Primary and secondary care service use and costs associated with frailty in an ageing population: longitudinal analysis of an English primary care cohort of adults aged 50 and over, 2006-2017.

BACKGROUND: Frailty becomes more prevalent and healthcare needs increase with age. Information on the impact of frailty on population level use of health services and associated costs is needed to plan for ageing populations. AIM: To describe primary and secondary care service use and associated costs by electronic Frailty Index (eFI) category. DESIGN AND SETTING: Retrospective cohort using electronic health records. Participants aged ≥50 registered in primary care practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre, 2006-2017. METHODS: Primary and secondary care use (totals and means) were stratified by eFI category and age group. Standardised 2017 costs were used to calculate primary, secondary and overall costs. Generalised linear models explored associations between frailty, sociodemographic characteristics. Adjusted mean costs and cost ratios were produced. RESULTS: Individual mean annual use of primary and secondary care services increased with increasing frailty severity. Overall cohort care costs for were highest in mild frailty in all 12 years, followed by moderate and severe, although the proportion of the population with severe frailty can be expected to increase over time. After adjusting for sociodemographic factors, compared to the fit category, individual annual costs doubled in mild frailty, tripled in moderate and quadrupled in severe. CONCLUSIONS: Increasing levels of frailty are associated with an additional burden of individual service use. However, individuals with mild and moderate frailty contribute to higher overall costs. Earlier intervention may have the most potential to reduce service use and costs at population level.

The impact of non-alcoholic fatty liver disease and liver fibrosis on adverse clinical outcomes and mortality in patients with chronic kidney disease: a prospective cohort study using the UK Biobank.

BACKGROUND: Chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) frequently co-exist. We assess the impact of having NAFLD on adverse clinical outcomes and all-cause mortality for people with CKD. METHODS: A total of 18,073 UK Biobank participants identified to have CKD (eGFR < 60 ml/min/1.73 m2 or albuminuria > 3 mg/mmol) were prospectively followed up by electronic linkage to hospital and death records. Cox-regression estimated the hazard ratios (HR) associated with having NAFLD (elevated hepatic steatosis index or ICD-code) and NAFLD fibrosis (elevated fibrosis-4 (FIB-4) score or NAFLD fibrosis score (NFS)) on cardiovascular events (CVE), progression to end-stage renal disease (ESRD) and all-cause mortality. RESULTS: 56.2% of individuals with CKD had NAFLD at baseline, and 3.0% and 7.7% had NAFLD fibrosis according to a FIB-4 > 2.67 and NFS ≥ 0.676, respectively. The median follow-up was 13 years. In univariate analysis, NAFLD was associated with an increased risk of CVE (HR 1.49 [1.38-1.60]), all-cause mortality (HR 1.22 [1.14-1.31]) and ESRD (HR 1.26 [1.02-1.54]). Following multivariable adjustment, NAFLD remained an independent risk factor for CVE overall (HR 1.20 [1.11-1.30], p < 0.0001), but not ACM or ESRD. In univariate analysis, elevated NFS and FIB-4 scores were associated with increased risk of CVE (HR 2.42 [2.09-2.80] and 1.64 [1.30-2.08]) and all-cause mortality (HR 2.82 [2.48-3.21] and 1.82 [1.47-2.24]); the NFS score was also associated with ESRD (HR 5.15 [3.52-7.52]). Following full adjustment, the NFS remained associated with an increased incidence of CVE (HR 1.19 [1.01-1.40]) and all-cause mortality (HR 1.31 [1.13-1.52]). CONCLUSIONS: In people with CKD, NAFLD is associated with an increased risk of CVE, and the NAFLD fibrosis score is associated with an elevated risk of CVE and worse survival.

Associations with age and glomerular filtration rate in a referred population with chronic kidney disease: methods and baseline data from a UK multicentre cohort study (NURTuRE-CKD).

BACKGROUND: Chronic kidney disease (CKD) is common but heterogenous and is associated with multiple adverse outcomes. The National Unified Renal Translational Research Enterprise (NURTuRE)-CKD cohort was established to investigate risk factors for clinically important outcomes in persons with CKD referred to secondary care. METHODS: Eligible participants with CKD stages G3-4 or stages G1-2 plus albuminuria >30 mg/mmol were enrolled from 16 nephrology centres in England, Scotland and Wales from 2017 to 2019. Baseline assessment included demographic data, routine laboratory data and research samples. Clinical outcomes are being collected over 15 years by the UK Renal Registry using established data linkage. Baseline data are presented with subgroup analysis by age, sex and estimated glomerular filtration rate (eGFR). RESULTS: A total of 2996 participants was enrolled. Median (interquartile range) age was 66 (54-74) years, eGFR 33.8 (24.0-46.6) mL/min/1.73 m2 and urine albumin to creatinine ratio 209 (33-926) mg/g; 58.5% were male. Of these participants, 1883 (69.1%) were in high-risk CKD categories. Primary renal diagnosis was CKD of unknown cause in 32.3%, glomerular disease in 23.4% and diabetic kidney disease in 11.5%. Older participants and those with lower eGFR had higher systolic blood pressure and were less likely to be treated with renin-angiotensin system inhibitors (RASi) but were more likely to receive a statin. Female participants were less likely to receive a RASi or statin. CONCLUSIONS: NURTuRE-CKD is a prospective cohort of persons who are at relatively high risk of adverse outcomes. Long-term follow-up and a large biorepository create opportunities for research to improve risk prediction and to investigate underlying mechanisms to inform new treatment development.

Frailty transitions and prevalence in an ageing population: longitudinal analysis of primary care data from an open cohort of adults aged 50 and over in England, 2006-2017.

INTRODUCTION: frailty is common in older adults and is associated with increased health and social care use. Longitudinal information is needed on population-level incidence, prevalence and frailty progression to plan services to meet future population needs. METHODS: retrospective open cohort study using electronic health records of adults aged ≥50 from primary care in England, 2006-2017. Frailty was calculated annually using the electronic Frailty Index (eFI). Multistate models estimated transition rates between each frailty category, adjusting for sociodemographic characteristics. Prevalence overall for each eFI category (fit, mild, moderate and severe) was calculated. RESULTS: the cohort included 2,171,497 patients and 15,514,734 person-years. Frailty prevalence increased from 26.5 (2006) to 38.9% (2017). The average age of frailty onset was 69; however, 10.8% of people aged 50-64 were already frail in 2006. Estimated transitions from fit to any level of frailty were 48/1,000 person-years aged 50-64, 130/1,000 person-years aged 65-74, 214/1,000 person-years aged 75-84 and 380/1,000 person-years aged ≥ 85. Transitions were independently associated with older age, higher deprivation, female sex, Asian ethnicity and urban dwelling. Mean time spent in each frailty category decreased with age, with the longest period spent in severe frailty at all ages. CONCLUSIONS: frailty is prevalent in adults aged ≥50 and time spent in successive frailty states is longer as frailty progresses, resulting in extended healthcare burden. Larger population numbers and fewer transitions in adults aged 50-64 present an opportunity for earlier identification and intervention. A large increase in frailty over 12 years highlights the urgency of informed service planning in ageing populations.

What makes a multidisciplinary medication review and deprescribing intervention for older people work well in primary care? A realist review and synthesis.

BACKGROUND: A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. METHODS: A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. FINDINGS: A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with 'quick wins', offering deprescribing as 'drug holidays', and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. CONCLUSION: We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.

Primary care consultations for respiratory tract symptoms during the COVID-19 pandemic: a cohort study including 70,000 people in South West England.

BACKGROUND: Primary care consultations for respiratory tract symptoms including identifying and managing COVID-19 during the pandemic have not been characterized. METHODS: A retrospective cohort analysis using routinely collected records from 70,431 adults aged 18+ in South England within the Electronic Care and Health Information Analytics (CHIA) database. Total volume and type of consultations (face-to-face, home visits, telephone, email/video, or out of hours) for respiratory tract symptoms between 1 January and 31 July 2020 (during the first wave of the pandemic) were compared with the equivalent period in 2019 for the same cohort. Descriptive statistics were used to summarize consultations by sociodemographic and clinical characteristics, and by COVID-19 diagnosis and outcomes (death, hospitalization, and pneumonia). RESULTS: Overall consultations for respiratory tract symptoms increased by 229% during the pandemic compared with the preceding year. This included significant increases in telephone consultations by 250%, a 1,574% increase in video/email consultations, 105% increase in home visits, and 92% increase in face-to-face consultations. Nearly 60% of people who presented with respiratory symptoms were tested for COVID-19 and 16% confirmed or clinically suspected to have the virus. Those with complications including pneumonia, requiring hospitalization, and who died were more likely to be seen in-person. CONCLUSION: During the pandemic, primary care substantially increased consultations for respiratory tract symptoms to identify and manage people with COVID-19. These findings should be balanced against national reports of reduced GP workload for non-COVID care.

The dynamics of frailty development and progression in older adults in primary care in England (2006-2017): a retrospective cohort profile.

BACKGROUND: Frailty is a common condition in older adults and has a major impact on patient outcomes and service use. Information on the prevalence in middle-aged adults and the patterns of progression of frailty at an individual and population level is scarce. To address this, a cohort was defined from a large primary care database in England to describe the epidemiology of frailty and understand the dynamics of frailty within individuals and across the population. This article describes the structure of the dataset, cohort characteristics and planned analyses. METHODS: Retrospective cohort study using electronic health records. Participants were aged ≥50 years registered in practices contributing to the Oxford Royal College of General Practitioners Research and Surveillance Centre between 2006 to 2017. Data include GP practice details, patient sociodemographic and clinical characteristics, twice-yearly electronic Frailty Index (eFI), deaths, medication use and primary and secondary care health service use. Participants in each cohort year by age group, GP and patient characteristics at cohort entry are described. RESULTS: The cohort includes 2,177,656 patients, contributing 15,552,946 person-years, registered at 419 primary care practices in England. The mean age was 61 years, 52.1% of the cohort was female, and 77.6% lived in urban environments. Frailty increased with age, affecting 10% of adults aged 50-64 and 43.7% of adults aged ≥65. The prevalence of long-term conditions and specific frailty deficits increased with age, as did the eFI and the severity of frailty categories. CONCLUSION: A comprehensive understanding of frailty dynamics will inform predictions of current and future care needs to facilitate timely planning of appropriate interventions, service configurations and workforce requirements. Analysis of this large, nationally representative cohort including participants aged ≥50 will capture earlier transitions to frailty and enable a detailed understanding of progression and impact. These results will inform novel simulation models which predict future health and service needs of older people living with frailty. STUDY REGISTRATION: Registered on www.clinicaltrials.gov October 25th 2019, NCT04139278 .

International prescribing patterns and polypharmacy in older people with advanced chronic kidney disease: results from the European Quality study.

BACKGROUND: People with chronic kidney disease (CKD) are at high risk of polypharmacy. However, no previous study has investigated international prescribing patterns in this group. This article aims to examine prescribing and polypharmacy patterns among older people with advanced CKD across the countries involved in the European Quality (EQUAL) study. METHODS: The EQUAL study is an international prospective cohort study of patients ≥65 years of age with advanced CKD. Baseline demographic, clinical and medication data were analysed and reported descriptively. Polypharmacy was defined as ≥5 medications and hyperpolypharmacy as ≥10. Univariable and multivariable linear regressions were used to determine associations between country and the number of prescribed medications. Univariable and multivariable logistic regression were used to determine associations between country and hyperpolypharmacy. RESULTS: Of the 1317 participants from five European countries, 91% were experiencing polypharmacy and 43% were experiencing hyperpolypharmacy. Cardiovascular medications were the most prescribed medications (mean 3.5 per person). There were international differences in prescribing, with significantly greater hyperpolypharmacy in Germany {odds ratio (OR) 2.75 [95% confidence interval (CI) 1.73-4.37]; P < 0.001, reference group UK}, the Netherlands [OR 1.91 (95% CI 1.32-2.76); P = 0.001] and Italy [OR 1.57 (95% CI 1.15-2.15); P = 0.004]. People in Poland experienced the least hyperpolypharmacy [OR 0.39 (95% CI 0.17-0.87); P = 0.021]. CONCLUSIONS: Hyperpolypharmacy is common among older people with advanced CKD, with significant international differences in the number of medications prescribed. Practice variation may represent a lack of consensus regarding appropriate prescribing for this high-risk group for whom pharmacological treatment has great potential for harm as well as benefit.

Dietary patterns and chronic kidney disease outcomes: A systematic review.

Chronic kidney disease (CKD) is a serious public health problem and its prevalence is growing in many countries, often related to issues resulting from the lifestyle in growing economies and the population's life expectancy. Nutritional therapy is a beneficial but still neglected strategy for preventing CKD and delaying disease progression. The aim of this study was to assess the association of dietary patterns with CKD development and progression. Observational studies conducted in adult humans and the correlation between the adopted dietary pattern and prevalent and incident cases of CKD were assessed. A significant association was observed between unhealthy dietary patterns and an increased risk of developing or worsening CKD, as well as an adverse effect. Whereas healthy eating patterns characterized by the consumption of fruit, vegetables and dietary fibre showed nephroprotective outcomes.

A systematic review of the evidence for deprescribing interventions among older people living with frailty.

BACKGROUND: Older people living with frailty are often exposed to polypharmacy and potential harm from medications. Targeted deprescribing in this population represents an important component of optimizing medication. This systematic review aims to summarise the current evidence for deprescribing among older people living with frailty. METHODS: The literature was searched using Medline, Embase, CINAHL, PsycInfo, Web of Science, and the Cochrane library up to May 2020. Interventional studies with any design or setting were included if they reported deprescribing interventions among people aged 65+ who live with frailty identified using reliable measures. The primary outcome was safety of deprescribing; whereas secondary outcomes included clinical outcomes, medication-related outcomes, feasibility, acceptability and cost-related outcomes. Narrative synthesis was used to summarise findings and study quality was assessed using Joanna Briggs Institute checklists. RESULTS: Two thousand three hundred twenty-two articles were identified and six (two randomised controlled trials) were included with 657 participants in total (mean age range 79-87 years). Studies were heterogeneous in their designs, settings and outcomes. Deprescribing interventions were pharmacist-led (n = 3) or multidisciplinary team-led (n = 3). Frailty was identified using several measures and deprescribing was implemented using either explicit or implicit tools or both. Three studies reported safety outcomes and showed no significant changes in adverse events, hospitalisation or mortality rates. Three studies reported positive impact on clinical outcomes including depression, mental health status, function and frailty; with mixed findings on falls and cognition; and no significant impact on quality of life. All studies described medication-related outcomes and reported a reduction in potentially inappropriate medications and total number of medications per-patient. Feasibility of deprescribing was reported in four studies which showed that 72-91% of recommendations made were implemented. Two studies evaluated and reported the acceptability of their interventions and further two described cost saving. CONCLUSION: There is a paucity of research about the impact of deprescribing in older people living with frailty. However, included studies suggest that deprescribing could be safe, feasible, well tolerated and can lead to important benefits. Research should now focus on understanding the impact of deprescribing on frailty status in high risk populations. TRIAL REGISTRATION: The review was registered on the international prospective register of systematic reviews (PROSPERO) ID number: CRD42019153367 .

Predictors of children's health system use: cross-sectional study of linked data.

BACKGROUND: Use of health services is increasing in many countries. Most health service research exploring determinants of use has focused on adults and on secondary care. Less is known about factors associated with the use of the emergency department (ED) and general practice (GP) among young children. OBJECTIVE: To explore factors associated with GP consultations and ED attendances among children under 5 in a single UK city. METHODS: Cross-sectional exploratory study using anonymized individual-level health service use data for children aged 0-4 from 21 GPs in Southampton, UK, linked to ED data, over a 1-year period. Univariate and multivariable logistic regression were used to explore the association of socio-demographic factors [using the 2015 Index of Multiple Deprivation (IMD) to define socio-economic status] with high service use (defined as more than eight GP consultations and/or two ED attendances respectively). RESULTS: Among 11 062 children, there were 76 092 GP consultations and 6107 ED attendances. Three thousand two hundred thirty-three (29%) children were high users of GP and 564 (5%) of ED services. Greater socio-economic deprivation was independently associated with high use of GP and ED services separately [odds ratios (OR) for most versus least deprived IMD quintile 1.45 (95% confidence interval, CI 1.20-1.75) and 2.21 (95% CI 1.41-3.46), respectively], and together [OR 2.62 (95% CI 1.48-4.65)]. CONCLUSION: Young children are frequent users of health services, particularly GP. Socio-economic deprivation is an important factor. Parents, carers and health services may benefit from interventions that support families in their management of children's health.

Ethnic minority disparities in progression and mortality of pre-dialysis chronic kidney disease: a systematic scoping review.

BACKGROUND: There are a growing number of studies on ethnic differences in progression and mortality for pre-dialysis chronic kidney disease (CKD), but this literature has yet to be synthesised, particularly for studies on mortality. METHODS: This scoping review synthesized existing literature on ethnic differences in progression and mortality for adults with pre-dialysis CKD, explored factors contributing to these differences, and identified gaps in the literature. A comprehensive search strategy using search terms for ethnicity and CKD was taken to identify potentially relevant studies. Nine databases were searched from 1992 to June 2017, with an updated search in February 2020. RESULTS: 8059 articles were identified and screened. Fifty-five studies (2 systematic review, 7 non-systematic reviews, and 46 individual studies) were included in this review. Most were US studies and compared African-American/Afro-Caribbean and Caucasian populations, and fewer studies assessed outcomes for Hispanics and Asians. Most studies reported higher risk of CKD progression in Afro-Caribbean/African-Americans, Hispanics, and Asians, lower risk of mortality for Asians, and mixed findings on risk of mortality for Afro-Caribbean/African-Americans and Hispanics, compared to Caucasians. Biological factors such as hypertension, diabetes, and cardiovascular disease contributed to increased risk of progression for ethnic minorities but did not increase risk of mortality in these groups. CONCLUSIONS: Higher rates of renal replacement therapy among ethnic minorities may be partly due to increased risk of progression and reduced mortality in these groups. The review identifies gaps in the literature and highlights a need for a more structured approach by researchers that would allow higher confidence in single studies and better harmonization of data across studies to advance our understanding of CKD progression and mortality.

Characterisation of a New Human Alveolar Macrophage-Like Cell Line (Daisy).

PURPOSE: There is currently no true macrophage cell line and in vitro experiments requiring these cells currently require mitogenic stimulation of a macrophage precursor cell line (THP-1) or ex vivo maturation of circulating primary monocytes. In this study, we characterise a human macrophage cell line, derived from THP-1 cells, and compare its phenotype to the THP-1 cells. METHODS: THP-1 cells with and without mitogenic stimulation were compared to the newly derived macrophage-like cell line (Daisy) using microscopy, flow cytometry, phagocytosis assays, antigen binding assays and gene microarrays. RESULTS: We show that the cell line grows predominantly in an adherent monolayer. A panel of antibodies were chosen to investigate the cell surface phenotype of these cells using flow cytometry. Daisy cells expressed more CD11c, CD80, CD163, CD169 and CD206, but less CD14 and CD11b compared with mitogen-stimulated THP-1 cells. Unlike stimulated THP-1 cells which were barely able to bind immune complexes, Daisy cells showed large amounts of immune complex binding. Finally, although not statistically significant, the phagocytic ability of Daisy cells was greater than mitogen-stimulated THP-1 cells, suggesting that the cell line is more similar to mature macrophages. CONCLUSIONS: The observed phenotype suggests that Daisy cells are a good model of human macrophages with a phenotype similar to human alveolar macrophages.

International comparison of trends in patients commencing renal replacement therapy by primary renal disease.

AIM: To examine international time trends in the incidence of renal replacement therapy (RRT) for end-stage renal disease (ESRD) by primary renal disease (PRD). METHODS: Renal registries reporting on patients starting RRT per million population for ESRD by PRD from 2005 to 2014, were identified by internet search and literature review. The average annual percentage change (AAPC) with a 95% confidence interval (CI) of the time trends was computed using Joinpoint regression. RESULTS: There was a significant decrease in the incidence of RRT for ESRD due to diabetes mellitus (DM) in Europe (AAPC = -0.9; 95%CI -1.3; -0.5) and to hypertension/renal vascular disease (HT/RVD) in Australia (AAPC = -1.8; 95%CI -3.3; -0.3), Canada (AAPC = -2.9; 95%CI -4.4; -1.5) and Europe (AAPC = -1.1; 95%CI -2.1; -0.0). A decrease or stabilization was observed for glomerulonephritis in all regions and for autosomal dominant polycystic kidney disease (ADPKD) in all regions except for Malaysia and the Republic of Korea. An increase of 5.2-16.3% was observed for DM, HT/RVD and ADPKD in Malaysia and the Republic of Korea. CONCLUSION: Large international differences exist in the trends in incidence of RRT by primary renal disease. Mapping of these international trends is the first step in defining the causes and successful preventative measures of CKD.

The clinical utility and cost impact of cystatin C measurement in the diagnosis and management of chronic kidney disease: A primary care cohort study.

BACKGROUND: To reduce over-diagnosis of chronic kidney disease (CKD) resulting from the inaccuracy of creatinine-based estimates of glomerular filtration rate (GFR), UK and international guidelines recommend that cystatin-C-based estimates of GFR be used to confirm or exclude the diagnosis in people with GFR 45-59 ml/min/1.73 m2 and no albuminuria (CKD G3aA1). Whilst there is good evidence for cystatin C being a marker of GFR and risk in people with CKD, its use to define CKD in this manner has not been evaluated in primary care, the setting in which most people with GFR in this range are managed. METHODS AND FINDINGS: A total of 1,741 people with CKD G3a or G3b defined by 2 estimated GFR (eGFR) values more than 90 days apart were recruited to the Renal Risk in Derby study between June 2008 and March 2010. Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, we compared GFR estimated from creatinine (eGFRcreat), cystatin C (eGFRcys), and both (eGFRcreat-cys) at baseline and over 5 years of follow-up. We analysed the proportion of participants with CKD G3aA1 reclassified to 'no CKD' or more advanced CKD with the latter two equations. We further assessed the impact of using cystatin-C-based eGFR in risk prediction equations for CKD progression and all-cause mortality and investigated non-GFR determinants of eGFRcys. Finally, we estimated the cost implications of implementing National Institute for Health and Care Excellence (NICE) guidance to use eGFRcys to confirm the diagnosis in people classified as CKD G3aA1 by eGFRcreat. Mean eGFRcys was significantly lower than mean eGFRcreat (45.1 ml/min/1.73 m2, 95% CI 44.4 to 45.9, versus 53.6 ml/min/1.73 m2, 95% CI 53.0 to 54.1, P < 0.001). eGFRcys reclassified 7.7% (50 of 653) of those with CKD G3aA1 by eGFRcreat to eGFR ≥ 60 ml/min/1.73 m2. However, a much greater proportion (59.0%, 385 of 653) were classified to an eGFR category indicating more severe CKD. A similar pattern was seen using eGFRcreat-cys, but lower proportions were reclassified. Change in eGFRcreat and eGFRcys over 5 years were weakly correlated (r = 0.33, P < 0.001), but eGFRcys identified more people as having CKD progression (18.2% versus 10.5%). Multivariable analysis using eGFRcreat as an independent variable identified age, smoking status, body mass index, haemoglobin, serum uric acid, serum albumin, albuminuria, and C reactive protein as non-GFR determinants of eGFRcys. Use of eGFRcys or eGFRcreat-cys did not improve discrimination in risk prediction models for CKD progression and all-cause mortality compared to similar models with eGFRcreat. Application of the NICE guidance, which assumed cost savings, to participants with CKD G3aA1 increased the cost of monitoring by £23 per patient, which if extrapolated to be applied throughout England would increase the cost of testing and monitoring CKD by approximately £31 million per year. Limitations of this study include the lack of a measured GFR and the potential lack of ethnic diversity in the study cohort. CONCLUSIONS: Implementation of current guidelines on eGFRcys testing in our study population of older people in primary care resulted in only a small reduction in diagnosed CKD but classified a greater proportion as having more advanced CKD than eGFRcreat. Use of eGFRcys did not improve risk prediction in this population and was associated with increased cost. Our data therefore do not support implementation of these recommendations in primary care. Further studies are warranted to define the most appropriate clinical application of eGFRcys and eGFRcreat-cys.

The ascending rank of chronic kidney disease in the global burden of disease study.

General population-based studies, the chronic kidney disease (CKD) prognosis consortium and renal registries worldwide have contributed to the description of the scale of CKD as a public health problem. Since 1990, CKD has been included in the list of non-communicable diseases investigated by the Global Burden of Disease (GBD) study. The GBD represents a systematic, high-quality, scientific effort to quantify the comparative magnitude of health loss from all major diseases, injuries and risk factors. This article provides an outline of the place of CKD in the ranking of these diseases and the change over time. Whereas age-standardized death and disability-adjusted life years (DALYs) rates due to non-communicable diseases in general have been declining, such favourable trends do not exist for CKD. Altogether the GBD reports indicate increasing rates for death and DALYs due to CKD with huge variation across the globe. A substantial component of the observed increase in mortality attributable to CKD relates to that caused by diabetes mellitus and hypertension. For the increase in DALYs, CKD due to diabetes mellitus appears to be the main contributor. It is possible that these trends are in part due to new data becoming available or different coding behaviour over time, including greater specificity of coding. Although some feel there is evidence of overdiagnosis, it seems clear that in many regions CKD and its risk factors are a growing public health problem and in some of them rank very high as cause of years of life lost and DALYs. Therefore, public health policies to address this problem as well as secondary prevention in high-risk groups remain greatly needed.

Validity of estimated prevalence of decreased kidney function and renal replacement therapy from primary care electronic health records compared with national survey and registry data in the United Kingdom.

BACKGROUND: Anonymous primary care records are an important resource for observational studies. However, their external validity is unknown in identifying the prevalence of decreased kidney function and renal replacement therapy (RRT). We thus compared the prevalence of decreased kidney function and RRT in the Clinical Practice Research Datalink (CPRD) with a nationally representative survey and national registry. METHODS: Among all people ≥25 years of age registered in the CPRD for ≥1 year on 31 March 2014, we identified patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, according to their most recent serum creatinine in the past 5 years using the Chronic Kidney Disease Epidemiology Collaboration equation and patients with recorded diagnoses of RRT. Denominators were the entire population in each age-sex band irrespective of creatinine measurement. The prevalence of eGFR <60 mL/min/1.73 m2 was compared with that in the Health Survey for England (HSE) 2009/2010 and the prevalence of RRT was compared with that in the UK Renal Registry (UKRR) 2014. RESULTS: We analysed 2 761 755 people in CPRD [mean age 53 (SD 17) years, men 49%], of whom 189 581 (6.86%) had an eGFR <60 mL/min/1.73 m2 and 3293 (0.12%) were on RRT. The prevalence of eGFR <60 mL/min/1.73 m2 in CPRD was similar to that in the HSE and the prevalence of RRT was close to that in the UKRR across all age groups in men and women, although the small number of younger patients with an eGFR <60 mL/min/1.73 m2 in the HSE might have hampered precise comparison. CONCLUSIONS: UK primary care data have good external validity for the prevalence of decreased kidney function and RRT.

Multimorbidity in people with chronic kidney disease: implications for outcomes and treatment.

PURPOSE OF REVIEW: With ageing populations, the prevalence of multimorbidity is increasing. This review discusses recent developments in the understanding of multimorbidity in the context of chronic kidney disease (CKD). It explores the associated treatment burden and the implications for key outcomes and patient care. RECENT FINDINGS: Comorbidity and polypharmacy are common in CKD, even at early stages, and are associated with significant treatment burden. Both 'concordant' and 'discordant' comorbidities have a negative impact on mortality, cardiovascular disease, hospitalisation and length of stay. In addition, quality of life is influenced by many factors beyond CKD, including comorbidities and certain medications. Several factors may reduce treatment burden for people with CKD, though research on this is at an early stage. Although patient activation is desirable to support self-management amongst people with multimorbidity, there are significant challenges that impact patient capacity amongst elderly populations with complex needs. SUMMARY: Comorbidities are common in CKD and have important implications for patients, clinicians and health services.

KDIGO-based acute kidney injury criteria operate differently in hospitals and the community-findings from a large population cohort.

BACKGROUND: Early recognition of acute kidney injury (AKI) is important. It frequently develops first in the community. KDIGO-based AKI e-alert criteria may help clinicians recognize AKI in hospitals, but their suitability for application in the community is unknown. METHODS: In a large renal cohort (n = 50 835) in one UK health authority, we applied the NHS England AKI 'e-alert' criteria to identify and follow three AKI groups: hospital-acquired AKI (HA-AKI), community-acquired AKI admitted to hospital within 7 days (CAA-AKI) and community-acquired AKI not admitted within 7 days (CANA-AKI). We assessed how AKI criteria operated in each group, based on prior blood tests (number and time lag). We compared 30-day, 1- and 5-year mortality, 90-day renal recovery and chronic renal replacement therapy (RRT). RESULTS: In total, 4550 patients met AKI e-alert criteria, 61.1% (2779/4550) with HA-AKI, 22.9% (1042/4550) with CAA-AKI and 16.0% (729/4550) with CANA-AKI. The median number of days since last blood test differed between groups (1, 52 and 69 days, respectively). Thirty-day mortality was similar for HA-AKI and CAA-AKI, but significantly lower for CANA-AKI (24.2, 20.2 and 2.6%, respectively). Five-year mortality was high in all groups, but followed a similar pattern (67.1, 64.7 and 46.2%). Differences in 5-year mortality among those not admitted could be explained by adjusting for comorbidities and restricting to 30-day survivors (hazard ratio 0.91, 95% confidence interval 0.80-1.04, versus hospital AKI). Those with CANA-AKI (versus CAA-AKI) had greater non-recovery at 90 days (11.8 versus 3.5%, P < 0.001) and chronic RRT at 5 years (3.7 versus 1.2%, P < 0.001). CONCLUSIONS: KDIGO-based AKI criteria operate differently in hospitals and in the community. Some patients may not require immediate admission but are at substantial risk of a poor long-term outcome.