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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.

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.

End-stage kidney disease patients who are candidates for surgical arteriovenous fistula creation commonly experience obstacles to a functional surgical arteriovenous fistula, including protracted wait time for creation, poor maturation, and surgical arteriovenous fistula dysfunction that can result in significant patient morbidity. The recent approval of two endovascular devices designed to create a percutaneous arteriovenous fistula enables arteriovenous fistula creation to be placed in the hands of interventionalists, thereby increasing the number of arteriovenous fistula providers, reducing wait times, and allowing the patient to avoid surgery. Moreover, current studies demonstrate that patients with percutaneous arteriovenous fistula experience improved time to arteriovenous fistula maturation. Yet, in order to realize the potential advantages of percutaneous arteriovenous fistula creation within our hemodialysis patient population, it is critical to select appropriate patients, ensure adequate patient and dialysis unit education, and provide sufficient instruction in percutaneous arteriovenous fistula cannulation and monitoring. In this White Paper by the American Society of Diagnostic and Interventional Nephrology, experts in interventional nephrology, surgery, and interventional radiology convened and provide recommendations on the aforementioned elements that are fundamental to a functional percutaneous arteriovenous fistula.

The Coronavirus Disease 2019 (COVID-19) has had a continuous and robust impact on world health. The resulting COVID-19 pandemic has had a devastating physical, mental and fiscal impact on the millions of people living with noncommunicable diseases (NCDs). In addition to older age, people living with CVD, stroke, obesity, diabetes, kidney disease, and hypertension are at a particularly greater risk for severe forms of COVID-19 and its consequences. Meta-analysis indicates that hypertension, diabetes, chronic kidney disease, and thrombotic complications have been observed as both the most prevalent and most dangerous co-morbidities in COVID-19 patients. And despite the nearly incalculable physical, mental, emotional, and economic toll of this pandemic, forthcoming public health figures continue to place cardiovascular disease as the number one cause of death across the globe in the year 2020. The world simply cannot wait for the next pandemic to invest in NCDs. Social determinants of health cannot be addressed only through the healthcare system, but a more holistic multisectoral approach with at its basis the Sustainable Development Goals (SDGs) is needed to truly address social and economic inequalities and build more resilient systems. Yet there is reason for hope: the 2019 UN Political Declaration on UHC provides a strong framework for building more resilient health systems, with explicit calls for investment in NCDs and references to fiscal policies that put such investment firmly within reach. By further cementing the importance of addressing circulatory health in a future Framework Convention on Emergency Preparedness, WHO Member States can take concrete steps towards a pandemic-free future. As the chief representatives of the global circulatory health community and patients, the Global Coalition for Circulatory Health calls for increased support for the healthcare workforce, global vaccine equity, embracing new models of care and digital health solutions, as well as fiscal policies on unhealthy commodities to support these investments.

Percutaneous catheter-based transluminal renal denervation (RDN) has emerged as a new approach to achieve sustained blood pressure reduction in patients with drug-resistant hypertension. Experts from ESH and ESC in their recently released position papers and consensus document have summarised the current evidence, unmet needs and practical recommendations for the application of this therapeutic strategy in clinical practice. Experts of the ESH Working Group for the interventional treatment of hypertension prepared this position paper in order to provide interventionalists with guidance through the procedure of RDN. Given that there is no established intraprocedural control of ablation success, interventionalists have to be familiar with the aspects related to the anatomy and imaging of the renal arteries, the distribution of renal sympathetic fibres, the special equipment necessary for RDN and the procedural details in order to maximise the success and minimise potential complications.

In the general population, moderate exercise is associated with several health benefits including a decreased risk of obesity, coronary heart disease, stroke, certain types of cancer and all-cause mortality. In chronic kidney disease (CKD), physical inability is an independent risk of death. Health benefits of regular exercise in CKD patients include improvements in functional and psychological measures such as aerobic and walking capacity and health-related quality of life. Nonetheless, in CKD patients exercise rehabilitation is not routinely prescribed. Renal patients are heterogeneous across the different stages of CKD so that the assessment of physical capability is mandatory for a correct exercise program prescription. To plan appropriate exercise programs in the CKD setting, targeted professional figures should be actively involved as many psychological or logistic barriers may hamper exercise implementation in these subjects. Different approaches, such as home exercise rehabilitation programs, supervised exercise training or in-hospital gym may theoretically be proposed. However, physical exercise should always be tailored to the individual capacity and comorbidities and each patient should ideally be involved in the decision-making process.

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.

Purpose: The AUA (American Urological Association) QIPS (Quality Improvement and Patient Safety) committee created a white paper on the diagnosis and management of nonneurogenic chronic urinary retention.Materials and Methods: Recommendations for the white paper were based on a review of the literature and consensus expert opinion from the workgroup.Results: The workgroup defined nonneurogenic chronic urinary retention as an elevated post-void residual of greater than 300 mL that persisted for at least 6 months and documented on 2 or more separate occasions. It is proposed that chronic urinary retention should be categorized by risk (high vs low) and symptomatology (symptomatic versus asymptomatic). High risk chronic urinary retention was defined as hydronephrosis on imaging, stage 3 chronic kidney disease or recurrent culture proven urinary tract infection or urosepsis. Symptomatic chronic urinary retention was defined as subjectively moderate to severe urinary symptoms impacting quality of life and/or a...

Pandemics over the years have been a constant threat towards mankind, the most recent COVID-19 outbreak is no exception to this. With the emerging demand of treating the outbreak, majority of the frontline workers have been assigned towards helping out the COVID-19 affected patients leaving the others behind. However, over time several healthcare practitioners have been using alternative forms of patient assessment tools. Heath Related Quality of Life (HRQOL) is one of the commonly used tools that have been widely used across Europe and America, using these, patients can self-evaluate their own conditions without requiring the assistance of a doctor. This paper focuses provides a conceptual framework that can be followed for quality of life assessment in chronic kidney patients using the Kidney Disease Quality of Life (KDQOL) questionnaire.

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.

Objective To evaluate the effects of a web-based clinical pathway (WCP) for radical nephrectomy on patient care, and to compare the effects with those of a paper-based clinical pathway (PCP). Patients and methods Patients with renal cell carcinoma and who underwent radical nephrectomy were enrolled into the study. The results of using the WCP for radical nephrectomy from July 2000 to August 2001 were compared with those using the PCP between May 1999 and June 2000. The mean hospital stay, average admission charges, six quality indicators, and the advantages of the WCP were determined. Results Using a WCP for radical nephrectomy reduced the hospital stay and admission charges by as much as the PCP. A similar number of patients had variances from the WCP as with the PCP ( P = 0.407), but the number of undetected variances and the variance detection time in the WCP were significantly less ( P = 0.0193 and 0.0162). Implementing a WCP also improved the quality of care by as much as a PCP. Conclusions Using a WCP for radical nephrectomy can improve health outcomes by reducing the hospital stay and admission charges, and by improving the quality of care by as much as a PCP. Furthermore, the WCP was more accurate and faster than the PCP in detecting variances.

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.

This week’s articles highlight structural insights into peptide loading of MHC; the mechanism by which light opens a channel protein; and how regulation of a host metabolic enzyme affects viral replication.

This week’s articles describe a stem cell–based therapy for chronic kidney disease and targets for treating diabetic nerve pain and acute respiratory distress in critically ill patients.

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.

Chronic kidney disease is associated with elevated cardiovascular risk, and heart failure and arrhythmias are the biggest causes of cardiovascular death in this population. Increased arterial stiffness is a hallmark of chronic kidney disease and is associated with adverse alterations in cardiac structure and function that may predispose to an increased risk of cardiovascular death. These changes are already apparent in early kidney disease, which is highly prevalent in the developed world. The mechanisms underlying increased arterial stiffness in chronic kidney disease are undoubtedly complex, but an understanding is paramount to enable the development of novel therapeutic strategies to prevent or reverse this pathophysiology and therefore reduce the cardiovascular disease burden in this high-risk cohort.

More than 20 years ago we reported an analysis of a case series of elderly critically ill patients with acute kidney injury (AKI)—then termed acute renal failure. At that time, AKI was regarded as a “simple” complication, but has since undergone a fundamental change and actually has become one of the central syndromes in the critically ill patient. We have analyzed elderly patients above 65 years of age with an AKI defined as serum creatinine above 3 mg/dl corresponding to modern KDIGO stage 3, most of them requiring renal replacement therapy (RRT). Using an extremely complete data set the diagnosis differentiated the underlying disease entity, the dominant cause of AKI, acute and chronic risk factors (comorbidities). Special aspects such as severity of disease, early AKI at admission versus late AKI, early versus later start of RRT, AKI not treated by RRT in spite of indication for RRT, various measures of short-term and long-term prognosis, renal outcome, patients dying with resolved AKI, and causes of death were evaluated. Crude mortality was 61 % which corresponds to modern studies with gross variation among the different subgroups. Age per se was not a determinant of survival either within the group of elderly patients or as compared to younger age groups. Despite an increase in mean age and disease severity during the observation period prognosis improved. A total of 17 % of patients developed a chronic kidney disease. Long-term survival as compared to the general population was low. A look back at the last two decades illustrates a remarkable evolution or rather metamorphosis of a syndrome. AKI has evolved as a central syndrome in intensive care patients, a systemic disease process associated with multiple systemic sequels and extra-renal organ injury and exerting a pronounced effect on the course of disease and short- and long-term prognosis not only of the patient but also of the kidney. Moreover, the “non-renal-naive” elderly patient with multiple comorbidities has become the most frequent ICU patient in industrialized nations.

TEST FOR ADULTS WITH CHRONIC KIDNEY DISEASE Katherine Baczewski Mary Julius and Elizabeth Kern, Louis Stokes Cleveland Veteran Affairs Medical Center, Cleveland, Ohio High plasma potassium levels are common in patients with chronic kidney disease (CKD) and cause life threatening cardiac dysrhythmia. Self management by dietary restriction of potassium is critical. Currently, there is no valid instrument to quickly assess patient’s knowledge of dietary potassium. The purpose of this observational study was to develop and validate a novel paperbased test of knowledge of foods containing high versus low potassium (test), designed for clinical use in adult patients with CKD who need to restrict dietary potassium intake. The 21 item test allows individuals to choose from two food items, asking them to select the item lower in dietary potassium. Two forms (A) and (B) of the test were designed as parallel forms. Statistical analysis was determined using SAS, version 9.1. 34 participants with high knowledge and 34 participants with low knowledge of dietary potassium and 10 renal dietitians participated in the research by taking the potassium test. 10 renal dietitians also rated each item as essential/non-essential for patient knowledge.

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.

PURPOSE: Though case management has been recommended to improve the outcomes of patients with costly or morbid conditions, it has seldom been studied in controlled trials. We performed a randomized, controlled clinical trial of an intensive, multidisciplinary case management program for patients with chronic renal insufficiency and followed patients for 5 years. PATIENTS AND METHODS: We enrolled 437 primary-care patients (73% of those eligible) with chronic renal insufficiency (estimated creatinine clearance consistently 1.4 mg/dL) who were attending an urban academic general internal medicine practice. The intensive case management, administered during the first 2 years after enrollment, consisted of mandatory repeated consultations in a nephrology case management clinic staffed by two nephrologists, a renal nurse, a renal dietitian, and a social worker. Control patients received usual care. Primary outcome measurements included serum creatinine level, estimated creatinine clearance, health services use, and mortality in the 5 years after enrollment. Secondary measures included use of renal sparing and potentially nephrotoxic drugs. RESULTS: There were no differences in renal function, health services use, or mortality in the first, second, or third through fifth years after enrollment. There were significantly more outpatient visits among intervention patients, mainly because of the added visits to the nephrology case management clinic. There were also no significant differences in the use of renal sparing or selected potentially nephrotoxic drugs. The annual direct costs of the intervention were $89,355 ($484 per intervention patient). CONCLUSION: This intensive, multidisciplinary case-management intervention had no effect on the outcomes of care among primary-care patients with established chronic renal insufficiency. Such expensive and intrusive interventions, despite representing state-of-the-art care, should be tested prospectively before being widely introduced into practice.

Purpose: To determine whether there is an independent association of acute renal failure requiring dialysis with operative mortality after cardiac surgery. Patients and Methods: The 42,773 patients who underwent coronary artery bypass or valvular heart surgery at 43 Department of Veterans Affairs Medical Centers between 1987 and 1994 were evaluated to determine the association between acute renal failure sufficient to require dialysis and operative mortality, with and without adjustment for comorbidity and postoperative complications. Crude and adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were derived from logistic regression analysis. Results: Acute renal failure occurred in 460 (1.1%) patients. Overall operative mortality was 63.7% in these patients, compared with 4.3% in patients without this complication. The unadjusted OR for death was 39 (95% CI 32 to 48). After adjustment for comorbid factors related to the development of acute renal failure (surgery type, baseline renal function, preoperative intraaortic balloon pump, prior heart surgery, NYHA class IV status, peripheral vascular disease, pulmonary rales, left ventricular ejection fraction below 35%, chronic obstructive pulmonary disease, systolic blood pressure, and the cross-product of systolic blood pressure and surgery type), the OR was 27 (95% CI 22 to 34). Further adjustment was made for seven postoperative complications (low cardiac output, cardiac arrest, perioperative myocardial infarction, prolonged mechanical ventilation, reoperation for bleeding or repeat cardiopulmonary bypass, stroke or coma, and mediastinitis), that were independently associated with operative mortality. The OR adjusted for comorbidity and postoperative complications associated with acute renal failure was 7.9 (95% CI 6 to 10). Conclusions: Acute renal failure was independently associated with early mortality following cardiac surgery, even after adjustment for comorbidity and postoperative complications. Interventions to prevent or improve treatment of this condition are urgently needed.

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.

This review of previous work provides credence that the fourth heart sound associated with electrocardiographic evidence of left atrial abnormality and hyperuricemia is an easily determined and cost-effective clinically determined functional surrogates of hypertensive heart and kidney involvement, respectively. These routinely obtained clinically measurable indexes are well established and are pathophysiologically related to the functional involvement of the heart and kidney from hypertensive cardiovascular disease. Moreover, these seemingly nonspecific findings provide strong clinical support for feasible means to determine the independent risk of hypertensive left ventricular hypertrophy and renal involvement in patients with hypertension. In these times of using routine clinical information for cost-effective outcomes, those measurements provide excellent surrogate pathophysiologic indices.

Despite tremendous advances in detection and treatment, including both non-pharmacologic and pharmacologic methods, hypertension continues to be a major health concern. In addition to efforts at reducing mortality, recent clinical and research attention has been focused on reducing morbidity from hypertension. Therefore, such efforts are focused on the effect of an elevated blood pressure on individual target organs and in particular on the heart, brain, and kidney. Although the role of blood pressure reduction alone in preserving target organ damage from hypertension is intensely debated, there is little debate that reducing blood pressure is important. The primary manner in which the blood pressure level is determined in the clinical setting continues to be the casual office measurement of blood pressure. However, the clinical use of ambulatory blood pressure determinations, including 24-hour automated blood pressure monitoring, is increasing. Recent data suggest that the determination of ambulatory blood pressures may be a better predictor not only of mortality but also of target organ damage from hypertension. This article will review recent key clinical studies addressing the role of ambulatory blood pressure on certain cardiac, cerebral, and renal manifestations of hypertension.

Chronic kidney disease (CKD) in children is a rare but devastating condition. Once a critical amount of nephron mass has been lost, progression of CKD is irreversible and results in end-stage renal disease (ESRD) and need of renal replacement therapy. The time course of childhood CKD is highly variable. While in children suffering from congenital anomalies of the kidneys and the urinary tract, progression of CKD in general is slow, in children with acquired glomerulopathies, disease progression can be accelerated resulting in ESRD within months. However, irrespective of the underlying kidney disease, hypertension and proteinuria are independent risk factors for progression. Thus, in order to prevent progression, the primary objective of treatment should always aim for efficient control of blood pressure and reduction of urinary protein excretion. Blockade of the renin–angiotensin–aldosterone system preserves kidney function not only by lowering blood pressure, but also by reducing proteinuria and exerting additional anti-proteinuric, anti-fibrotic, and anti-inflammatory effects. Besides, intensified blood pressure control, aiming for a target blood pressure below the 50th percentile, may exert additive renoprotective effects. Additionally, other modifiable risk factors, such as anemia, metabolic acidosis, dyslipidemia, and altered bone-mineral homeostasis may also contribute to CKD progression. In conclusion, beyond strict blood pressure control and reduction of urinary protein excretion, identification and treatment of both, renal disease-related and conventional risk factors are mandatory in children with CKD in order to prevent deterioration of kidney function.

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.

www.thelancet.com Vol 383 May 24, 2014 1791 On May 23, 2015, in collaboration with the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA), The Lancet will publish a themed issue dedicated to renal care and research. Chronic kidney disease is often not considered a key non-communicable disease (NCD), but as specifi ed by WHO it acts as a risk multiplier for four major categories of NCD—cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes. Chronic kidney disease therefore needs to be embedded into the post-2015 health agenda. The aim of our themed issue will be to publish highquality original research on any aspect of kidney disease. Priority will be given to randomised trials that advance the evidence base relevant to treatment of disease, but any studies that have the potential to change clinical practice are welcome. Authors of accepted papers will be invited to present their research at The Lancet/ERAEDTA symposium during the Annual Scientifi c Sessions of the ERA-EDTA, which is being held in London, UK, on May 28–31, 2015. Articles should be submitted online with an accompanying covering letter referring to this call, the deadline for submissions being Nov 17, 2014. Reports of Late-Breaking clinical trials will be considered for fasttrack review, and the deadline is Feb 16, 2015 for these fast-track submissions. In these cases, we recommend that authors contact us as early as possible to discuss the trial and to allow possible coordination of timing of publication with presentation at The Lancet/ERAEDTA symposium. Authors should consult The Lancet’s Information for Authors for guidelines on manuscript preparation and submission. High-quality manuscripts submitted to The Lancet that are not of suffi ciently high priority for publication in The Lancet may be referred to another journal within The Lancet family. If also submitting your research to ERA-EDTA as an abstract for the annual meeting, please inform the conference organisers of your simultaneous submission to The Lancet so that publication can be scheduled appropriately.

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].