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Atherosclerotic renovascular disease (ARVD) is the most common type of renal artery stenosis. It represents a common health clinical problem with clinical presentations relevant to many medical specialties and carries high risk for future cardiovascular and renal events, as well as overall mortality. The available evidence regarding the management of ARVD is conflicting. Randomized controlled trials failed to demonstrate superiority of percutaneous transluminal renal artery angioplasty (PTRA) with or without stenting in addition to standard medical therapy compared with medical therapy alone in lowering blood pressure levels or preventing adverse renal and cardiovascular outcomes in patients with ARVD, but they carried several limitations and met important criticism. Observational studies showed that PTRA is associated with future cardiorenal benefits in patients presenting with high-risk ARVD phenotypes (i.e. flash pulmonary oedema, resistant hypertension, or rapid loss of kidney function). This clinical practice document prepared by experts from the European Renal Best Practice (ERBP) board of the European Renal Association (ERA) and from the Working Group on Hypertension and the Kidney of the European Society of Hypertension (ESH) summarizes current knowledge in epidemiology, pathophysiology and diagnostic assessment of ARVD and presents, following a systematic literature review, key evidence relevant to treatment, with an aim to support clinicians in decision-making and everyday management of patients with this condition.

People living with kidney disease are among the most vulnerable at times of natural or man-made disasters. In addition to their unpredictable course, armed conflicts impose a major threat given the disruption of infrastructure, sanitation and access to food, water and medical care. The ongoing war in Ukraine has once more demonstrated the importance of preparedness, organization, coordination and solidarity during disasters. People living with kidney disease face serious challenges given their dependence on life-sustaining treatment, irrespective of whether they remain in the war zone or are displaced internally or externally. This especially affects those requiring kidney replacement therapy, dialysis or transplantation, but also patients with other kidney diseases and the medical staff who care for them. Soon after the war started, the European Renal Association assigned a Renal Disaster Relief Task Force dedicated to support the people living with kidney disease and the nephrology community in Ukraine. This report summarizes the major challenges faced, actions taken and lessons learned by this task force. We anticipate that the experience will help to increase preparedness and mitigate the devastating effects of armed conflicts on the kidney community in the future and propose to establish an international collaboration to extend this effort to other parts of the world facing similar challenges.

IntroductionCOVID-19 pandemic represents a major worldwide challenge, with a great impact on health systems and economic mechanisms. SARS-CoV-2, the pathogen agent that generates COVID-19, creates a wide variety of organ dysfunctions, from acute respiratory distress syndrome (ARDS) to acute myocardial infarction or pulmonary embolism. Mechanical circulatory support devices such as Extracorporeal Membrane Circulatory Oxygenation (ECMO) have shown their efficacy in maintaining organs perfusion in respiratory and cardiac impairments. With this review, we aimed to assess the impact of ECMO use in COVID-19 patients with ARDS.Material and methodsWe performed a systematic review to find the studies using ECMO in COVID-19. Comorbidities, side effects, and survival rate to discharge were analysed. The literature search was done using PubMed/MEDLINE, Web of Science, Embase (Elsevier), the Cochrane Central Register of Controlled Trials (Wiley) and clinicaltrials.gov databases (inception (December 2019) to October 16, 2021), by 2 authors.ResultsWe included 33 studies from 10 countries with a total of 4.760 patients receiving ECMO for COVID-19. Survival rate varied from 9% to 90,6% at discharge. The most serious adverse events were acute kidney injury (up to 87%), major bleeding (up to 92,1%), strokes or cerebral hemorrhage (up to 34%). Other complications such as pulmonary embolism, peripheral bleeding, or sepsis had a major impact on survival rates.ConclusionsECMO in COVID-19 patients may be a useful rescue therapy instrument, but due to the great variability of studies and still unknown mechanisms and effects of the SARS-CoV-2, further studies are need to be done.

During conflicts, people with kidney disease, either those remaining in the affected zones or those who are displaced, may be exposed to additional threats because of medical and logistical challenges. Acute kidney injury developing on the battlefield, in field hospitals or in higher-level hospital settings is characterized by poor outcomes. People with chronic kidney disease may experience treatment interruptions, contributing to worsening kidney function. Patients living on dialysis or with a functioning graft may experience limitations of dialysis possibilities or availability of immunosuppressive medications, increasing the risk of severe complications including death. When patients must flee, these threats are compounded by unhealthy and insecure conditions both during displacement and/or at their destination. Measures to attenuate these risks may only be partially effective. Local preparedness for overall and medical/kidney-related disaster response is essential. Due to limitations in supply, adjustments in dialysis frequency or dose, switching between hemodialysis and peritoneal dialysis and changes in immunosuppressive regimens may be required. Telemedicine (if possible) may be useful to support inexperienced local physicians in managing medical and logistical challenges. Limited treatment possibilities during warfare may necessitate referral of patients to distant higher-level hospitals, once urgent care has been initiated. Preparation for disasters should occur ahead of time. Inclusion of disaster nephrology in medical and nursing curricula and training of patients, families and others on self-care and medical practice in austere settings may enhance awareness and preparedness, support best practices adapted to the demanding circumstances and prepare non-professionals to lend support.

Clostridioides difficile infection (CDI) is a health issue of utmost significance in Europe and North America, due to its high prevalence, morbidity, and mortality rate. The clinical spectrum of CDI is broad, ranging from asymptomatic to deadly fulminant colitis. When associated with chronic kidney disease (CKD), CDI is more prevalent and more severe than in the general population, due to specific risk factors such as impaired immune system, intestinal dysmotility, high antibiotic use leading to disturbed microbiota, frequent hospitalization, and PPI use. We performed a systematic review on the issue of prevention and treatment of CDI in the CKD population, analysing the suitable randomized controlled cohort studies published between 2000 and 2021. The results show that the most important aspect of prevention is isolation and disinfection with chlorine-based solution and hydrogen peroxide vapour to stop the spread of bacteria. In terms of prevention, using Lactobacillus plantarum (LP299v) proved to be more efficient than disinfection measures in transplant patients, leading to higher cure rates and less recurrent episodes of CDI. Treatment with oral fidaxomycin is more effective than with oral vancomycin for the initial episode of CDI in CKD patients. Faecal microbiota transplantation (FMT) is more effective than vancomycin in recurrent CDI in CKD patients. More large-sample RCTs are necessary to conclude on the best treatment and prevention strategy of CDI in CKD patients.

In this study we aim to study in what way the Strength of motivation of the Romanian medical students has been influenced by harsh economic conditions that led to a massive migration. We conducted a cross-sectional study on a sample size of N=1516. We applied The Strength of Motivation for Medical School-Revised (SMMS) questionnaire and a questionnaire that examines the opinion of the students about migration. The mean value of motivation was 48 (maximum score is 75), 85% of the students have the intention to migrate. The determining factor of studying medicine abroad that correlates significantly with the Strength of motivation is represented by the better work conditions. Students studying in the South of the country want to practice primary in France, students in the North West and in the Center choose to practice medicine in Germany, and students from the East would like to go to Great Britain. The students with a high Strength of motivation are driven by the desire of the students to practice medicine abroad. Higher salaries don’t represent the principal factor for leaving the country. The percent of 85% of the students aiming to practice medicine abroad, represent a concerning result for all of us because it took the form of brain drain.

Background: A bidirectional kidney–gut axis was described in patients with chronic kidney disease (CKD). On the one hand, gut dysbiosis could promote CKD progression, but on the other hand, studies reported specific gut microbiota alterations linked to CKD. Therefore, we aimed to systematically review the literature on gut microbiota composition in CKD patients, including those with advanced CKD stages and end-stage kidney disease (ESKD), possibilities to shift gut microbiota, and its impact on clinical outcomes. Materials and methods: We performed a literature search in MEDLINE, Embase, Scopus, and Cochrane databases to find eligible studies using pre-specified keywords. Additionally, key inclusion and exclusion criteria were pre-defined to guide the eligibility assessment. Results: We retrieved 69 eligible studies which met all inclusion criteria and were analyzed in the present systematic review. Microbiota diversity was decreased in CKD patients as compared to healthy individuals. Ruminococcus and Roseburia had good power to discriminate between CKD patients and healthy controls (AUC = 0.771 and AUC = 0.803, respectively). Roseburia abundance was consistently decreased in CKD patients, especially in those with ESKD (p < 0.001). A model based on 25 microbiota dissimilarities had an excellent predictive power for diabetic nephropathy (AUC = 0.972). Several microbiota patterns were observed in deceased ESKD patients as compared to the survivor group (increased Lactobacillus, Yersinia, and decreased Bacteroides and Phascolarctobacterium levels). Additionally, gut dysbiosis was associated with peritonitis and enhanced inflammatory activity. In addition, some studies documented a beneficial effect on gut flora composition attributed to synbiotic and probiotic therapies. Large randomized clinical trials are required to investigate the impact of different microbiota modulation strategies on gut microflora composition and subsequent clinical outcomes. Conclusions: Patients with CKD had an altered gut microbiome profile, even at early disease stages. Different abundance at genera and species levels could be used in clinical models to discriminate between healthy individuals and patients with CKD. ESKD patients with an increased mortality risk could be identified through gut microbiota analysis. Modulation therapy studies are warranted.

Background. Cardiogenic shock is associated with high mortality, despite new strategies for reperfusion therapy. Short-term circulatory support devices may provide adequate support for appropriate myocardial and organ perfusion. Objectives. This review is aimed at evaluating the impact on survival when using venoarterial extracorporeal membrane oxygenation (V-A ECMO) in patients with cardiogenic shock due to acute myocardial infarction (AMI). Methods. We performed a systematic review that included studies using V-A ECMO in patients with cardiogenic shock. Time on ECMO, side effects, and the number of deceased patients, transplanted or upgraded to durable assist devices were analysed. Literature search was done using PubMed/MEDLINE (inception (1969) to January 10, 2019), ProQuest (inception (January 14, 1988) to January 10, 2019), and clinicaltrials.gov (inception (September 12, 2005) to January 10, 2019), by 2 authors. This protocol is registered with PROSPERO (no. CRD42019123982). Results. We included 9 studies with a total of 1,998 adult patients receiving V-A ECMO for AMI-induced cardiogenic shock. Survival rate varied from 30.0% to 79.2% at discharge and from 23.2% to 36.1% at 12 months. Time on ECMO varied between 1.96 and 6.0 days. Reported serious adverse events were gastrointestinal bleeding (3.6%) and peripheral complications (8.5%). Conclusion. The use of V-A ECMO among patients with AMI-induced cardiogenic shock may provide survival benefits. However, V-A ECMO treatment effects are inconclusive because of limitations in cohort design and reporting.

The clinical practice guideline Management of Obesity in Kidney Transplant Candidates and Recipients was developed to guide decision-making in caring for people with end-stage kidney disease (ESKD) living with obesity. The document considers the challenges in defining obesity, weighs interventions for treating obesity in kidney transplant candidates as well as recipients and reflects on the impact of obesity on the likelihood of wait-listing as well as its effect on transplant outcomes. It was designed to inform management decisions related to this topic and provide the backdrop for shared decision-making. This guideline was developed by the European Renal Association’s Developing Education Science and Care for Renal Transplantation in European States working group. The group was supplemented with selected methodologists to supervise the project and provide methodological expertise in guideline development throughout the process. The guideline targets any healthcare professional treating or caring for people with ESKD being considered for kidney transplantation or having received a donor kidney. This includes nephrologists, transplant physicians, transplant surgeons, general practitioners, dialysis and transplant nurses. Development of this guideline followed an explicit process of evidence review. Treatment approaches and guideline recommendations are based on systematic reviews of relevant studies and appraisal of the quality of the evidence and the strength of recommendations followed the Grading of Recommendations Assessment, Development and Evaluation approach. Limitations of the evidence are discussed and areas of future research are presented.

Risk assessment tools for predicting mortality and end-stage renal disease (ESRD) in the elderly with CKD have received growing attention. However, integrating risk equations into a multidimensional approach of elderly with CKD stage 3b-4 is lacking.In this prospective observational study, we enrolled CKD stage 3b-4 patients aged ≥ 65 years. Bansal score for predicting mortality risk and Kidney Failure Risk Equation (KFRE) for estimating progression to ESRD were applied. Predicted outcome was compared with actual clinical end-points. All patients underwent comprehensive geriatric assessment (CGA), which is an interdisciplinary multidimensional process for geriatric evaluation and management.Participants (N = 184) were divided into two groups, according to Bansal score: Group 1 (low-risk of death, Bansal score 7, N = 69) and Group 2 (high-risk of death, Bansal score ≥ 7, N = 115). Group 2 displayed a substantially higher cardiovascular disease burden than Group 1 and was significantly more likely to be depressed and at risk of malnutrition, according to CGA. Thirty-seven patients died, and 16 started dialysis. Group 2 displayed significantly higher all-cause mortality. In the univariable Cox regression, Group 2 had a fourfold increase in the risk of all-cause mortality, as compared with Group 1 (HR = 4.29, 95% CI 1.88-10.26, P 0.001). Multivariable stepwise Cox analysis showed that Bansal score above 7 remained significantly associated with all-cause mortality (HR = 3.96, 95% CI 1.68-9.29, P 0.001). Group 2 also displayed higher event rates for dialysis initiation. In Group 1, only four patients started dialysis, and three out of them had a high-risk of progression at baseline, according to KFRE.Using risk stratification tools and CGA in a population of elderly with advanced CKD, we found that two-thirds of the patients were at high risk of death, malnutrition and depression, with multimorbidity and four times worse probability of survival than those at lower risk of death.

Heart failure with preserved ejection fraction (HFpEF) is a common disorder generating high mortality and important morbidity prevalence, with a very limited medical treatment available. Studies have shown that the pathophysiological hallmark of this condition is an elevated left intra-atrial pressure (LAP), exertional dyspnea being its clinical manifestation. The increasing pressure from LA is not based on volume overload (such as in heart failure with reduced ejection fraction) but on a diastolic left ventricular (LV) dysfunction combined with an inter-atrial dyssynchrony mimicking a pseudo-pacemaker syndrome. In this review, we aimed to summarize current knowledge and discuss future directions of the newest interventional percutaneous therapies of HFpEF. Novel interventional approaches developed to counter these mechanisms are as follows: LA decompression (inter-atrial shunt devices), enhancement of LV compliance (LV expanders), and inter-atrial resynchronization therapy (LA permanent pacing). To date, inter-atrial shunt devices (IASD) are the most studied, being the only devices currently tested in a phase 3 trial. Recent data showed that IASD are feasible, safe, and have a short-term clinical benefit in HFpEF patients. LV expanders and LA pacing therapy present with a smaller clinical benefit compared with IASD, but they are safe, without any major adverse outcomes currently noted. With further development and improvement of these mechanism-specific devices, it will be interesting to determine in the future whether a complex intervention of multiple HFpEF device implantation will be safe and have further benefits in HFpEF patients.

End-stage renal disease (ESRD) patients often report a combination of disturbing physical symptoms and psychological distress which result in significantly reduced quality of life (QoL). Coping with a chronic disease is a complex matter involving also the family and a multi-disciplinary team. Recently, observational studies suggested that spirituality (S) and religiosity (R) are two important determinants in coping with a chronic/terminal disease. Both concepts were studied in various settings, involving ESRD and QoL. This systematic review aims to synthesize all instruments used to assess R/S, to examine the strategies evaluating QoL of dialysis patients and to analyse their correlations. In accordance with the PRISMA, a systematic search was conducted in PubMed and SCOPUS (between Jan 1980—Dec 2018, PROSPERO number CRD42019116837). Eligible studies included patients on dialysis therapy, religiously/spiritually assessed and contained QoL evaluation. Of the initial 311 studies, 261 papers were excluded. Consequently, 50 papers with a total 9265 patients were available for inclusion. From a list of 177 R/S scales available worldwide, we identified 24 tools. We organized all QoL parameters into 10 classes. In all studies, R/S variables were positively correlated with at least one QoL variable. In this systematic review, we synthesized the studies involving R/S assessment in dialysis patients and their benefit on QoL. R/S has a positive impact on most QoL parameters in 5D-CKD. We suggest that nephrology guidelines on palliative care and/or elderly should include specific recommendations on R/S support and opportunities for integrated specific therapies.

Introduction Acute decompensated heart failure (ADHF), with an incidence of 1-2%, is a clinical syndrome with significant morbidity and mortality despite therapeutic advancements and ongoing clinical trials. A recent therapeutic approach to patients with ADHF includes combination therapy with hypertonic saline solution (HSS) and furosemide, based on the hypothesis that resistance to loop diuretics occurs because of achievement of plateau in water and sodium excretion in patients receiving long-term loop diuretic therapy. Objective Our aim was to conduct a meta-analysis to evaluate the efficiency of combination HSS plus furosemide therapy in patients with ADHF in terms of mortality, readmissions, length of hospital stay, kidney function, urine output, body weight, and B-type natriuretic peptide (BNP). Methods A total of 14 studies-four observational and ten randomized studies (total 3398 patients)-were included in the meta-analysis. Results Our results demonstrate the superiority of combination HSS plus furosemide therapy over furosemide alone in terms of kidney function preservation (mean creatinine difference - 0.33 mg/dL; P < 0.00001), improved diuresis (mean difference [MD] 581.94 mL/24 h; P < 0.00001) and natriuresis (MD 57.19; P < 0.00001), weight loss (MD 0.99 kg; P < 0.00001), duration of hospital stay (MD - 2.72 days; P < 0.00001), readmissions (relative risk 0.63; P = 0.01), and mortality (relative risk 0.55; P < 0.00001). However, no difference in BNP levels was detected (MD 19.88 pg/mL; P = 0.50). Conclusion Despite the heterogeneity and possible risk of bias among the studies, results appear promising on multiple aspects. A clear need exists for future randomized controlled trials investigating the role of combination HSS plus furosemide therapy to clarify these effects and their possible mechanisms.

BackgroundOlder adults at a higher risk of adverse outcomes and mortality if they get infected with Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2). These undesired outcomes are because ageing is associated with other conditions like multimorbidity, frailty and disability. This paper describes the impact of frailty on coronavirus disease 2019 (COVID-19) management and outcomes. We also try to point out the role of inflamm-ageing, immunosenescence and reduced microbiota diversity in developing a severe form of COVID-19 and a different response to COVID-19 vaccination among older frail adults. Additionally, we attempt to highlight the impact of frailty on intensive care unit (ICU) outcomes, and hence, the rationale behind using frailty as an exclusion criterion for critical care admission. Similarly, the importance of using a time-saving, validated, sensitive, and user-friendly tool for frailty screening in an acute setting as COVID-19 triage.We performed a narrative review. Publications from 1990 to March 2021 were identified by searching the electronic databases MEDLINE, CINAHL and SCOPUS.Based on this search, we have found that in older frail adults, many mechanisms contribute to the severity of COVID-19, particularly cytokine storm; those mechanisms include lower immunological capacity and status of ongoing chronic inflammation and reduced gut microbiota diversity.Higher degrees of frailty were associated with poor outcomes and higher mortality rates during and after ICU admission. Also, the response to COVID-19 vaccination among frail older adults might differ from the general population regarding effectiveness and side effects.Researches also had shown that there are many tools for identifying frailty in an acute setting that could be used in COVID-19 triage, and before ICU admission, the clinical frailty scale (CFS) was the most recommended tool.ConclusionOlder frail adults have a pre-existing immunopathological base that puts them at a higher risk of undesired outcomes and mortality due to COVID-19 and poor response to COVID-19 vaccination. Also, their admission in ICU should depend on their degree of frailty rather than their chronological age, which is better to be screened using the CFS.

Background. Patients on kidney replacement therapy comprise a vulnerable population and may be at increased risk of death from coronavirus disease 2019 (COVID-19). Currently, only limited data are available on outcomes in this patient population. Methods. We set up the ERACODA (European Renal Association COVID-19 Database) database, which is specifically designed to prospectively collect detailed data on kidney transplant and dialysis patients with COVID-19. For this analysis, patients were included who presented between 1 February and 1 May 2020 and had complete information available on the primary outcome parameter, 28-day mortality. Results. Of the 1073 patients enrolled, 305 (28%) were kidney transplant and 768 (72%) dialysis patients with a mean age of 60 ± 13 and 67 ± 14 years, respectively. The 28-day probability of death was 21.3% [95% confidence interval (95% CI) 14.3–30.2%] in kidney transplant and 25.0% (95% CI 20.2–30.0%) in dialysis patients. Mortality was primarily associated with advanced age in kidney transplant patients, and with age and frailty in dialysis patients. After adjusting for sex, age and frailty, in-hospital mortality did not significantly differ between transplant and dialysis patients [hazard ratio (HR) 0.81, 95% CI 0.59–1.10, P = 0.18]. In the subset of dialysis patients who were a candidate for transplantation (n = 148), 8 patients died within 28 days, as compared with 7 deaths in 23 patients who underwent a kidney transplantation Conclusions. The 28-day case-fatality rate is high in patients on kidney replacement therapy with COVID-19 and is primarily driven by the risk factors age and frailty. Furthermore, in the first year after kidney transplantation, patients may be at increased risk of COVID-19-related mortality as compared with dialysis patients on the waiting list for transplantation. This information is important in guiding clinical decision-making, and for informing the public and healthcare authorities on the COVID-19-related mortality risk in kidney transplant and dialysis patients.

Almost all CKD patients have a poor nutritional status, while elderly CKD patients are specifically frail and malnourished. Our aim is to conduct a systematic review of the up to date primary studies that look at methods of improving nutritional status in CKD patients in the elderly demographic. A focussed and sensitive search strategy was applied to the PUBMED database to identify relevant English language articles. Once articles were identified a detailed quality and bias assessment was performed. Two independent researchers (MZ and SM) then subsequently carried out detailed data extraction and analysis and this was subsequently verified by a third researcher (IN). A total of 19 studies were included in our systematic review which included 7 non-randomised control trials and 15 randomised controlled trials. The outcomes that we considered to be most relevant for our subject title were: mortality data, SGA, albumin, total protein, isoleucine, leucine, prealbumin, transferrin, leptin, valine, TAG, HDL, LDL and total amino acids. Detailed bias analysis of the different studies was also conducted. This is the first systematic review of the literature, so far, on the subject, involving elderly CKD patients. The quality of trials is low, very heterogenic in patients, methods and outcomes. However, we found a positive effect of dietary interventions on the nutritional status of most patients studied, highlighted by improvement in serum albumin and SGA, the most measured outcomes.

Protocol withdrawn due to lack of progress

Background and Aims In Europe, the share of the elderly (≥65 years of age) in the total population is estimated to increase from 19.2% in 2016 to 29.1% by 2080. In 2016, European Renal Best Practice (ERBP) group published a clinical practice guideline on management of older patients with CKD stage3b or higher (eGFR Method In this retrospective cohort study we included patients aged ≥65 years with CKD stage 3b-4, evaluated at the Outpatient Nephrology Department of Dr. C. I. Parhon Hospital from Iași, Romania, between October 2016 – October 2018. Individual risk for mortality was predicted using Bansal score, a nine-variable equation model. A total score of 7 (associated with a mortality risk of 53.82%) was established as cut-off value to differentiate between 2 groups: high risk of mortality (Bansal ≥ 7) and low risk of mortality (Bansal < 7), given the fact that the ERBP guidelines don’t define a threshold for high risk in respect to mortality outcome. According to the algorithm proposed by the guideline, individual risk for progression to ESRD at 5 years was calculated in the low mortality risk group, using the 4-variable Kidney Failure Risk Equation (KFRE). Results The final cohort included 958 patients, with a mean age of 74 years (SD: 7), and with similar gender distribution (50.6% female vs. 49.4% male). Predicted trajectory in terms of reaching ESRD / death: When we applied Bansal score for mortality, the total study population (N=958) was divided in two groups: N1 with high risk of mortality, which comprised more than half of the cohort (548 patients, 57.2%) and N2 with low risk of mortality (410 patients, 42.8%). Individual risk of progression to ESRD was then estimated in N2 group, using 4-variable KFRE. Nearly ¾ of this group (75.4%, 309 subjects) presented a low-risk of progression and ¼ (24.6%, 101 subjects) had high-risk. Real-life trajectory in terms of reaching ESRD / death: From the entire cohort, 31 patients started renal replacement therapy (RRT) and 164 patients died as their first clinical event. The RRT initiation rate was 3.6% of N1 group (20 subjects) versus 2.7% of N2 group (11 subjects). The mortality rate was 15.5% of N1 group (85 deaths) versus 19.3% of N2 group (79 deaths). Figure 1 depicts the real-life trajectory of the population groups in terms of reaching ESRD / death. Conclusion In a large population from Eastern Europe, the application of the algorithm from the Clinical Practice Guideline on management of older patients with advanced CKD showed that risk prediction for death and end-stage renal disease does not parallel the real-life trajectory of the population. More than half of the subjects had a high risk of mortality, however we found similar death rates in the 2 groups (high versus low risk of mortality). Also, the RRT initiation rates were similar, irrespective of predicted mortality risk or kidney failure risk, suggesting that implementing the guideline in real-life settings is still a challenge.

Background/objective Data regarding the nephrotoxicity of the peptide receptor radionuclide therapy (PRRT) with Yttrium- and Lutetium-radiolabeled somatostatin analogs (RSA) are inconclusive. We aimed to evaluate the short- and long-term nephrotoxicity following PRRT usage in patients with all types of neuroendocrine tumors (NETs). Methods A systematic review of observational studies reporting data about nephrotoxicity after treatment with Yttrium and Lutetium RSA was performed. Data on serum creatinine, creatinine clearance, glomerular filtration rate (GFR) and need for renal replacement therapy were compiled. We included patients with progressive, inoperable symptomatic G1, G2 and G3 different types of NETs. After searching in three electronic databases PubMed, Scopus and the Cochrane Library, from 1 January 1978 to November 2018, data were extracted and summarized using a random-effects model. Results The final analysis included 34 studies, comprising 5386 participants, enrolling patients with G1, G2, G3 NETs and a follow-up from 12 up to 191 months. Compared with renal function before treatment, measured/estimated glomerular filtration rate (m/eGFR) values changed after PRRT, with a mean annual decrease following PRRT between 2 and 4 mL/min/1.73 m suggesting different grades of nephrotoxicity after PRRT. When compared, Y-RSA and the Y-RSA-Lu-RSA combination are associated with a higher m/eGFR decline compared to Lu-RSA alone. Conclusions PRRT can be followed by potentially serious long-term nephrotoxicity, despite kidney protection. The use of the quantified renal function combined with a long follow-up period and personalized dosimetry-based PRRT can reduce nephrotoxicity, in order to use the whole PRRT potential in the management of NETs.

IgA nephropathy (IgAN), or Berger's disease, is the most common primary glomerular disease worldwide, but varies largely in its geographic distribution. A systematic review of 1,619 publications from the five continental regions of the world was performed to assess the prevalence of IgAN in different worldwide regions and analyze factors responsible for geographic differences. All observational studies that described the prevalence and incidence data on glomerulonephritis were considered. IgAN is more frequent in Asian populations (45 cases per million population/y in Japan) than in Caucasians (31 cases per million population/y in France). These differences are owing to some relevant aspects: (1) systematic mass screening of urine in populations, as occurring in some Asian countries (Hong Kong, Japan, Korea, and Singapore), is not common in Western countries; (2) general practitioners and health care professionals in Western countries underestimate persistent microscopic hematuria and/or mild proteinuria in apparently healthy individuals causing late referral to a nephrologist; and (3) nephrologists adopt different indications for kidney biopsy in individuals with persistent urinary abnormalities. In addition, differences also are owing to the source of data, because the frequency of IgAN observed in a nephrology center with a high incidence of kidney biopsies is higher than in a regional renal biopsy registry that receives data from many centers. In conclusion, greater efforts should be made to diagnose IgAN earlier in individuals who manifest persistent microhematuria and/or mild proteinuria and to introduce less stringent indications for kidney biopsies. This preventive approach, followed by early therapy, may reduce the global burden of end-stage kidney disease caused by IgAN.

Although promising, data regarding the renal impact and safety of bariatric surgery (BS) are insufficient. We aimed at investigating the benefits and harms of BS for weight loss on kidney function. A systematic review and meta-analysis of observational studies reporting data about the impact of BS (any techniques) on serum/plasma creatinine, creatinine clearance, glomerular filtration rate (GFR), proteinuria, nephrolithiasis, and need for renal replacement therapy (RRT)) was performed. Obese adults (non-chronic kidney disease (CKD), CKD or transplanted patients) that underwent BS for weight loss were included. After searching MEDLINE (inception to August 2017), the Cochrane Library (Issue 10–12, October 2017), and the websiteclinicaltrials.gov (August 2017), data were extracted and summarized using a random-effects model. The final analysis included 23 cohort studies, comprising 3015 participants. Compared with renal function before treatment, BS significantly decreased serum creatinine level (mean difference (MD), − 0.08 mg dl−1; 95% confidence interval (CI), − 0.10 to − 0.06); p

Current guidelines for dialysis specify a minimum Kt/V. For haemodialysis (HD) patients, minimum treatment time and frequency is also specified. The guidelines allow for modification to take account of renal function. The guidelines are not specifically aimed at the elderly and may not be appropriate for all patients in this group. Increasing age is accompanied by physiological and pathological changes that may modify the patient's response to uraemia and dialysis. Frailty and multi-morbidity are likely, but to a variable extent. Elderly patients could be more susceptible to the effects of uraemia and require a higher dose of dialysis. Conversely, the generation rate of uraemic toxins is lower in elderly patients, potentially reducing the need for dialysis. In the elderly, quality of life may be more adversely affected by multimorbidity than uraemic symptoms, thus the dose of dialysis may be less relevant. Higher doses of dialysis may be more difficult to achieve in the elderly and may be less well tolerated. We conclude that the prescription of dialysis in the elderly should be individualized, taking multiple factors into account. An individualized Kt/V may be useful in controlling dialysis dose and detecting problems in delivery. However, achievement of a specified Kt/V may not result in any benefit to an elderly patient and could be counterproductive.

Volume overload is a common complication in patients with end-stage kidney disease who undergo maintenance dialysis therapy and associated with hypertension, left ventricular hypertrophy and mortality in this population. Although bioimpedance analysis (BIA), an objective method to assess overhydration, is associated with poor outcomes in observational studies, in randomized controlled trials (RCTs) the results were conflicting. We have examined the role of BIA for assessing the “dry weight” and fluid status in order to improve fluid overload in comparison with a control or clinical-based prescription in patients with ESKD receiving haemodialysis or peritoneal dialysis. All RCTs and quasi-RCTs in which BIA was used to improve fluid overload and assess the effect on all-cause mortality, cardiovascular morbidity, systolic blood pressure and volume control and arterial stiffness were included. Seven RCTs with 1312 patients could be included in this review. In low-to-medium quality of the evidence, the use of BIA did not reduce all-cause mortality (relative risk 0.87, 95% CI 0.54–1.39) and had small to no effect on body change, but it improved systolic blood pressure control (mean difference (MD) −2.73 mmHg, 95% CI −5.00 to −0.46 mmHg) and reduce overhydration, as measured by BIA, with 0.43 L [(MD), 95% CI 0.71–0.15 L]. In ESKD patients, BIA-based interventions for correction of overhydration have little to no effect on all-cause mortality, whereas BIA improved systolic blood pressure control. Our results should be interpreted with caution as the size and power of the included studies are low. Further studies, larger or with a longer follow-up period, should be performed to better describe the effect of BIA-based strategies on survival.

Chronic kidney disease (CKD) is common and is associated with increased mortality, morbidity and cost. However, insufficient high-quality trial data are available to answer many relevant clinical questions in this field. In addition, a wide range of variable outcomes are used in studies, and often they are incompletely reported. Furthermore, there is a lack of patient-relevant outcomes, such as mortality, morbidity, quality of life, pain, need for dialysis or costs. Common problems with outcome reporting are as follows: choosing the wrong domains to measure; within domains, choosing the wrong measures (invalid surrogates, composite, non-patient relevant); within measures, choosing the wrong/variable metrics; and within metrics, choosing variable presentation methods. With this article, we aim to underline why standardized outcome reporting is key to achieving evidence-based guidance and improving clinical care for patients; highlight the frameworks available for achieving core outcome sets; and starting from these frameworks, we propose steps needed to develop a core outcome set in the field of CKD. We hope that standardized core outcome sets for nephrology will lead to the most important outcome of guideline production, improving outcomes for our patients.

Fluid overload is associated with adverse outcomes in hemodialysis (HD) patients. The precise assessment of hydration status in HD patients remains a major challenge for nephrologists. Our study aimed to explore whether combining two bedside methods, lung ultrasonography (LUS) and bioimpedance, may provide complementary information to guide treatment in specific HD patients. In total, 250 HD patients from two dialysis units were included in this randomized clinical trial. Patients were randomized 1:1 to have a dry weight assessment based on clinical (control) or LUS with bioimpedance in case of clinical hypovolemia (active)-guided protocol. The primary outcome was to assess the difference between the two groups on a composite of all-cause mortality and first cardiovascular event (CVE)—including death, stroke, and myocardial infarction. During a mean follow-up period was 21.3 ± 5.6 months, there were 54 (21.6%) composite events in the entire population. There was a nonsignificant 9% increase in the risk of this outcome in the active arm (HR = 1.09, 95% CI 0.64–1.86, p = 0.75). Similarly, there were no differences between the two groups when analyzing separately the all-cause mortality and CVE outcomes. However, patients in the active arm had a 19% lower relative risk of pre-dialytic dyspnea (rate ratio—0.81, 95% CI 0.68–0.96), but a 26% higher relative risk of intradialytic cramps (rate ratio—1.26, 95% CI 1.16–1.37). This study shows that a LUS–bioimpedance-guided dry weight adjustment protocol, as compared to clinical evaluation, does not reduce all-cause mortality and/or CVE in HD patients. A fluid management protocol based on bioimpedance with LUS on indication might be a better strategy.

Background In routine intensive care unit (ICU) practice, fluids are often administered without a safety limit, which may lead to fluid overload and decreased survival. Recently, B-lines score (BLS) has been validated as a lung ultrasound (LUS) quantification of pulmonary congestion. This suggests that LUS may provide a safety threshold to conduct fluid therapy and to avoid overhydration. However, there is no randomized study to test the utility of LUS in guiding fluid management in ICU patients by using a pre-specified BLS cut-off value as a threshold for fluid removal. Methods LUS Guided Fluid Management Protocol for the Critically Ill Patient is a prospective, multi-centre, randomized controlled trial. Five hundred ICU patients will be randomly assigned in a 1:1 ratio, to protocolized LUS-based fluid management or usual care. The trial intervention will start on ICU admission and will consist in daily assessment of BLS and triggered evacuation of excessive fluids with loop diuretics (Furosemide) when BLS ≥ 15. If rebalancing volume status with diuretics fails, forced evacuation by ultrafiltration will be used. The main endpoint is death from all causes at 28 days from randomization. The secondary outcomes are presence and time-course evolution of organ dysfunctions, ICU- and hospital length of stay, all-cause mortality at 90 days, and health economics data. Discussion If study results will show that LUS guided fluid management protocol improves outcome in ICU patients, it will be the base for other studies to refine this protocol or track those categories of critically ill patients to whom it may bring maximum benefits. Trial registration ClinicalTrials.gov, NCT03393065. Registered on 8 January 2018. Electronic supplementary material The online version of this article (10.1186/s13063-019-3345-0) contains supplementary material, which is available to authorized users.

The treatment of most glomerulonephritides is still based on a combination of an oral corticosteroid and an alkylating agent, with favorable outcomes, but with serious side effects. The objective of this study was to reduce the cumulative corticosteroid dose in patients with high risk of corticosteroid-related adverse events by replacing daily oral corticosteroids with intravenous (iv) methylprednisolone pulses, associated with monthly pulse i.v. cyclophosphamide (according to KDIGO guidelines) in patients with glomerulonephritis.This was a retrospective cohort study conducted at a single nephrology centre. In the course of a 6-month run-in phase, all the patients received non-immunosuppressive pathogenic treatment. High-risk patients, who still had urinary protein excretion of at least 3.5 g per day at the end of these 6 months, received a combination of corticosteroids and cyclophosphamide. Patients were divided in two groups: group 1 (23 patients)-included patients with high risk of corticosteroid-related adverse events received monthly methylprednisolone 1 g/day, 3 days and i.v. cyclophosphamide for 6 months, and group 2 (84 patients)-received oral corticosteroids (as per KDIGO recommended dose) and i.v. cyclophosphamide. The primary outcome-time to a combined end-point of doubling of serum creatinine, ESRD, need for chronic renal replacement therapy or death; secondary outcomes: complete remission [proteinuria 0.3 g per 24 h (urinary protein-creatinine rate 300 mg/g [ 30 mg/mmol]]; partial remission (proteinuria 0.3 but 3.5 g per 24 h or a decrease in proteinuria by at least 50% from the initial value) and adverse events.At 6 months, there was no difference in the primary composite end-point: 8.7% patients from the group 1 and 20.2% patients from the group 2 (P = 0.199) reached this end-point. Similar data were also recorded at 12 months. Secondary end-points were also similar between treatment groups. More patients receiving oral corticosteroids experienced infections, but without statistical significance.Our data indicate that low i.v. dose corticosteroids and cyclophosphamide administered monthly in patients with high risk of corticosteroid-related adverse events and primary glomerulonephritis are equally effective, with fewer metabolic disorders and infections.

Background The anaemia seen in chronic kidney disease (CKD) may be exacerbated by iron deficiency. Iron can be provided through different routes, with advantages and drawbacks of each route. It remains unclear whether the potential harms and additional costs of intravenous (IV) compared with oral iron are justified. This is an update of a review first published in 2012. Objectives To determine the benefits and harms of IV iron supplementation compared with oral iron for anaemia in adults and children with CKD, including participants on dialysis, with kidney transplants and CKD not requiring dialysis. Search methods We searched the Cochrane Kidney and Transplant Register of Studies up to 7 December 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. Selection criteria We included randomised controlled trials (RCTs) and quasi‐RCTs in which IV and oral routes of iron administration were compared in adults and children with CKD. Data collection and analysis Two authors independently assessed study eligibility, risk of bias, and extracted data. Results were reported as risk ratios (RR) with 95% confidence intervals (CI) for dichotomous outcomes. For continuous outcomes the mean difference (MD) was used or standardised mean difference (SMD) if different scales had been used. Statistical analyses were performed using the random‐effects model. Subgroup analysis and univariate meta‐regression were performed to investigate between study differences. The certainty of the evidence was assessed using GRADE. Main results We included 39 studies (3852 participants), 11 of which were added in this update. A low risk of bias was attributed to 20 (51%) studies for sequence generation, 14 (36%) studies for allocation concealment, 22 (56%) studies for attrition bias and 20 (51%) for selective outcome reporting. All studies were at a high risk of performance bias. However, all studies were considered at low risk of detection bias because the primary outcome in all studies was laboratory‐based and unlikely to be influenced by lack of blinding. There is insufficient evidence to suggest that IV iron compared with oral iron makes any difference to death (all causes) (11 studies, 1952 participants: RR 1.12, 95% CI 0.64, 1.94) (absolute effect: 33 participants per 1000 with IV iron versus 31 per 1000 with oral iron), the number of participants needing to start dialysis (4 studies, 743 participants: RR 0.81, 95% CI 0.41, 1.61) or the number needing blood transfusions (5 studies, 774 participants: RR 0.86, 95% CI 0.55, 1.34) (absolute effect: 87 per 1,000 with IV iron versus 101 per 1,000 with oral iron). These analyses were assessed as having low certainty evidence. It is uncertain whether IV iron compared with oral iron reduces cardiovascular death because the certainty of this evidence was very low (3 studies, 206 participants: RR 1.71, 95% CI 0.41 to 7.18). Quality of life was reported in five studies with four reporting no difference between treatment groups and one reporting improvement in participants treated with IV iron. IV iron compared with oral iron may increase the numbers of participants, who experience allergic reactions or hypotension (15 studies, 2607 participants: RR 3.56, 95% CI 1.88 to 6.74) (absolute harm: 24 per 1000 with IV iron versus 7 per 1000) but may reduce the number of participants with all gastrointestinal adverse effects (14 studies, 1986 participants: RR 0.47, 95% CI 0.33 to 0.66) (absolute benefit: 150 per 1000 with IV iron versus 319 per 1000). These analyses were assessed as having low certainty evidence. IV iron compared with oral iron may increase the number of participants who achieve target haemoglobin (13 studies, 2206 participants: RR 1.71, 95% CI 1.43 to 2.04) (absolute benefit: 542 participants per 1,000 with IV iron versus 317 per 1000 with oral iron), increased haemoglobin (31 studies, 3373 participants: MD 0.72 g/dL, 95% CI 0.39 to 1.05); ferritin (33 studies, 3389 participants: MD 224.84 µg/L, 95% CI 165.85 to 283.83) and transferrin saturation (27 studies, 3089 participants: MD 7.69%, 95% CI 5.10 to 10.28), and may reduce the dose required of erythropoietin‐stimulating agents (ESAs) (11 studies, 522 participants: SMD ‐0.72, 95% CI ‐1.12 to ‐0.31) while making little or no difference to glomerular filtration rate (8 studies, 1052 participants: 0.83 mL/min, 95% CI ‐0.79 to 2.44). All analyses were assessed as having low certainty evidence. There were moderate to high degrees of heterogeneity in these analyses but in meta‐regression, definite reasons for this could not be determined. Authors' conclusions The included studies provide low certainty evidence that IV iron compared with oral iron increases haemoglobin, ferritin and transferrin levels in CKD participants, increases the number of participants who achieve target haemoglobin and reduces ESA requirements. However, there is insufficient evidence to determine whether IV iron compared with oral iron influences death (all causes), cardiovascular death and quality of life though most studies reported only short periods of follow‐up. Adverse effects were reported in only 50% of included studies. We therefore suggest that further studies that focus on patient‐centred outcomes with longer follow‐up periods are needed to determine if the use of IV iron is justified on the basis of reductions in ESA dose and cost, improvements in patient quality of life, and with few serious adverse effects.

Atrial fibrillation (AF), one of the most common dysrhythmia in clinical practice, remains frequently in people with chronic kidney disease (CKD). AF is associated with a fivefold risk of stroke, a threefold incidence of heart failure, and an increased risk of death. Co-existence of AF and CKD raises substantially morbidity and mortality. Moreover, the optimal treatment approach (rate versus rhythm control) remains debated due to lack of hard evidence. Oral anticoagulation is challenging, since these patients have both a prothrombotic state and an increased risk of stroke and an inherent platelet and vascular dysfunction and an amplified rate of bleeding. Although promising, the newer anticoagulation agents were not tested in severe CKD. Furthermore, fatal bleeding has been reported.

Contrast-induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired acute kidney injury (AKI). We evaluated the evidence that uric acid (UA) plays a pathogenic role in CI-AKI. Ten studies were eligible for inclusion for meta-analysis. Hyperuricemia predicted risk for cases with AKI in prospective cohort studies. Higher levels of serum UA (SUA), as defined by the authors, were associated with a 2-fold increased risk to develop AKI (pooled odds ratio 2.03; 95% confidence interval [CI] 1.48-2.78). Significant heterogeneity was found in cohort studies ( P = .001, I2 = 85.7%). In 2 clinical trials, lowering of SUA with saline hydration was significantly associated with reduced risk for AKI compared with saline hydration alone or saline hydration with N-acetyl cysteine. An analysis of 2 randomized controlled trials found that allopurinol with saline hydration had a significant protective effect on renal function (assessed by serum creatinine values) compared with hydration alone (mean difference: −0.52 mg/dL; 95% CI: −0.81 to −0.22). Hyperuricemia independently predicts CI-AKI. Two clinical trials suggest lowering SUA may prevent CI-AKI. The mechanism by which UA induces CI-AKI is likely related to acute uricosuria.

Introduction Cognitive impairment is a major, but underdiagnosed, risk factor for negative outcomes in patients with chronic kidney disease (CKD). The main goal of this study was to evaluate, for the first time, the relationship between arterial stiffness and cognitive impairment in a cohort of hemodialysis patients. Methods We prospectively analyzed the cognitive function and pulse wave velocity (PWV) of 72 hemodialysis patients, mean age 56.54 ± 13.96 y, from two Romanian dialysis centers. We administered to all patients the Mini Mental State Examination (MMSE), Trail Making Test Part-A (TMTA) and Part-B (TMTB), and Mini-Cog Test. Radial arterial waveforms during 40 cardiac cycles were recorded in each patient. Findings Mean MMSE score was 25.13 ± 3.47, mean MiniCog score was 3.51 ± 1.18, mean TMTA (sec) was 103.77 ± 53.13 and mean TMTB (sec) was 214.93 ± 112.25. In linear unadjusted regression, PWV values were associated with worse MMSE scores (β = -0.36, P = 0.001, 95% CI: -0.68 to -0.17), and MiniCog scores (β = -0.26, P = 0.02, 95% CI: -0.19 to -0.01). Also, PWV value was significant associated with TMTA test, but not with TMTB. After further adjustments, PWV remained a strong predictor for cognitive impairment measured by MMSE, TMTA, MiniCog, but not for TMTB. Discussion Cognitive impairment was associated with higher PWV values in our cohort. Further evidence is needed in order to support arterial stiffness as a long-term predictor for cognitive decline in ESRD patients.

Type 2 diabetes mellitus (T2DM) is associated with increased risk of cardiovascular disease and nephropathy—now the leading cause of end-stage renal disease and dialysis in Europe and the United States. Inflammation and oxidative stress play a pivotal role in the development of diabetic complications. Silymarin, an herbal drug with antioxidant and anti-inflammatory properties, may improve glycemic control and prevent the progression of the complications. In a systematic review and meta-analysis including five randomized controlled trials and 270 patients, routine silymarin administration determines a significant reduction in fasting blood glucose levels (−26.86 mg/dL; 95% CI −35.42–18.30) and HbA1c levels (−1.07; 95% CI −1.73–0.40) and has no effect on lipid profile. Benefits for silymarin on proteinuria and CKD progressions are reported in only one small study and are uncertain. However, being aware of the low quality of the available evidence and elevated heterogeneity of these studies, no recommendation can be made and further studies are needed.

PURPOSE: To identify and prioritize potential topics to be addressed in the development of European multidisciplinary guidelines on the management of chronic kidney disease stage 3b-5 in older patients.METHODS: We composed a list of 47 potential guideline topics by reviewing the literature, consulting online 461 nephrologists and 107 geriatricians, and obtaining expert input. A multidisciplinary panel of twelve experts then prioritized the topics during a face-to-face consensus meeting, following a nominal group technique structure with two voting rounds. Topics were rated on a 9-point scale ranging from 1 ('not at all important') to 9 ('critically important').RESULTS: The highest rating (median; range) was assigned to 'Screening and referral' (8.5; 2.0). Eight topics shared the second highest rating with a median priority score of 8.0 (2.0) and included 'Starting dialysis or not' and 'Accurate assessment of renal function.' 'Targets for and treatment of diabetes' received the lowest rating with (3.0; 6.0).CONCLUSIONS: This joint initiative of the European Renal Association-European Dialysis Transplant Association (ERA-EDTA) and the European Union Geriatric Medicine Society (EUGMS) prioritized the development of guidance on interdisciplinary referral of older patients with chronic kidney disease stage 3b-5. Future guidance will therefore focus on identifying prognostic scores to predict death and progression to end-stage renal disease, as well as accurate tests for assessment of renal function in older kidney patients. This will contribute to more informed treatment decision making in this growing patient population.