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.

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.

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.

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.

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.

Dialysis modality choice in elderly patients with end-stage renal disease: a narrative review of the available evidence.

The number of elderly patients on maintenance dialysis has rapidly increased in the past few decades, particularly in developed countries, imposing a growing burden on dialysis centres. Hence, many nephrologists and healthcare authorities feel that greater emphasis should be placed on the promotion of home dialysis therapies such as peritoneal dialysis (PD) and home haemodialysis (HD). There is currently no general consensus as to the best dialysis modality for elderly patients with end-stage renal disease. In-centre HD is predominant in most countries, although it is widely recognized that PD has several advantages over HD, including the lack of need for vascular access, continuous slow ultrafiltration, less interference with patients' lifestyle and lower costs. Comparisons of outcomes between elderly patients on PD and HD rely on observational studies, as randomized controlled trials are lacking. The results of these studies are variable. However, most of them suggest that survival rates are largely similar between the two modalities, except for elderly patients with diabetes and/or beyond 1-3 years from dialysis initiation, in which cases HD appears to be superior. An equally important aspect to consider when choosing dialysis modality, particularly in this age group, is the quality of life, and in this regard most studies found no significant differences between PD and HD. In these circumstances, we believe that dialysis modality selection should be guided by patient's preference, based on comprehensive and unbiased information. A multidisciplinary team should review elderly patients starting on dialysis, aiming to identify possible barriers to PD and home HD, including physical, visual, cognitive, psychological and social problems, and to overcome such barriers by adequate care, education, psychological counselling and dialysis assistance.

Clearance of Sclerostin, Osteocalcin, Fibroblast Growth Factor 23, and Osteoprotegerin by Dialysis.

INTRODUCTION: Fibroblast growth factor (FGF23), sclerostin, osteocalcin, and osteoprotegerin are important factors that control mineral bone metabolism. End-stage renal disease is associated with the pronounced dysregulation of mineral bone metabolism; however, the impact and clearance of mineral bone metabolism factors during dialysis remain largely undescribed. METHODS: In a cross-sectional study, 10 chronic hemodialysis patients were treated with hemodialysis for 8 h using a high-flux filter and a dialysate bath of 50% calculated total body water continuously recycled at a rate of 500 mL/min. Plasma and dialysate concentrations of FGF23, sclerostin, osteoprotegerin, and osteocalcin were measured at 1, 2, 4, 6, and 8 h permitting the estimation of dialysis clearance. RESULTS: Clearance of FGF23 was 7.7 mL/min, of sclerostin was 7.6 mL/min, of osteoprotegerin was 1.2 mL/min, and of osteocalcin was 19.7 mL/min. Clearance of FGF23 was correlated to sclerostin and osteoprotegerin clearance and also to the ultrafiltration rate. Although, osteocalcin blood concentrations decreased during dialysis, they rebounded within 6 h. Overall, no significant changes in blood concentrations of the measure mineral bone metabolism factors were observed. CONCLUSIONS: The intradialytic clearance of osteocalcin, FGF23, sclerostin, and osteoprotegerin occurs; however, only clearance of FGF23 is directly correlated with the ultrafiltration rate. The effects of dialytic clearance on mineral bone metabolism are, however, uncertain and intradialytic plasma concentrations of the studied substrates remained largely unchanged.

Mortality risk in European children with end-stage renal disease on dialysis.

We aimed to describe survival in European pediatric dialysis patients and compare the differential mortality risk between patients starting on hemodialysis (HD) and peritoneal dialysis (PD). Data for 6473 patients under 19 years of age or younger were extracted from the European Society of Pediatric Nephrology, the European Renal Association, and European Dialysis and Transplant Association Registry for 36 countries for the years 2000 through 2013. Hazard ratios (HRs) were adjusted for age at start of dialysis, sex, primary renal disease, and country. A secondary analysis was performed on a propensity score-matched (PSM) cohort. The overall 5-year survival rate in European children starting on dialysis was 89.5% (95% confidence interval [CI] 87.7%-91.0%). The mortality rate was 28.0 deaths per 1000 patient years overall. This was highest (36.0/1000) during the first year of dialysis and in the 0- to 5-year age group (49.4/1000). Cardiovascular events (18.3%) and infections (17.0%) were the main causes of death. Children selected to start on HD had an increased mortality risk compared with those on PD (adjusted HR 1.39, 95% CI 1.06-1.82, PSM HR 1.46, 95% CI 1.06-2.00), especially during the first year of dialysis (HD/PD adjusted HR 1.70, 95% CI 1.22-2.38, PSM HR 1.79, 95% CI 1.20-2.66), when starting at older than 5 years of age (HD/PD: adjusted HR 1.58, 95% CI 1.03-2.43, PSM HR 1.87, 95% CI 1.17-2.98) and when children have been seen by a nephrologist for only a short time before starting dialysis (HD/PD adjusted HR 6.55, 95% CI 2.35-18.28, PSM HR 2.93, 95% CI 1.04-8.23). Because unmeasured case-mix differences and selection bias may explain the higher mortality risk in the HD population, these results should be interpreted with caution.

Kidney Versus Combined Kidney and Liver Transplantation in Young People With Autosomal Recessive Polycystic Kidney Disease: Data From the European Society for Pediatric Nephrology/European Renal Association-European Dialysis and Transplant (ESPN/ERA-EDTA) Registry.

BACKGROUND: The choice for either kidney or combined liver-kidney transplantation in young people with kidney failure and liver fibrosis due to autosomal recessive polycystic kidney disease (ARPKD) can be challenging. We aimed to analyze the characteristics and outcomes of transplantation type in these children, adolescents, and young adults. STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: We derived data for children, adolescents, and young adults with ARPKD with either kidney or combined liver-kidney transplants for 1995 to 2012 from the ESPN/ERA-EDTA Registry, a European pediatric renal registry collecting data from 36 European countries. FACTOR: Liver transplantation. OUTCOMES & MEASUREMENTS: Transplantation and patient survival. RESULTS: 202 patients with ARPKD aged 19 years or younger underwent transplantation after a median of 0.4 (IQR, 0.0-1.4) years on dialysis therapy at a median age of 9.0 (IQR, 4.1-13.7) years. 32 (15.8%) underwent combined liver-kidney transplantation, 163 (80.7%) underwent kidney transplantation, and 7 (3.5%) were excluded because transplantation type was unknown. Age- and sex-adjusted 5-year patient survival posttransplantation was 95.5% (95% CI, 92.4%-98.8%) overall: 97.4% (95% CI, 94.9%-100.0%) for patients with kidney transplantation in contrast to 87.0% (95% CI, 75.8%-99.8%) with combined liver-kidney transplantation. The age- and sex-adjusted risk for death after combined liver-kidney transplantation was 6.7-fold (95% CI, 1.8- to 25.4-fold) greater than after kidney transplantation (P=0.005). Five-year death-censored kidney transplant survival following combined liver-kidney and kidney transplantation was similar (92.1% vs 85.9%; P=0.4). LIMITATIONS: No data for liver disease of kidney therapy recipients. CONCLUSIONS: Combined liver-kidney transplantation in ARPKD is associated with increased mortality compared to kidney transplantation in our large observational study and was not associated with improved 5-year kidney transplant survival. Long-term follow-up of both kidney and liver involvement are needed to better delineate the optimal transplantation strategy.

Differences in survival on chronic dialysis treatment between ethnic groups in Denmark: a population-wide, national cohort study.

BACKGROUND: In Western countries, black and Asian dialysis patients experience better survival compared with white patients. The aim of this study is to compare the survival of native Danish dialysis patients with that of dialysis patients originating from other countries and to explore the association between the duration of residence in Denmark before the start of dialysis and the mortality on dialysis. METHODS: We performed a population-wide national cohort study of incident chronic dialysis patients in Denmark (≥18 years old) who started dialysis between 1995 and 2010. RESULTS: In total, 8459 patients were native Danes, 344 originated from other Western countries, 79 from North Africa or West Asia, 173 from South or South-East Asia and 54 from sub-Saharan Africa. Native Danes were more likely to die on dialysis compared with the other groups (crude incidence rates for mortality: 234, 166, 96, 110 and 53 per 1000 person-years, respectively). Native Danes had greater hazard ratios (HRs) for mortality compared with the other groups {HRs for mortality adjusted for sociodemographic and clinical characteristics: 1.32 [95% confidence interval (CI) 1.14-1.54]; 2.22 [95% CI 1.51-3.23]; 1.79 [95% CI 1.41-2.27]; 2.00 [95% CI 1.10-3.57], respectively}. Compared with native Danes, adjusted HRs for mortality for Western immigrants living in Denmark for ≤10 years, >10 to ≤20 years and >20 years were 0.44 (95% CI 0.27-0.71), 0.56 (95% CI 0.39-0.82) and 0.86 (95% CI 0.70-1.04), respectively. For non-Western immigrants, these HRs were 0.42 (95% CI 0.27-0.67), 0.52 (95% CI 0.33-0.80) and 0.48 (95% CI 0.35-0.66), respectively. CONCLUSIONS: Incident chronic dialysis patients in Denmark originating from countries other than Denmark have a better survival compared with native Danes. For Western immigrants, this survival benefit declines among those who have lived in Denmark longer. For non-Western immigrants, the survival benefit largely remains over time.

The changing trends and outcomes in renal replacement therapy: data from the ERA-EDTA Registry.

BACKGROUND: This study examines the time trends in incidence, prevalence, patient and kidney allograft survival and causes of death (COD) in patients receiving renal replacement therapy (RRT) in Europe. METHODS: Eighteen national or regional renal registries providing data to the European Renal Association-European Dialysis and Transplant Association Registry between 1998 and 2011 were included. Incidence and prevalence time trends between 2001 and 2011 were studied with Joinpoint and Poisson regression. Patient and kidney allograft survival and COD between 1998 and 2011 were analysed using Kaplan-Meier and competing risk methods and Cox regression. RESULTS: From 2001 to 2008, the adjusted incidence of RRT rose by 1.1% (95% CI: 0.6, 1.7) annually to 131 per million population (pmp). During 2008-2011, the adjusted incidence fell by 2.2% (95% CI: -4.2, -0.2) annually to 125 pmp. This decline occurred predominantly in patients aged 45-64 years, 65-74 years and in the primary renal diseases diabetes mellitus type 1 and 2, renovascular disease and glomerulonephritis. Between 2001 and 2011, the overall adjusted prevalence increased from 724 to 1032 pmp (+3.3% annually, 95% CI: 2.8, 3.8). The adjusted 5-year patient survival on RRT improved between 1998-2002 and 2003-2007 [adjusted hazard ratio (HRa) 0.85, 95% CI: 0.84, 0.86]. Comparing these time periods, the risk of cardiovascular deaths fell by 25% (HRa 0.75, 95% CI: 0.74, 0.77). However the risk of malignant death rose by 9% (HRa 1.09, 95% CI: 1.03, 1.16) in patients ≥65 years. CONCLUSION: This European study shows a declining RRT incidence, particularly in patients aged 45-64 years, 65-74 years and secondary to diabetic nephropathy. Encouragingly, the adjusted RRT patient survival continues to improve. The risk of cardiovascular death has decreased, though the risk of death from malignancy has increased in the older population.

Characteristics and Outcomes of Granulomatosis With Polyangiitis (Wegener) and Microscopic Polyangiitis Requiring Renal Replacement Therapy: Results From the European Renal Association-European Dialysis and Transplant Association Registry.

BACKGROUND: This study describes the incidence and outcomes of European patients requiring renal replacement therapy (RRT) for kidney failure due to antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). STUDY DESIGN: Cohort study. SETTING & PARTICIPANTS: 12 renal registries providing individual RRT patient data to the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry in 1993-2012 participated. PREDICTOR: Cause of primary kidney disease: AAV (ie, granulomatosis with polyangiitis [Wegener] and microscopic polyangiitis) versus 3 separate matched control groups without AAV: (1) primary glomerulonephritis, (2) diabetes mellitus, and (3) disease other than diabetes mellitus as the cause of primary kidney disease, including glomerulonephritis (termed "nondiabetes"). OUTCOMES: Incidence, causes of death, and survival. MEASUREMENTS: ERA-EDTA primary renal disease codes. RESULTS: 2,511 patients with AAV (1,755, granulomatosis with polyangiitis; 756, microscopic polyangiitis) were identified, representing an incidence of 1.05 per million population (pmp) for granulomatosis with polyangiitis (predominating in Northern Europe) and 0.45 pmp for microscopic polyangiitis (prevailing in Southern Europe). Kidney transplantation was performed in 558 (22.2%) patients with vasculitis. The 10-year probability for survival on RRT after day 91 was 32.5% (95% CI, 29.9%-35.1%) in patients with vasculitis. Survival on RRT after day 91 did not differ between AAV and matched nondiabetes patients. Patient and transplant survival after kidney transplantation, adjusted for time period and country, was better in AAV than in matched nondiabetes patients (HRs of 0.81 [95% CI, 0.67-0.99] and 0.82 [95% CI, 0.69-0.96], respectively). LIMITATIONS: No data for extrarenal manifestations, treatment, and relapses. CONCLUSIONS: Geographical differences in the incidence of RRT for kidney failure due to granulomatosis with polyangiitis and microscopic polyangiitis copied their distribution in the general population. Overall survival on RRT after day 91 for patients with AAV was similar to that for patients with nondiabetes diagnoses. Our results suggest that patients with AAV are suitable candidates for kidney transplantation with favorable survival outcomes.