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.

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.

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.

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.

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.

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.

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.

Do routine hospital data accurately record comorbidity in advanced kidney disease populations? A record linkage cohort study.

BACKGROUND: Routine healthcare datasets capturing clinical and administrative information are increasingly being used to examine health outcomes. The accuracy of such data is not clearly defined. We examine the accuracy of diagnosis recording in individuals with advanced chronic kidney disease using a routine healthcare dataset in England with comparison to information collected by trained research nurses. METHODS: We linked records from the Access to Transplant and Transplant Outcome Measures study to the Hospital Episode Statistics dataset. International Classification of Diseases (ICD-10) and Office for Population Censuses and Surveys Classification of Interventions and Procedures (OPCS-4) codes were used to identify medical conditions from hospital data. The sensitivity, specificity, positive and negative predictive values were calculated for a range of diagnoses. RESULTS: Comorbidity information was available in 96% of individuals prior to starting kidney replacement therapy. There was variation in the accuracy of individual medical conditions identified from the routine healthcare dataset. Sensitivity and positive predictive values ranged from 97.7 and 90.4% for diabetes and 82.6 and 82.9% for ischaemic heart disease to 44.2 and 28.4% for liver disease. CONCLUSIONS: Routine healthcare datasets accurately capture certain conditions in an advanced chronic kidney disease population. They have potential for use within clinical and epidemiological research studies but are unlikely to be sufficient as a single resource for identifying a full spectrum of comorbidities.

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

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

Causes of renal allograft failure in the UK: trends in UK Renal Registry and National Health Service Blood and Transplant data from 2000 to 2013.

Background: Improvement in long-term renal allograft survival is impeded by incomplete or erroneous coding of causes of allograft loss. This study reports 13-year trends in causes of graft failure across the UK. Methods: National Health Service Blood and Transplant (NHSBT) and UK Renal Registry data were linked to describe UK kidney patients transplanted in 2000-13. NHSBT graft failure categories were used, with 'other' recoded when free text was available. Adjusted analyses examined the influence of age, ethnicity and donor type on causes of graft failure. Results: In 22 730 recipients, 5389 (23.7%) grafts failed within a median follow-up of 5 years. The two most frequent causes were death with a functioning graft (40.8%) and alloimmune pathology (25.0%). Graft survival was higher in recipients who were younger (mean 47.3 versus 50.7 years), received a pre-emptive transplant (20.2% versus 10.4%), spent less time on dialysis (median 1.6 versus 2.4 years) and received a living donor transplant (36.3% versus 22.2%), with no differences by sex, ethnicity or human leucocyte antigen mismatch. Allograft failure within 2 years of transplantation fell from 12.5% (2000-4) to 9.8% (2009-13). Surgical- and alloimmune-related failures decreased over time while death with a functioning graft became more common. Age, ethnicity and donor type were factors in recurrent primary disease and alloimmune pathology. Conclusions: Since 2000 there have been reductions in surgical and alloimmune graft failures in the UK. However, graft failure codes need to be revised if they are to remain useful and effective in epidemiological and quality improvement trials.

Randomized Trial Comparing Proactive, High-Dose versus Reactive, Low-Dose Intravenous Iron Supplementation in Hemodialysis (PIVOTAL): Study Design and Baseline Data.

BACKGROUND: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. METHODS: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin < 400 µg/L and transferrin saturation (TSAT) levels < 30% receiving erythropoiesis-stimulating agents (ESA) were eligible. Enrolled patients were randomized to a proactive, high-dose IV iron arm (iron sucrose 400 mg/month unless ferritin > 700 µg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 µg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. RESULTS: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. CONCLUSIONS: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. TRIAL REGISTRATION: EudraCT number: 2013-002267-25.

Predicting 6-month mortality risk of patients commencing dialysis treatment for end-stage kidney disease.

BACKGROUND: There is evidence that end-stage kidney disease patients who are older or with more comorbidity may have a poor trade-off between benefits of dialysis and potential harms. We aimed to develop a tool for predicting patient mortality in the early stages of receiving dialysis. METHODS: In 23 658 patients aged 15+ years commencing dialysis between 2000 and 2009 in Australia and New Zealand a point score tool was developed to predict 6-month mortality based on a logistic regression analysis of factors available at dialysis initiation. Temporal validation used 2009-11 data from Australia and New Zealand. External validation used the UK Renal Registry. RESULTS: Within 6 months of commencing dialysis 6.1% of patients had died. A small group (4.7%) of patients had a high predicted mortality risk (>20%), as predicted by the point score tool. Predictive variables were: older age, underweight, chronic lung disease, coronary artery disease, peripheral vascular disease, cerebrovascular disease (particularly for patients <60 years of age), late referral to nephrologist care and underlying cause of renal disease. The new point score tool outperformed existing models, and had an area under the receiver operating characteristic curve of 0.755 on temporal validation with acceptable calibration and 0.713 on external validation with poor calibration. CONCLUSION: Our point score tool for predicting 6-month mortality in patients at dialysis commencement has sufficient prognostic accuracy to use in Australia and New Zealand for prognosis and identification of high risk patients who may be given appropriate supportive care. Use in other countries requires further study.

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).

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.

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.

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.

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.

UK Renal Registry 15th annual report: Chapter 5 survival and causes of death of UK adult patients on renal replacement therapy in 2011: national and centre-specific analyses.

INTRODUCTION: These analyses examine a) survival from the start of renal replacement therapy (RRT) based on the total incident UK RRT population reported to the UK Renal Registry, b) survival of prevalent patients. Changes in survival between 1997 and 2011 are also reported. METHODS: Survival was calculated for both incident and prevalent patients on RRT and compared between the UK countries after adjustment for age. Survival of incident patients (starting RRT during 2010) was calculated both from the start of RRT and from 90 days after starting RRT, both with and without censoring at transplantation. Prevalent dialysis patients were censored at transplantation; this means that the patient is considered alive up to the point of transplantation, but the patient's status post-transplant is not considered. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. Causes of death were analysed for both groups. The relative risk of death was calculated compared with the general UK population. RESULTS: The unadjusted 1 year after 90 day survival for patients starting RRT in 2010 was 87.3%, representing an increase from the previous year (86.6%). In incident patients aged 18-64 years, the unadjusted 1 year survival had risen from 86.0% in patients starting RRT in 1997 to 92.6% in patients starting RRT in 2010 and for those aged ≥65 it had increased from 63.9% to 77.0% over the same period. The age-adjusted one year survival (adjusted to age 60) of prevalent dialysis patients increased from 88.1% in the 2001 cohort to 89.8% in the 2010 cohort. Prevalent diabetic patient one year survival rose from 82.1% in the 2002 cohort to 84.7% in the 2010 cohort. The age-standardised mortality ratio for prevalent RRT patients compared with the general population was 18 for age group 30-34 and 2.5 at age 85+ years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 22% of deaths, infection and treatment withdrawal 18% each and 25% were recorded as other causes of death. Treatment withdrawal was a more frequent cause of death in those incident patients aged ≥65 than in younger patients. The median life years remaining for a 25-29 year old on RRT was 18 years and approximately three years for a 75+ year old. CONCLUSIONS: Survival of patients starting RRT has improved in the 2010 incident cohort. The relative risk of death on RRT compared with the general population has fallen since 2001.

UK Renal Registry 16th annual report: chapter 5 comorbidities and current smoking status amongst patients starting renal replacement therapy in England, Wales and Northern Ireland from 2011 to 2012.

INTRODUCTION: Comorbidities are significant predictors of mortality and other adverse outcomes. Case-mix adjustment is integral to quality reporting, risk adjustment in clinical research, resource allocation and management of patients with comorbid conditions in day to day practice such as dialysis access formation and transplant wait-listing. This study describes the comorbidity data submitted to the UK Renal Registry (UKRR) in incident renal replacement therapy (RRT) patients and examines the association between these comorbidities and early mortality. METHODS: Incident patients reported to the UKRR with comorbidity data in 2011 and 2012 (n = 7,085) were included in analyses exploring the association of comorbidities with patient demographics and treatment modality. For analyses examining the association between comorbidities and survival, adult patients starting RRT between 2007 and 2012 in centres reporting to the UKRR with comorbidity data were included. The relationship between comorbidities and mortality at 90 days and one year after 90 days from start of RRT were explored using Cox regression. RESULTS: Completeness of comorbidity data was 55% in 2012 compared with 56% in 2007. Of patients with data, 52.9% had one or more comorbidities. Diabetes mellitus and ischaemic heart disease were the most common conditions, observed in 35% and 19% of patients respectively. Fourteen percent of incident RRT patients in the 2-year period were recorded as current smokers. The prevalence of comorbidity increased with increasing age across all ethnic groups. In multivariable survival analysis, malignancy and liver disease were strong independent predictors of poor survival at 1-year after 90 days from the start of RRT in patients <65 years. CONCLUSIONS: Continuing efforts from renal centres to improve data capture in addition to the use of data linkage and statistical techniques such as multiple imputation by the UKRR are likely to lead to enhanced case mix adjustment in the future.

UK Renal Registry 16th annual report: chapter 8 survival and cause of death of UK adult patients on renal replacement therapy in 2012: national and centre-specific analyses.

INTRODUCTION: These analyses examine: a) survival from the start of renal replacement therapy (RRT); b) survival amongst all prevalent dialysis patients alive on 31st December 2011; c) the cause of death for incident and prevalent patients and d) the projected life years remaining for patients starting RRT. Changes in survival between the 1997 and 2011 cohort are also reported. METHODS: Survival was calculated for both incident and prevalent patients on RRT. Survival of incident patients (starting RRT during 2011) was calculated both from the start of RRT and from 90 days after starting RRT, both with and without censoring at transplantation. Prevalent dialysis patients were censored at transplantation. Both Kaplan-Meier and Cox adjusted models were used to calculate survival. The relative risk of death was calculated and compared with the UK general population. RESULTS: The unadjusted 1 year after 90 day survival for patients starting RRT in 2011 was 87.5%, representing an increase from the previous year (87.3%). The age-adjusted one year survival (adjusted to age 60) of prevalent dialysis patients increased from 88.2% in the 2002 cohort to 89.7% in the 2011 cohort. Prevalent diabetic patient one year survival rose from 81.6% in the 2002 cohort to 84.9% in the 2011 cohort. The age-standardised mortality ratio for prevalent RRT patients compared with the general population was 16.6 for age group 35-39 and 2.7 at age 85+ years. In the prevalent RRT dialysis population, cardiovascular disease accounted for 22% of deaths, infection 17% and treatment withdrawal 19%. The median life years remaining for a 25-29 year old on RRT was 18.5 years and approximately 2.5 for a 75+ year old. CONCLUSIONS: Survival of patients starting RRT has improved in the 2011 incident cohort. The relative risk of death on RRT compared with the general population has fallen since 2001.