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Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of the ERA.)

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., (© The Author(s) 2021. Published by Oxford University Press on behalf of the ERA.)

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., (© The Author(s) 2021. Published byOxford University Press on behalf of ERA.)

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., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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.

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.

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.

Coronary artery disease and acute coronary syndrome (ACS) are both common in patients with chronic kidney disease (CKD). CKD patients have higher risks of bleeding and thrombosis. However, they remain under-represented in major randomized clinical trials (RCTs), and there is no medical evidence-based foundation on which to issue specific recommendations about the management of ACS in CKD. CKD patients with ACS frequently are diagnosed later, receive fewer acute interventions and are at increased risk of over-dosage of medications and under-prescription/under-performance of interventional treatments than CKD patients without ACS. The lack of RCTs should not discourage reliance on clinical common sense, while clearer decisional algorithms with better outcomes are a priority for urgent development. Future guidelines should further refine the assessment of CKD with ACS while placing much greater emphasis on the correct dosing of medications based on contemporaneous renal function. Until a strategy is designed with specific measures translated into the actual decrease of bleeding risk, providers will be forced to balance the equilibrium on a thin red line that is not clearly established., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Severe adverse systemic drug events occur commonly as a result of treatment of cancer patients. Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. A variety of renal disease and electrolyte disorders can result from the drugs that are used to treat malignant disease. The kidneys are a major elimination pathway for many antineoplastic drugs and their metabolites. Tumour lysis syndrome, an emergency in haematooncology, occurs most often after the initiation of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukaemia. Chemotherapeutic agents can affect the glomerulus, tubules, interstitium and renal microvasculature, with clinical manifestations that range from asymptomatic elevation of serum creatinine to acute renal failure requiring dialysis. Some factors such as intravascular volume depletion, as well as concomitant use of other drugs or radiographic ionic contrast media, can potentiate or contribute to the nephrotoxicity. Cytotoxic agents can cause nephrotoxicity by a variety of mechanisms. The most nephrotoxic chemotherapeutic drug is cisplatin, which is often associated with acute kidney injury. Many other drugs such as alkylating agents, antimetabolites, vascular endothelial growth factor pathway inhibitors and epidermal growth factor receptor pathway inhibitors may have toxic effects on the kidneys. The aim of this review is to discuss the issue of nephrotoxicity associated with chemotherapy. In routine clinical practice, monitoring of kidney function is mandatory in order to identify nephrotoxicity early, allowing dosage adjustments or withdrawal of the offending drug., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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., (© The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

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 (CV(1)) was calculated and potential factors affecting CV(1) were also examined., Results: The median CV(1) (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 CV(1) was similar in those patients receiving and those not receiving regular intravenous iron. The CV(1) 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.

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., Methods: Thirty-nine ESRD patients on regular dialysis underwent elective coronary angiography. Coronary artery stenosis >75% was defined as significant. TFC for the three main coronary vessels was calculated. Higher TFC values reflected slower flow., Results: In 19 patients (49%), significant epicardial coronary artery disease was found. Distribution of the TFC for the three main coronary arteries reflected prevalence for higher TFC values. Mean corrected TFC for the left anterior descending artery (LAD) was 34.7 +/- 16, for the circumflex artery (Cx) 41.5 +/- 25 and for the right coronary artery (RCA) 30.9 +/- 18 frames. For the three main coronary vessels, there were no statistically significant differences between the mean TFC values according to the presence or absence of the severe coronary artery stenoses on angiography (LAD: 30.2 +/- 12 vs 36.3 +/- 18; Cx: 41.5 +/- 20 vs 41.5 +/- 27; RCA: 34.9 +/- 16 vs 30.0 +/- 19, respectively)., Conclusions: Our results demonstrate for the first time the reduction in blood flow velocity, assessed with TFC method, in the coronary arteries of ESRD patients. This phenomenon was observed regardless of the presence of the significant epicardial coronary artery stenosis. Therefore, TFC cannot be applied as a marker of significant coronary artery stenosis in ESRD population.

Background: 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., Methods: The study was performed on 33 patients with chronic renal failure, 64 haemodialysed patients, 54 kidney allograft recipients and 38 healthy volunteers. Thyroid volume was estimated sonographically, thyroid hormones were determined by Micropartide Enzyme Immunoassay (MEIA), and serum adiponectin and leptin were assessed by radioimmunoassay., Results: Serum thyroid-stimulating hormone (TSH), free T4 and free T3 were within the normal range. Adiponectin correlated significantly with free T3, haematocrit, haemoglobin, platelet count, body mass index (BMI) and urea in kidney allograft recipients. In haemodialysed patients, adiponectin correlated with free T4 and TSH, whereas leptin correlated with free T3. Multiple regression analysis showed that adiponectin was independently related only to the serum concentration of free T3 and urea in kidney transplant recipients and to free T4 and adequacy of dialysis in haemodialysed patients. In univariate analysis in patients with chronic renal failure, adiponectin correlated with free T3 and platelet count, and in healthy volunteers adiponectin correlated only with free T3 and triglycerides, and leptin correlated with BMI., Conclusions: We described novel relationships between adiponectin and thyroid hormones in patients with kidney diseases. However, possible pre-existing thyroid dysfunction prior to transplantation (during dialysis therapy) and immunosuppression after transplantation make all these findings relatively complex. Therefore, the relationships between adiponectin and the thyroid axis in patients with chronic renal failure, in haemodialysed subjects or in kidney transplant recipients merit additional studies.