Prospective study of the effect of rituximab on kidney function in membranous nephropathy.

Background: Patients with membranous nephropathy (MN) and poor kidney function or active disease despite previous immunosuppression are underrepresented in clinical trials. It is unknown how effective rituximab is in this population. Methods: This prospective, multi-centre, single-arm, real-world study of patients with active MN [urine protein-creatinine ratio (uPCR) >350 mg/mmol and serum albumin <30 g/L, or a fall in estimated glomerular filtration rate (eGFR) of at least 20% or more over at least 3 months] evaluated rituximab in those with contraindications to calcineurin inhibitors and cytotoxic therapy. The primary outcome was change in rate of eGFR decline before and after rituximab. Complete or partial remission were defined as uPCR <30 mg/mmol or uPCR <350 mg/mmol with a ≥50% fall from baseline, respectively. Results: A total of 180 patients [median age 59 years, interquartile range (IQR) 48-68] received rituximab and were followed up for a median duration of 17 months. Seventy-seven percent had prior immunosuppression. Median eGFR and uPCR at baseline were 49.2 mL/min/1.73 m2 (IQR 34.4-80.6) and 766 mg/mmol (IQR 487-1057), respectively. The annual rate of decline of eGFR fell from 13.9 to 1.7 mL/min/1.73 m2/year following rituximab (Z score = 2.48, P < .0066). At 18 months 12% and 42% of patients were in complete or partial remission, respectively. Rituximab was well tolerated; patient survival was 95.6% at 2 years and in patients in whom eGFR was available, kidney survival was 93% at 2 years. Conclusion: Rituximab significantly reduced the rate of eGFR decline in active MN including those who had received prior immunosuppression or with poor baseline kidney function.

The spectrum of co-existing disease in children with established kidney failure using registry and linked electronic health record data.

BACKGROUND: Children with established kidney failure may have additional medical conditions influencing kidney care and outcomes. This cross-sectional study aimed to examine the prevalence of co-existing diseases captured in the electronic hospital record compared to UK Renal Registry (UKRR) data and differences in coding. METHODS: The study population comprised children aged < 18 years receiving kidney replacement therapy (KRT) in England and Wales on 31/12/2016. Comorbidity data at KRT start was examined in the hospital record and compared to UKRR data. Agreement was assessed by the kappa statistic. Associations between patient and clinical factors and likelihood of coding were examined using multivariable logistic regression. RESULTS: A total of 869 children (62.5% male) had data linkage for inclusion. UKRR records generally reported a higher prevalence of co-existing disease than electronic health records; congenital, non-kidney disease was most commonly reported across both datasets. The highest sensitivity in the hospital record was seen for congenital heart disease (odds ratio (OR) 0.65, 95% confidence interval (CI) 0.51, 0.78) and malignancy (OR 0.63, 95% CI 0.41, 0.85). At best, moderate agreement (kappa ≥ 0.41) was seen between the datasets. Factors associated with higher odds of coding in hospital records included age, while kidney disease and a higher number of comorbidities were associated with lower odds of coding. CONCLUSIONS: Health records generally under-reported co-existing disease compared to registry data with fair-moderate agreement between datasets. Electronic health records offer a non-selective overview of co-existing disease facilitating audit and research, but registry processes are still required to capture paediatric-specific variables pertinent to kidney disease.

Description and Cross-Sectional Analyses of 25,880 Adults and Children in the UK National Registry of Rare Kidney Diseases Cohort.

Introduction: The National Registry of Rare Kidney Diseases (RaDaR) collects data from people living with rare kidney diseases across the UK, and is the world's largest, rare kidney disease registry. We present the clinical demographics and renal function of 25,880 prevalent patients and sought evidence of bias in recruitment to RaDaR. Methods: RaDaR is linked with the UK Renal Registry (UKRR, with which all UK patients receiving kidney replacement therapy [KRT] are registered). We assessed ethnicity and socioeconomic status in the following: (i) prevalent RaDaR patients receiving KRT compared with patients with eligible rare disease diagnoses receiving KRT in the UKRR, (ii) patients recruited to RaDaR compared with all eligible unrecruited patients at 2 renal centers, and (iii) the age-stratified ethnicity distribution of RaDaR patients with autosomal dominant polycystic kidney disease (ADPKD) was compared to that of the English census. Results: We found evidence of disparities in ethnicity and social deprivation in recruitment to RaDaR; however, these were not consistent across comparisons. Compared with either adults recruited to RaDaR or the English population, children recruited to RaDaR were more likely to be of Asian ethnicity (17.3% vs. 7.5%, P-value < 0.0001) and live in more socially deprived areas (30.3% vs. 17.3% in the most deprived Index of Multiple Deprivation (IMD) quintile, P-value < 0.0001). Conclusion: We observed no evidence of systematic biases in recruitment of patients into RaDaR; however, the data provide empirical evidence of negative economic and social consequences (across all ethnicities) experienced by families with children affected by rare kidney diseases.

Identification of patients undergoing chronic kidney replacement therapy in primary and secondary care data: validation study based on OpenSAFELY and UK Renal Registry.

Objective: To validate primary and secondary care codes in electronic health records to identify people receiving chronic kidney replacement therapy based on gold standard registry data. Design: Validation study using data from OpenSAFELY and the UK Renal Registry, with the approval of NHS England. Setting: Primary and secondary care electronic health records from people registered at 45% of general practices in England on 1 January 2020, linked to data from the UK Renal Registry (UKRR) within the OpenSAFELY-TPP platform, part of the NHS England OpenSAFELY covid-19 service. Participants: 38 745 prevalent patients (recorded as receiving kidney replacement therapy on 1 January 2020 in UKRR data, or primary or secondary care data) and 10 730 incident patients (starting kidney replacement therapy during 2020), from a population of 19 million people alive and registered with a general practice in England on 1 January 2020. Main outcome measures: Sensitivity and positive predictive values of primary and secondary care code lists for identifying prevalent and incident kidney replacement therapy cohorts compared with the gold standard UKRR data on chronic kidney replacement therapy. Agreement across the data sources overall, and by treatment modality (transplantation or dialysis) and personal characteristics. Results: Primary and secondary care code lists were sensitive for identifying the UKRR prevalent cohort (91.2% (95% confidence interval (CI) 90.8% to 91.6%) and 92.0% (91.6% to 92.4%), respectively), but not the incident cohort (52.3% (50.3% to 54.3%) and 67.9% (66.1% to 69.7%)). Positive predictive values were low (77.7% (77.2% to 78.2%) for primary care data and 64.7% (64.1% to 65.3%) for secondary care data), particularly for chronic dialysis (53.7% (52.9% to 54.5%) for primary care data and 49.1% (48.0% to 50.2%) for secondary care data). Sensitivity decreased with age and index of multiple deprivation in primary care data, but the opposite was true in secondary care data. Agreement was lower in children, with 30% (295/980) featuring in all three datasets. Half (1165/2315) of the incident patients receiving dialysis in UKRR data had a kidney replacement therapy code in the primary care data within three months of the start date of the kidney replacement therapy. No codes existed whose exclusion would substantially improve the positive predictive value without a decrease in sensitivity. Conclusions: Codes used in primary and secondary care data failed to identify a small proportion of prevalent patients receiving kidney replacement therapy. Codes also identified many patients who were not recipients of chronic kidney replacement therapy in UKRR data, particularly dialysis codes. Linkage with UKRR kidney replacement therapy data facilitated more accurate identification of incident and prevalent kidney replacement therapy cohorts for research into this vulnerable population. Poor coding has implications for any patient care (including eligibility for vaccination, resourcing, and health policy responses in future pandemics) that relies on accurate reporting of kidney replacement therapy in primary and secondary care data.

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).

Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Impact of COVID-19 on patient experience of kidney care: a rapid review.

INTRODUCTION: In March 2020, a pandemic state was declared due to SARS-COV-2 (COVID-19). Patients with kidney disease, especially those on replacement therapies, proved more susceptible to severe infection. This rapid literature review aims to help understand how the pandemic impacted patient experience of kidney care. METHODS: It was conducted in accordance with Cochrane Rapid Review interim guidance. Search terms, 'coronavirus', 'kidney care', and 'patient-reported experience' and terms with similar semantic meaning, identified 1,117 articles in Medline, Scopus, and Worldwide Science. Seventeen were included in the narrative synthesis. RESULTS: The findings were summarised into three themes: remote consultation and telemedicine (n = 9); psychosocial impact (n = 2); and patient satisfaction and patient-reported experience (n = 6). Patients were mostly satisfied with remote consultations, describing them as convenient and allowing avoidance of hospital visits. Anxieties included missing potentially important clinical findings due to lack of physical examination, poor digital literacy, and technical difficulties. Psychosocial impact differed between treatment modalities-transplant recipients expressing feelings of instability and dread of having to return to dialysis, and generally, were less satisfied, citing reduced ability to work and difficulty accessing medications. Those on home dialysis treatments tended to feel safer. Findings focused on aspects of patient experience of kidney care during the pandemic rather than a holistic view. CONCLUSIONS: There was little direct evaluation of modality differences and limited consideration of health inequalities in care experiences. A fuller understanding of these issues would guide policy agendas to support patient experience during future public health crises.

Impact of the COVID-19 pandemic on services for patients with chronic kidney disease: findings of a national survey of UK kidney centres.

BACKGROUND: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. METHODS: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. RESULTS: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. CONCLUSION: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions.

Comparative effectiveness of sotrovimab and molnupiravir for preventing severe COVID-19 outcomes in patients on kidney replacement therapy: observational study using the OpenSAFELY-UKRR and SRR databases.

Background: Due to limited inclusion of patients on kidney replacement therapy (KRT) in clinical trials, the effectiveness of coronavirus disease 2019 (COVID-19) therapies in this population remains unclear. We sought to address this by comparing the effectiveness of sotrovimab against molnupiravir, two commonly used treatments for non-hospitalised KRT patients with COVID-19 in the UK. Methods: With the approval of National Health Service England, we used routine clinical data from 24 million patients in England within the OpenSAFELY-TPP platform linked to the UK Renal Registry (UKRR) to identify patients on KRT. A Cox proportional hazards model was used to estimate hazard ratios (HRs) of sotrovimab versus molnupiravir with regards to COVID-19-related hospitalisations or deaths in the subsequent 28 days. We also conducted a complementary analysis using data from the Scottish Renal Registry (SRR). Results: Among the 2367 kidney patients treated with sotrovimab (n = 1852) or molnupiravir (n = 515) between 16 December 2021 and 1 August 2022 in England, 38 cases (1.6%) of COVID-19-related hospitalisations/deaths were observed. Sotrovimab was associated with substantially lower outcome risk than molnupiravir {adjusted HR 0.35 [95% confidence interval (CI) 0.17-0.71]; P = .004}, with results remaining robust in multiple sensitivity analyses. In the SRR cohort, sotrovimab showed a trend toward lower outcome risk than molnupiravir [HR 0.39 (95% CI 0.13-1.21); P = .106]. In both datasets, sotrovimab had no evidence of an association with other hospitalisation/death compared with molnupiravir (HRs ranged from 0.73 to 1.29; P > .05). Conclusions: In routine care of non-hospitalised patients with COVID-19 on KRT, sotrovimab was associated with a lower risk of severe COVID-19 outcomes compared with molnupiravir during Omicron waves.

The ERA Registry Annual Report 2020: a summary.

Background: The European Renal Association (ERA) Registry collects data on kidney replacement therapy (KRT) in patients with ESKD. This paper is a summary of the ERA Registry Annual Report 2020, also including comparisons among primary renal disease (PRD) groups. Methods: Data were collected from 52 national and regional registries from 34 European countries and countries bordering the Mediterranean Sea: 35 registries from 18 countries providing individual level data and 17 registries from 17 countries providing aggregated data. Using this data, KRT incidence and prevalence, kidney transplantation rates, expected remaining lifetimes and survival probabilities were calculated. Results: A general population of 654.9 million people was covered by the ERA Registry in 2020. The overall incidence of KRT was 128 per million population (p.m.p.). In incident KRT patients, 54% were older than 65 years, 63% were men and the most common PRD was diabetes mellitus (21%). Regarding initial treatment modality in incident patients, 85% received haemodialysis (HD), 11% received peritoneal dialysis (PD) and 4% received a pre-emptive kidney transplant. On 31 December 2020, the prevalence of KRT was 931 p.m.p. In prevalent patients, 45% were older than 65 years, 60% were men and glomerulonephritis was the most common PRD (18%). Of these patients, 58% were on HD, 5% on PD and 37% were living with a kidney transplant. The overall kidney transplantation rate in 2020 was 28 p.m.p., with a majority of kidney grafts from deceased donors (71%). The unadjusted 5-year survival, based on incident dialysis patient from 2011-15, was 41.8%. For patients having received a deceased donor transplant, the unadjusted 5-year survival probability was 86.2% and for patients having received a living donor transplant it was 94.4%. When comparing data by PRD group, differences were found regarding the distribution of age groups, sex and treatment modality received.

Do outcomes for patients with hospital-acquired Acute Kidney Injury (H-AKI) vary across specialties in England?

BACKGROUND: Acute Kidney Injury (AKI) is a common and serious clinical syndrome. There is increasing recognition of heterogeneity in observed AKI across different clinical settings. In this analysis we have utilised a large national dataset to outline, for the first time, differences in burden of hospital acquired AKI (H-AKI) and mortality risk across different treatment specialities in the English National Health Service (NHS). METHODS: A retrospective observational study was conducted using a large national dataset of patients who triggered a biochemical AKI alert in England during 2019. This dataset was enriched through linkage with NHS hospitals administrative and mortality data. Episodes of H-AKI were identified and attributed to the speciality of the supervising consultant during the hospitalisation episode in which the H-AKI alert was generated. Associations between speciality and death in hospital or within 30 days of discharge (30-day mortality) was modelled using logistic regression, adjusting for patient age, sex, ethnicity, socioeconomic status, AKI severity, season and method of admission. RESULTS: In total, 93,196 episodes of H-AKI were studied. The largest number of patients with H-AKI were observed under general medicine (21.9%), care of the elderly (18.9%) and general surgery (11.2%). Despite adjusting for differences in patient case-mix, 30-day mortality risk was consistently lower for patients in surgical specialities compared to general medicine, including general surgery (OR 0.65, 95% CI 0.61 to 0.7) and trauma and orthopaedics (OR 0.52, 95% CI 0.48 to 0.56). Mortality risk was highest in critical care (OR 1.78, 95% CI 1.56 to 2.03) and oncology (OR 1.74, CI 1.54 to 1.96). CONCLUSIONS: Significant differences were identified in the burden of H-AKI and associated mortality risk for patients across different specialities in the English NHS. This work can help inform future service delivery and quality improvement activity for patients with AKI across the NHS.

Comparative effectiveness of two- and three-dose COVID-19 vaccination schedules involving AZD1222 and BNT162b2 in people with kidney disease: a linked OpenSAFELY and UK Renal Registry cohort study.

Background: Kidney disease is a key risk factor for COVID-19-related mortality and suboptimal vaccine response. Optimising vaccination strategies is essential to reduce the disease burden in this vulnerable population. We therefore compared the effectiveness of two- and three-dose schedules involving AZD1222 (AZ; ChAdOx1-S) and BNT162b2 (BNT) among people with kidney disease in England. Methods: With the approval of NHS England, we performed a retrospective cohort study among people with moderate-to-severe kidney disease. Using linked primary care and UK Renal Registry records in the OpenSAFELY-TPP platform, we identified adults with stage 3-5 chronic kidney disease, dialysis recipients, and kidney transplant recipients. We used Cox proportional hazards models to compare COVID-19-related outcomes and non-COVID-19 death after two-dose (AZ-AZ vs BNT-BNT) and three-dose (AZ-AZ-BNT vs BNT-BNT-BNT) schedules. Findings: After two doses, incidence during the Delta wave was higher in AZ-AZ (n = 257,580) than BNT-BNT recipients (n = 169,205; adjusted hazard ratios [95% CIs] 1.43 [1.37-1.50], 1.59 [1.43-1.77], 1.44 [1.12-1.85], and 1.09 [1.02-1.17] for SARS-CoV-2 infection, COVID-19-related hospitalisation, COVID-19-related death, and non-COVID-19 death, respectively). Findings were consistent across disease subgroups, including dialysis and transplant recipients. After three doses, there was little evidence of differences between AZ-AZ-BNT (n = 220,330) and BNT-BNT-BNT recipients (n = 157,065) for any outcome during a period of Omicron dominance. Interpretation: Among individuals with moderate-to-severe kidney disease, two doses of BNT conferred stronger protection than AZ against SARS-CoV-2 infection and severe disease. A subsequent BNT dose levelled the playing field, emphasising the value of heterologous RNA doses in vulnerable populations. Funding: National Core Studies, Wellcome Trust, MRC, and Health Data Research UK.

What data collection methods work best for COVID19 outbreak surveillance for people with end stage kidney disease? An observational cohort study using the UK Renal Registry.

BACKGROUND: Patients on kidney replacement therapy (KRT) are vulnerable to severe illness from COVID-19. Timely, accurate surveillance is essential for planning and implementing infection control at local, regional and national levels. Our aim was to compare two methods of data collection for COVID-19 infections amongst KRT patients in England. METHODS: Adults receiving KRT in England were linked to two sources of data on positive COVID-19 tests recorded March-August 2020: (1) submissions from renal centres to the UK Renal Registry (UKRR) and (2) Public Health England (PHE) laboratory data. Patient characteristics, cumulative incidence by modality (in-centre haemodialysis (ICHD), home HD, peritoneal dialysis (PD) and transplant), and 28-day survival were compared between the two sources. RESULTS: 2,783/54,795 patients (5.1%) had a positive test in the combined UKRR-PHE dataset. Of these 2,783, 87% had positive tests in both datasets. Capture was consistently high for PHE (> 95% across modalities) but varied for UKRR (ranging from ICHD 95% to transplant 78%, p < 0.0001). Patients captured only by PHE were more likely to be on transplant or home therapies (OR 3.5 95% CI [2.3-5.2] vs. ICHD) and to be infected in later months (OR 3.3 95%CI [2.4-4.6] for May-June, OR 6.5 95%CI [3.8-11.3] for July-August, vs. March-April), compared to patients in both datasets. Stratified by modality, patient characteristics and 28-day survival were similar between datasets. CONCLUSIONS: For patients undergoing ICHD treatment the collection of data submitted directly by renal centres allows constant monitoring in real time. For other KRT modalities, using a national swab test dataset through frequent linkage may be the most effective method. Optimising central surveillance can improve patient care by informing interventions and assisting planning at local, regional and national levels.

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.

Long-Term Outcomes in IgA Nephropathy.

BACKGROUND: IgA nephropathy can progress to kidney failure, and risk assessment soon after diagnosis has advantages both for clinical management and the development of new therapeutics. We present relationships among proteinuria, eGFR slope, and lifetime risks for kidney failure. METHODS: The IgA nephropathy cohort (2299 adults and 140 children) of the UK National Registry of Rare Kidney Diseases (RaDaR) was analyzed. Patients enrolled had a biopsy-proven diagnosis of IgA nephropathy plus proteinuria >0.5 g/d or eGFR <60 ml/min per 1.73 m 2 . Incident and prevalent populations and a population representative of a typical phase 3 clinical trial cohort were studied. Analyses of kidney survival were conducted using Kaplan-Meier and Cox regression. eGFR slope was estimated using linear mixed models with random intercept and slope. RESULTS: The median (Q1, Q3) follow-up was 5.9 (3.0, 10.5) years; 50% of patients reached kidney failure or died in the study period. The median (95% confidence interval [CI]) kidney survival was 11.4 (10.5 to 12.5) years; the mean age at kidney failure/death was 48 years, and most patients progressed to kidney failure within 10-15 years. On the basis of eGFR and age at diagnosis, almost all patients were at risk of progression to kidney failure within their expected lifetime unless a rate of eGFR loss ≤1 ml/min per 1.73 m 2 per year was maintained. Time-averaged proteinuria was significantly associated with worse kidney survival and more rapid eGFR loss in incident, prevalent, and clinical trial populations. Thirty percent of patients with time-averaged proteinuria of 0.44 to <0.88 g/g and approximately 20% of patients with time-averaged proteinuria <0.44 g/g developed kidney failure within 10 years. In the clinical trial population, each 10% decrease in time-averaged proteinuria from baseline was associated with a hazard ratio (95% CI) for kidney failure/death of 0.89 (0.87 to 0.92). CONCLUSIONS: Outcomes in this large IgA nephropathy cohort are generally poor with few patients expected to avoid kidney failure in their lifetime. Significantly, patients traditionally regarded as being low risk, with proteinuria <0.88 g/g (<100 mg/mmol), had high rates of kidney failure within 10 years.

Predicting mortality after start of long-term dialysis-International validation of one- and two-year prediction models.

BACKGROUND: Mortality prediction is critical on long-term kidney replacement therapy (KRT), both for individual treatment decisions and resource planning. Many mortality prediction models already exist, but as a major shortcoming most of them have only been validated internally. This leaves reliability and usefulness of these models in other KRT populations, especially foreign, unknown. Previously two models were constructed for one- and two-year mortality prediction of Finnish patients starting long-term dialysis. These models are here internationally validated in KRT populations of the Dutch NECOSAD Study and the UK Renal Registry (UKRR). METHODS: We validated the models externally on 2051 NECOSAD patients and on two UKRR patient cohorts (5328 and 45493 patients). We performed multiple imputation for missing data, used c-statistic (AUC) to assess discrimination, and evaluated calibration by plotting average estimated probability of death against observed risk of death. RESULTS: Both prediction models performed well in the NECOSAD population (AUC 0.79 for the one-year model and 0.78 for the two-year model). In the UKRR populations, performance was slightly weaker (AUCs: 0.73 and 0.74). These are to be compared to the earlier external validation in a Finnish cohort (AUCs: 0.77 and 0.74). In all tested populations, our models performed better for PD than HD patients. Level of death risk (i.e., calibration) was well estimated by the one-year model in all cohorts but was somewhat overestimated by the two-year model. CONCLUSIONS: Our prediction models showed good performance not only in the Finnish but in foreign KRT populations as well. Compared to the other existing models, the current models have equal or better performance and fewer variables, thus increasing models' usability. The models are easily accessible on the web. These results encourage implementing the models into clinical decision-making widely among European KRT populations.

Factors associated with COVID-19 vaccine uptake in people with kidney disease: an OpenSAFELY cohort study.

OBJECTIVE: To characterise factors associated with COVID-19 vaccine uptake among people with kidney disease in England. DESIGN: Retrospective cohort study using the OpenSAFELY-TPP platform, performed with the approval of NHS England. SETTING: Individual-level routine clinical data from 24 million people across GPs in England using TPP software. Primary care data were linked directly with COVID-19 vaccine records up to 31 August 2022 and with renal replacement therapy (RRT) status via the UK Renal Registry (UKRR). PARTICIPANTS: A cohort of adults with stage 3-5 chronic kidney disease (CKD) or receiving RRT at the start of the COVID-19 vaccine roll-out was identified based on evidence of reduced estimated glomerular filtration rate (eGFR) or inclusion in the UKRR. MAIN OUTCOME MEASURES: Dose-specific vaccine coverage over time was determined from 1 December 2020 to 31 August 2022. Individual-level factors associated with receipt of a 3-dose or 4-dose vaccine series were explored via Cox proportional hazards models. RESULTS: 992 205 people with stage 3-5 CKD or receiving RRT were included. Cumulative vaccine coverage as of 31 August 2022 was 97.5%, 97.0% and 93.9% for doses 1, 2 and 3, respectively, and 81.9% for dose 4 among individuals with one or more indications for eligibility. Delayed 3-dose vaccine uptake was associated with younger age, minority ethnicity, social deprivation and severe mental illness-associations that were consistent across CKD severity subgroups, dialysis patients and kidney transplant recipients. Similar associations were observed for 4-dose uptake. CONCLUSION: Although high primary vaccine and booster dose coverage has been achieved among people with kidney disease in England, key disparities in vaccine uptake remain across clinical and demographic groups and 4-dose coverage is suboptimal. Targeted interventions are needed to identify barriers to vaccine uptake among under-vaccinated subgroups identified in the present study.

Association between practice coding of chronic kidney disease (CKD) in primary care and subsequent hospitalisations and death: a cohort analysis using national audit data.

OBJECTIVE: To examine the association between practice percentage coding of chronic kidney disease (CKD) in primary care with risk of subsequent hospitalisations and death. DESIGN: Retrospective cohort study using linked electronic healthcare records. SETTING: 637 general practitioner (GP) practices in England. PARTICIPANTS: 167 208 patients with CKD stages 3-5 identified by 2 measures of estimated glomerular filtration rate <60 mL/min/1.73 m2, separated by at least 90 days, excluding those with coded initiation of renal replacement therapy. MAIN OUTCOME MEASURES: Hospitalisations with cardiovascular (CV) events, heart failure (HF), acute kidney injury (AKI) and all-cause mortality RESULTS: Participants were followed for (median) 3.8 years for hospital outcomes and 4.3 years for deaths. Rates of hospitalisations with CV events and HF were lower in practices with higher percentage CKD coding. Trends of a small reduction in AKI but no substantial change in rate of deaths were also observed as CKD coding increased. Compared with patients in the median performing practice (74% coded), patients in practices coding 55% of CKD cases had a higher rate of CV hospitalisations (HR 1.061 (95% CI 1.015 to 1.109)) and HF hospitalisations (HR 1.097 (95% CI 1.013 to 1.187)) and patients in practices coding 88% of CKD cases had a reduced rate of CV hospitalisations (HR 0.957 (95% CI 0.920 to 0.996)) and HF hospitalisations (HR 0.918 (95% CI 0.855 to 0.985)). We estimate that 9.0% of CV hospitalisations and 16.0% of HF hospitalisations could be prevented by improving practice CKD coding from 55% to 88%. Prescription of antihypertensives was the most dominant predictor of a reduction in hospitalisation rates for patients with CKD, followed by albuminuria testing and use of statins. CONCLUSIONS: Higher levels of CKD coding by GP practices were associated with lower rates of CV and HF events, which may be driven by increased use of antihypertensives and regular albuminuria testing, although residual confounding cannot be ruled out.

Comparison of Outcomes of In-Centre Haemodialysis Patients between the 1st and 2nd COVID-19 Outbreak in England, Wales, and Northern Ireland: A UK Renal Registry Analysis.

INTRODUCTION: This retrospective cohort study compares in-centre haemodialysis (ICHD) patients' outcomes between the 1st and 2nd waves of the COVID-19 pandemic in England, Wales, and Northern Ireland. METHODS: All people aged ≥18 years receiving ICHD at 31 December 2019, who were still alive and not in receipt of a kidney transplant at 1 March and who had a positive polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 31 January 2021, were included. The COVID-19 infections were split into two "waves": wave 1 from March to August 2020 and wave 2 from September 2020 to January 2021. Cumulative incidence of COVID-19, multivariable Cox models for risk of positivity, median, and 95% credible interval of reproduction number in dialysis units were calculated separately for wave 1 and wave 2. Survival and hazard ratios for mortality were described with age- and sex-adjusted Kaplan-Meier plots and multivariable Cox proportional models. RESULTS: 4,408 ICHD patients had COVID-19 during the study period. Unadjusted survival at 28 days was similar in both waves (wave 1 75.6% [95% confidence interval [CI]: 73.7-77.5], wave 2 76.3% [95% CI 74.3-78.2]), but death occurred more rapidly after detected infection in wave 1. Long vintage treatment and not being on the transplant waiting list were associated with higher mortality in both waves. CONCLUSIONS: Risk of death of patients on ICHD treatment with COVID-19 remained unchanged between the first and second outbreaks. This highlights that this vulnerable patient group needs to be prioritized for interventions to prevent severe COVID-19, including vaccination, and the implementation of measures to reduce the risk of transmission alone is not sufficient.

Centre variation in mortality following post-hospitalization acute kidney injury: analysis of a large national cohort.

BACKGROUND: Routine monitoring of outcomes for patients with acute kidney injury (AKI) is important to drive ongoing quality improvement in patient care. In this study we describe the development of a case mix-adjusted 30-day mortality indicator for patients with post-hospitalization AKI (PH-AKI) across England to facilitate identification of any unwarranted centre variation in outcomes. METHODS: We utilized a routinely collected national dataset of biochemically detected AKI cases linked with national hospitals administrative and mortality data. A total of 250 504 PH-AKI episodes were studied across 103 National Health Service hospital trusts between January 2017 and December 2018. Standardized mortality ratios (SMRs) were calculated for each trust using logistic regression, adjusting for age, sex, primary diagnosis, comorbidity score, AKI severity, month of AKI and admission method. RESULTS: The mean 30-day mortality rate was high, at 28.6%. SMRs for 23/103 trusts were classed as outliers, 12 above and 11 below the 95% confidence limits. Patients with PH-AKI had mortality rates >5 times higher than the overall hospitalized population in 90/136 diagnosis groups and >10 times higher in 60/136 groups. Presentation at trusts with a co-located specialist nephrology service was associated with a lower mortality risk, as was South Asian or Black ethnicity. Deprivation, however, was associated with higher mortality. CONCLUSIONS: This is the largest multicentre analysis of mortality for patients with biochemically ascertained PH-AKI to date, demonstrating once again the considerable risk associated with developing even mild elevations in serum creatinine. Mortality rates varied considerably across centres and those identified as outliers will now need to carefully interrogate local care pathways to understand and address the reasons for this, with national policy required to tackle the identified health disparities.