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Pauline WM Voskamp,1 Friedo W Dekker,1 Maarten B Rookmaaker,2 Marianne C Verhaar,2 Willem Jan W Bos,3 Merel van Diepen,1 Gurbey Ocak2 1Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; 2Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, the Netherlands; 3Department of Nephrology, Sint Antonius Hospital, Nieuwegein, the Netherlands Purpose: A post hoc analysis of a recent trial on direct oral anticoagulants versus vitamin K antagonists showed that amongst patients with mildly decreased kidney function, use of vitamin K antagonists was associated with a greater decline in renal function than use of direct oral anticoagulants. Whether these vitamin K antagonist effects are the same in pre-dialysis patients is unknown. Therefore, the aim of this study was to investigate the association between vitamin K antagonist use and the rate of renal function decline and time until start of dialysis in incident pre-dialysis patients.Methods: Data from 984 patients from the PREdialysis PAtient REcord study, a multicenter follow-up study of patients with chronic kidney disease who started pre-dialysis care in the Netherlands (1999–2011), were analyzed. Of these patients, 101 used a vitamin K antagonist. Linear mixed models were used to compare renal function decline between vitamin K antagonist users and non-users. Cox proportional hazards models were used to estimate the HR with 95% CI for starting dialysis.Results: Vitamin K antagonist use was associated with an extra change in renal function of –0.09 (95% CI –1.32 to 1.13) mL/min/1.73 m2 per year after adjustment for confounding. The adjusted HR for the start of dialysis was 1.20 (95% CI 0.85 to 1.69) in vitamin K antagonist users, compared to non-users. Conclusion: In incident pre-dialysis patients, the use of vitamin K antagonists was not associated with an accelerated kidney function decline or an earlier start of dialysis compared to non-use. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication. Keywords: coumarins, epidemiology, chronic kidney disease, glomerular filtration rate

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Cardiovascular diseases are highly prevalent among patients on dialysis. For these diseases, antiplatelets and antithrombotic therapies including heparin, vitamin K antagonists, and direct oral anticoagulants, are being used. However, the benefit-risk balance of these therapies could differ for dialysis patients compared with the general population. This review article focuses on the bleeding risk associated with the use of heparin, antiplatelets, vitamin K antagonists, and direct oral anticoagulants in patients receiving hemodialysis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Since the beginning of the SARS-CoV-2 pandemic, studies have been reporting inconsistently on migration background as a risk factor for COVID-19 outcomes. The aim of this study was to evaluate the association between migration background and clinical outcomes with COVID-19 in the Netherlands., Methods: This cohort study included 2,229 adult COVID-19 patients admitted in two Dutch hospitals between February 27, 2020 and March 31, 2021. Odds ratios (ORs) for hospital admission, intensive care unit (ICU) admission and mortality with 95% confidence intervals (CIs) were calculated for non-Western (Moroccan, Turkish, Surinamese or other) persons as compared with Western persons in the general population of the province of Utrecht (the Netherlands) as source population. Furthermore, among hospitalized patients, Hazard ratios (HRs) with 95% CIs for in-hospital mortality and intensive care unit (ICU) admission were calculated using Cox proportional hazard analyses. Hazard ratios were adjusted for age, sex, body mass index, hypertension, Charlson Comorbidity Index, chronic corticosteroid use before admission, income, education and population density to investigate explanatory variables., Results: Of the 2,229 subjects, 1,707 were of Western origin and 522 were of non-Western origin. There were 313 in-hospital deaths and 503 ICU admissions. As compared with persons with a Western origin in the general population of the province of Utrecht, the ORs for non-Western persons was 1.8 (95% CI 1.7-2.0) for hospitalization, 2.1 (95% CI 1.7-2.5) for ICU admission and 1.3 (95% CI 1.0-1.7) for mortality. Among hospitalized patients, HR for ICU admission was 1.1 (95% CI 0.9-1.4) and 0.9 (95% CI 0.7-1.3) for mortality for non-Western hospitalized persons as compared with hospitalized patients of Western origin after adjustment., Conclusion: Non-Western persons, including Moroccan, Turkish and Surinamese subjects, had increased risks of hospital admission, ICU admission and COVID-19 related death on a population level. Among hospitalized COVID-19 patients, no association was found between migration background and ICU admission or mortality., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ocak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: After decades of increasing dialysis incidence, we observed a decreasing trend in the Netherlands in the last decade. We compared this trend with trends in other European countries., Materials and Methods: Aggregated data for calendar years 2001-2019 from the Dutch registries of kidney replacement therapy patients and the European Renal Association Registry were used. Dialysis incidence in the Netherlands was compared with that in 11 other European countries/regions using three age groups: 20-64, 65-74, and ≥75 years, taking into account pre-emptive kidney transplantation (PKT) incidence. Time trends were assessed as annual percentage change (APC) with 95% confidence intervals (CI) using joinpoint regression analysis., Results: Between 2001 and 2019 the Dutch dialysis incidence decreased slightly among patients aged 20-64 years (APC -0.9, 95% CI -1.4; -0.5). For patients 65-74 and ≥75 years old, a peak was seen in 2004 and 2009, respectively. Afterwards, the decrease was most marked in patients aged ≥75 years: APC -3.2 (-4.1; -2.3) versus APC -1.8 (-2.2; -1.3) for patients 65-74 years old. PKT incidence increased significantly during the study period but remained limited compared to the observed decrease in dialysis incidence, especially among older patients. Large differences in dialysis incidence were observed among European countries/regions. A decreasing dialysis incidence among older patients was also seen in Austria, Denmark, England/Wales, Finland, Scotland, and Sweden., Conclusions: The Dutch dialysis incidence decreased most profoundly among older patients. This was also observed in several other European countries/regions. Although PKT incidence increased, it can only explain a minor part of the decrease in dialysis incidence., Competing Interests: M.O, A.A., M.B., and W.B. are investigators for the DIALysis or not: Outcomes in older kidney patients with GerIatriC Assessment (DIALOGICA) study, which is supported by Leading the Change, a Dutch healthcare efficiency evaluation project by Zorgevaluatie Nederland. K.J. received funding from the European Renal Association (ERA) for running the ERA Registry. W.B. received grant support from Zilveren Kruis Insurance, outside the submitted work. All other authors declare they have no competing interests., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Objective: A fixed 6 mg dexamethasone dose for 10 days is the standard treatment for all hospitalised COVID-19 patients who require supplemental oxygen. Yet, the pharmacokinetic properties of dexamethasone can lead to diminishing systemic dexamethasone exposure with increasing body mass index (BMI). The present study examines whether this translates to overweight and obesity being associated with worse clinical outcomes, defined as ICU admission or in hospital death, in COVID-19 patients treated with fixed-dose dexamethasone., Methods: We conducted a single centre retrospective cohort study in COVID-19 patients who were admitted to a non-ICU ward and were treated with dexamethasone (6 mg once daily for a maximum of ten days) between June 2020 and January 2021. Univariable and multivariable logistic regression analyses were conducted to assess the association between BMI-categories and an unfavourable clinical course (ICU admission and/or in hospital death). Analyses were adjusted for age, comorbidities, inflammatory status, and oxygen requirement at admission. For reference, similar analyses were repeated in a cohort of patients hospitalised before dexamethasone was introduced (March 2020 through May 2020)., Results: In patients treated with dexamethasone (n = 385) an unfavourable clinical course was most prevalent in patients with normal weight (BMI < 25) compared to patients with overweight (BMI 25-30) and patients with obesity (BMI ≥ 30) with percentages of 33, 26 and 21% respectively. In multivariable analyses, there was no association between BMI-category and an unfavourable clinical course (respectively with aORs of 0.81 (0.43-1.53) and 0.61 (0.30-1.27) with normal weight as reference). In the reference cohort (n = 249) the opposite was observed with an unfavourable clinical course being most prevalent in patients with overweight (39% vs 28%; aOR 2.17 (0.99-4.76)). In both cohorts, CRP level at admission was higher and lymphocyte count was lower in patients with normal weight compared to patients with obesity., Conclusions: Overweight and obesity are not associated with an unfavourable clinical course in COVID-19 patients admitted to a non-ICU ward and treated with 6 mg dexamethasone once daily., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Chronic kidney disease (CKD) and atrial fibrillation (AF) are both risk factors for bleeding, stroke and mortality. The aim of our study was to investigate the interaction between CKD and atrial fibrillation and outcomes., Methods: We included 12,394 subjects referred to the University Medical Center Utrecht (the Netherlands) from September 1996 to February 2018 for an out-patient visit (Utrecht Cardiovascular Cohort Second Manifestation of Arterial disease cohort). Hazard ratios (HRs) with 95% confidence intervals (CIs) for bleeding, ischemic stroke or mortality were calculated with Cox proportional hazard analyses. Presence of interaction between AF and CKD was examined by calculating the relative excess risk due to interaction (RERI), the attributable proportion (AP) due to interaction and the synergy index (S)., Results: Of the 12,394 patients, 699 patients had AF, 2,752 patients had CKD and 325 patients had both AF and CKD. Patients with both CKD and AF had a 3.0-fold (95% CI 2.0-4.4) increased risk for bleeding, a 4.2-fold (95% CI 3.0-6.0) increased ischemic stroke risk and a 2.2-fold (95% CI 1.9-2.6) increased mortality risk after adjustment as compared with subjects without atrial fibrillation and CKD. We did not find interaction between AF and CKD for bleeding and mortality. However, we found interaction between AF and CKD for ischemic stroke risk (RERI 1.88 (95% CI 0.31-3.46), AP 0.45 (95% CI 0.17-0.72) and S 2.40 (95% CI 1.08-5.32))., Conclusion: AF and CKD are both associated with bleeding, ischemic stroke and mortality. There is a positive interaction between AF and CKD for ischemic stroke risk, but not for bleeding or mortality., Competing Interests: The authors have declared that no competing interests exist.

Importance: During the past decades, improvements in the prevention and management of myocardial infarction, stroke, and pulmonary embolism have led to a decline in cardiovascular mortality in the general population. However, it is unknown whether patients receiving dialysis have also benefited from these improvements., Objective: To assess the mortality rates for myocardial infarction, stroke, and pulmonary embolism in a large cohort of European patients receiving dialysis compared with the general population., Design, Setting, and Participants: In this cohort study, adult patients who started dialysis between 1998 and 2015 from 11 European countries providing data to the European Renal Association Registry were and followed up for 3 years. Data were analyzed from September 2020 to February 2022., Exposures: Start of dialysis., Main Outcomes and Measures: The age- and sex-standardized mortality rate ratios (SMRs) with 95% CIs were calculated by dividing the mortality rates in patients receiving dialysis by the mortality rates in the general population for 3 equal periods (1998-2003, 2004-2009, and 2010-2015)., Results: In total, 220 467 patients receiving dialysis were included in the study. Their median (IQR) age was 68.2 (56.5-76.4) years, and 82 068 patients (37.2%) were female. During follow-up, 83 912 patients died, of whom 7662 (9.1%) died because of myocardial infarction, 5030 (6.0%) died because of stroke, and 435 (0.5%) died because of pulmonary embolism. Between the periods 1998 to 2003 and 2010 to 2015, the SMR of myocardial infarction decreased from 8.1 (95% CI, 7.8-8.3) to 6.8 (95% CI, 6.5-7.1), the SMR of stroke decreased from 7.3 (95% CI, 7.0-7.6) to 5.8 (95% CI, 5.5-6.2), and the SMR of pulmonary embolism decreased from 8.7 (95% CI, 7.6-10.1) to 5.5 (95% CI, 4.5-6.6)., Conclusions and Relevance: In this cohort study of patients receiving dialysis, mortality rates for myocardial infarction, stroke, and pulmonary embolism decreased more over time than in the general population.

The early recognition of acute kidney injury (AKI) is essential to improve outcomes and prevent complications such as chronic kidney disease, the need for renal-replacement therapy, and an increased length of hospital stay. Increasing evidence shows that inflammation plays an important role in the pathophysiology of AKI and mortality. Several inflammatory hematological ratios can be used to measure systemic inflammation. Therefore, the association between these ratios and outcomes (AKI and mortality) in patients suspected of having an infection at the emergency department was investigated. Data from the SPACE cohort were used. Cox regression was performed to investigate the association between seven hematological ratios and outcomes. A total of 1889 patients were included, of which 160 (8.5%) patients developed AKI and 102 (5.4%) died in <30 days. The Cox proportional-hazards model revealed that the neutrophil-to-lymphocyte ratio (NLR), segmented-neutrophil-to-monocyte ratio (SMR), and neutrophil-lymphocyte-platelet ratio (NLPR) are independently associated with AKI <30 days after emergency-department presentation. Additionally, the NLR, SMR and NLPR were associated with 30-day all-cause mortality. These findings are an important step forward for the early recognition of AKI. The use of these markers might enable emergency-department physicians to recognize and treat AKI in an early phase to potentially prevent complications.

Background: Acute kidney injury (AKI) is a major health problem associated with considerable mortality and morbidity. Studies on clinical outcomes and mortality of AKI in the emergency department are scarce. The aim of this study is to assess incidence, mortality and renal outcomes after AKI in patients with suspected infection at the emergency department., Methods: We used data from the SPACE-cohort (SePsis in the ACutely ill patients in the Emergency department), which included consecutive patients that presented to the emergency department of the internal medicine with suspected infection. Hazard ratios (HR) were assessed using Cox regression to investigate the association between AKI, 30-days mortality and renal function decline up to 1 year after AKI. Survival in patients with and without AKI was assessed using Kaplan-Meier analyses., Results: Of the 3105 patients in the SPACE-cohort, we included 1716 patients who fulfilled the inclusion criteria. Of these patients, 10.8% had an AKI episode. Mortality was 12.4% for the AKI group and 4.2% for the non-AKI patients. The adjusted HR for all-cause mortality at 30-days in AKI patients was 2.8 (95% CI 1.7-4.8). Moreover, the cumulative incidence of renal function decline was 69.8% for AKI patients and 39.3% for non-AKI patients. Patients with an episode of AKI had higher risk of developing renal function decline (adjusted HR 3.3, 95% CI 2.4-4.5) at one year after initial AKI-episode at the emergency department., Conclusion: Acute kidney injury is common in patients with suspected infection in the emergency department and is significantly associated with 30-days mortality and renal function decline one year after AKI., Competing Interests: The authors have declared that no competing interests exist.

Background: Non-dialytic conservative care (CC) has been proposed as a viable alternative to maintenance dialysis for selected older patients to treat end-stage kidney disease (ESKD). This systematic review compares both treatment pathways on health-related quality of life (HRQoL) and symptoms, which are major outcomes for patients and clinicians when deciding on preferred treatment., Methods: We searched PubMed, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL) Plus and PsycINFO from inception to 1 October 2019 for studies comparing patient-reported HRQoL outcomes or symptoms between patients who chose either CC or dialysis for ESKD., Results: Eleven observational cohort studies were identified comprising 1718 patients overall. There were no randomized controlled trials. Studies were susceptible to selection bias and confounding. In most studies, patients who chose CC were older and had more comorbidities and worse functional status than patients who chose dialysis. Results were broadly consistent across studies, despite considerable clinical and methodological heterogeneity. Patient-reported physical health outcomes and symptoms appeared to be worse in patients who chose CC compared with patients who chose dialysis but had not yet started, but similar compared with patients on dialysis. Mental health outcomes were similar between patients who chose CC or dialysis, including before and after dialysis start. In patients who chose dialysis, the burden of kidney disease and impact on daily life increased after dialysis start., Conclusions: The available data, while heterogeneous, suggest that in selected older patients, CC has the potential to achieve similar HRQoL and symptoms compared with a dialysis pathway. High-quality prospective studies are needed to confirm these provisional findings., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Von Willebrand Factor (VWF) multimers are cleaved into smaller and less coagulant forms by the metalloprotease ADAMTS13. The aim of this study was to investigate the association between VWF and ADAMTS13 and mortality in dialysis patients., Methods: We prospectively followed 956 dialysis patients. VWF levels and ADAMTS13 activity were measured. Cox proportional hazard analyses were used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) to investigate the association between quartiles of VWF levels and ADAMTS13 activity and all-cause mortality. HRs were adjusted for age, sex, body mass index, cardiovascular disease, dialysis modality, primary kidney disease, use of antithrombotic medication, systolic blood pressure, albumin, C-reactive protein and residual GFR., Results: Of the 956 dialysis patients, 288 dialysis patients died within three years (mortality rate 151 per 1000 person-years). The highest quartile of VWF as compared with lower levels of VWF was associated with a 1.4-fold (95 %CI 1.1-1.8) increased mortality risk after adjustment. The lowest quartile of ADAMTS13 activity as compared with other quartiles was associated with a 1.3-fold (95 %CI 1.0-1.7) increased mortality risk after adjustment. The combination of the highest VWF quartile and lowest ADAMTS13 quartile was associated with a 2.0-fold (95 %CI 1.3-3.0) increased mortality risk as compared with the combination of the lowest VWF quartile and highest ADAMTS13 quartile., Conclusions: High VWF levels and low ADAMTS13 activity were associated with increased mortality risks in dialysis patients.

Background: Immune checkpoint inhibitors, approved for the treatment of various types of cancer, are known to cause a unique spectrum of side effects, including acute kidney injury (AKI). The aim of this study was to describe the incidence, risk factors, renal outcomes, and mortality of AKI in patients receiving checkpoint inhibitors., Methods: Patients receiving checkpoint inhibitors between January 2013 and May 2020 at the University Medical Center Utrecht, the Netherlands, were identified using the Utrecht Patient Oriented Database. AKI was defined as an increase in serum creatinine of ≥1.5 times the baseline value, based on the Kidney Disease: Improving Global Outcomes criteria. Cox proportional hazard regression analysis was used to assess risk factors for AKI and to evaluate the relationship between AKI and mortality. Persistent renal dysfunction was diagnosed in AKI patients with a final serum creatinine measurement of >1.3 times the baseline value., Results: Among 676 patients receiving checkpoint inhibitors, the overall incidence of AKI was 14.2%. Baseline variables independently associated with AKI were a gynecologic malignancy, monotherapy with ipilimumab, and the use of a diuretic, angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker, or proton pump inhibitor at baseline. AKI was checkpoint inhibitor-associated in one third of all patients with AKI. Checkpoint inhibitor-associated AKI was mostly low-grade, occurred a median of 15 weeks after checkpoint inhibitor initiation, and resulted in persistent renal dysfunction in approximately 40% of the patients. Patients with all-cause AKI had a twofold increased mortality risk, but checkpoint inhibitor-associated AKI was not associated with increased mortality., Conclusions: In this study, patients receiving checkpoint inhibitors frequently developed AKI due to various etiologies. AKI directly related to the effect of checkpoint inhibitor toxicity did not increase mortality. However, AKI not related to the effect of checkpoint inhibitor toxicity was associated with increased mortality., Competing Interests: The authors have declared that no competing interests exist.

Aims: The increasing prevalence of ischaemic stroke (IS) can partly be explained by the likewise growing number of patients with chronic kidney disease (CKD). Risk scores have been developed to identify high-risk patients, allowing for personalized anticoagulation therapy. However, predictive performance in CKD is unclear. The aim of this study is to validate six commonly used risk scores for IS in atrial fibrillation (AF) patients across the spectrum of kidney function., Methods and Results: Overall, 36 004 subjects with newly diagnosed AF from SCREAM (Stockholm CREAtinine Measurements), a healthcare utilization cohort of Stockholm residents, were included. Predictive performance of the AFI, CHADS2, Modified CHADS2, CHA2DS2-VASc, ATRIA, and GARFIELD-AF risk scores was evaluated across three strata of kidney function: normal kidney function [estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2], mild CKD (eGFR 30-60 mL/min/1.73 m2), and advanced CKD (eGFR <30 mL/min/1.73 m2). Predictive performance was assessed by discrimination and calibration. During 1.9 years, 3069 (8.5%) patients suffered an IS. Discrimination was dependent on eGFR: the median c-statistic in normal eGFR was 0.75 (range 0.68-0.78), but decreased to 0.68 (0.58-0.73) and 0.68 (0.55-0.74) for mild and advanced CKD, respectively. Calibration was reasonable and largely independent of eGFR. The Modified CHADS2 score showed good performance across kidney function strata, both for discrimination [c-statistic: 0.78 (95% confidence interval 0.77-0.79), 0.73 (0.71-0.74) and 0.74 (0.69-0.79), respectively] and calibration., Conclusion: In the most clinically relevant stages of CKD, predictive performance of the majority of risk scores was poor, increasing the risk of misclassification and thus of over- or undertreatment. The Modified CHADS2 score performed good and consistently across all kidney function strata, and should therefore be preferred for risk estimation in AF patients., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Dialysis patients have an increased bleeding risk as compared with the general population. However, there is limited information whether bleeding risks are different for patients treated with haemodialysis (HD) or peritoneal dialysis (PD). From a clinical point of view, this information could influence therapy choice. Therefore the aim of this study was to investigate the association between dialysis modality and bleeding risk., Methods: Incident dialysis patients from the Netherlands Cooperative Study on the Adequacy of Dialysis were prospectively followed for major bleeding events over 3 years. Hazard ratios with 95% confidence intervals (CIs) were calculated for HD compared with PD using a time-dependent Cox regression analysis, with updates on dialysis modality., Results: In total, 1745 patients started dialysis, of whom 1211 (69.4%) received HD and 534 (30.6%) PD. The bleeding rate was 60.8/1000 person-years for HD patients and 34.6/1000 person-years for PD patients. The time-dependent Cox regression analysis showed that after adjustment for age, sex, primary kidney disease, prior bleeding, cardiovascular disease, antiplatelet drug use, vitamin K antagonist use, erythropoietin use, arterial hypertension, residual glomerular filtratin rate, haemoglobin and albumin levels, bleeding risk for HD patients compared with PD increased 1.5-fold (95% CI 1.0-2.2)., Conclusions: In this large prospective cohort of incident dialysis patients, HD patients had an increased bleeding risk compared with PD patients. In particular, HD patients with a history of prior bleeding had an increased bleeding risk., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: To prevent bio-accumulation of low molecular weight heparins (LMWHs) in patients with decreased kidney function, dosage reduction and anti-Xa monitoring has been suggested. The aim of this study was to investigate the effect of pre-emptive dosage reduction of LMWH on anti-Xa levels. Furthermore, we investigated the association between anti-Xa levels and bleeding, thrombotic events and mortality., Methods: In this single center study, we followed 499 patients with decreased renal function in whom anti-Xa levels were measured. We observed how many patients had anti-Xa levels that fell within the reference range, with a standard protocol of a pre-emptive dosage reduction of LMWH (25% reduction in patients with an estimated glomerular filtration rate (eGFR) between 30 and 60 ml/min/1.73m2 and a reduction of 50% in patients with an eGFR below the 30 ml/min/1.73m2). Furthermore, Cox proportional hazard analyses were used to estimate hazard ratios to investigate the association between anti-Xa levels and major bleeding, thrombotic events and mortality within three months of follow-up., Results: In a cohort of 499 patients (445 dalteparin and 54 nadroparin users), a pre-emptive dosage reduction of LMWH led to adequate levels of anti-Xa in only 19% of the patients (12% for the dalteparin users and 50% for nadroparin users). We did not find an association between anti-Xa levels and bleeding, thrombosis or mortality., Conclusion: Pre-emptive dosage reduction of LMWH leads to low anti-Xa levels in a large proportion, but this was not associated with bleeding, thrombosis or mortality., Competing Interests: The authors have declared that no competing interests exist.

Objectives: The objective of this study was to systematically review and externally assess the predictive performance of models for ischemic stroke in incident dialysis patients., Study Design and Setting: Two reviewers systematically searched and selected ischemic stroke models. Risk of bias was assessed with the PROBAST. Predictive performance was evaluated within The Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), a large prospective multicenter cohort of incident dialysis patients. For discrimination, c-statistics were calculated; calibration was assessed by plotting predicted and observed probabilities for stroke, and calibration-in-the-large., Results: Seventy-seven prediction models for stroke were identified, of which 15 were validated. Risk of bias was high, with all of these models scoring high risk in one or more domains. In NECOSAD, of the 1,955 patients, 127 (6.5%) suffered an ischemic stroke during the follow-up of 2.5 years. Compared with the original studies, most models performed worse with all models showing poor calibration and discriminative abilities (c-statistics ranging from 0.49 to 0.66). The Framingham showed reasonable calibration; however, with a c-statistic of 0.57 (95% CI 0.50-0.63), the discrimination was poor., Conclusion: This external validation demonstrates the weak predictive performance of ischemic stroke models in incident dialysis patients. Instead of using these models in this fragile population, either existing models should be updated, or novel models should be developed and validated., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Nondialytic conservative care has been recognized as a viable alternative to chronic dialysis in older patients with end-stage kidney disease, but little is known about its consequences on hospital utilization and costs., Methods: We performed a retrospective cohort study to compare outpatient and inpatient hospital utilization, place of death, and hospital costs in patients aged ≥70 years old who chose conservative care (n = 100) or dialysis (n = 162) after shared decision making in a nonacademic teaching hospital between 2008 and 2016., Results: Patients who chose conservative care were older than patients who chose dialysis (82.5 vs. 76.3 years). Comorbidity did not differ between the 2 patient groups. The incidence rates of outpatient visits per year were 7.1 in patients who chose conservative care and 10.7 in patients who chose dialysis (incidence rate ratio 0.67, 95% CI 0.55-0.81). The incidence rates of in-hospital days per year were, respectively, 6.0 and 9.8 (incidence rate ratio 0.50, 95% CI 0.29-0.88). Also in the final month of life, patients on conservative care had less outpatient visits, were less frequently hospitalized, and died less frequently in hospital than the dialysis patient group. The cost rates per year, measured from original treatment decision, were EUR 5,859 in conservative care patients and EUR 28,354 in patients who chose dialysis comprising both the predialysis and dialysis period (cost rate ratio 0.42, 95% CI 0.27-0.65). Patients who chose dialysis had higher costs on dialysis sessions, outpatient care, inpatient care, laboratory tests, and medical imaging., Conclusions: Patients who decided to forego dialysis and chose conservative care had less outpatient and inpatient hospital utilization than patients who chose dialysis, including less intensive hospital utilization near the end of life. Both overall and nondialysis-related costs were lower in patients on a conservative care pathway., (© 2020 S. Karger AG, Basel.)

Background: Bleeding risk scores have been created to identify patients with an increased bleeding risk, which could also be useful in dialysis patients. However, the predictive performances of these bleeding risk scores in dialysis patients are unknown. Therefore, the aim of this study was to validate existing bleeding risk scores in dialysis patients., Methods: A cohort of 1745 incident dialysis patients was prospectively followed for 3 years during which bleeding events were registered. We evaluated the discriminative performance of the Hypertension, Abnormal kidney and liver function, Stroke, Bleeding, Labile INR, Elderly and Drugs or alcohol (HASBLED), the AnTicoagulation and Risk factors In Atrial fibrillation (ATRIA), the Hepatic or kidney disease, Ethanol abuse, Malignancy, Older age, Reduced platelet count or Reduced platelet function, Hypertension, Anaemia, Genetic factors, Excessive fall risk and Stroke (HEMORR2HAGES) and the Outcomes Registry for Better Informed Treatment (ORBIT) bleeding risk scores by calculating C-statistics with 95% confidence intervals (CI). In addition, calibration was evaluated by comparing predicted and observed risks., Results: Of the 1745 dialysis patients, 183 patients had a bleeding event, corresponding to an incidence rate of 5.23/100 person-years. The HASBLED [C-statistic of 0.58 (95% CI 0.54-0.62)], ATRIA [C-statistic of 0.55 (95% CI 0.51-0.60)], HEMORR2HAGES [C-statistic of 0.56 (95% CI 0.52-0.61)] and ORBIT [C-statistic of 0.56 (95% CI 0.52-0.61)] risk scores had poor discriminative performances in dialysis patients. Furthermore, the calibration analyses showed that patients with a low risk of bleeding according to the HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had higher incidence rates for bleeding in our cohort than predicted., Conclusions: The HASBLED, ATRIA, HEMORR2HAGES and ORBIT bleeding risk scores had poor predictive abilities in dialysis patients. Therefore, these bleeding risk scores may not be useful in this population., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: The risk-benefit ratio of vitamin K antagonists for different CHA2DS2-VASc scores in patients with end-stage renal disease treated with dialysis is unknown. The aim of this study was to investigate the association between vitamin K antagonist use and mortality for different CHA2DS2-VASc scores in a cohort of end-stage renal disease patients receiving dialysis treatment., Methods: We prospectively followed 1718 incident dialysis patients. Hazard ratios were calculated for all-cause and cause-specific (stroke, bleeding, cardiovascular and other) mortality associated with vitamin K antagonist use., Results: Vitamin K antagonist use as compared with no vitamin K antagonist use was associated with a 1.2-fold [95% confidence interval (95% CI) 1.0-1.5] increased all-cause mortality risk, a 1.5-fold (95% CI 0.6-4.0) increased stroke mortality risk, a 1.3-fold (95% CI 0.4-4.2) increased bleeding mortality risk, a 1.2-fold (95% CI 0.9-1.8) increased cardiovascular mortality risk and a 1.2-fold (95% CI 0.8-1.6) increased other mortality risk after adjustment. Within patients with a CHA2DS2-VASc score ≤1, vitamin K antagonist use was associated with a 2.8-fold (95% CI 1.0-7.8) increased all-cause mortality risk as compared with no vitamin K antagonist use, while vitamin K antagonist use within patients with a CHA2DS2-VASc score ≥2 was not associated with an increased mortality risk after adjustment., Conclusion: Vitamin K antagonist use was not associated with a protective effect on mortality in the different CHA2DS2-VASc scores in dialysis patients. The lack of knowledge on the indication for vitamin K antagonist use could lead to confounding by indication., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Acute rejection (AR) of kidney transplants is associated with the loss of endothelial integrity, microvascular rarefaction and, ultimately, graft dysfunction. Circulating angiogenic microRNAs (miRNAs) may serve as markers for microvascular injury. Here, we investigated the short- and long-term effects of AR after kidney transplantation on systemic vascular injury and the associated circulating miRNA profile., Methods: Systemic vascular injury was determined by measuring capillary tortuosity and density within the oral mucosa as well as by assessing circulating levels of angiopoietin-2/angiopoietin-1 ratio, vascular endothelial growth factor and soluble thrombomodulin. After a pilot study, we selected 48 miRNAs to assess the AR- and microvascular injury associated circulating miRNAs., Results: In stable transplant recipients (n = 25) and patients with AR (n = 13), which were also studied longitudinally (1, 6, and 12 months post-AR), we found an AR-associated increase in markers of systemic vascular injury, of which vascular endothelial growth factor and soluble thrombomodulin normalized within 1 year after AR. Of the 48 selected miRNAs, 8 were either decreased (miR-135a, miR-199a-3p, and miR-15a) or increased (miR-17, miR-140-3p, miR-130b, miR-122 and miR-192) in AR. Of these, miR-130b, miR-199a, and miR-192 associated with markers of vascular injury, whereas miR-140-3p, miR-130b, miR-122, and miR-192 normalized within 1 year after AR., Conclusions: AR after kidney transplantation is characterized by systemic microvascular injury and associates with specific circulating miRNA levels., Competing Interests: The authors declare no conflicts of interest.

Objective: Frequency of thyroid cancer in incidental thyroid nodules identified by imaging techniques in cancer patients is higher than that in the normal population. In the retrospective study, we have both investigated the incidence of thyroid cancer in incidentally identified nodules and compared the imaging techniques to determine whether there is any difference between them in detection of malign nodules., Methods: A total of 7319 patients who underwent thyroid fine-needle aspiration biopsy (FNAB) were included in the study. The data of 174 patients who had previously been diagnosed with a hematologic or solid malignancy prior to the FNAB procedure and had incidentally identified thyroid nodules were evaluated retrospectively., Results: Eighty-six (49.5%) of the incidental nodules were identified with ultrasonography (USG), 62 (35.6%) with positron emission tomography (PET) or PET/computed tomography (PET/CT), and 26 (14.9%) with CT. As a result of thyroidectomy, papillary carcinoma was identified in 8 (4.6%) patients, and metastasis to the thyroid of a primary cancer was found in 3 (1.7%) patients. While the papillary carcinoma proportion in the nodules identified by USG was 3.4%, PET/CT was 8.9%. A cut-off maximal standardized uptake value of 11.6 in PET/CT indicated malignancy achieving a sensitivity of 83.3% and a specificity of 91.1%., Conclusion: Whether the nodule in the incidental thyroid nodules of cancer patients is identified using USG or PET/CT, the risk of thyroid cancer is similar. However, cancer risk is higher in the event of a higher focal uptake in the nodules identified by PET/CT., (Copyright © 2017 National Medical Association. Published by Elsevier Inc. All rights reserved.)

Background: Dialysis patients have high cardiovascular mortality risk. This study aimed to investigate the association between SNPs of genes involved in vascular processes and mortality in dialysis patients., Methods: Forty two SNPs in 25 genes involved in endothelial function, vascular remodeling, cell proliferation, inflammation, coagulation and calcium/phosphate metabolism were genotyped in 1330 incident dialysis patients. The effect of SNPs on 5-years cardiovascular and non-cardiovascular mortality was investigated., Results: The mortality rate was 114/1000 person-years and 49.4% of total mortality was cardiovascular. After correction for multiple testing, VEGF rs699947 was associated with all-cause mortality (HR1.48, 95% CI 1.14-1.92). The other SNPs were not associated with mortality., Conclusions: This study provides further evidence that a SNP in the VEGF gene may contribute to the comorbid conditions of dialysis patients. Future studies should unravel the underlying mechanisms responsible for the increase in mortality in these patients.