independently associated with increased 3-year mortality among HF patients (P < 0.001). Conclusions Increased level of circulating hepcidin characterizes an early stage of HF, and is not accompanied by either anaemia or inflammation. The progression of HF is associated with the decline in circulating hepcidin and the development of ID. Low hepcidin independently relates to unfavourable outcome. [ABSTRACT FROM PUBLISHER]

Background Measurement of serum hepcidin levels may provide a useful alternative to the current methods of determining iron status in chronic haemodialysis (HD) patients. However, the biological variability of this pivotal regulator of iron homeostasis is unclear, and the impact of inflammation, dialysis clearance and iron therapy on hepcidin variability has not been established. Methods Two independent studies in chronic HD patients were conducted; serum hepcidin levels were measured at the start of dialysis sessions in 20 UK patients and in 43 Dutch patients by mass spectrometry (MS). Samples from UK patients were also analysed by a competitive enzyme-linked immunosorbent assay (cELISA). Coefficient of variance (CV1) was calculated and potential factors affecting CV1 were also examined. Results The median CV1 (inter-quartile range) was 23% (17–28) for the UK MS, 26% (17–48) for the Dutch MS and 23% (17–39) for the UK cELISA. The CV1 was similar in those patients receiving and those not receiving regular intravenous iron. The CV1 was not associated with the degree of inflammation. Hepcidin levels were higher following an inter-dialytic period of 3 versus 2 days (P = 0.02). Conclusions These findings suggest considerable variability of serum hepcidin levels in HD patients. Inflammation and the use of iron did not impact on the degree of variability, and hepcidin levels were higher after an inter-dialytic period of 3 versus 2 days. These findings need to be taken into account in future studies assessing the utility of serum hepcidin as a guide to the use of iron or erythropoiesis-stimulating agents therapy. [ABSTRACT FROM PUBLISHER]

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]

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. [ABSTRACT FROM PUBLISHER]

A response by Bozena Sobkowicz, Anna Tomaszuk-Kazberuk, and Jolanta Malyszko to a letter to the editor about their article "Coronary blood flow in patients with end-stage renal disease assessed by thrombolysis in myocardial infarction frame count method" in the 2010 issue is presented.