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Background: Previous US studies have indicated that haemodialysis with ≥6-h sessions [extended-hours haemodialysis (EHD)] may improve patient survival. However, patient characteristics and treatment practices vary between the USA and Europe. We therefore investigated the effect of EHD three times weekly on survival compared with conventional haemodialysis (CHD) among European patients., Methods: We included patients who were treated with haemodialysis between 2010 and 2017 from eight countries providing data to the European Renal Association-European Dialysis and Transplant Association Registry. Haemodialysis session duration and frequency were recorded once every year or at every change of haemodialysis prescription and were categorized into three groups: CHD (three times weekly, 3.5-4 h/treatment), EHD (three times weekly, ≥6 h/treatment) or other. In the primary analyses we attributed death to the treatment at the time of death and in secondary analyses to EHD if ever initiated. We compared mortality risk for EHD to CHD with causal inference from marginal structural models, using Cox proportional hazards models weighted for the inverse probability of treatment and censoring and adjusted for potential confounders., Results: From a total of 142 460 patients, 1338 patients were ever treated with EHD (three times, 7.1 ± 0.8 h/week) and 89 819 patients were treated exclusively with CHD (three times, 3.9 ± 0.2 h/week). Crude mortality rates were 6.0 and 13.5/100 person-years. In the primary analyses, patients treated with EHD had an adjusted hazard ratio (HR) of 0.73 [95% confidence interval (CI) 0.62-0.85] compared with patients treated with CHD. When we attributed all deaths to EHD after initiation, the HR for EHD was comparable to the primary analyses [HR 0.80 (95% CI 0.71-0.90)]., Conclusions: EHD is associated with better survival in European patients treated with haemodialysis three times weekly., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

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.

Background: The risk of stroke in end-stage renal disease (ESRD) on renal replacement therapy (RRT) is up to 10-fold greater than the general population. However, whether this increased risk differs by RRT modality is unclear., Methods: We used data contained in the Scottish Renal Registry and the Scottish Stroke Care Audit to identify stroke in all adult patients who commenced RRT for ESRD from 2005 to 2013. Incidence rate was calculated and regression analyses were performed to identify variables associated with stroke. We explored the effect of RRT modality at initiation and cumulative dialysis exposure by time-dependent regression analysis, using transplant recipients as the reference group., Results: A total of 4957 patients commenced RRT for ESRD. Median age was 64.5 years, 41.5% were female and 277 patients suffered a stroke (incidence rate was 18.6/1000 patient-years). Patients who had stroke were older, had higher blood pressure and were more likely to be female and have diabetes. On multivariable regression older age, female sex, diabetes and higher serum phosphate were associated with risk of stroke. RRT modality at initiation was not. On time-dependent analysis, haemodialysis (HD) exposure was independently associated with increased risk of stroke., Conclusions: In patients with ESRD who initiate RRT, HD use independently increases risk of stroke compared with transplantation. Use of peritoneal dialysis did not increase risk on adjusted analysis.

Background: The modality by which haemodialysis (HD) is delivered [arteriovenous fistula (AVF), arteriovenous graft (AVG) or central venous catheter (CVC)] varies widely and is influenced by clinical evidence, patient factors and the prevailing service configuration. The aim of this study was to determine the outcome and impact of access strategy on patient outcome by mapping out the HD journey in a cohort of incident patients., Methods: A 2-year cohort of consecutive incident HD patients from the point of referral for first dialysis access to completion of the first 365 days of HD was prospectively reviewed. Data were sought on access type; radiological, surgical and other access-related activity; bacteraemic events; admission rates and cumulative financial cost., Results: A total of 144 patients started RRT for the first time with HD over the 2-year period. All were followed up to 1 year after starting HD, generating a total of 47 753 observed HD days.  Activity prior to starting HD for the full cohort was found to average 0.92 arteriovenous (AV) access creation procedures, 0.40 CVC insertions, 0.14 interventional radiology procedures and 0.41 ultrasound examinations per patient. The small number of patients who started on an AVG had a tendency towards higher pre-HD surgical and imaging activity than those who started on an AVF or CVC.  Activity after starting HD varied greatly with the access type used at the start of HD, with AVF patients experiencing less hospitalization, procedure and imaging activity and financial costs compared with those who start HD with a CVC. Patients who started on an AVG had a tendency towards lower surgical activity rates and financial costs than those who started on a CVC., Conclusions: Providing, maintaining and dealing with the complications of HD vascular access places a significant burden of activity that is shared across nephrology, surgery and imaging services. A well-functioning AVF is associated with the lowest burden, whereas a failed AVF or CVC access is associated with the highest burden. Patient journeys are shaped by the vascular access that they use and we suggest that the contemporary pursuit of HD access should focus on delivering personalized access solutions.

Background: Bone fractures are an important cause of morbidity and mortality in patients on renal replacement therapy (RRT). The aim of this multicentre observational study was to quantify the incidence of radiologically proven bone fracture by anatomical site in prevalent RRT groups and study its relationship to potential risk factors., Methods: We performed a retrospective analysis of electronic records of all 2096 adults prevalent on RRT in the West of Scotland on 7 July 2010 across all hospitals (except one where inception was 1 August 2011) to identify all subsequent radiologically proven fractures during a median 3-year follow-up., Results: There were 340 fractures, with an incidence of 62.8 per 1000 patient-years. The incidences were 37.6, 99.2 and 57.6 per 1000 patient-years in the transplant, haemodialysis (HD) and peritoneal dialysis (PD) groups, respectively (P < 0.05). In the multivariable model, age and HD (relative to transplant or PD) were independently associated with increased risk of fractures, while primary glomerular disease, increasing serum albumin and taking alfacalcidol or lanthanum were associated with decreased risk. In a multivariable model of only HD patients, age was independently associated with an increased risk of fractures, while glomerular disease, high serum albumin and being on alfacalcidol and lanthanum were associated with decreased risk. In a multivariable model in transplant patients, there were no significant independent predictors of fracture., Conclusions: The risk of symptomatic bone fracture is high in RRT patients and is ∼2.5 times higher in HD than in renal transplant patients, with the increased risk being independent of baseline factors. Fracture risk increases with age and lower serum albumin and is reduced if the primary renal diagnosis is glomerular disease. The possible protective role of alfacalcidol and lanthanum in HD patients deserves further exploration., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Upcoming KDIGO guidelines for the evaluation of living kidney donors are expected to move towards a personal risk-based evaluation of potential donors. We present the age and sex-specific lifetime risk of renal replacement therapy (RRT) for end-stage renal disease in 10 European countries., Methods: We defined lifetime risk of RRT as the cumulative incidence of RRT up to age 90 years. We obtained RRT incidence rates per million population by 5-year age groups and sex using data from the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, and used these to estimate the cumulative incidence of RRT, adjusting for competing mortality risk., Results: Lifetime risk of RRT varied from 0.44% to 2.05% at age 20 years and from 0.17% to 1.59% at age 70 years across countries, and was twice as high in men as in women. Lifetime RRT risk decreased with age, ranging from an average of 0.77% to 0.44% in 20- to- 70-year-old women, and from 1.45% to 0.96% in 20- to- 70-year-old men. The lifetime risk of RRT increased slightly over the past decade, more so in men than in women. However, it appears to have stabilized or even decreased slightly in more recent years., Conclusions: The lifetime risk of RRT decreased with age, was lower in women as compared with men of equal age and varied considerably throughout Europe. Given the substantial differences in lifetime risk of RRT between the USA and Europe, country-specific estimates should be used in the evaluation and communication of the risk of RRT for potential living kidney donors., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Severe acute kidney injury (AKI) among hospitalized patients often necessitates initiation of short-term dialysis. Little is known about the long-term outcome of those who recover to normal renal function. The aim of this study was to determine the long-term renal outcome of patients experiencing AKI requiring dialysis secondary to hypoperfusion injury and/or sepsis who recovered to apparently normal renal function., Methods: All adult patients with AKI requiring dialysis in our centre between 1 January 1980 and 31 December 2010 were identified. We included patients who had estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m 2 12 months or later after the episode of AKI. Patients were followed up until 3 March 2015. The primary outcome was time to chronic kidney disease (CKD) (defined as eGFR persistently <60 mL/min/1.73 m 2 ) from first dialysis for AKI., Results: Among 2922 patients with a single episode of dialysis-requiring AKI, 396 patients met the study inclusion criteria. The mean age was 49.8 (standard deviation 16.5) years and median follow-up was 7.9 [interquartile range (IQR) 4.8-12.7] years. Thirty-five (8.8%) of the patients ultimately developed CKD after a median of 5.3 (IQR 2.8-8.0) years from first dialysis for AKI giving an incidence rate of 1 per 100 person-years. Increasing age, diabetes and vascular disease were associated with higher risk of progression to CKD [adjusted hazard ratios (95% confidence interval): 1.06 (1.03, 1.09), 3.05 (1.41, 6.57) and 3.56 (1.80, 7.03), respectively]., Conclusions: Recovery from AKI necessitating in-hospital dialysis was associated with a very low risk of progression to CKD. Most of the patients who progressed to CKD had concurrent medical conditions meriting monitoring of renal function. Therefore, it seems unlikely that regular follow-up of renal function is beneficial in patients who recover to eGFR >60 mL/min/1.73 m 2 by 12 months after an episode of AKI., (© The Author 2017. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Dialysis withdrawal is the third most common cause of death in patients receiving dialysis for established renal failure (ERF) in Scotland. We describe incidence, risk factors and themes influencing decision-making in a national renal registry., Methods: Details of deaths in those receiving renal replacement therapy (RRT) for ERF in Scotland are reported to the Scottish Renal Registry via a unique mortality report. We extracted patient demographics and comorbidity, cause and location of death, duration of RRT and pertinent free text comments from 1 January 2008 to 31 December 2014. Withdrawal incidence was calculated and logistic regression used to identify significantly influential variables. Themes emerging from clinician comments were tabulated for descriptive purposes., Results: There were 2596 deaths; median age at death was 68 [interquartile range (IQR) 58, 76] years, 41.5% were female. Median duration on RRT was 1110 (IQR 417, 2151) days. Dialysis withdrawal was the primary cause of death in 497 (19.1%) patients and withdrawal contributed to death in a further 442 cases (17.0%). The incidence was 41 episodes per 1000 patient-years. Regression analysis revealed increasing age, female sex and prior cerebrovascular disease were associated with dialysis withdrawal as a primary cause of death. Conversely, interstitial renal disease, angiographically proven ischaemic heart disease, valvular heart disease and malignancy were negatively associated. Analysis of free text comments revealed common themes, portraying an image of physical and psychological decline accelerated by acute illnesses., Conclusions: Death following dialysis withdrawal is common. Factors important to physical independence-prior cerebrovascular disease and increasing age-are associated with withdrawal. When combined with clinician comments this study provides an insight into the clinical decline affecting patients and the complexity of this decision. Early recognition of those likely to withdraw may improve end of life care., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Patients receiving treatment with renal replacement therapy (RRT) have high mortality, and ensuring patient safety in this population is difficult. We aimed to estimate the incidence and nature of medical adverse events contributing to the death of patients being treated with RRT., Methods: This population registry-based retrospective case review study included all patients being treated with RRT for established renal failure in Scotland and who died between 1 January 2008 and 30 June 2011. Deaths were reviewed by consultant nephrologists using a structured questionnaire to identify factors contributing to death occurring in both the inpatient and outpatient setting. Reviewers were able to use any information source deemed relevant, including paper and electronic clinical records, mortality and morbidity meetings and procurator fiscal (Scottish coroner) investigations. Deaths occurring in 2008 and 2009 where avoidable factors were identified that may have or did lead to death of a patient were subject to further review and root cause analysis, in order to identify recurrent themes., Results: Of 1551 deaths in the study period, 1357 were reviewed (87.5%). Cumulative RRT exposure in the cohort was 2.78 million person-days. RRT complications were the primary cause of death in 28 (2.1%). Health-care-associated infection had contributed to 9.6% of all deaths. In 3.5% of deaths, factors were identified which may have or did contribute to death. These were both organizational and human error related and were largely due to five main causes: management of hyperkalaemia, prescribing, out of hours care, infection and haemodialysis vascular access., Conclusions: Adverse events contributing to death in RRT recipients mainly relate to the everyday management of common medical problems and not the technical aspects of RRT. Efforts to avoid harm in this population should address these ubiquitous causes of harm.

Background: It is still not known whether patients survive longer on one modality of dialysis compared to the other. We have tried to answer this question using data from the Scottish Renal Registry., Methods: To avoid the confounding effects of co-morbidity, we limited our survival analysis to those patients listed for a renal transplant and excluded patients with a primary renal diagnosis (PRD) of diabetic nephropathy. We studied patients starting dialysis between 01 January 1982 and 31 December 2006., Results: Three thousand one hundred and ninety-seven patients fulfilled our criteria. A Kaplan-Meier plot showed no difference in survival between initial dialysis modality (log-rank P = 0.996). In the Cox regression model, initial dialysis modality was not a significant predictor of survival; hazard ratio = 0.97 (95% CI 0.80 to 1.18) after adjusting for age, sex and PRD. Age at the start of dialysis, hazard ratio = 1.05 (95% CI 1.04 to 1.06) and a PRD group of 'multi-system disease' or 'unknown' were found to significantly influence survival. When survival was also censored for change in modality, there was no difference in survival over the whole study period with the hazard of death for patients on haemodialysis compared to those on peritoneal dialysis being 1.04 (95% CI 0.78 to 1.38; P = 0.803). Age at the start of dialysis remained a significant predictor of death., Conclusions: This study shows that there was no survival advantage between initial dialysis modalities in non-diabetic patients who are deemed healthy enough for listing for a renal transplant.

Background: The aims of this European study were (i) to compare the level of renal function at the start of dialysis between age groups, gender, primary renal disease, comorbid conditions, treatment modality, time periods and countries, and (ii) to determine which baseline characteristics are associated with the level of renal function at the start of dialysis., Methods: Renal registries participating in the European Renal Association-European Dialysis and Transplant Association Registry provided data on serum creatinine 0-4 weeks before the start of dialysis in incident dialysis patients in 1999 and 2003. Data were available in 11 472 patients from nine renal registries. Glomerular filtration rate (GFR) was estimated by the four-variable Modification of Diet in Renal Disease equation., Results: The unadjusted median eGFR at the start of dialysis was 7.0 mL/min/1.73 m(2) in the 1999 data (median serum creatinine 7.5 mg/dL) and 7.7 mL/min/1.73 m(2) in the 2003 data (serum creatinine 7.0 mg/dL). Using linear regression with adjustment for the other covariates, older patients, males, patients with diabetes mellitus, hypertension/renal vascular disease (HT/RVD) as primary renal disease (vs glomerulonephritis), ischaemic heart disease or peripheral vascular disease and patients starting on peritoneal dialysis (PD) initiated dialysis at higher levels of eGFR (range Δ eGFR: 0.1-1.2 mL/min/1.73 m(2)). Using the same analyses, eGFR differed between countries (range: 6.5-8.6 mL/min/1.73 m(2))., Conclusions: During 2003, patients started dialysis at somewhat higher eGFR levels than those starting during 1999. There were also international differences in eGFR. Such differences may, at least in part, be explained by differences in creatinine measurement methods between countries and time periods. Finally, older patients, males, patients with HT/RVD or comorbidity and those starting on PD had slightly higher eGFR levels than younger patients, females, those with glomerulonephritis, without comorbidity and those starting on haemodialysis. Further research is needed into other, more clinically related factors affecting the decision to start dialysis.

Background: Quantification of proteinuria is important in the assessment of chronic kidney disease (CKD). The aim of this study was to investigate the optimal test to identify significant proteinuria., Methods: We retrospectively assessed the relationship between total protein:creatinine ratio (TPCR), albumin:creatinine ratio (ACR) and 24-h urine total protein in 6842 patients with CKD focusing on performance at thresholds of 0.5 and 1 g/day of proteinuria., Results: The relationship between ACR and TPCR is non-linear. TPCR is highly correlated with 24-h urine protein (Spearman's rho = 0.91), though ACR also performs well (rho = 0.84). Using receiver-operator characteristic curve analysis, TPCR outperforms ACR at predicting 0.5 g/day [area under the curve (AUC) 0.967 vs 0.951, P < 0.001] and 1 g/day of proteinuria (AUC 0.968 vs 0.947, P = 0.004). A TPCR threshold of 100 mg/mmol had a higher sensitivity (94% vs 79%) but lower specificity (88% vs 95%) than an ACR of 70 mg/mmol to predict 1 g/day of total proteinuria. To achieve comparable sensitivity, the ACR threshold falls to 17.5 mg/mmol, with lower specificity than TPCR (69.8%). Sensitivity of TPCR rose with increasing age, and in females: to achieve 95% sensitivity in a man <49 years, requires a TPCR of 65 mg/mmol, compared to 179 mg/mmol in a woman >79 years. Non-albumin proteinuria was a lower proportion of total proteinuria in patients receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockade than in those who were not (P < 0.001)., Conclusions: TPCR is a more sensitive screening test than ACR to predict clinically relevant proteinuria. The diagnostic performance of both tests varies substantially with age and gender, and should be taken into consideration when interpreting results. Total proteinuria cannot be adequately predicted from ACR, and our results suggest that caution is appropriate before utilizing ACR in patients with non-diabetic CKD.

Background: This study evaluates the association between estimated GFR (eGFR) at the start of dialysis and mortality within Europe., Methods: Renal registries participating in the ERA-EDTA Registry were asked to provide data on serum creatinine recorded 0-4 weeks before the start of dialysis in incident dialysis patients in 1999 and 2003. Within this cohort study, data were available in 11 472 patients from nine national or regional European renal registries. Cox regression analyses were performed to examine the association between GFR estimated by the four-variable MDRD equation (eGFR) and all-cause mortality, using a follow-up through 31 December 2005., Results: In the 2003 data, the mean eGFR was 8.6 ml/min/1.73 m(2). The unadjusted survival analyses showed that an increase in eGFR of 1 ml/min/1.73 m(2) was associated with a higher mortality risk (HR = 1.03; 95% CI: 1.03-1.04) that remained similar after adjustment for age, gender, primary renal disease, treatment modality, country and comorbidity. The findings were consistent across gender, treatment modalities, geographical regions and time periods (2003 versus 1999), but the association between a higher eGFR at the start of dialysis and mortality was the strongest in the youngest age groups and in patients with glomerulonephritis. Analyses at centre level showed that a 10% increase in the percentage of patients starting dialysis at high eGFR levels (>or=10.5 ml/min) was associated with a 22% higher mortality risk (HR = 1.22; 95% CI: 1.18-1.26)., Conclusions: This European study showed that a higher eGFR at the start of dialysis was associated with a higher mortality risk. However, an answer to the question when to start dialysis needs to come from randomized controlled trials.