A stepped wedge cluster randomized trial of graphical surveillance of kidney function data to reduce late presentation for kidney replacement therapy.

Late presentation for kidney replacement therapy (KRT) is an important cause of avoidable morbidity and mortality. Here, we evaluated the effect of a complex intervention of graphical estimated glomerular filtration rate (eGFR) surveillance across 15% of the United Kingdom population on the rate of late presentation using data routinely collected by the United Kingdom Renal Registry. A stepped wedge cluster randomized trial was established across 19 sites with eGFR graphs generated from all routine blood tests (community and hospital) across the population served by each site. Graphs were reviewed by trained laboratory or clinical staff and high-risk graphs reported to family doctors. Due to delays outside the control of clinicians and researchers few laboratories activated the intervention in their randomly assigned time period, so the trial was converted to a quasi-experimental design. We studied 6,100 kidney failure events at 20 laboratories served by 17 main kidney units. A total of 63,981 graphs were sent out. After adjustment for calendar time there was no significant reduction in the rate of presentation during the intervention period. Therefore, implementation of eGFR graph surveillance did not reduce the rate of late presentation for KRT after adjustment for secular trends. Thus, graphical surveillance is an intervention aimed at reducing late presentation, but more evidence is required before adoption of this strategy can be recommended.

Ambient heat and acute kidney injury: case-crossover analysis of 1 354 675 automated e-alert episodes linked to high-resolution climate data.

BACKGROUND: As global temperatures continue to rise, the effects of ambient heat on acute kidney injury (AKI) are of growing concern. We used a novel nationwide electronic alert (e-alert) system to detect increases in AKI risk associated with high temperatures. METHODS: We used a case-crossover design to link 1 354 675 AKI episodes occurring in England between April and September in years 2017-2021 to daily maximum temperature data at postcode sector level. AKI episode data were obtained from the UK Renal Registry. There were no further inclusion or exclusion criteria. Conditional logistic regression employing distributed lag non-linear models was used to assess odds of AKI episode on case days compared with day-of-week matched control days. Effects during heatwaves were also assessed using heat-episode analysis. FINDINGS: There were strongly increased odds of AKI episode associated with high temperatures, with odds ratio (OR) 1·623 (95% CI 1·319-1·997) on a day of temperature 32°C compared with one of 17°C, the effects being strongest on a lag of 1 day. There was an OR of 1·020 (1·019-1·020) per 1°C increase in temperature above 17°C. The odds of a heat-related AKI episode were similar between AKI stages 1 and 2, but considerably lower for stage 3 events. A 7-day heatwave in July 2021 was associated with a 28·6% increase in AKI counts (95% CI 26·5-30·7). INTERPRETATION: Heat-related AKI is a growing public health challenge. As even small changes in renal function can affect patient outcomes, susceptible individuals should be advised to take preventive measures whenever hot weather is forecast. Use of an e-alert system allows effects in milder cases that do not require secondary care to also be detected. FUNDING: National Institute for Health and Care Research (NIHR).

Comparative Effectiveness of Dynamic Treatment Strategies for Medication Use and Dosage: Emulating a Target Trial Using Observational Data.

BACKGROUND: Availability of detailed data from electronic health records (EHRs) has increased the potential to examine the comparative effectiveness of dynamic treatment strategies using observational data. Inverse probability (IP) weighting of dynamic marginal structural models can control for time-varying confounders. However, IP weights for continuous treatments may be sensitive to model choice. METHODS: We describe a target trial comparing strategies for treating anemia with darbepoetin in hemodialysis patients using EHR data from the UK Renal Registry 2004 to 2016. Patients received a specified dose (microgram/week) or did not receive darbepoetin. We compared 4 methods for modeling time-varying treatment: (A) logistic regression for zero dose, standard linear regression for log dose; (B) logistic regression for zero dose, heteroscedastic linear regression for log dose; (C) logistic regression for zero dose, heteroscedastic linear regression for log dose, multinomial regression for patients who recently received very low or high doses; and (D) ordinal logistic regression. RESULTS: For this dataset, method (C) was the only approach that provided a robust estimate of the mortality hazard ratio (HR), with less-extreme weights in a fully weighted analysis and no substantial change of the HR point estimate after weight truncation. After truncating IP weights at the 95th percentile, estimates were similar across the methods. CONCLUSIONS: EHR data can be used to emulate target trials estimating the comparative effectiveness of dynamic strategies adjusting treatment to evolving patient characteristics. However, model checking, monitoring of large weights, and adaptation of model strategies to account for these is essential if an aspect of treatment is continuous.

Epidemiology of childhood acute kidney injury in England using e-alerts.

Background: Few studies describe the epidemiology of childhood acute kidney injury (AKI) nationally. Laboratories in England are required to issue electronic (e-)alerts for AKI based on serum creatinine changes. This study describes a national cohort of children who received an AKI alert and their clinical course. Methods: A cross-section of AKI episodes from 2017 are described. Hospital record linkage enabled description of AKI-associated hospitalizations including length of stay (LOS) and critical care requirement. Risk associations with critical care (hospitalized cohort) and 30-day mortality (total cohort) were examined using multivariable logistic regression. Results: In 2017, 7788 children (52% male, median age 4.4 years, interquartile range 0.9-11.5 years) experienced 8927 AKI episodes; 8% occurred during birth admissions. Of 5582 children with hospitalized AKI, 25% required critical care. In children experiencing an AKI episode unrelated to their birth admission, Asian ethnicity, young (<1 year) or old (16-<18 years) age (reference 1-<5 years), and high peak AKI stage had higher odds of critical care. LOS was higher with peak AKI stage, irrespective of critical care admission. Overall, 30-day mortality rate was 3% (n = 251); youngest and oldest age groups, hospital-acquired AKI, higher peak stage and critical care requirement had higher odds of death. For children experiencing AKI alerts during their birth admission, no association was seen between higher peak AKI stage and critical care admission. Conclusions: Risk associations for adverse AKI outcomes differed among children according to AKI type and whether hospitalization was related to birth. Understanding the factors driving AKI development and progression may help inform interventions to minimize morbidity.

Seasonal mortality trends for hospitalised patients with acute kidney injury across England.

BACKGROUND: Incidence of acute kidney injury (AKI) is known to peak in winter months. This is likely influenced by seasonality of commonly associated acute illnesses. We set out to assess seasonal mortality trends for patients who develop AKI across the English National Health Service (NHS) and to better understand associations with patient 'case-mix'. METHODS: The study cohort included all hospitalised adult patients in England who triggered a biochemical AKI alert in 2017. We modelled the impact of season on 30-day mortality using multivariable logistic regression; adjusting for age, sex, ethnicity, index of multiple deprivation (IMD), primary diagnosis, comorbidity (RCCI), elective/emergency admission, peak AKI stage and community/hospital acquired AKI. Seasonal odds ratios for AKI mortality were then calculated and compared across individual NHS hospital trusts. RESULTS: The crude 30-day mortality for hospitalised AKI patients was 33% higher in winter compared to summer. Case-mix adjustment for a wide range of clinical and demographic factors did not fully explain excess winter mortality. The adjusted odds ratio of patients dying in winter vs. summer was 1.25 (1.22-1.29), this was higher than for Autumn and Spring vs. Summer, 1.09 (1.06-1.12) and 1.07 (1.04-1.11) respectively and varied across different NHS trusts (9 out of 90 centres outliers). CONCLUSION: We have demonstrated an excess winter mortality risk for hospitalised patients with AKI across the English NHS, which could not be fully explained by seasonal variation in patient case-mix. Whilst the explanation for worse winter outcomes is not clear, unaccounted differences including 'winter-pressures' merit further investigation.

Increasing numbers and improved overall survival of patients on kidney replacement therapy over the last decade in Europe: an ERA Registry study.

BACKGROUND: The aim of this study was to describe the trends in the incidence, prevalence and survival of patients on kidney replacement therapy (KRT) for end-stage kidney disease (ESKD) across Europe from 2008 to 2017. METHODS: Data from renal registries in 9 countries and 16 regions that provided individual patient data to the ERA Registry from 2008 to 2017 were included. These registries cover 34% of the general population in Europe. Crude and standardized incidence and prevalence per million population (pmp) were determined. Trends over time were studied using Joinpoint regression. Survival probabilities were estimated using Kaplan-Meier analysis and hazard ratios (HRs) using Cox regression analysis. RESULTS: The standardized incidence of KRT was stable [annual percentage change (APC): -1.48 (-3.15; 0.21)] from 2008 (146.0 pmp) to 2011 (141.6 pmp), followed by a slight increase [APC: 1.01 (0.43; 1.60)] to 148.0 pmp in 2017, although trends in incidence varied across countries. This increase was primarily due to a rise in the incidence of KRT in men older than 65 years. Moreover, as a cause of kidney failure, diabetes mellitus is increasing. The standardized prevalence increased from 2008 (990.0 pmp) to 2017 (1166.8 pmp) [APC: 1.82 (1.75; 1.89)]. Patient survival on KRT improved in the time period 2011-13 compared with 2008-[adjusted HR: 0.94 (0.93; 0.95)]. CONCLUSION: This study showed an overall increase in the incidence and prevalence of KRT for ESKD as well as an increase in the KRT patient survival over the last decade in Europe.

Advanced chronic kidney disease among UK children.

The UK Renal Registry currently collects information on UK children with kidney failure requiring long-term kidney replacement therapy (KRT), which supports disease surveillance and auditing of care and outcomes; however, data are limited on children with chronic kidney disease (CKD) not on KRT. METHODS: In March 2020, all UK Paediatric Nephrology centres submitted data on children aged <16 years with severely reduced kidney function as of December 2019, defined as an estimated glomerular filtration rate <30 mL/min/1.73 m2. RESULTS: In total, 1031 children had severe CKD, the majority of whom (80.7%) were on KRT. The overall prevalence was 81.2 (95% CI 76.3 to 86.3) per million of the age-related population. CONCLUSIONS: The prevalence of severe CKD among UK children is largely due to a high proportion of children on long-term KRT. Expanding data capture to include children with CKD before reaching failure will provide greater understanding of the CKD burden in childhood.

The UK Chinese population with kidney failure: Clinical characteristics, management and access to kidney transplantation using 20 years of UK Renal Registry and NHS Blood and Transplant data.

BACKGROUND: Little is known about the clinical demographics of and access to transplantation for Chinese diaspora populations with kidney disease. METHODS: The UK Renal Registry provided data on adults with ethnicity recorded as 'Chinese' or 'White' starting Kidney Replacement Therapy (KRT) 1/1/97-31/12/17. Baseline characteristics were compared between Chinese and White patients. Multivariable logistic regression models were used to investigate the relationships between Chinese ethnicity and i) being listed for deceased-donor transplantation at start of KRT, ii) being listed 2 years after start of KRT, iii) pre-emptive kidney transplantation, iv) kidney transplantation 3 years after start of KRT, and v) living-donor kidney transplantation (LDKT). RESULTS: UK Chinese patients were younger at start of KRT (61.6 vs 65.6 years, p <0.001) and had more diabetic kidney disease (29% vs 20%, p<0.001) and glomerulonephritis (21% vs 13%, p<0.001) than White patients. We found evidence of interaction between ethnicity and sex. Compared to UK White men, UK Chinese men had lower odds of pre-emptive transplant (aOR 0.28, 95% CI [0.10-0.76]) and transplant within 3 years of KRT start (aOR 0.65, [95% CI 0.49-0.87], P = 0.004). UK White women and Chinese women had the same likelihood of pre-emptive transplant (aOR 0.78, 95% CI [0.38-1.61]), or transplant within 3 years of KRT start (aOR 0.94, 95% CI [0.60-1.46]). Both UK Chinese men and women had markedly lower odds of LDKT compared to Whites aOR 0.34 [95% CI 0.21-0.53]. CONCLUSIONS: UK Chinese are less likely to receive a LDKT. UK Chinese men have lower odds of accessing pre-emptive wait-listing and transplantation. Understanding whether these disparities reflect modifiable barriers will help ensure equitable access to transplantation.

Increasing trends in hemodialysis and living donor kidney transplantation for children and young people in the United Kingdom.

BACKGROUND: The UK Renal Registry is responsible for the national collection and reporting of data on all children receiving long-term kidney replacement therapy [KRT], including kidney transplantation. METHODS: All 13 UK pediatric nephrology centers contributed to providing individual patient data from the pediatric population incident to and prevalent to KRT as per the date 31 December 2018. Data for children aged 16-<18 years were presented separately as some were managed under adult care settings with different methods of data collection. Demographics and biochemical data, including kidney function and prevalence of cardiovascular risk factors [hypertension, hypercholesterolemia, BMI] were reported. RESULTS: Eight hundred and twenty-six children (65.4 per million age-related population [pmarp]) and 199 young people (139.4pmarp) in the United Kingdom were prevalent to KRT on 31 December 2018. Overall, the incidence of KRT during 2018 was 9.1 pmarp and 12.6 pmarp in children and young people, respectively. Congenital anomalies of the kidney and urinary tract (CAKUT) were the most prevalent primary diagnoses (52%). Living and deceased donor transplantation was the most common treatment modality (78%). Patients on dialysis had lower age standardized mean height and weight ranges recorded in comparison to transplant patients [median height z score -1.8 vs. -1.1]. 73.1% patients had one or more cardiovascular disease risk factors. CONCLUSIONS: This study highlights increasing prevalence of hemodialysis and living donor transplantation as modalities for KRT. Of those incident to KRT, the highest patient survival was seen among 8-12 years and lowest <2 years. Moreover, there was a demographic shift from Caucasian toward Asian/other ethnicity and from CAKUT to other primary kidney diseases.

Quality assuring early dialysis care: evaluating rates of death and recovery within 90 days of first dialysis using the UK Renal Registry.

Background: Kidney disease registries typically report populations incident to kidney replacement therapy (KRT) after excluding reversible disease. Registry-based audit and quality assurance is thus based on populations depleted of those with the highest early mortality. It is now mandatory for UK kidney units to report all recipients of dialysis, both acute and chronic. This work presents 90-day survival and recovery outcomes for all reported adults. Methods: Seventy adult centres reporting to the UK Renal Registry were included. Those assessed as underreporting death and recovery were excluded. Survival was evaluated using a Kaplan-Meier estimator. Cox regression was used to describe hazard ratios (HRs) for age, sex and acute/chronic dialysis coding on day 1. Analysis of all-cause 90-day mortality with recovery as a competing risk is presented. Results: Twenty-four centres were assessed as underreporting, with rates of death/recovery below the 99.7th centile. Of 5784 dialysis starters in the remaining 46 centres, 2163 (37.4%) were coded as receiving acute dialysis on day 1. Ninety days after starting, 3860 (66.7%) of all starters were receiving KRT, 1157 (20.0%) were alive having stopped, 716 (12.4%) were dead and 51 (0.9%) were lost to follow-up. Mortality was higher among those coded as receiving acute dialysis on day 1 (HR 4.88, P < 0.001). The sub-HR for recovery among those coded as receiving acute compared with chronic dialysis was 56.14 (P < 0.001). Conclusions: Death and recovery rates are substantially higher than reported in conventional incident populations. This work highlights a vulnerable subgroup of patients largely overlooked by most national quality assurance systems.

Acute kidney injury identification for pharmacoepidemiologic studies: Use of laboratory electronic acute kidney injury alerts versus electronic health records in Hospital Episode Statistics.

PURPOSE: A laboratory-based acute kidney injury (AKI) electronic-alert (e-alert) system, with e-alerts sent to the UK Renal Registry (UKRR) and collated in a master patient index (MPI), has recently been implemented in England. The aim of this study was to determine the degree of correspondence between the UKRR-MPI and AKI International Classification Disease-10 (ICD-10) N17 coding in Hospital Episode Statistics (HES) and whether hospital N17 coding correlated with 30-day mortality and emergency re-admission after AKI. METHODS: AKI e-alerts in people aged ≥18 years, collated in the UKRR-MPI during 2017, were linked to HES data to identify a hospitalised AKI population. Multivariable logistic regression was used to analyse associations between absence/presence of N17 codes and clinicodemographic features. Correlation of the percentage coded with N17 and 30-day mortality and emergency re-admission after AKI were calculated at hospital level. RESULTS: In 2017, there were 301 540 adult episodes of hospitalised AKI in England. AKI severity was positively associated with coding in HES, with a high degree of inter-hospital variability-AKI stage 1 mean of 48.2% [SD 14.0], versus AKI stage 3 mean of 83.3% [SD 7.3]. N17 coding in HES depended on demographic features, especially age (18-29 years vs. ≥85 years OR 0.22, 95% CI 0.21-0.23), as well as sex and ethnicity. There was no evidence of association between the proportion of episodes coded for AKI with short-term AKI outcomes. CONCLUSION: Coding of AKI in HES is influenced by many factors that result in an underestimation of AKI. Using e-alerts to triangulate the true incidence of AKI could provide a better understanding of the factors that affect hospital coding, potentially leading to improved coding, patient care and pharmacoepidemiologic research.

Randomized Controlled Trial Evidence of Cost-Effectiveness of a Multifaceted AKI Intervention Approach.

INTRODUCTION: Acute kidney injury (AKI) is associated with increased health care utilization and higher costs. The Tackling AKI study was a multicenter, pragmatic, stepped-wedge cluster randomized trial that demonstrated a reduced hospital length of stay after implementation of a multifaceted AKI intervention (e-alerts, care bundle, and an education program). We tested whether this would result in cost savings. METHODS: A decision-analytic tree model from the payer perspective (National Health Service in the United Kingdom) was generated on which cost-effectiveness analyses were performed using a probabilistic sensitivity analysis, accounting only for direct medical costs. Clinical data from the Tackling AKI study were used as inputs and economic and utility data derived from relevant published literature. RESULTS: A total of 24,059 AKI episodes occurred during the study period, and in 18,887 admissions the patient was discharged alive. When all AKI stages were considered together, the cost per AKI admission was £5065 in the control arm and £4333 in the intervention arm, representing an incremental cost saving of £732 per admission with the intervention. Similar results were obtained when AKI stages were included as separate variables. Costs per quality-adjusted life year were £61,194 in the control group and £51,161 in the intervention group. At a willingness to pay threshold of £20,000 per quality-adjusted life year, the probability of the intervention being cost-effective compared with standard care was 90%. CONCLUSION: An organizational level approach to improve standards of AKI care reduces the cost of hospital admissions and is cost effective within the National Health Service in the United Kingdom.

Associations between Deprivation, Geographic Location, and Access to Pediatric Kidney Care in the United Kingdom.

BACKGROUND AND OBJECTIVES: Pre-emptive kidney transplantation is advocated as best practice for children with kidney failure who are transplant eligible; however, it is limited by late presentation. We aimed to determine whether socioeconomic deprivation and/or geographic location (distance to the center and rural/urban residence) are associated with late presentation, and to what degree these factors could explain differences in accessing pre-emptive transplantation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A cohort study using prospectively collected United Kingdom Renal Registry and National Health Service Blood and Transplant data from January 1, 1996 to December 31, 2016 was performed. We included children aged >3 months to ≤16 years at the start of KRT. Multivariable logistic regression models were used to determine associations between the above exposures and our outcomes: late presentation (defined as starting KRT within 90 days of first nephrology review) and pre-emptive transplantation, with a priori specified covariates. RESULTS: Analysis was performed on 2160 children (41% females), with a median age of 3.8 years (interquartile range, 0.2-9.9 years) at first nephrology review. Excluding missing data, 478 were late presenters (24%); 565 (26%) underwent pre-emptive transplantation, none of whom were late presenting. No association was seen between distance or socioeconomic deprivation with late presentation, in crude or adjusted analyses. Excluding late presenters, greater area affluence was associated with higher odds of pre-emptive transplantation, (odds ratio, 1.20 per quintile greater affluence; 95% confidence interval, 1.10 to 1.31), with children of South Asian (odds ratio, 0.52; 95% confidence interval, 0.36 to 0.76) or Black ethnicity (odds ratio, 0.31; 95% confidence interval, 0.12 to 0.80) less likely to receive one. A longer distance to the center was associated with pre-emptive transplantation on crude analyses; however, this relationship was attenuated (odds ratio, 1.02 per 10 km; 95% confidence interval, 0.99 to 1.05) in the multivariable model. CONCLUSIONS: Socioeconomic deprivation or geographic location are not associated with late presentation in children in the United Kingdom. Geographic location was not independently associated with pre-emptive transplantation; however, children from more affluent areas were more likely to receive a pre-emptive transplant.

Associations with kidney transplant survival and eGFR decline in children and young adults in the United Kingdom: a retrospective cohort study.

BACKGROUND: Although young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes. METHODS: Retrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged < 30 years transplanted 1998-2014. Associations with death-censored graft failure were investigated with multivariable Cox proportional hazards. Multivariable linear regression was used to establish associations with eGFR slope gradients calculated over the last 5 years of observation per individual. RESULTS: The cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3). Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15-19-year and 20-24-year age groups, compared to 25-29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p < 0.0001. However, compared to < 60 mL/min/1.73m2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; - 3.55 mL/min/1.73m2/year (95% CI -4.37, - 2.72), p < 0.0001). CONCLUSIONS: In conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.

Sociodemographic features and mortality of individuals on haemodialysis treatment who test positive for SARS-CoV-2: A UK Renal Registry data analysis.

Kidney disease is a recognised risk factor for poor COVID-19 outcomes. Up to 30 June 2020, the UK Renal Registry (UKRR) collected data for 2,385 in-centre haemodialysis (ICHD) patients with COVID-19 in England and Wales. Overall unadjusted survival at 1 week after date of positive COVID-19 test was 87.5% (95% CI 86.1-88.8%); mortality increased with age, treatment vintage and there was borderline evidence of Asian ethnicity (HR 1.16, 95% CI 0.94-1.44) being associated with higher mortality. Compared to the general population, the relative risk of mortality for ICHD patients with COVID-19 was 45.4 and highest in younger adults. This retrospective cohort study based on UKRR data supports efforts to protect this vulnerable patient group.

The ERA-EDTA Registry Annual Report 2017: a summary.

BACKGROUND: This article presents a summary of the 2017 Annual Report of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry and describes the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in 37 countries. METHODS: The ERA-EDTA Registry received individual patient data on patients undergoing RRT for ESRD in 2017 from 32 national or regional renal registries and aggregated data from 21 registries. The incidence and prevalence of RRT, kidney transplantation activity and survival probabilities of these patients were calculated. RESULTS: In 2017, the ERA-EDTA Registry covered a general population of 694 million people. The incidence of RRT for ESRD was 127 per million population (pmp), ranging from 37 pmp in Ukraine to 252 pmp in Greece. A total of 62% of patients were men, 52% were ≥65 years of age and 23% had diabetes mellitus as the primary renal disease. The treatment modality at the onset of RRT was haemodialysis for 85% of patients. On 31 December 2017, the prevalence of RRT was 854 pmp, ranging from 210 pmp in Ukraine to 1965 pmp in Portugal. The transplant rate in 2017 was 33 pmp, ranging from 3 pmp in Ukraine to 103 pmp in the Spanish region of Catalonia. For patients commencing RRT during 2008-12, the unadjusted 5-year patient survival probability for all RRT modalities combined was 50.8%.