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Patients with the dual burden of chronic kidney disease (CKD) and cardiovascular disease (CVD) experience unacceptably high rates of morbidity and mortality, which also entail unfavorable effects on healthcare systems. Currently, concerted efforts to identify, prevent and treat CVD in CKD patients are lacking at the institutional level, with emphasis still being placed on individual specialty views on this topic. The authors of this position paper endorse the need for a dedicated interdisciplinary team of subspecialists in cardio-nephrology that manages appropriate clinical interventions across the inpatient and outpatient settings. There is a critical need for training programs, guidelines and best clinical practice models, and research funding from nephrology, cardiology and other professional societies, to support the development of the subspecialty of cardio-nephrology. This position paper from the coordinating committee from the Working Group for Cardiorenal Medicine of the Spanish Society of Nephrology (S.E.N.) is intended to be the starting point to develop the subspecialty of cardio-nephrology within the S.E.N.. The implementation of the subspecialty in day-to-day nephrological practice will help to diagnose, treat, and prevent CVD in CKD patients in a precise, clinically effective, and health cost-favorable manner. Resumen: Los pacientes con enfermedad renal crónica (ERC) que presentan enfermedad cardiovascular (ECV) tienen índices de morbilidad y mortalidad inaceptablemente elevados, que impactan desfavorablemente sobre los sistemas de salud. En la actualidad, se requieren actuaciones multidisciplinares para identificar, prevenir y tratar la ECV en los pacientes con ERC, debiendo pues superarse la época de las actuaciones de las especialidades individuales. Los autores de este artículo respaldan la necesidad de un equipo interdisciplinar de subespecialistas en cardionefrología que gestione las intervenciones clínicas adecuadas en el entorno hospitalario y en el ambulatorio. Existe una gran necesidad de programas de formación, de guías y modelos de práctica clínica, y de fondos para la investigación en las sociedades de nefrología, cardiología y otras, para apoyar el desarrollo de la subespecialidad de cardio-nefrología. Este documento de opinión del comité coordinador del Grupo de Trabajo de Medicina Cardiorenal de la Sociedad Española de Nefrología (S.E.N.) pretende ser el inicio del desarrollo de la subespecialidad de Cardionefrología en el marco de la S.E.N. La implementación de la subespecialidad en la práctica nefrológica diaria contribuirá a diagnosticar, tratar y prevenir la ECV en los pacientes con ERC de una manera precisa, clínicamente efectiva y sanitariamente rentable.

Direct oral anticoagulants (DOAC) are mostly prescribed to prevent cardioembolic stroke in patients with non-valvular atrial fibrillation (AF). An increasing number of guidelines recommend DOAC in AF patients with preserved renal function for the prevention of thromboembolism and an increased use of DOAC in daily practice is recorded also in elderly patients. Aging is associated with a reduction of glomerular filtration rate and impaired renal function, regardless of the cause, increases the risk of bleeding. Multiple medication use (polypharmacy) for treating superimposed co-morbidities is common in both elderly and chronic kidney disease (CKD) patients and drug-drug interaction may cause accumulation of DOAC, thereby increasing the risk of bleeding. There is uncertainty on the safety profile of DOAC in patients with CKD, particularly in those with severely impaired renal function or end stage renal disease, due to the heterogeneity of studies and the relative paucity of data. This document reports the position of three Italian scientific societies engaged in the management of patients with atrial fibrillation who are treated with DOAC and present with CKD.

Bone mineral abnormalities (defined as Chronic Kidney Disease Mineral Bone Disorder; CKD-MBD) are prevalent and associated with a substantial risk burden and poor prognosis in CKD population. Several lines of evidence support the notion that a large proportion of patients receiving maintenance dialysis experience a suboptimal biochemical control of CKD-MBD. Although no study has ever demonstrated conclusively that CKD-MBD control is associated with improved survival, an expanding therapeutic armamentarium is available to correct bone mineral abnormalities. In this position paper of Lombardy Nephrologists, a summary of the state of art of CKD-MBD as well as a summary of the unmet clinical needs will be provided. Furthermore, this position paper will focus on the potential and drawbacks of a new injectable calcimimetic, etelcalcetide, a drug available in Italy since few months ago.

Chronic kidney disease (CKD) represents a major public health issue worldwide and entails a high burden of cardiovascular events and mortality. Dyslipidaemia is common in patients with CKD and it is characterized by a highly atherogenic profile with relatively low levels of HDL-cholesterol and high levels of triglyceride and oxidized LDL-cholesterol. Overall, current literature indicates that lowering LDL-cholesterol is beneficial for preventing major atherosclerotic events in patients with CKD and in kidney transplant recipients while the evidence is less clear in patients on dialysis. Lipid lowering treatment is recommended in all patients with stage 3 CKD or worse, independently of baseline LDL-cholesterol levels. Statin and ezetimibe are the cornerstones in the management of dyslipidaemia in patients with CKD, however alternative and emerging lipid-lowering therapies may acquire a central role in near future. This position paper endorsed by the Italian Society of Nephrology aims at providing useful information on the topic of dyslipidaemia in CKD and at assisting decision making in the management of these patients.

Liver and kidney are strictly connected in a reciprocal manner, in both the physiological and pathological condition. The Italian Association for the Study of Liver, in collaboration with the Italian Society of Nephrology, with this position paper aims to provide an up-to-date overview on the principal relationships between these two important organs. A panel of well-recognized international expert hepatologists and nephrologists identified five relevant topics: 1) The diagnosis of kidney damage in patients with chronic liver disease; 2) Acute kidney injury in liver cirrhosis; 3) Association between chronic liver disease and chronic kidney disease; 4) Kidney damage according to different etiology of liver disease; 5) Polycystic kidney and liver disease. The discussion process started with a review of the literature relating to each of the five major topics and clinical questions and related statements were subsequently formulated. The quality of evidence and strength of recommendations were graded according to the GRADE system. The statements presented here highlight the importance of strong collaboration between hepatologists and nephrologists for the management of critically ill patients, such as those with combined liver and kidney impairment.

The increasing availability of novel biological anticancer agents has greatly improved the outcome of several cancer patients; unfortunately, data regarding efficacy, safety and pharmacokinetics of many of these agents in patients with chronic renal disease or on hemodialysis are scanty. Furthermore these results are controversial and a treatment strategy has not yet been established. Therefore, the Associazione Italiana di Oncologia Medica and the Societa italiana di Nefrologia undertook the present work aiming at providing health professionals with a tool for easier clinical management of target therapies in this setting of patients. A web-based search of MEDLINE/PubMed library data published from 2000 to June 2018 has been performed. More than one hundred papers, including recommendations and expert opinions, were selected and discussed by the authors. A panel of experts provided additional biological and clinical information, helping in clarifying some issues in the absence of clear-cut information from the literature.

Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with kidney disease, particularly in those in whom diabetes and heart failure are present or are on treatment with renin–angiotensin–aldosterone system inhibitors (RAASIs). HK is recognised as a major risk of potentially life threatening cardiac arrhythmic complications. When an acute reduction of renal function manifests, both in patients with chronic kidney disease (CKD) and in those with previously normal renal function, HK is the main indication for the execution of urgent medical treatment and the recourse to extracorporeal replacement therapies. In patients with end-stage renal disease, the presence of HK not responsive to medical therapy is an indication at the beginning of chronic renal replacement therapy. HK can also be associated indirectly with the progression of CKD, because the finding of high potassium values leads to withdrawal of treatment with RAASIs, which constitute the first choice nephro-protective treatment. It is therefore essential to identify patients at risk of developing HK, and to implement therapeutic interventions aimed at preventing and treating this dangerous complication of kidney disease. Current strategies aimed at the prevention and treatment of HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials where optimal treatment and monitoring are mandatory. This position paper will review the main therapeutic interventions to be implemented for the prevention, detection and treatment of HK in patients with CKD on conservative care, in those on dialysis, in patients in whom renal disease is associated with diabetes, heart failure, resistant hypertension and who are on treatment with RAASIs, and finally in those presenting with severe acute HK.

The dramatic increase in prevalence of chronic kidney disease (CKD) with ageing makes the recognition and correct referral of these patients of paramount relevance in order to implement interventions preventing or delaying the development of CKD complications and end-stage renal disease. Nevertheless, several issues make the diagnosis of CKD in the elderly cumbersome. Among these are age related changes in structures and functions of the kidney, which may be difficult to distinguish from CKD, and multimorbidity. Thus, symptoms, clinical findings and laboratory abnormalities should be considered as potential clues to suspect CKD and to suggest screening. Comprehensive geriatric assessment is essential to define the clinical impact of CKD on functional status and to plan treatment. Correct patient referral is very important: patients with stage 4–5 CKD, as well as those with worsening proteinuria or progressive nephropathy (i.e. eGFR reduction > 5 ml/year) should be referred to nephrologist. Renal biopsy not unfrequently may be the key diagnostic exam and should not be denied simply on the basis of age. Indeed, identifying the cause(s) of CKD is highly desirable to perform a targeted therapy against the pathogenetic mechanisms of CKD, which complement and may outperform in efficacy the general measures for CKD.

Diffusion-weighted magnetic resonance imaging (DWI) is a non-invasive method sensitive to local water motion in the tissue. As a tool to probe the microstructure, including the presence and potentially the degree of renal fibrosis, DWI has the potential to become an effective imaging biomarker. The aim of this review is to discuss the current status of renal DWI in diffuse renal diseases. DWI biomarkers can be classified in the following three main categories: (i) the apparent diffusion coefficient—an overall measure of water diffusion and microcirculation in the tissue; (ii) true diffusion, pseudodiffusion and flowing fraction—providing separate information on diffusion and perfusion or tubular flow; and (iii) fractional anisotropy—measuring the microstructural orientation. An overview of human studies applying renal DWI in diffuse pathologies is given, demonstrating not only the feasibility and intra-study reproducibility of DWI but also highlighting the need for standardization of methods, additional validation and qualification. The current and future role of renal DWI in clinical practice is reviewed, emphasizing its potential as a surrogate and monitoring biomarker for interstitial fibrosis in chronic kidney disease, as well as a surrogate biomarker for the inflammation in acute kidney diseases that may impact patient selection for renal biopsy in acute graft rejection. As part of the international COST (European Cooperation in Science and Technology) action PARENCHIMA (Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease), aimed at eliminating the barriers to the clinical use of functional renal magnetic resonance imaging, this article provides practical recommendations for future design of clinical studies and the use of renal DWI in clinical practice.

Background Chronic kidney disease (CKD) is characterized by dysbiosis, elevated levels of uremic toxins, systemic inflammation, and increased markers of oxidative stress. These factors lead to an increased risk of cardiovascular disease (CVD) which is common among CKD patients. Supplementation with high amylose maize resistant starch type 2 (RS-2) can change the composition of the gut microbiota, and reduce markers of inflammation and oxidative stress in patients with end-stage renal disease. However, the impact of RS-2 supplementation has not been extensively studied in CKD patients not on dialysis. Aerobic exercise training lowers certain markers of inflammation in CKD patients. Whether combining aerobic training along with RS-2 supplementation has an additive effect on the aforementioned biomarkers in predialysis CKD patients has not been previously investigated. Methods The study is being conducted as a 16-week, double-blind, placebo controlled, parallel arm, randomized controlled trial. Sixty stage 3–4 CKD patients (ages of 30–75 years) are being randomized to one of four groups: RS-2 & usual care, RS-2 & aerobic exercise, placebo (cornstarch) & usual care and placebo & exercise. Patients attend four testing sessions: Two baseline (BL) sessions with follow up visits 8 (wk8) and 16 weeks (wk16) later. Fasting blood samples, resting brachial and central blood pressures, and arterial stiffness are collected at BL, wk8 and wk16. A stool sample is collected for analysis of microbial composition and peak oxygen uptake is assessed at BL and wk16. Blood samples will be assayed for p-cresyl sulphate and indoxyl sulphate, c-reactive protein, tumor necrosis factor α, interleukin 6, interleukin 10, monocyte chemoattractant protein 1, malondialdehyde, 8-isoprostanes F2a, endothelin-1 and nitrate/nitrite. Following BL, subjects are randomized to their group. Individuals randomized to conditions involving exercise will attend three supervised moderate intensity (55–65% peak oxygen uptake) aerobic training sessions (treadmills, bikes or elliptical machine) per week for 16 weeks. Discussion This study has the potential to yield information about the effect of RS-2 supplementation on key biomarkers believed to impact upon the development of CVD in patients with CKD. We are examining whether there is an additive effect of exercise training and RS-2 supplementation on these key variables. Trial registration Clinicaltrials.gov Trial registration#NCT03689569. 9/28/2018, retrospectively registered.

Penetrating head trauma (PHT) includes any traumatic injury where an object pierces the skull and breaches the dural membrane surrounding the brain. PHTs are less prevalent than blunt head injuries. However, they often have more complex damage, worse prognosis, and higher rates of morbidity and mortality. An 83-year-old man fell at his home and hit his head on the right side toward a shoji (a Japanese-style paper sliding door). He reported to the emergency room the following day with his family. He had a small wound before the right ear, which was sutured in the emergency room. A CT scan demonstrated tiny pieces of bone fragments inside the brain, as well as right temporal subcortical hemorrhage and pneumocephalus. He was admitted to the hospital and received intensive prophylaxis with antibiotics. He developed life-threatening skin disease and subsequent acute kidney disease requiring hemodialysis. He fully recovered from his life-threatening condition. Here, we report an unprecedented case of a penetrating head injury of an older adult caused by a shoji.

Tissue hypoxia plays a key role in the development and progression of many kidney diseases. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) is the most promising imaging technique to monitor renal tissue oxygenation in humans. BOLD-MRI measures renal tissue deoxyhaemoglobin levels voxel by voxel. Increases in its outcome measure R2* (transverse relaxation rate expressed as per second) correspond to higher deoxyhaemoglobin concentrations and suggest lower oxygenation, whereas decreases in R2* indicate higher oxygenation. BOLD-MRI has been validated against micropuncture techniques in animals. Its reproducibility has been demonstrated in humans, provided that physiological and technical conditions are standardized. BOLD-MRI has shown that patients suffering from chronic kidney disease (CKD) or kidneys with severe renal artery stenosis have lower tissue oxygenation than controls. Additionally, CKD patients with the lowest cortical oxygenation have the worst renal outcome. Finally, BOLD-MRI has been used to assess the influence of drugs on renal tissue oxygenation, and may offer the possibility to identify drugs with nephroprotective or nephrotoxic effects at an early stage. Unfortunately, different methods are used to prepare patients, acquire MRI data and analyse the BOLD images. International efforts such as the European Cooperation in Science and Technology (COST) action ‘Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease’ (PARENCHIMA) are aiming to harmonize this process, to facilitate the introduction of this technique in clinical practice in the near future. This article represents an extensive overview of the studies performed in this field, summarizes the strengths and weaknesses of the technique, provides recommendations about patient preparation, image acquisition and analysis, and suggests clinical applications and future developments.

The kidney exerts multiple functions, and pathophysiological interactions between the kidney and the heart have important clinical implications, but it has only recently become clear that these interactions should be studied across the whole spectrum of reduced kidney function and not only in cases with severe, end-stage renal disease (ESRD), as has been done for many years.1 The prevalence of chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) of 3 months, exceeds 10% in the adult population and reaches 47% in subjects older than 70 years, according to data from the USA, with a trend towards a recent increasing prevalence.1,2 Many interactions between kidney and cardiovascular functions have important implications for clinical management and health policy ( Figure 1 ), since even mild forms of kidney disease are associated with an increased risk of cardiovascular morbidity and overall mortality, and renal function may worsen over time.1,3 Figure 1 Stages of the development and progression of chronic kidney disease (CKD), including complications and strategies to improve outcomes. Modified from Eckardt et al. 1 GFR, glomerular filtration rate. Although cardiovascular disease (CVD) and cardiac disorders are more frequent and severe in CKD, they are often not recognized, or undertreated, in view of the complexity of patient management in this setting.4 On the other hand, the presence and evolution of CKD is often not evaluated and monitored in patients with various forms of heart diseases, including patients with cardiac rhythm disturbances, a setting where CKD is associated with challenging decision-making on the management of specific treatments and interventions. In patients with cardiac diseases, CKD predisposes to acute kidney injury and vice versa , and both may strongly influence clinical management of cardiac conditions. Considering the need for increasing the awareness of …

ObjectivePhase-contrast magnetic resonance imaging (PC-MRI) is a non-invasive method used to compute blood flow velocity and volume. This systematic review aims to discuss the current status of renal PC-MRI and provide practical recommendations which could inform future clinical studies and its adoption in clinical practice.MethodologyA comprehensive search of all the PC-MRI studies in human healthy subjects or patients related to the kidneys was performed.ResultsA total of 39 studies were included in which PC-MRI was used to measure renal blood flow (RBF) alongside other derivative hemodynamic parameters. PC-MRI generally showed good correlation with gold standard methods of RBF measurement, both in vitro and in vivo, and good reproducibility. Despite PC-MRI not being routinely used in clinical practice, there are several clinical studies showing its potential to support diagnosis and monitoring of renal diseases, in particular renovascular disease, chronic kidney disease and autosomal dominant polycystic kidney disease.DiscussionRenal PC-MRI shows promise as a non-invasive technique to reliably measure RBF, both in healthy volunteers and in patients with renal disease. Future multicentric studies are needed to provide definitive normative ranges and to demonstrate the clinical potential of PC-MRI, likely as part of a multi-parametric renal MRI protocol.

Patients with cancer are subjected to several imaging examinations which frequently require the administration of contrast medium (CM). However, it has been estimated that acute kidney injury (AKI) due to the injection of iodinated CM accounts for 11% of all cases of AKI, and it is reported in up to 2% of all computed tomography (CT) examinations. Remarkably, the risks of developing AKI are increased in the elderly, in patients with chronic kidney disease or diabetes, and with dehydration or administration of nephrotoxic chemotherapeutics. Given the common occurrence of post-contrast acute kidney injury (PC-AKI) in clinical practice, primary care physicians and all specialists involved in managing patients with cancer should be aware of the strategies to reduce the risk of this event. In 2018, a panel of five experts from the specialties of radiology, oncology and nephrology were speakers at the annual meeting of the Italian Society of Medical Radiology (Società Italiana di Radiologia Medica e Interventistica), with the aim of commenting on existing evidence and providing their experience on the incidence and management of PC-AKI in patients with cancer. The discussion represented the basis for this white paper, which is intended to be a practical guide organised by statements describing methods to reduce renal injury risks related to CM-enhanced CT examinations in patients with cancer.

IntroductionChronic kidney disease (CKD) management in the UK is usually primary care based, with National Institute for Health and Care Excellence (NICE) guidelines defining criteria for referral to secondary care nephrology services. Estimated glomerular filtration rate (eGFR) is commonly used to guide timing of referrals and preparation of patients approaching renal replacement therapy. However, eGFR lacks sensitivity for progression to end-stage renal failure; as a consequence, the international guideline group, Kidney Disease: Improving Global Outcomes has recommended the use of a risk calculator. The validated Kidney Failure Risk Equation may enable increased precision for the management of patients with CKD; however, there is little evidence to date for the implication of its use in routine clinical practice. This study will aim to determine the impact of the Kidney Failure Risk Equation on the redesignation of patients with CKD in the UK for referral to secondary care, compared with NICE CKD guidance.Method and analysisThis is a cross-sectional population-based observational study using The Health Improvement Network database to identify the impact of risk-based designation for referral into secondary care for patients with CKD in the UK. Adult patients registered in primary care and active in the database within the period 1 January 2016 to 31 March 2017 with confirmed CKD will be analysed. The proportion of patients who meet defined risk thresholds will be cross-referenced with the current NICE guideline recommendations for referral into secondary care along with an evaluation of urinary albumin–creatinine ratio monitoring.Ethics and disseminationApproval was granted by The Health Improvement Network Scientific Review Committee (Reference number: 18THIN061). Study outcomes will inform national and international guidelines including the next version of the NICE CKD guideline. Dissemination of findings will also be through publication in a peer-reviewed journal, presentation at conferences and inclusion in the core resources of the Think Kidneys programme.

Renal perfusion provides the driving pressure for glomerular filtration and delivers the oxygen and nutrients to fuel solute reabsorption. Renal ischaemia is a major mechanism in acute kidney injury and may promote the progression of chronic kidney disease. Thus, quantifying renal tissue perfusion is critically important for both clinicians and physiologists. Current reference techniques for assessing renal tissue perfusion have significant limitations. Arterial spin labelling (ASL) is a magnetic resonance imaging (MRI) technique that uses magnetic labelling of water in arterial blood as an endogenous tracer to generate maps of absolute regional perfusion without requiring exogenous contrast. The technique holds enormous potential for clinical use but remains restricted to research settings. This statement paper from the PARENCHIMA network briefly outlines the ASL technique and reviews renal perfusion data in 53 studies published in English through January 2018. Renal perfusion by ASL has been validated against reference methods and has good reproducibility. Renal perfusion by ASL reduces with age and excretory function. Technical advancements mean that a renal ASL study can acquire a whole kidney perfusion measurement in less than 5–10 min. The short acquisition time permits combination with other MRI techniques that might inform drug mechanisms and renal physiology. The flexibility of renal ASL has yielded several variants of the technique, but there are limited data comparing these approaches. We make recommendations for acquiring and reporting renal ASL data and outline the knowledge gaps that future research should address.

The American Diabetes Association recently recommended routine screening of glomerular filtration rate (GFR) in adolescents with type 1 diabetes, although this is not routinely performed clinically [1]. Current estimates of GFR lack precision and accuracy before stage 3 of chronic kidney disease (GFR \60 mL/min/1.73 m). Also, measurement of urinary albumin excretion, currently recommended as part of routine screening, does not directly measure kidney function. This is of particular concern in adolescents and young adults with type 1 diabetes, in whom renal hyperfiltration may promote renal injury, or rapid change in GFR may be missed due to the lack of acceptable screening methods for GFR. Perrin and Berg [2] recently reported that estimated GFR cannot accurately replace measured GFR to defect hyperfiltration in young patients with type 1 diabetes. We recently reported that iohexol clearance measured with dried blood spots (DBS) on filter paper performed better than the estimates of GFR using the CKD-EPI equations and was comparable to gold-standard iohexol plasma clearance in adults with type 1 diabetes [3]. GFR measured by iohexol clearance on DBS has also been evaluated in adults with a wide range of GFRs showing strong agreement to gold-standard measurements [4]. Standard iohexol GFR (iGFR) measurement requires more than 4 h in a research center, making it impractical for routine clinical monitoring of GFR. Here, we present data from a pilot study in youth with type 1 diabetes (n = 8, 70 % female, 17 ± 4 years, type 1 diabetes duration of 6.3 ± 5.0 years, HbA1c 8.9 ± 2.5 %) with the goal of demonstrating feasibility of translating this method to an ambulatory setting. Kidney function was measured by iGFR with DBS and estimated by Bouvet (cystatin C and creatinine-based GFR equation) and Schwartz (creatinine-based GFR equation). The participants had blood drawn, then iohexol injected intravenously prior to their regular diabetes visit and were sent home with filter paper to collect DBS at 120, 150, 180, 210 and 240 min after iohexol injection followed by mailing the filter paper back to our laboratory. There appeared to be less variability of GFR with the iGFR than the estimated GFR methods (Bouvet and Schwartz) (Fig. 1). As this study was performed on an outpatient basis to determine feasibility, we did not perform an in-patient gold-standard iGFR study to serve as a comparator for these three GFR measurements. However, our previous publication in adults with type 1 diabetes demonstrated that iGFR measured in DBS on filter paper was significantly less biased and more comparable to a gold-standard iGFR measurement than estimated GFR [3]. Moreover, using two spots at 120 and 240 min was comparable to using five spots [3], which if validated would further decrease burden to the patient and cost of this method. The adolescents also rated eight statements on a 7-point non-validated Likert scale (Fig. 2). All participants agreed or strongly agreed that the procedure was preferable Managed by Massimo Federici.

Prevention is a very topical issue that any modern health system cannot ignore. The discussion about the concept of cardiovascular (CV) prevention is very wide and has been lasting for a long time. In this context, the research has never been stopped. A schematic classification of different types of prevention, as well as raised by the literature, implies some limitations, not always suitable to our complex patients. According to evidence-based medicine we should refer to the best available guidelines. Unfortunately the quality of evidence-based guidelines is far from optimal. The Federation of Associations of Hospital Doctors on Internal Medicine (FADOI) faced the problem of CV prevention in the higher risk complex patients with its experts in ischemic heart disease, heart failure, stroke, chronic kidney disease, peripheral arterial disease and diabetes mellitus, by asking the following questions: i) which are the methods of risk assessment and prognostic stratification (also with respect to the existing comorbidities)?; ii) which are the tailored actions to implement for the individual patient? For the purposes of a CV risk evaluation in complex patient we cannot be satisfied with a single high baseline risk strategy: we should resize our assessment parameters to the real world, implementing a high multidimensional CV complexity risk assessment strategy, in respect of an anthropological approach to the complexity of our patients. Essentially, hospital internists are called to exercise a proactive role of experts for each single complex patient, also in CV prevention.

Renal osteodystrophy (ROD) is a heterogeneous group of metabolic bone diseases complicating progressive chronic kidney disease (CKD). Bone biomarkers and bone imaging techniques may help to assess bone health and predict fractures in CKD but do have important inherent limitations. By informing on bone turnover and mineralization, a bone biopsy may help to guide prevention and treatment of ROD and its consequences. According to a recent survey conducted among European nephrologists, bone biopsies are performed rather exceptionally, both for clinical and research purposes. Obviously, clinical research in the field of ROD is threatened by vanishing clinical and pathological expertise, small patient cohorts and scientific isolation. In March 2016, the European Renal Osteodystrophy (EU-ROD) initiative was created under the umbrella of the ERA-EDTA CKD-mineral and bone disorder (MBD) Working Group to revitalize bone biopsy as a clinically useful tool in the diagnostic workup of CKD-MBD and to foster research on the epidemiology, implications and reversibility of ROD. As such, the EU-ROD initiative aims to increase the understanding of ROD and ultimately to improve outcomes in CKD patients. info:eu-repo/semantics/publishedVersion

The pediatric ESRD patient is a member of a unique subpopulation of ESRD patients. The cause of ESRD in the pediatric patient differs markedly from the adult patient; treatment modality in the pediatric ESRD patient differs substantially from the adult patient; and outcomes such as growth

The prevalence of chronic kidney disease (CKD) continues to increase worldwide as does end stage renal disease. The most common, but not only, causes of CKD are hypertension and diabetes. CKD is associated with a significant increase in cardiovascular (CV) risk as most patients with CKD die of a CV cause. Moreover, CV risk increases proportionally as estimated glomerular filtration rate falls below 60 mL/min. CV causes of death in CKD are more prevalent than those from cancer; as a result, the identification and reduction of CKD is a public health priority. High blood pressure is a key pathogenic factor that contributes to the deterioration of kidney function. The presence of kidney disease is a common and underappreciated preexisting medical cause of resistant hypertension. Therefore, treatment of hypertension has become the most important intervention in the management of all forms of CKD. For this reason, World Kidney Day on March 12, 2009 will emphasize the role of hypertension.

Renal dysfunction is frequent in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Chronic kidney disease (CKD) is associated with very poor prognosis and is an independent predictor of early and late mortality and major bleeding in patients with NSTE-ACS. Patients with NSTE-ACS and CKD are still rarely treated according to guidelines. Medical registers reveal that patients with CKD are usually treated with too high doses of antithrombotics, especially anticoagulants and inhibitors of platelet glycoprotein (GP) IIb/IIIa receptors, and therefore they are more prone to bleeding. Drugs which are excreted mainly or exclusively by the kidney should be administered in a reduced dose or discontinued in patients with CKD. These drugs include enoxaparin, fondaparinux, bivalirudin, and small molecule inhibitors of GP IIb/IIIa inhibitors. In long-term treatment of patients after myocardial infarction, anti-platelet therapy, lipid-lowering therapy and β-blockers are used. Chronic kidney disease patients before qualification for coronary interventions should be carefully selected in order to avoid their use in the group of patients who could not benefit from such procedures. This paper presents schemes of non-ST and ST-segment elevation myocardial infarction treatment in CKD patients in accordance with the current recommendations of the European Society of Cardiology (ESC).

In January 2013, the international recommendations of the KDIGO (for “Kidney Disease: Improving Global Outcomes”) to define chronic kidney disease (CKD) and classify patients in CKD stages have been published. In this opinion article, we will review and discuss the most important guidelines proposed about CKD staging and glomerular filtration rate (GFR) estimating. In particular, we question the choice of fixed knot values at 60 mL/min/1.73 m² to define CKD. We also question the strategies proposed to measure and use cystatin C results.

n-3 Polyunsaturated fatty acids (PUFAs) are organic acids, essential for mammals, whose deficiency is associated with different diseases. The American Heart Association recommends that all adults increase food-derived n-3 PUFA intake and also suggests that patients with documented coronary heart disease consume approximately 1 g of eicosapentaenoic acid and docosahexaenoic acid per day. However, recent evidence broadens their potential application to many other health disorders directly or indirectly associated with cardiovascular disease risk such as rheumatological diseases, mood depression, chronic kidney disease, chronic inflammatory lung diseases and others. These effects seem to be largely dependent on the dosages employed and on the characteristics of the selected patients. The cardiometabolic effects of PUFAs have been largely reviewed elsewhere, so the aim of our review is to point out the potential usefulness of such drugs with pleiotropic effects in the management of the actual typical aging patient, with co-morbidities and multidrug therapies.

This systematic review, initiated by the European Cooperation in Science and Technology Action Magnetic Resonance Imaging Biomarkers for Chronic Kidney Disease (PARENCHIMA), focuses on potential clinical applications of magnetic resonance imaging in renal non-tumour disease using magnetic resonance relaxometry (MRR), specifically, the measurement of the independent quantitative magnetic resonance relaxation times T1 and T2 at 1.5 and 3Tesla (T), respectively. Healthy subjects show a distinguishable cortico-medullary differentiation (CMD) in T1 and a slight CMD in T2. Increased cortical T1 values, that is, reduced T1 CMD, were reported in acute allograft rejection (AAR) and diminished T1 CMD in chronic allograft rejection. However, ambiguous findings were reported and AAR could not be sufficiently differentiated from acute tubular necrosis and cyclosporine nephrotoxicity. Despite this, one recent quantitative study showed in renal transplants a direct correlation between fibrosis and T1 CMD. Additionally, various renal diseases, including renal transplants, showed a moderate to strong correlation between T1 CMD and renal function. Recent T2 studies observed increased values in renal transplants compared with healthy subjects and in early-stage autosomal dominant polycystic kidney disease (ADPKD), which could improve diagnosis and progression assessment compared with total kidney volume alone in early-stage ADPKD. Renal MRR is suggested to be sensitive to renal perfusion, ischaemia/oxygenation, oedema, fibrosis, hydration and comorbidities, which reduce specificity. Due to the lack of standardization in patient preparation, acquisition protocols and adequate patient selection, no widely accepted reference values are currently available. Therefore this review encourages efforts to optimize and standardize (multi-parametric) protocols to increase specificity and to tap the full potential of renal MRR in future research. Copyright © 2018, Oxford University Press. Open Access. This article is available under the Creative Commons CC-BY-NC license and permits non-commercial use, distribution and reproduction in any medium, provided the original work is properly cited.

A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events.A total of 19 257 hypertensive subjects were randomized to an amlodipine-based regimen or an atenolol-based regimen. Of these, 10 305 subjects with total cholesterolor =6.5 mmol/L were further randomized to atorvastatin 10 mg daily or placebo. In this analysis, the effects of atorvastatin were compared with placebo on coronary heart disease (CHD), cardiovascular and stroke events in those assigned amlodipine-based and atenolol-based regimens. In the ASCOT lipid-lowering arm (LLA), overall, atorvastatin reduced the relative risk of the primary endpoint of non-fatal myocardial infarction and fatal CHD events by 36% (HR 0.64, CI 0.50-0.83, P=0.0005), total cardiovascular events by 21% (HR 0.79, CI 0.69-0.90, P=0.0005), and stroke by 27% (HR 0.73, CI 0.56-0.96, P=0.024). However, atorvastatin reduced the relative risk of CHD events by 53% (HR 0.47, CI 0.32-0.69, P0.0001) among those allocated the amlodipine-based regimen, and by 16% (HR 0.84, CI 0.60-1.17, p: n.s.) among those allocated the atenolol-based regimen (P=0.025 for heterogeneity). There were no significant differences between the effects of atorvastatin on total cardiovascular events or strokes among those assigned amlodipine (HR 0.73, CI 0.60-0.88, P0.005 and HR 0.69, CI 0.45-1.06, P: n.s., respectively) or atenolol (HR 0.85, CI 0.71-1.02, P: n.s and HR 0.76, CI 0.53-1.08, P: n.s, respectively). Differences in blood pressure and lipid parameters (placebo corrected) between the two antihypertensive treatment limbs could not account for the differences observed in CHD outcome.These findings of an apparent interaction between atorvastatin and an amlodipine-based regimen in the prevention of CHD events are of borderline significance, and hence generate an hypothesis that merits independent evaluation in other trials.

Bone morphogenic protein-7 (BMP-7), a novel therapy for diabetic nephropathy.BackgroundBone morphogenic protein-7 (BMP-7), an essential developmental renal morphogen, is a secreted differentiation factor of the adult collecting duct. It activates receptors in the collecting duct, distal nephron, proximal tubule, and glomerulus. BMP-7 is therapeutic in tubulointerstitial nephritis raising the question of broader efficacy in chronic kidney disease (CKD).MethodsDiabetes was induced in 200g rats by a single dose of streptozotocin. After 16 weeks, glomerular hypertrophy and proteinuria were established, and therapy with BMP-7 (10, 30, or 100 μg/kg intravenously twice a week), enalapril (20 mg/kg), or vehicle was begun and continued until 32 weeks. Kidney weight, glomerular filtration rate (GFR), urine albumin excretion, blood pressure, pathology, and BMP-7 expression were measured.ResultsDiabetic vehicle-treated rats developed renal insufficiency by 32 weeks (GFR, 0.34±0.02 mL/min/100 g body weight vs. 0.55±0.02 in normal). In the diabetic BMP-7 high-dose–treated rats, GFR was preserved (0.70±0.08, P < 0.01 vs. vehicle), and higher than diabetic enalapril-treated rats (0.58±0.06). Kidney weights of vehicle-treated animals were not affected, but were reduced in all of the treatment groups (P < 0.001). Proteinuria was reversed to normal by BMP-7 in a dose-dependent manner. The reduction in proteinuria by the intermediate dose of BMP-7 was similar to the effect of enalapril therapy. Glomerular area and interstitial volume were significantly decreased in the BMP-7 and enalapril-treated animals. Glomerular sclerosis was prevented by BMP-7 therapy more effectively than by enalapril. Enalapril controlled hypertension throughout the course of therapy while BMP-7 did not affect blood pressure until the final 4 weeks of therapy. Diabetic vehicle-treated rats lost BMP-7 expression in the kidney. BMP-7 and enalapril therapy restored BMP-7 expression at high levels.ConclusionBMP-7 partially reversed diabetic-induced kidney hypertrophy, restoring GFR, urine albumin excretion, and glomerular histology toward normal. Restoration of BMP-7 expression was associated with a successful repair reaction and a reversal of the ill-fated injury response.

Background. Over the past decade, chronic kidney disease (CKD) has become an area of intensive clinical and epidemiological research. Despite the clarity provided by the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines, there appears to be within the CKD research literature significant disagreement on how to define CKD and measure kidney function. Methods. The objectives of this study were to investigate the variety of methods used to define CKD and to measure kidney function in original research papers as well as to investigate whether the quality of the journal had any effect on the quality of the methodology used. This was a descriptive review and not a meta-analysis. Information was extracted from each article including publication details (including the journal's impact factor), definition of CKD, method used to estimate kidney function and quantity of serum creatinine readings used to define CKD. An electronic search of MEDLINE through OVID was completed using the search term CKD. The search was limited to articles in English published in 2009. Studies were included in the review only if they were original research articles including patients with CKD. Articles were excluded if they reported data from a paediatric population, a population solely on dialysis or if there was no full-text access through OVID. Each article was assessed for quality with respect to using KDOQI CKD definition criteria. A description of the pooled data was completed and chi-square tests were used to investigate the relation between article quality and journal quality. Analysis was carried out using SPSS (15.0) and a P-value of < 0.05 was considered to indicate statistical significance. Results. The final review included 301 articles. There were a variety of methods used to define CKD in original research articles. Less than 20% (n = 59) of the articles adhered to the established international criteria for defining CKD. The majority of articles (52.1%) did not indicate the quantity of serum creatinine measurements used to define CKD. The impact factor or specialist nature of the scientific journal appears to have no bearing on whether or not published articles use the gold standard KDOQI guidelines for labelling a patient with a diagnosis of CKD. Conclusions. This review of literature found that a variety of definitions are being used in original research articles to define CKD and measure kidney function which calls into question the validity and reliability of such research findings and associated clinical guidelines. International consensus is urgently required to improve validity and generalizability of CKD research findings.

Early chronic kidney disease (CKD) is now known to be a relatively common problem. Prevalence studies worldwide have estimated that between 6% and 11% of the population has CKD [1]. One recent estimate carried out in the UK found that 4.9% of the general practice population studied had an estimated glomerular filtration rate equivalent to stages 3–5 CKD [2]. There is now reliable research evidence to support a variety of clinical interventions that will benefit patients with CKD [3]. However, very little evidence is available in the literature to recommend the most effective way of delivering healthcare for patients with early CKD [3]. These patients comprise a complex group and unfortunately they often have significant comorbid conditions [4,5]. Specialist services would be overwhelmed if they attempted to manage all patients with early CKD [5]. It is important that all countries carefully consider how best to deliver healthcare for this large group of patients in future. This paper will describe the guidance currently available from formal guidelines, research evidence and proposed models of care.

Diabetic nephropathy is the leading cause of end stage renal failure in New Zealand.1 Cadaveric organs are in short supply here, as elsewhere, and we need to consider living related donation. Kidneys from living related donors also provide a better graft and improved survival of transplant patients. However, donors from ethnic groups who have a high incidence of end stage renal failure because of diabetes and glomerulonephritis are also at increased risk of developing diabetes.2 This risk is compounded by environmental factors such as obesity. In New Zealand the ethics of living related donation within the diabetic family are being questioned. Renal transplantation is preferred to dialysis in diabetic patients who are fit enough for surgery. It is associated with an improved quality of life, lower morbidity and mortality, reduced long term costs, and greater incremental benefit in diabetic patients compared with patients without diabetes.3 The main reason for not transplanting kidneys into suitable candidates is the low availability of compatible organs for transplantation. Some ethnic groups object to donating body parts after death for cultural and spiritual reasons. The resulting underrepresentation of these ethnic groups in the donor pool further reduces the likelihood that patients with end stage renal failure from these ethnic groups will receive an organ. Organ donation from living relatives is therefore particularly encouraged in these groups. Diabetes and the development of nephropathy once diabetes has occurred are familial and cluster in families. 4 5 It is therefore important to be able to advise a potential donor of his or her personal risk of developing end stage renal failure. Apart from …

The article depicts the situation of a 57-year-old Caucasian man, on renal replacement therapy since 1979 because of membranous and proliferative glomerulonephritis, who came to the hospital dialysis ward complaining of severe foot pain. His long clinical history included about 17 years on dialysis and 8 years of transplantation (three kidney grafts, which failed because of various combinations of acute rejection and chronic allograft disease). He experienced a myocardial infarction at the age of 45 and angina at the time of the third graft. Three months before the episode described here, he suffered a worsening of claudicatio intermittens and was treated by angioplasty, with stenting of the left iliac artery and the right superficial femoral artery; the results of the intervention were considered highly satisfactory. However, severe diffuse vascular disease was present at all the levels examined (Figure 1). Despite an initial improvement, he experienced recurrence of local pain after a couple of months and, in the last few days, had noticed a bluish discolouration of his feet (Figure 2). The most likely clinical diagnosis is cholesterol crystal emboli syndrome, superimposed on severe diffuse peripheral vascular disease. The differential diagnosis of subacute painful vascular lesions, as presented by our patient, takes into account both the evolution of peripheral vascular disease and vasculitis or vasculitis-like lesions. The vascular echo Doppler, performed taking into account the hypothesis of closure of the previously treated vessels, was unchanged and revealed the presence of diffuse vessel lesions but no critical stenosis, thus ruling out ‘simple’ large/medium vessel occlusion. As shown in Figure 2, the patient presented diffuse livedo reticularis and two small necrotic lesions. Livedo is a generic sign, common to several systemic microvascular diseases including anti-phospholipid antibodies, calciphylaxis and vasculitis [1]. It is a major form of cutaneous involvement in cholesterol crystal emboli syndrome, together with ‘blue toes’, vasculitis-like lesions and necrotic lesions [1–4]. Concerning the necrotic lesions, an interesting diagnostic clue came from the location—while ‘pure’ obstructive diseases usually lead to very distal lesions, microembolic lesions often appear in more capricious ‘non-terminal’ sites, as seen in the figures [1].

Parathyroid hormone (PTH) determination is of greatest importance for patients suffering from parathyroid gland disorders and for the follow-up of bone turnover in patients suffering from chronic kidney disease (CKD). Two generations of PTH assays are simultaneously present on the market for PTH quantification. As these assays are not yet standardized, this results in a significant level of confusion in the care of CKD patients. One key objective of the IFCC Committee for Bone Metabolism is to improve this situation. In this position paper, we will highlight the current state of PTH testing and propose a pathway to ultimately overcome issues resulting from PTH assay variability.

Objectives The Kidney Team at Home program is an educational intervention aimed at patients with chronic kidney disease to assist them in their choice for kidney replacement therapy. Previous studies have shown that the intervention results in an increase in knowledge and communication on kidney replacement therapy, and eventually in an increase in the number of living donor kidney transplantations. The study assesses the cost-effectiveness of the intervention compared to standard care. Methods A dynamic probabilistic Markov model was used to estimate the monetary and health benefits of the intervention in The Netherlands over 10 years. Data on costs and health-related quality of life were derived from the literature. Transition probabilities, prevalence, and incidence rates were calculated using a large national database. An optimistic and a pessimistic implementation scenario were compared to a base case scenario with standard care. Results In both the optimistic and pessimistic scenario, the intervention is cost-effective and dominant compared to standard care: savings were €108,681,985 and €51,770,060 and the benefits were 1382 and 695 QALYs, respectively. Conclusions The superior cost-effectiveness of the intervention is caused by the superior health effects and the reduction of costs associated with transplantation, and the relatively small incremental costs of the intervention. The favorable findings of this implementation project resulted in national uptake of the intervention in The Netherlands as of 2021. This is the first time a psychosocial intervention has been implemented as part of standard care in a kidney replacement therapy program worldwide.