Far infrared treatment on the arteriovenous fistula induces changes in sVCAM and sICAM in patients on hemodialysis.

INTRODUCTION: There is a substantial risk of developing stenosis and dysfunction in the arteriovenous fistula (AVF) in patients on hemodialysis (HD). Far infrared radiation (FIR) is a non-invasive local intervention with a potentially beneficial effect on AVF patency. The underlying mechanism is not clear. It was hypothesized that a single FIR treatment reduces factors of inflammation and promotes endothelial vasodilators in the AVF. METHODS: Forty HD patients with an AVF were included in an open-label intervention study. Patients were randomized to receive either FIR (FIR group) or no FIR (control group). Blood samples were drawn directly from the AVF and from a peripheral vein in the non-AVF arm before (T0) and 40 min after (T40) treatment during a HD session. The changes [median (interquartile range)] in circulating factors of inflammation, endothelial function and vasoreactivity during FIR were measured. RESULTS: In the AVF a single FIR treatment during dialysis resulted in a significantly diminished decrease in soluble vascular cell adhesion molecule, sVCAM [-31.6 (-54.3; 22.1) vs -89.9 (-121.6; -29.3), P = .005] and soluble intercellular adhesion molecule, sICAM [-24.2 (-43.5; 25.3) vs -49 (-79.9; -11.6), P = .02] compared with the control group. Other factors, such as interleukins, nitrite, nitrate and tumor necrosis factor 1, also declined during dialysis, but with no significant differences related to FIR in either the AVF or the non-AVF arm. CONCLUSION: A single FIR treatment attenuated the decrease in sVCAM and sICAM in the AVF compared with a control group during HD. Findings do not support the hypothesis of a vaso-protective effect of FIR. The long-term effects of FIR on the AVF are unknown.

Prevalence and incidence of chronic kidney disease stage 3-5 - results from KidDiCo.

BACKGROUND: Chronic kidney disease (CKD) is a global challenge. CKD prevalence estimation is central to management strategies and prevention. It is necessary to predict end stage kidney disease (ESKD) and, subsequently, the burden for healthcare systems. In this study we characterize CKD stage 3-5 prevalence and incidence in a cohort covering the majority of the Region of Southern Denmark and investigate individuals' demographic, socioeconomic, and comorbidity status. METHODS: We used data from the Kidney Disease Cohort (KidDiCo) combining laboratory data from Southern Denmark with Danish national databases. Chronic kidney disease was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. RESULTS: The prevalence varied between 4.83 and 4.98% and incidence rate of CKD was 0.49%/year. The median age was 76.4 years. The proportion of individuals with CKD stage 3-5 in the entire population increased consistently with age. The percentage of women in the CKD 3-5 group was higher than in the background population. Diabetes mellitus, hypertension and cardiovascular disease were more prominent in patients with CKD. CKD stage 5 and ESKD were more frequent as incident CKD stages in the 18-49 year olds when compared to older individuals. CKD patients tended to have a lower socioeconomic status. CONCLUSION: Chronic kidney disease stage 3-5 is common, especially in the elderly. Patients with CKD stage 3-5 are predominantly female. The KidDiCo data suggests an association between lower socioeconomic status and prevalence of CKD.

First-year mortality in incident dialysis patients: results of the Peridialysis study.

BACKGROUND: Controversy surrounds which factors are important for predicting early mortality after dialysis initiation (DI). We investigated associations of predialysis course and circumstances affecting planning and execution of DI with mortality following DI. METHODS: Among 1580 patients participating in the Peridialysis study, a study of causes and timing of DI, we registered features of predialysis course, clinical and biochemical data at DI, incidence of unplanned suboptimal DI, contraindications to peritoneal dialysis (PD) or hemodialysis (HD), and modality preference, actual choice, and cause of modality choice. Patients were followed for 12 months or until transplantation. A flexible parametric model was used to identify independent factors associated with all-cause mortality. RESULTS: First-year mortality was 19.33%. Independent factors predicting death were high age, comorbidity, clinical contraindications to PD or HD, suboptimal DI, high eGFR, low serum albumin, hyperphosphatemia, high C-reactive protein, signs of overhydration and cerebral symptoms at DI. Among 1061 (67.2%) patients who could select dialysis modality based on personal choice, 654 (61.6%) chose PD, 368 (34.7%) center HD and 39 (3.7%) home HD. The 12-months survival did not differ significantly between patients receiving PD and in-center HD. CONCLUSIONS: First-year mortality in incident dialysis patients was in addition to high age and comorbidity, associated with clinical contraindications to PD or HD, clinical symptoms, hyperphosphatemia, inflammation, and suboptimal DI. In patients with a "free" choice of dialysis modality based on their personal preferences, PD and in-center HD led to broadly similar short-term outcomes.

Non-medical barriers reported by nephrologists when providing renal replacement therapy or comprehensive conservative management to end-stage kidney disease patients: a systematic review.

BACKGROUND: Large international differences exist in access to renal replacement therapy (RRT) modalities and comprehensive conservative management (CCM) for patients with end-stage kidney disease (ESKD), suggesting that some patients are not receiving the most appropriate treatment. Previous studies mainly focused on barriers reported by patients or medical barriers (e.g. comorbidities) reported by nephrologists. An overview of the non-medical barriers reported by nephrologists when providing the most appropriate form of RRT (other than conventional in-centre haemodialysis) or CCM is lacking. METHODS: We searched in EMBASE and PubMed for original articles with a cross-sectional design (surveys, interviews or focus groups) published between January 2010 and September 2018. We included studies in which nephrologists reported barriers when providing RRT or CCM to adult patients with ESKD. We used the barriers and facilitators survey by Peters et al. [Ruimte Voor Verandering? Knelpunten en Mogelijkheden Voor Verbeteringen in de Patiëntenzorg. Nijmegen: Afdeling Kwaliteit van zorg (WOK), 2003] as preliminary framework to create our own model and performed meta-ethnographic analysis of non-medical barriers in text, tables and figures. RESULTS: Of the 5973 articles screened, 16 articles were included using surveys (n = 10), interviews (n = 5) and focus groups (n = 1). We categorized the barriers into three levels: patient level (e.g. attitude, role perception, motivation, knowledge and socio-cultural background), level of the healthcare professional (e.g. fears and concerns, working style, communication skills) and level of the healthcare system (e.g. financial barriers, supportive staff and practice organization). CONCLUSIONS: Our systematic review has identified a number of modifiable, non-medical barriers that could be targeted by, for example, education and optimizing financing structure to improve access to RRT modalities and CCM.

Effect of comorbidities on survival in patients >80 years of age at onset of renal replacement therapy: data from the ERA-EDTA Registry.

BACKGROUND: The number of elderly patients on renal replacement therapy (RRT) is increasing. The survival and quality of life of these patients may be lower if they have multiple comorbidities at the onset of RRT. The aim of this study was to explore whether the effect of comorbidities on survival is similar in elderly RRT patients compared with younger ones. METHODS: Included were 9333 patients ≥80 years of age and 48 352 patients 20-79 years of age starting RRT between 2010 and 2015 from 15 national or regional registries submitting data to the European Renal Association-European Dialysis and Transplantation Association Registry. Patients were followed until death or the end of 2016. Survival was assessed by Kaplan-Meier curves and the relative risk of death associated with comorbidities was assessed by Cox regression analysis. RESULTS: Patients ≥80 years of age had a greater comorbidity burden than younger patients. However, relative risks of death associated with all studied comorbidities (diabetes, ischaemic heart disease, chronic heart failure, cerebrovascular disease, peripheral vascular disease and malignancy) were significantly lower in elderly patients compared with younger patients. Also, the increase in absolute mortality rates associated with an increasing number of comorbidities was smaller in elderly patients. CONCLUSIONS: Comorbidities are common in elderly patients who enter RRT, but the risk of death associated with comorbidities is less than in younger patients. This should be taken into account when assessing the prognosis of elderly RRT patients.

The association of living donor source with patient and graft survival among kidney transplant recipients in the ERA-EDTA Registry - a retrospective study.

In this study we aimed to compare patient and graft survival of kidney transplant recipients who received a kidney from a living-related donor (LRD) or living-unrelated donor (LUD). Adult patients in the ERA-EDTA Registry who received their first kidney transplant in 1998-2017 were included. Ten-year patient and graft survival were compared between LRD and LUD transplants using Cox regression analysis. In total, 14 370 patients received a kidney from a living donor. Of those, 9212 (64.1%) grafts were from a LRD, 5063 (35.2%) from a LUD and for 95 (0.7%), the donor type was unknown. Unadjusted five-year risks of death and graft failure (including death as event) were lower for LRD transplants than for LUD grafts: 4.2% (95% confidence interval [CI]: 3.7-4.6) and 10.8% (95% CI: 10.1-11.5) versus 6.5% (95% CI: 5.7-7.4) and 12.2% (95% CI: 11.2-13.3), respectively. However, after adjusting for potential confounders, associations disappeared with hazard ratios of 0.99 (95% CI: 0.87-1.13) for patient survival and 1.03 (95% CI: 0.94-1.14) for graft survival. Unadjusted risk of death-censored graft failure was similar, but after adjustment, it was higher for LUD transplants (1.19; 95% CI: 1.04-1.35). In conclusion, patient and graft survival of LRD and LUD kidney transplant recipients was similar, whereas death-censored graft failure was higher in LUD. These findings confirm the importance of both living kidney donor types.

Ten-year trends in epidemiology and outcomes of pediatric kidney replacement therapy in Europe: data from the ESPN/ERA-EDTA Registry.

BACKGROUND: For 10 consecutive years, the ESPN/ERA-EDTA Registry has included data on children with stage 5 chronic kidney disease (CKD 5) receiving kidney replacement therapy (KRT) in Europe. We examined trends in incidence and prevalence of KRT and patient survival. METHODS: We included all children aged <15 years starting KRT 2007-2016 in 22 European countries participating in the ESPN/ERA-EDTA Registry since 2007. General population statistics were derived from Eurostat. Incidence and prevalence were expressed per million age-related population (pmarp) and time trends studied with JoinPoint regression. We analyzed survival trends using Cox regression. RESULTS: Incidence of children commencing KRT <15 years remained stable over the study period, varying between 5.5 and 6.6 pmarp. Incidence by treatment modality was unchanged over time: 2.0 for hemodialysis (HD) and peritoneal dialysis (PD) and 1.0 for transplantation. Prevalence increased in all age categories and overall rose 2% annually from 26.4 pmarp in 2007 to 32.1 pmarp in 2016. Kidney transplantation prevalence increased 5.1% annually 2007-2009, followed by 1.5% increase/year until 2016. Prevalence of PD steadily increased 1.4% per year over the entire period, and HD prevalence started increasing 6.1% per year from 2011 onwards. Five-year unadjusted patient survival on KRT was around 94% and similar for those initiating KRT 2007-2009 or 2010-2012 (adjusted HR: 0.98, 95% CI:0.71-1.35). CONCLUSIONS: We found a stable incidence and increasing prevalence of European children on KRT 2007-2016. Five-year patient survival was good and was unchanged over time. These data can inform patients and healthcare providers and aid health policy makers on future resource planning of pediatric KRT in Europe.

The ratio of measured to estimated glomerular filtration rate may be a marker of early mortality and dialysis requirement.

BACKGROUND: It has been suggested that, in patients with CKD stage 5, measured GFR (mGFR), defined as the mean of urea and creatinine clearance, as measured by a 24-h urine collection, is a better measure of renal function than estimated GFR (eGFR), based on the CKD-EPI formula. This could be due to reduced muscle mass in this group. Its use is recommended in the ERBP guidelines. Unplanned dialysis initiation (DI) is associated with increased morbidity, mortality, and reduced modality choice and is generally considered undesirable. We hypothesized that the ratio mGFR/eGFR (M/E) aids prediction of death and DI. METHODS: All 24-h measurements of urea and creatinine excretion were extracted from the clinical biochemistry databases in Zealand. Data concerning renal diagnosis, comorbidity, biochemistry, medical treatment, mortality and date of DI, were extracted from patient notes, the National Patient Registry and the Danish Nephrology Registry. Patients were included if their eGFR was < 30 ml/min/1.73m2. The last available value for each patient was included. Follow-up was 12 months. RESULTS: One thousand two hundred sixty-five patients were included. M/E was median 0.91 ± 0.43. It was highly correlated to previous determinations. It was negatively correlated to eGFR, comorbidity, high age and female sex. It was positively related to albumin and negatively to C-reactive protein. M/E was higher in patients treated with ACE inhibitors and diuretics but no other treatment groups. On a multivariate analysis, M/E was negatively correlated with mortality and combined mortality/DI, but not DI. A post hoc analysis showed a negative correlation to DI at 3 months. For patients with an eGFR 10-15 ml/min/1.73m2, combined mortality and DI at 3 months was for low M/E (< 0.75) 36%, medium (0.75-1.25) 20%, high (> 1.25) 8%. A low M/E predicted increased need for unplanned DI. A supplementary analysis in 519 patients where body surface area values were available, allowing BSA-corrected M/E to be analyzed, revealed similar results. CONCLUSION: A low mGFR/eGFR ratio is associated with comorbidity, malnutrition, and inflammation. It is a marker of early DI, mortality, and unplanned dialysis initiation, independently of eGFR, age and comorbidity. Particular attention paid to patients with a low M/E may lower the incidence of unplanned dialysis requirement.

Data from the ERA-EDTA Registry were examined for trends in excess mortality in European adults on kidney replacement therapy.

The objective of this study was to investigate whether the improvement in survival seen in patients on kidney replacement therapy reflects the enhanced survival of the general population. Patient and general population statistics were obtained from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and the World Health Organization databases, respectively. Relative survival models were composed to examine trends over time in all-cause and cause-specific excess mortality, stratified by age and modality of kidney replacement therapy, and adjusted for sex, primary kidney disease and country. In total, 280,075 adult patients started kidney replacement therapy between 2002 and 2015. The excess mortality risk in these patients decreased by 16% per five years (relative excess mortality risk (RER) 0.84; 95% confidence interval 0.83-0.84). This reflected a 14% risk reduction in dialysis patients (RER 0.86; 0.85-0.86), and a 16% increase in kidney transplant recipients (RER 1.16; 1.07-1.26). Patients on dialysis showed a decrease in excess mortality risk of 28% per five years for atheromatous cardiovascular disease as the cause of death (RER 0.72; 0.70-0.74), 10% for non-atheromatous cardiovascular disease (RER 0.90; 0.88-0.92) and 10% for infections (RER 0.90; 0.87-0.92). Kidney transplant recipients showed stable excess mortality risks for most causes of death, although it did worsen in some subgroups. Thus, the increase in survival in patients on kidney replacement therapy is not only due to enhanced survival in the general population, but also due to improved survival in the patient population, primarily in dialysis patients.

Results in the ESPN/ERA-EDTA Registry suggest disparities in access to kidney transplantation but little variation in graft survival of children across Europe.

One of the main objectives of the European health policy framework is to ensure equitable access to high-quality health services across Europe. Here we examined country-specific kidney transplantation and graft failure rates in children and explore their country- and patient-level determinants. Patients under 20 years of age initiating kidney replacement therapy from January 2007 through December 2015 in 37 European countries participating in the ESPN/ERA-EDTA Registry were included in the analyses. Countries were categorized as low-, middle-, and high-income based on gross domestic product. At five years of follow-up, 4326 of 6909 children on kidney replacement therapy received their first kidney transplant. Overall median time from kidney replacement therapy start to first kidney transplantation was 1.4 (inter quartile range 0.3-4.3) years. The five-year kidney transplantation probability was 48.8% (95% confidence interval: 45.9-51.7%) in low-income, 76.3% (72.8-79.5%) in middle-income and 92.3% (91.0-93.4%) in high-income countries and was strongly associated with macro-economic factors. Gross domestic product alone explained 67% of the international variation in transplantation rates. Compared with high-income countries, kidney transplantation was 76% less likely to be performed in low-income and 58% less likely in middle-income countries. Overall five-year graft survival in Europe was 88% and showed little variation across countries. Thus, despite large disparities transplantation access across Europe, graft failure rates were relatively similar. Hence, graft survival in low-risk transplant recipients from lower-income countries seems as good as graft survival among all (low-, medium-, and high-risk) graft recipients from high-income countries.

Young deceased donor kidneys show a survival benefit over older donor kidneys in transplant recipients aged 20-50 years: a study by the ERA-EDTA Registry.

BACKGROUND: Updated survival outcomes of young recipients receiving young or old deceased donor kidneys are required when considering accepting a deceased donor kidney. METHODS: We examined outcomes in 6448 European kidney allografts donated from younger (≥20-<50 years) and older (≥50-<70 years) deceased donors when transplanted into very young (≥20-<35 years) or young (≥35-<50 years) adult recipients. Outcomes of first kidney transplantations during 2000-13 and followed-up to 2015 were determined via competing risk, restricted mean survival and Cox regression methods. RESULTS: The 10-year cumulative incidence of graft failure was lowest in very young {22.0% [95% confidence interval (95% CI) 19.1-24.9]} and young [15.3% (95% CI 13.7-16.9)] recipients of younger donor kidneys and highest in very young [36.7% (95% CI 31.9-41.5)] and young [29.2% (95% CI 25.1-33.2)] recipients of older donor kidneys. At the 10-year follow-up, younger donor kidneys had a 1 year (very young) or 9 months (young) longer mean graft survival time compared with older donor kidneys. Graft failure risk in younger donor kidneys was 45% [very young adjusted hazard ratio (aHR) 0.55 (95% CI 0.44-0.68)] and 40% [young aHR 0.60 (95% CI 0.53-0.67)] lower compared with older donor kidneys. A 1-year increase in donor age resulted in a 2% [very young aHR 1.02 (95% CI 1.00-1.04)] or 1% [young aHR 1.01 (95% CI 1.00-1.01)] increase in the 10-year risk of death. CONCLUSIONS: Younger donor kidneys show survival benefits over older donor kidneys in adult recipients ages 20-50 years. Updated survival outcomes from older deceased donors are necessary due to advances in transplantation medicine and the increasing role these donors play in organ transplantation.

Characteristics and Outcomes of Patients With Systemic Sclerosis (Scleroderma) Requiring Renal Replacement Therapy in Europe: Results From the ERA-EDTA Registry.

RATIONALE & OBJECTIVE: Data for outcomes of patients with end-stage renal disease (ESRD) secondary to systemic sclerosis (scleroderma) requiring renal replacement therapy (RRT) are limited. We examined the incidence and prevalence of ESRD due to scleroderma in Europe and the outcomes among these patients following initiation of RRT. STUDY DESIGN: Registry study of incidence and prevalence and a matched cohort study of clinical outcomes. SETTING & PARTICIPANTS: Patients represented in any of 19 renal registries that provided data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry between 2002 and 2013. PREDICTOR: Scleroderma as the identified cause of ESRD. OUTCOMES: Incidence and prevalence of ESRD from scleroderma. Recovery from RRT dependence, patient survival after ESRD, and graft survival after kidney transplantation. ANALYTICAL APPROACH: Incidence and prevalence were calculated using population data from the European Union and standardized to population characteristics in 2005. Patient and graft survival were compared with 2 age- and sex-matched control groups without scleroderma: (1) diabetes mellitus as the cause of ESRD and (2) conditions other than diabetes mellitus as the cause of ESRD. Survival analyses were performed using Kaplan-Meier analysis and Cox regression. RESULTS: 342 patients with scleroderma (0.14% of all incident RRT patients) were included. Between 2002 and 2013, the range of adjusted annual incidence and prevalence rates of RRT for ESRD due to scleroderma were 0.11 to 0.26 and 0.73 to 0.95 per million population, respectively. Recovery of independent kidney function was greatest in the scleroderma group (7.6% vs 0.7% in diabetes mellitus and 2.0% in other primary kidney diseases control group patients, both P<0.001), though time required to achieve recovery was longer. The 5-year survival probability from day 91 of RRT among patients with scleroderma was 38.9% (95% CI, 32.0%-45.8%), whereas 5-year posttransplantation patient survival and 5-year allograft survival were 88.2% (95% CI, 75.3%-94.6%) and 72.4% (95% CI, 55.0%-84.0%), respectively. Adjusted mortality from day 91 on RRT was higher among patients with scleroderma than observed in both control groups (HRs of 1.25 [95% CI, 1.05-1.48] and 2.00 [95% CI, 1.69-2.39]). In contrast, patient and graft survival after kidney transplantation did not differ between patients with scleroderma and control groups. LIMITATIONS: No data for extrarenal manifestations, treatment, or recurrence. CONCLUSIONS: Survival of patients with scleroderma who receive dialysis for more than 90 days was worse than for those with other causes of ESRD. Patient survival after transplantation was similar to that observed among patients with ESRD due to other conditions. Patients with scleroderma had a higher rate of recovery from RRT dependence than controls.

Association between timing of dialysis initiation and clinical outcomes in the paediatric population: an ESPN/ERA-EDTA registry study.

BACKGROUND: There is no consensus regarding the timing of dialysis therapy initiation for end-stage kidney disease (ESKD) in children. As studies investigating the association between timing of dialysis initiation and clinical outcomes are lacking, we aimed to study this relationship in a cohort of European children who started maintenance dialysis treatment. METHODS: We used data on 2963 children from 21 different countries included in the European Society of Pediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry who started renal replacement therapy before 18 years of age between 2000 and 2014. We compared two groups according to the estimated glomerular filtration rate (eGFR) at start: eGFR ≥8 mL/min/1.73 m2 (early starters) and eGFR <8 mL/min/1.73 m2 (late starters). The primary outcomes were patient survival and access to transplantation. Secondary outcomes were growth and cardiovascular risk factors. Sensitivity analyses were performed to account for selection- and lead time-bias. RESULTS: The median eGFR at the start of dialysis was 6.1 for late versus 10.5 mL/min/1.73 m2 for early starters. Early starters were older [median: 11.0, interquartile range (IQR): 5.7-14.5 versus 9.4, IQR: 2.6-14.1 years]. There were no differences observed between the two groups in mortality and access to transplantation at 1, 2 and 5 years of follow-up. One-year evolution of height standard deviation scores was similar among the groups, whereas hypertension was more prevalent among late initiators. Sensitivity analyses resulted in similar findings. CONCLUSIONS: We found no evidence for a clinically relevant benefit of early start of dialysis in children with ESKD. Presence of cardiovascular risk factors, such as high blood pressure, should be taken into account when deciding to initiate or postpone dialysis in children with ESKD, as this affects the survival.

International comparison of trends in patients commencing renal replacement therapy by primary renal disease.

AIM: To examine international time trends in the incidence of renal replacement therapy (RRT) for end-stage renal disease (ESRD) by primary renal disease (PRD). METHODS: Renal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression. RESULTS: There was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC = -0.9; 95%CI -1.3; -0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC = -1.8; 95%CI -3.3; -0.3), Canada (AAPC = -2.9; 95%CI -4.4; -1.5) and Europe (AAPC = -1.1; 95%CI -2.1; -0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2-16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea. CONCLUSION: Large international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD.

Mortality risk disparities in children receiving chronic renal replacement therapy for the treatment of end-stage renal disease across Europe: an ESPN-ERA/EDTA registry analysis.

BACKGROUND: We explored the variation in country mortality rates in the paediatric population receiving renal replacement therapy across Europe, and estimated how much of this variation could be explained by patient-level and country-level factors. METHODS: In this registry analysis, we extracted patient data from the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association (ESPN/ERA-EDTA) Registry for 32 European countries. We included incident patients younger than 19 years receiving renal replacement therapy. Adjusted hazard ratios (aHR) and the explained variation were modelled for patient-level and country-level factors with multilevel Cox regression. The primary outcome studied was all-cause mortality while on renal replacement therapy. FINDINGS: Between Jan 1, 2000, and Dec 31, 2013, the overall 5 year renal replacement therapy mortality rate was 15·8 deaths per 1000 patient-years (IQR 6·4-16·4). France had a mortality rate (9·2) of more than 3 SDs better, and Russia (35·2), Poland (39·9), Romania (47·4), and Bulgaria (68·6) had mortality rates more than 3 SDs worse than the European average. Public health expenditure was inversely associated with mortality risk (per SD increase, aHR 0·69, 95% CI 0·52-0·91) and explained 67% of the variation in renal replacement therapy mortality rates between countries. Child mortality rates showed a significant association with renal replacement therapy mortality, albeit mediated by macroeconomics (eg, neonatal mortality reduced from 1·31 [95% CI 1·13-1·53], p=0·0005, to 1·21 [0·97-1·51], p=0·10). After accounting for country distributions of patient age, the variation in renal replacement therapy mortality rates between countries increased by 21%. INTERPRETATION: Substantial international variation exists in paediatric renal replacement therapy mortality rates across Europe, most of which was explained by disparities in public health expenditure, which seems to limit the availability and quality of paediatric renal care. Differences between countries in their ability to accept and treat the youngest patients, who are the most complex and costly to treat, form an important source of disparity within this population. Our findings can be used by policy makers and health-care providers to explore potential strategies to help reduce these health disparities. FUNDING: ERA-EDTA and ESPN.

Changes in co-morbidity pattern in patients starting renal replacement therapy in Europe-data from the ERA-EDTA Registry.

Background: Patients starting renal replacement therapy (RRT) for end-stage renal disease often present with one or more co-morbidities. This study explored the prevalence of co-morbidities in patients who started RRT in Europe during the period from 2005 to 2014. Methods: Using data from patients aged 20 years or older from all 11 national or regional registries providing co-morbidity data to the European Renal Association - European Dialysis and Transplant Association Registry, we examined the prevalence of the following co-morbidities: diabetes mellitus (DM) (primary renal disease and/or co-morbidity), ischaemic heart disease (IHD), congestive heart failure (CHF), peripheral vascular disease (PVD), cerebrovascular disease (CVD) and malignancy. Results: Overall, 70% of 7578 patients who initiated RRT in 2014 presented with at least one co-morbidity: 39.0% presented with DM, 25.0% with IHD, 22.3% with CHF, 17.7% with PVD, 16.4% with malignancy and 15.5% with CVD. These percentages differed substantially between countries. Co-morbidities were more common in men than in women, in older patients than in younger patients, and in patients on haemodialysis at Day 91 when compared with patients on peritoneal dialysis. Between 2005 and 2014 the prevalence of DM and malignancy increased over time, whereas the prevalence of IHD and PVD declined. Conclusions: More than two-thirds of patients initiating RRT in Europe have at least one co-morbidity. With the rising age at the start of RRT over the last decade, there have been changes in the co-morbidity pattern: the prevalence of cardiovascular co-morbidities decreased, while the prevalence of DM and malignancy increased.

Performance of an easy-to-use prediction model for renal patient survival: an external validation study using data from the ERA-EDTA Registry.

Background: An easy-to-use prediction model for long-term renal patient survival based on only four predictors [age, primary renal disease, sex and therapy at 90 days after the start of renal replacement therapy (RRT)] has been developed in The Netherlands. To assess the usability of this model for use in Europe, we externally validated the model in 10 European countries. Methods: Data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry were used. Ten countries that reported individual patient data to the registry on patients starting RRT in the period 1995-2005 were included. Patients <16 years of age and/or with missing predictor variable data were excluded. The external validation of the prediction model was evaluated for the 10- (primary endpoint), 5- and 3-year survival predictions by assessing the calibration and discrimination outcomes. Results: We used a data set of 136 304 patients from 10 countries. The calibration in the large and calibration plots for 10 deciles of predicted survival probabilities showed average differences of 1.5, 3.2 and 3.4% in observed versus predicted 10-, 5- and 3-year survival, with some small variation on the country level. The concordance index, indicating the discriminatory power of the model, was 0.71 in the complete ERA-EDTA Registry cohort and varied according to country level between 0.70 and 0.75. Conclusions: A prediction model for long-term renal patient survival developed in a single country, based on only four easily available variables, has a comparably adequate performance in a wide range of other European countries.

Factors associating with differences in the incidence of renal replacement therapy among elderly: data from the ERA-EDTA Registry.

Background: The incidence of renal replacement therapy (RRT) in the general population ≥75 years of age varies considerably between countries and regions in Europe. Our aim was to study characteristics and survival of elderly RRT patients and to find explanations for differences in RRT incidence. Methods: Patients ≥75 years of age at the onset of RRT in 2010-2013 from 29 national or regional registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry were included. Chi-square and Mann-Whitney U tests were used to assess variation in patient characteristics and linear regression was used to study the association between RRT incidence and various factors. Kaplan-Meier curves and Cox regression were employed for survival analyses. Results: The mean annual incidence of RRT in the age group ≥75 years of age ranged from 157 to 924 per million age-related population. The median age at the start of RRT was higher and comorbidities were less common in areas with higher RRT incidence, but overall the association between patient characteristics and RRT incidence was weak. The unadjusted survival was lower in high-incidence areas due to an older age at onset of RRT, but the adjusted survival was similar [relative risk 1.00 (95% confidence interval, 0.97-1.03)] in patients from low- and high-incidence areas. Conclusions: Variation in the incidence of RRT among the elderly across European countries and regions is remarkable and could not be explained by the available data. However, the survival of patients in low- and high-incidence areas was remarkably similar.

Risk of death after first-time blood stream infection in incident dialysis patients with specific consideration on vascular access and comorbidity.

BACKGROUND: The mortality following blood stream infection (BSI) and risk of subsequent BSI in relation to dialysis modality, vascular access, and other potential risk factors has received relatively little attention. Consequently, we assessed these matters in a retrospective cohort study, by use of the Danish nation-wide registries. METHODS: Patients more than 17 years of age, who initiated dialysis between 1.1.2010 and 1.1.2014, were grouped according to their dialysis modality and vascular access. Survival was modeled in time-dependent Cox proportional hazard analyses. Potential risk factors confined by a modified Charlson comorbidity index (MCCI), were subsequently assessed in stepwise selection models. RESULTS: At baseline, 764 patients received peritoneal dialysis (PD), and 434, 479, and 782 hemodialysis (HD) patients were dialyzed by use of arteriovenous fistulas (AVFs), tunneled catheters (TCs), and non-tunneled catheters (NTCs), respectively. We identified 1069 BSIs with an overall incidence rate of 17.7 episodes per 100 person years, and 216 BSIs occurred more than one time in the same patient. HRs of post BSI mortality relative to PD were 3.20 (95% CI 1.86-5.50; p < 0.001) with NTCs; whereas no associations were found for AVF and TC. The risk of subsequent BSIs was higher with NTCs [HR 2.29 (95% CI 1.09-4.82), p = 0.030], and no significant difference was found for AVF and TC, in relation to PD. There was an increased risk of both outcomes with TC relative to AVF [death: 1.57 (95% CI 1.07-2.29, P < 0.021); BSI: 1.78 (95% CI 1.13-2.83, P < 0.014], and risk of death was reduced in patients who changed to AVF after first-time BSI. The MCCI was significantly associated with the risk of subsequent BSI and post BSI death; however, only some of the variables contained in the index were found to be significant risk predictors when analyzed in the fitted model. CONCLUSIONS: While NTC was the most predominant risk factor for subsequent BSI and post BSI mortality, AVF appeared protective.

Access to kidney transplantation in European adults aged 75-84 years and related outcomes: an analysis of the European Renal Association-European Dialysis and Transplant Association Registry.

To what extent access to, and allocation of kidney transplants and survival outcomes in patients aged ≥75 years have changed over time in Europe is unclear. We included patients aged ≥75-84 years (termed older adults) receiving renal replacement therapy in thirteen European countries between 2005 and 2014. Country differences and time trends in access to, and allocation of kidney transplants were examined. Survival outcomes were determined by Cox regression analyses. Between 2005 and 2014, 1392 older adult patients received 1406 transplants. Access to kidney transplantation varied from ~0% (Slovenia, Greece and Denmark) to ~4% (Norway and various Spanish regions) of all older adult dialysis patients, and overall increased from 0.3% (2005) to 0.9% (2014). Allocation of kidney transplants to older adults overall increased from 0.8% (2005) to 3.2% (2014). Seven-year unadjusted patient and graft survival probabilities were 49.1% (95% confidence interval, 95% CI: 43.6; 54.4) and 41.7% (95% CI: 36.5; 46.8), respectively, with a temporal trend towards improved survival outcomes. In conclusion, in the European dialysis population aged ≥75-84 years access to kidney transplantation is low, and allocation of kidney transplants remains a rare event. Though both are increasing with time and vary considerably between countries. The trend towards improved survival outcomes is encouraging. This information can aid informed decision-making regarding treatment options.