Rates of adverse clinical events in patients with chronic kidney disease: analysis of electronic health records from the UK clinical practice research datalink linked to hospital data.

BACKGROUND: Further understanding of adverse clinical event rates in patients with chronic kidney disease (CKD) is required for improved quality of care. This study described baseline characteristics, adverse clinical event rates, and mortality risk in patients with CKD, accounting for CKD stage and dialysis status. METHODS: This retrospective, noninterventional cohort study included data from adults (aged ≥ 18 years) with two consecutive estimated glomerular filtration rates of < 60 ml/min/1.73 m2, recorded ≥ 3 months apart, from the UK Clinical Practice Research Datalink of electronic health records obtained between January 1, 2004, and December 31, 2017. Select adverse clinical events, associated with CKD and difficult to quantify in randomized trials, were assessed; defined by Read codes and International Classification of Diseases, Tenth Revision codes. Clinical event rates were assessed by dialysis status (dialysis-dependent [DD], incident dialysis-dependent [IDD], or non-dialysis-dependent [NDD]), dialysis modality (hemodialysis [HD] or peritoneal dialysis [PD]), baseline NDD-CKD stage (3a-5), and observation period. RESULTS: Overall, 310,953 patients with CKD were included. Comorbidities were more common in patients receiving dialysis than in NDD-CKD, and increased with advancing CKD stage. Rates of adverse clinical events, particularly hyperkalemia and infection/sepsis, also increased with advancing CKD stage and were higher in patients on HD versus PD. Mortality risk during follow-up (1-5-year range) was lowest in patients with stage 3a NDD-CKD (2.0-18.5%) and highest in patients with IDD-CKD (26.3-58.4%). CONCLUSIONS: These findings highlight the need to monitor patients with CKD for comorbidities and complications, as well as signs or symptoms of clinical adverse events.

Epidemiology and outcomes in patients with anemia of CKD not on dialysis from a large US healthcare system database: a retrospective observational study.

BACKGROUND: Optimal management of anemia of chronic kidney disease (CKD) remains controversial. This retrospective study aimed to describe the epidemiology and selected clinical outcomes of anemia in patients with CKD in the US. METHODS: Data were extracted from Henry Ford Health System databases. Adults with stages 3a-5 CKD not on dialysis (estimated glomerular filtration rate < 60 mL/min/1.73m2) between January 1, 2013 and December 31, 2017 were identified. Patients on renal replacement therapy or with active cancer or bleeding were excluded. Patients were followed for ≥12 months until December 31, 2018. Outcomes included incidence rates per 100 person-years (PY) of anemia (hemoglobin < 10 g/dL), renal and major adverse cardiovascular events, and of bleeding and hospitalization outcomes. Adjusted Cox proportional hazards models identified factors associated with outcomes after 1 and 5 years. RESULTS: Among the study cohort (N = 50,701), prevalence of anemia at baseline was 23.0%. Treatments used by these patients included erythropoiesis-stimulating agents (4.1%), iron replacement (24.2%), and red blood cell transfusions (11.0%). Anemia incidence rates per 100 PY in patients without baseline anemia were 7.4 and 9.7 after 1 and 5 years, respectively. Baseline anemia was associated with increased risk of renal and major cardiovascular events, hospitalizations (all-cause and for bleeding), and transfusion requirements. Increasing CKD stage was associated with increased risk of incident anemia, renal and major adverse cardiovascular events, and hospitalizations. CONCLUSIONS: Anemia was a prevalent condition associated with adverse renal, cardiovascular, and bleeding/hospitalization outcomes in US patients with CKD. Anemia treatment was infrequent.

Risk factors associated with the incidence and recurrence of hyperkalaemia in patients with cardiorenal conditions.

INTRODUCTION: Hyperkalaemia (HK) is associated with increased mortality risk. Prior studies suggest that the causes of HK are multifactorial. This study aimed to examine risk factors for incident and recurrent HK in six large real-world cohorts of UK patients that could be considered at elevated HK risk because of underlying disease pathology and/or medication use. METHODS: This retrospective, observational cohort study utilised UK primary and secondary care data from Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES), respectively. Patients were included if they were aged ≥18 years and had a record of ≥1 condition of interest (chronic kidney disease [CKD] stage 3+, heart failure, resistant hypertension [RHTN], dialysis, diabetes) and/or renin-angiotensin-aldosterone system inhibitors (RAASi) use between 01 January 2003 and 30 June 2018. Based on their diagnosis/ RAASi prescription record, patients were assigned to overlapping cohorts. The outcomes assessed were HK and recurrent HK, the latter defined as second or subsequent HK episode during follow-up. HK was defined as a serum K+ measurement ≥5.0 mmol/L; thresholds of ≥5.5 and ≥ 6.0 mmol/L were also explored. RESULTS: Of 931 460 meeting the eligibility criteria, 310 535 (33.3%) patients experienced ≥1 HK event and 187 719 (20.2%) experienced HK recurrence. The probability of subsequent HK events increased with event number from 60.5% for the second event to 76.5% for the sixth and the corresponding time to the next HK event decreased from 15.8 months to 6.1 months. Amongst the key risk factors, serum creatinine, serum phosphorus, systolic blood pressure, and white cell count demonstrated direct relationships with incidence and recurrence of HK, while inverse relationships were observed for estimated glomerular filtration rate (eGFR), haemoglobin and diastolic blood pressure. The relationship for Charlson's Comorbidity Index was mixed. The use of RAASi and anti-hyperglycaemic agents was associated with an increased risk of HK, while the use of diuretics (non-K+ -sparing) was protective against HK. CONCLUSION: Several risk factors for HK that are easily measured in routine clinical practice were identified, facilitating the identification of patients who are at the highest risk of experiencing HK, including recurrent HK.

Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

PURPOSE: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease. METHODS: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands. RESULTS: We identified 191,933 newly diagnosed dementia patients in the four databases between 1997 and 2017 with 39,836 (IPCI (NL): 3281, HSD (IT): 1601, AUH (DK): 4474, THIN (UK): 30,480) fulfilling the inclusion criteria, and of these, 21,131 had received a specific diagnosis of Alzheimer's disease. The most common first line therapy initiated within a year (± 365 days) of diagnosis were Acetylcholinesterase inhibitors, namely rivastigmine in IPCI, donepezil in HSD and the THIN and the N-methyl-D-aspartate blocker memantine in AUH. CONCLUSION: We provide a real-world insight into the heterogeneous management and treatment pathways of newly diagnosed dementia patients and a subset of Alzheimer's Disease patients from across Europe.

Associations of Hemoglobin Levels With Health-Related Quality of Life, Physical Activity, and Clinical Outcomes in Persons With Stage 3-5 Nondialysis CKD.

OBJECTIVE: Conflicting findings and knowledge gaps exist regarding links between anemia, physical activity, health-related quality of life (HRQOL), chronic kidney disease (CKD) progression, and mortality in moderate-to-advanced CKD. Using the CKD Outcomes and Practice Patterns Study, we report associations of hemoglobin (Hgb) with HRQOL and physical activity, and associations of Hgb and physical activity with CKD progression and mortality in stage 3-5 nondialysis (ND)-CKD patients. DESIGN AND METHODS: Prospectively collected data were analyzed from 2,121 ND-CKD stage 3-5 patients, aged ≥18 years, at 43 nephrologist-run US and Brazil CKD Outcomes and Practice Patterns Study-participating clinics. Cross-sectional associations were assessed of Hgb levels with HRQOL and physical activity levels (from validated Kidney Disease Quality of Life Instrument and Rapid Assessment of Physical Activity surveys). CKD progression (first of ≥40% estimated glomerular filtration rate [eGFR] decline, eGFR<10 mL/min/1.73 m2, or end-stage kidney disease) and all-cause mortality with Hgb and physical activity levels were also evaluated. Linear, logistic, and Cox regression analyses were adjusted for country, demographics, smoking, eGFR, serum albumin, very high proteinuria, and 13 comorbidities. RESULTS: HRQOL was worse, with severe anemia (Hgb<10 g/dL), but also evident for mild/moderate anemia (Hgb 10-12 g/dL), relative to Hgb>12 g/dL. Odds of being highly physically active were substantially greater at Hgb>10.5 g/dL. Lower Hgb was strongly associated with greater CKD progression and mortality, even after extensive adjustment. Physical inactivity was strongly associated with greater mortality and weakly associated with CKD progression. Possible residual confounding is a limitation. CONCLUSION: This multicenter international study provides real-world observational evidence for greater HRQOL, physical activity, lower CKD progression, and greater survival in ND-CKD patients with Hgb levels >12 g/dL, exceeding current treatment guideline recommendations. These findings help inform future studies aimed at understanding the impact of new anemia therapies and physical activity regimens on improving particular dimensions of ND-CKD patient well-being and clinical outcomes.

Characteristics, Symptom Severity, and Experiences of Patients Reporting Chronic Kidney Disease in the PatientsLikeMe Online Health Community: Retrospective and Qualitative Study.

BACKGROUND: Chronic kidney disease (CKD) is a major global health burden, and is associated with increased adverse outcomes, poor quality of life, and substantial health care costs. While there is an increasing need to build patient-centered pathways for improving CKD management in clinical care, data in this field are scarce. OBJECTIVE: The aim of this study was to understand patient-reported experiences, symptoms, outcomes, and treatment journeys among patients with CKD through a retrospective and qualitative approach based on data available through PatientsLikeMe (PLM), an online community where patients can connect and share experiences. METHODS: Adult members (aged ≥18 years) with self-reported CKD within 30 days of enrollment, who were not on dialysis, and registered between 2011 and 2018 in the PLM community were eligible for the retrospective study. Patient demographics and disease characteristics/symptoms were collected from this retrospective data set. Qualitative data were collected prospectively through semistructured phone interviews in a subset of patients, and questions were oriented to better understand patients' experiences with CKD and its management. RESULTS: The retrospective data set included 1848 eligible patients with CKD, and median age was 56 years. The majority of patients were female (1217/1841, 66.11%) and most were US residents (1450/1661, 87.30%). Of the patients who reported comorbidities (n=1374), the most common were type 2 diabetes (783/1374, 56.99%), hypertension (664/1374, 48.33%), hypercholesterolemia (439/1374, 31.95%), and diabetic neuropathy (376/1374, 27.37%). The most commonly reported severe or moderate symptoms in patients reporting these symptoms were fatigue (347/484, 71.7%) and pain (278/476, 58.4%). In the qualitative study, 18 eligible patients (13 females) with a median age of 60 years and who were mainly US residents were interviewed. Three key concepts were identified by patients to be important to optimal care and management: listening to patient needs, coordinating health care across providers, and managing clinical care. CONCLUSIONS: This study provides a unique source of real-world information on the patient experience of CKD and its management by utilizing the PLM network. The results reveal the challenges these patients face living with an array of symptoms, and report key concepts identified by patients that can be used to further improve clinical care and management and inform future CKD studies.

Comparison of variation in frequency for SNPs associated with asthma or liver disease between Estonia, HapMap populations and the 1000 genome project populations.

Allele-specific analyses to understand frequency differences across populations, particularly populations not well studied, are important to help identify variants that may have a functional effect on disease mechanisms and phenotypic predisposition, facilitating new Genome-Wide Association Studies (GWAS). We aimed to compare the allele frequency of 11 asthma-associated and 16 liver disease-associated single nucleotide polymorphisms (SNPs) between the Estonian, HapMap and 1000 genome project populations. When comparing EGCUT with HapMap populations, the largest difference in allele frequencies was observed with the Maasai population in Kinyawa, Kenya, with 12 SNP variants reporting statistical significance. Similarly, when comparing EGCUT with 1000 genomes project populations, the largest difference in allele frequencies was observed with pooled African populations with 22 SNP variants reporting statistical significance. For 11 asthma-associated and 16 liver disease-associated SNPs, Estonians are genetically similar to other European populations but significantly different from African populations. Understanding differences in genetic architecture between ethnic populations is important to facilitate new GWAS targeted at underserved ethnic groups to enable novel genetic findings to aid the development of new therapies to reduce morbidity and mortality.

The MOSAICC study: Assessing feasibility for biological sample collection in epidemiology studies and comparison of DNA yields from saliva and whole blood samples.

Biological sample collection is becoming more common in epidemiology research to obtain DNA for genetic analysis. There are many different DNA collection methods but little evidence on their relative effectiveness. Therefore, we took the opportunity of a prospective case-control study in myeloproliferative neoplasms (MPNs) to compare DNA yield from 8.5 mL PAXgene tubes for whole blood collection versus 2 mL Oragene OG-500 saliva collection kits. MPNs include polycythaemia vera, essential thrombocythaemia, and primary myelofibrosis. These are rare diseases and our exploratory case-control study (MOSAICC) sought to improve knowledge regarding their aetiology and to determine optimal methodology for a larger UK-wide study. Overall, 233 participants were recruited to the MOSIACC study, and we collected 187 blood and 214 saliva samples. The mean DNA yield from blood was 659.18 ng/µL, significantly higher than the mean DNA yield from saliva samples (275.79 ng/µL). The higher provision of saliva samples might reflect its non-invasive and more convenient nature, compared to blood sample provision. The differences in mean DNA yields might reflect differences in clinical assistance, adherence to instructions, and health status of individuals. In conclusion, both sample collection techniques are simple, effective, and suitable for DNA collection for genetic analysis in future epidemiological research studies but OG-500 kits offer a less invasive alternative for those who refuse to provide blood.

Myeloproliferative neoplasm patient symptom burden and quality of life: evidence of significant impairment compared to controls.

The myeloproliferative neoplasms (MPN) including polycythaemia vera (PV), essential thrombocythaemia and primary myelofibrosis (PMF) are rare diseases contributing to significant morbidity. Symptom management is a prime treatment objective but current symptom assessment tools have not been validated compared to the general population. The MPN-symptom assessment form (MPN-SAF), a reliable and validated clinical tool to assess MPN symptom burden, was administered to MPN patients (n = 106) and, for the first time, population controls (n = 124) as part of a UK case-control study. Mean symptom scores were compared between patients and controls adjusting for potential confounders. Mean patient scores were compared to data collected by the Mayo Clinic, USA on 1,446 international MPN patients to determine patient group representativeness. MPN patients had significantly higher mean scores than controls for 25 of the 26 symptoms measured (P < 0.05); fatigue was the most common symptom (92.4% and 78.1%, respectively). Female MPN patients suffered worse symptom burden than male patients (P < 0.001) and substantially worse burden than female controls (P < 0.001). Compared to the Mayo clinic patients, MPN-UK patients reported similar symptom burden but lower satiety (P = 0.046). Patients with PMF reported the worst symptom burden (88.3%); significantly higher than PV patients (P < 0.001). For the first time we report quality of life was worse in MPN-UK patients compared with controls (P < 0.001).

Characteristics of patients with chronic kidney disease and Type 2 diabetes initiating finerenone in the USA: a multi-database, cross-sectional study.

Aim: Finerenone is safe and efficacious for treating patients with chronic kidney disease (CKD) and Type 2 diabetes (T2D). Evidence on the use of finerenone in clinical practice is lacking. Objective: To describe demographic and clinical characteristics of early adopters of finerenone in the United States, according to sodium-glucose cotransporter 2 inhibitor (SGLT2i) use and urine albumin-creatinine ratio (UACR) levels. Methods: Multi-database, observational, cross-sectional study, using data from two US databases (Optum Claims and Optum EHR). Three cohorts were included: finerenone initiators with prior CKD-T2D, finerenone initiators with prior CKD-T2D and concomitant SGLT2i use, finerenone initiators with prior CKD-T2D stratified according to UACR. Results: In total, 1015 patients were included, 353 from Optum Claims and 662 from Optum EHR. Mean age was 72.0 and 68.4 years in Optum claims and EHR, respectively. Median eGFR was 44 and 44 ml/min/1.73 m2; and median UACR was 132 (28-698)/365 (74-1185.4) mg/g, in Optum Claims and EHR, respectively. 70.5/70.4% were taking renin-angiotensin system inhibitors, 42.5/53.3% SGLT2i. Overall, 9.0/6.3% of patients had baseline UACR <30 mg/g, 15.0/20.2% had UACR 30-300 mg/g, and 14.4/27.6% had UACR >300 mg/g. Conclusion: Current management of patients with CKD-T2D reflects use of finerenone independently from background therapies and clinical characteristics, suggesting implementation of therapeutic strategies based on different modes of action.

The JAK2V617F mutation and the role of therapeutic agents in alleviating myeloproliferative neoplasm symptom burden.

Alleviating symptom burden in patients with myeloproliferative neoplasms (MPNs) is imperative to achieving optimal management. Research remains to elucidate the relationship between the JAK2V617F (Janus kinase 2) mutation present in many MPN patients, and the symptomatology they experience. This retrospective study analysed data collected from MPN patients included in the Myeloproliferative Neoplasms: An In-depth Case-Control (MOSAICC) pilot study. The MPN Symptom Assessment Form was administered, and median symptom scores were compared between JAK2V617F-positive and JAK2V617F-negative groups. Multivariate logistic regression analysis adjusted for confounding variables. Overall, 106 MPN patients participated: 65.1% were JAK2V617F positive, 30.2% were JAK2V617F negative and 4.7% had an unknown status. Multivariate analysis revealed a low symptom burden for early satiety (p < 0.01), dizziness (p < 0.05), cough (p < 0.05) and bone pain (p < 0.01) in those receiving venesection alone. Interferon alpha was significantly associated (p < 0.05) with severe burden for 16 of the 27 symptoms. JAK2V617F-positive females experienced a greater symptom burden than JAK2V617F-positive males. There was no discernible relationship between the JAK2V617F mutation and symptom burden in MPN patients, unlike the therapeutic agents investigated. Larger studies are required to validate these results and identify mechanisms of symptom development and control in MPN patients.

Health Care Resource Utilization and Related Costs of Patients With CKD From the United States: A Report From the DISCOVER CKD Retrospective Cohort.

Introduction: It is well established that chronic kidney disease (CKD) results in a significant burden on patients' health and health care providers. However, detailed estimates of the health care resource utilization (HCRU) of CKD are limited, particularly those which consider severity, comorbidities, and payer type. This study aimed to bridge this evidence gap by reporting contemporary HCRU and costs in patients with CKD across the US health care providers. Methods: Cost and HCRU estimates of CKD and reduced kidney function without CKD (estimated glomerular filtration rate [eGFR]: 60-75 and urine albumin-to-creatinine ratio [UACR]: <30) were derived for US patients included in the DISCOVER CKD cohort study, using linked inpatient and outpatient data from the limited claims-EMR data set (LCED) and TriNetX database. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using UACR and eGFR. Results: Overall health care costs ranged from $26,889 (A1) to $42,139 (A3), and from $28,627 (G2) to $42,902 (G5) per patient per year (PPPY), demonstrating a considerable early disease burden which continued to increase with declining kidney function. The PPPY costs of later stage CKD were particularly notable for patients with concomitant heart failure ($50,191 [A3]) and those covered by commercial payers ($55,735 [A3]). Conclusions: Health care costs and resource use associated with CKD and reduced kidney function pose a substantial burden across health care systems and payers, increasing in line with CKD progression. Early CKD screening, particularly of UACR, paired with proactive disease management may provide both an improvement to patient outcomes and a significant HCRU and cost saving to health care providers.

Developing a common data model approach for DISCOVER CKD: A retrospective, global cohort of real-world patients with chronic kidney disease.

OBJECTIVES: To describe a flexible common data model (CDM) approach that can be efficiently tailored to study-specific needs to facilitate pooled patient-level analysis and aggregated/meta-analysis of routinely collected retrospective patient data from disparate data sources; and to detail the application of this CDM approach to the DISCOVER CKD retrospective cohort, a longitudinal database of routinely collected (secondary) patient data of individuals with chronic kidney disease (CKD). METHODS: The flexible CDM approach incorporated three independent, exchangeable components that preceded data mapping and data model implementation: (1) standardized code lists (unifying medical events from different coding systems); (2) laboratory unit harmonization tables; and (3) base cohort definitions. Events between different coding vocabularies were not mapped code-to-code; for each data source, code lists of labels were curated at the entity/event level. A study team of epidemiologists, clinicians, informaticists, and data scientists were included within the validation of each component. RESULTS: Applying the CDM to the DISCOVER CKD retrospective cohort, secondary data from 1,857,593 patients with CKD were harmonized from five data sources, across three countries, into a discrete database for rapid real-world evidence generation. CONCLUSIONS: This flexible CDM approach facilitates evidence generation from real-world data within the DISCOVER CKD retrospective cohort, providing novel insights into the epidemiology of CKD that may expedite improvements in diagnosis, prognosis, early intervention, and disease management. The adaptable architecture of this CDM approach ensures scalable, fast, and efficient application within other therapy areas to facilitate the combined analysis of different types of secondary data from multiple, heterogeneous sources.

Serum potassium as a predictor of adverse clinical outcomes in patients with increasing comorbidity burden.

AIMS: The aim of this study was to establish whether patients with multiple comorbidities may be at elevated risk of hyperkalaemia (HK), a potentially life-threatening electrolyte imbalance, and the associated adverse clinical outcomes. METHODS AND RESULTS: This was a retrospective, observational cohort study using UK primary and secondary care data. Adult patients with at least one of: resistant hypertension, chronic kidney disease stage 3+, dialysis, heart failure (HF), and diabetes, were eligible for inclusion. According to their diagnoses, patients were grouped into overlapping cohorts that were updated as multimorbidity progressed. Outcomes of interest were incident HK, all-cause mortality (ACM), and major adverse cardiovascular events (MACE). A total of 673 686 patients met the eligibility criteria, 36.3% of whom developed multimorbidity during the study period. A consistent U-shaped association was observed between serum K+ level and adjusted incidence of ACM and MACE. Hyperkalaemia was progressively more common with increasing Charlson Comorbidity Index (CCI). Relative to a CCI <3, scores of ≥3 to <6, and ≥6 were associated with 2.9- and 6.2-fold increases, respectively, in crude HK (serum K+ ≥5.0 mmol/L) incidence rate. In all condition-based cohorts except for HF, there was a clear correlation between increasing CCI and the risk of ACM and MACE associated with hypokalaemia and HK. CONCLUSION: Patients with a higher CCI are at an increased risk of developing HK and appear more prone to adverse clinical outcomes associated with abnormal serum K+ levels, warranting additional routine clinical monitoring.

How common is hyperkalaemia? A systematic review and meta-analysis of the prevalence and incidence of hyperkalaemia reported in observational studies.

Background: The prevalence and incidence of hyperkalaemia, a potassium abnormality that can potentially have life-threatening consequences, are unclear. Methods: The objective was to provide the most comprehensive overview of the epidemiology of hyperkalaemia to date within the general population, across different continents, in different healthcare settings and within pre-specified subgroups. Embase and MEDLINE were searched from database inception to 2 February 2021 using the Ovid SP platform. Relevant congress proceedings from 2018 to 2020 were also reviewed for inclusion. There was no language constraint applied. Observational studies from any time period and language reporting prevalence or incidence of hyperkalaemia within both adult and paediatric populations. Four investigators independently screened abstracts and assessed study quality of those meeting the pre-determined inclusion/exclusion criteria. Data extraction was conducted by the lead author with oversight from the senior author and data were pooled using a random-effects model. The measures assessed were the prevalence and incidence of hyperkalaemia. Prevalence was reported as a percentage, whilst incidence was reported as the rate per 100 person years. Results: In total, 542 articles were included from an initial search of 14 112 articles. Across all adult studies, we report a prevalence of hyperkalaemia (by any definition/threshold) of 6.3% [95% confidence interval (CI): 5.8-6.8%], with an incidence of hyperkalaemia in the adult population of 2.8 (2.3-3.3) cases per 100 person years. Prevalence within the general population was 1.3% (1.0-1.8%), whilst incidence was 0.4 (0.2-0.8) cases per 100 person years. There was a variation by sex with a prevalence of 6.3% (4.9-8.0%) in males and 5.1% (4.0-6.6%) in females. Prevalence also varied according to the definition/threshold of hyperkalaemia used: >5 mmol/L-8.0% (7.2-8.9), ≥5.5 mmol/L-5.9% (3.5-10.0) and ≥6.0 mmol/L-1.0% (0.8-1.4); hyperkalaemia (by any definition/threshold) was highest amongst patients with end-stage kidney disease (21.5%; 18.3-25.3), kidney transplant patients (21.8%; 16.1-29.5) and patients with acute kidney injury (24.3%; 19.3-30.7). Conclusions: This novel review provides a comprehensive and valuable resource on the prevalence and incidence of hyperkalaemia to better inform clinicians, healthcare providers and health policy makers on the burden of hyperkalaemia across different healthcare settings, patient populations and continents.

Clinical outcomes associated with the emergency treatment of hyperkalaemia with intravenous insulin-dextrose.

BACKGROUND: Hyperkalaemia occurs in up to 10% of hospital admissions but its treatment in the emergency setting is inconsistent. OBJECTIVES: To describe the emergency management of hyperkalaemia in adults with insulin-dextrose (IDex) and to explore clinical outcomes associated with IDex treatment. DESIGN AND SETTING: Cohort study using comprehensive electronic health records of all emergency admissions to a large university hospital in the United Kingdom between April 2015 and August 2018. PARTICIPANTS: Adult patients aged ≥16 years with at least one emergency admission and one blood potassium result during the study period. MAIN OUTCOMES AND MEASURES: Emergency hyperkalaemia treatment was evaluated including the requirement for re-treatment with IDex, episodes of glucose dysregulation, intensive care (ICU) admission and length of hospital stay. Associations with hyperkalaemia, adverse events and IDex treatment were explored by logistic regression. RESULTS: Amongst 211,993 patients attending the Emergency Department (ED) we identified 11,107 hyperkalaemic adult patients, of whom 1,284 were treated with IDex. Multiple doses were required in 542 patients (42.2%). Hypoglycaemia (plasma glucose < 4 mmol/L) occurred in 249 patients (19.4%) within 6 hours of IDex. Repeated doses were associated with an increased risk of hypoglycaemia (OR 2.94, 95% CI 2.20 to 3.93) compared to patients receiving a single dose, which, after adjustment was also associated with an increased risk of death (OR 1.56, 95% CI 1.16 to 2.09) during the study period. Patients who received multiple doses of IDex (OR 2.2, 95% CI 1.6-3.1) and those who received a dose of insulin above the guideline recommended limit (OR 5.6 3.1-10.3) were more likely to be admitted to ICU following IDex than those who received a single dose or the guideline recommended dose of insulin. CONCLUSIONS AND RELEVANCE: This study provides novel insight into the emergency management of hyperkalaemia in a large population, demonstrates the high risk of hypoglycaemia and highlights the urgent need for an improved, evidence-based approach to the emergency management of hyperkalaemia.

Contemporary outcomes of anemia in US patients with chronic kidney disease.

BACKGROUND: Long-term clinical outcome data from patients with non-dialysis-dependent (NDD) chronic kidney disease (CKD) are lacking. We characterized patients with NDD-CKD and anemia using real-world data from the USA. METHODS: This retrospective longitudinal observational study evaluated integrated Limited Claims and Electronic Health Record Data (IBM Health, Armonk, NY), including patients ≥18 years with two or more estimated glomerular filtration rate (eGFR) measures <60 mL/min/1.73 m2 ≥90 days apart. Anemia was defined as the first observed hemoglobin <10 g/dL within 6-month pre- and post-CKD index date. Data were analyzed from January 2012 to June 2018. Patients with documented iron-deficiency anemia at baseline were excluded. RESULTS: Comprising 22 720 patients (57.4% female, 63.9% CKD stage 3, median hemoglobin 12.5 g/dL), median (interquartile range) follow-up for patients with and without anemia were 2.9 (1.5-4.4) and 3.8 (2.2-4.8) years, respectively. The most prevalent comorbidities were dyslipidemia (57.6%), type 2 diabetes mellitus (38.8%) and uncontrolled hypertension (20.0%). Overall, 23.3% of patients had anemia, of whom 1.9% and <0.1% received erythropoiesis-stimulating agents (ESAs) or intravenous iron, respectively. Anemia prevalence increased with CKD stage from 18.2% (stage 3a) to 72.8% (stage 5). Patients with anemia had a higher incidence rate of hospitalizations for heart failure (1.6 versus 0.8 per 100 patient-years), CKD stage advancement (43.5 versus 27.5 per 100 patient-years), and a 40% eGFR decrease (18.1 versus 7.3 per 100 patient-years) versus those without anemia. CONCLUSIONS: Anemia, frequently observed in NDD-CKD and associated with adverse clinical outcomes, is rarely treated with ESAs and intravenous iron. These data suggest that opportunities exist for improved anemia management in patients with NDD-CKD.

Serum potassium variability as a predictor of clinical outcomes in patients with cardiorenal disease or diabetes: a retrospective UK database study.

Background: Hyperkalaemia is an electrolyte abnormality associated with adverse clinical outcomes; however, few studies have investigated the relationship with patterns of hyperkalaemia over time. This study explored the impact of time spent in a hyperkalaemic state and variability of serum potassium (sK+) on major adverse cardiovascular events (MACE) and all-cause mortality in patients with chronic kidney disease (CKD), resistant hypertension, heart failure and diabetes. Methods: Cohorts comprised adult patients diagnosed with CKD stage 3+, resistant hypertension, heart failure or diabetes, and/or renin-angiotensin-aldosterone system inhibitor prescription, between 1 January 2003 and 30 June 2018, from the UK Clinical Practice Research Datalink. Associations between percentage of follow-up spent in a hyperkalaemic state (sK+ ≥5.0 mmol/L, ≥5.5 mmol/L, ≥6.0 mmol/L) or sK+ variability (standard deviation above or below median standard deviation) and all-cause mortality or MACE were investigated. Results: For sK+ ≥5.0 mmol/L, time spent in a hyperkalaemic state was associated with reduced risk of all-cause mortality across all cohorts. For higher sK+ thresholds, this trend was attenuated or reversed; for time spent in a hyperkalaemic state at sK+ ≥6.0 mmol/L, an increased risk of mortality was seen in the overall cohort and for patients with diabetes, resistant hypertension or prescribed renin-angiotensin-aldosterone system inhibitors, with no consistent association seen for patients with CKD or heart failure. Risk of MACE in the overall cohort and in patients with CKD, diabetes or resistant hypertension increased with time spent in a hyperkalaemic state at all sK+ thresholds; however, no correlation was seen in patients with heart failure or those receiving dialysis. High sK+ variability was associated with a higher risk of MACE compared with low sK+ variability across most sK+ categories in the overall population and in all disease cohorts, except patients on dialysis; however, no association between sK+ variability and all-cause mortality was observed. Conclusions: Patterns of hyperkalaemia, including time spent in hyperkalaemia and sK+ variability, are associated with adverse clinical outcomes. Regular monitoring of sK+ in high-risk populations in broader community, primary care and outpatient settings may enable guideline-recommended management of hyperkalaemia and help avoid adverse events.

Cost of End-of-Life Inpatient Encounters in Patients with Chronic Kidney Disease in the United States: A Report from the DISCOVER CKD Retrospective Cohort.

INTRODUCTION: Real-world data reporting healthcare resource utilisation and costs associated with end-of-life care for patients with chronic kidney disease (CKD) are limited. We examined length of hospitalisation and costs associated with end-of-life inpatient encounters using retrospective data from DISCOVER CKD. METHODS: Data on inpatient encounters for patients with CKD aged ≥ 18 years between January 2016 and March 2020 were extracted from the US Premier Hospital Database. Encounters ending in death were identified and grouped by reason for the encounter, using the International Classification of Diseases, Tenth Revision, and by their insurance coverage. Encounters were evaluated overall and stratified according to cardiovascular (CV), kidney failure and infection-related reasons, and by their coverage by commercial, Medicaid, Medicare or other insurers. Length of hospitalisation and total costs were calculated for encounters. RESULTS: Among 237,734 encounters ending in death, the mean [standard deviation (SD)] age was 74.2 (12.4) years, and 45.3% of patients were female. In total, 25,118, 4210 and 76,307 encounters were classified as relating to CV reasons, kidney failure and infection, respectively. Among all encounters, the mean (SD) length of hospitalisation ranged from 9.1 (11.2) (Medicare) to 12.8 (18.4) (Medicaid) days. Across insurers, encounters related to kidney failure were associated with the longest hospitalisations compared with CV and infection [mean range (days): 10.7-15.9 vs. 7.5-10.5 and 8.7-12.7, respectively]. The median [interquartile range (IQR)] total cost of any inpatient encounter was $17,057 ($8040-35,873). Kidney failure-related encounters had higher costs compared with CV and infection [median (IQR), $18,469 ($8673-38,315) vs. $17,503 ($7766-39,693) and $16,403 ($7762-34,910), respectively]. Medicaid-covered encounters had the highest costs of all insurers [median (IQR), $16,189 ($7725-33,443)]. CONCLUSIONS: Among patients with CKD, end-of-life encounters were most frequently related to infection. Encounters relating to kidney failure incurred the highest costs. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04034992.

Healthcare resource utilisation and related costs of patients with CKD from the UK: a report from the DISCOVER CKD retrospective cohort.

Background: Chronic kidney disease (CKD) is widely reported to decrease quality of life, increase morbidity and mortality and cause increased healthcare resource utilisation (HCRU) as the disease progresses. However, there is a relative paucity of accurate and recent estimates of HCRU in this patient population. Our aim was to address this evidence gap by reporting HCRU and related costs in patients with CKD from the UK primary and secondary care settings. Methods: HCRU and cost estimates of CKD were derived for UK patients included in the DISCOVER CKD cohort study using clinical records from the Clinical Practice Research Datalink linked to external databases. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using the urinary albumin:creatinine ratio (UACR) and estimated glomerular filtration rate. Results: Hospitalisation rates more than tripled between low (A1) and high (A3) UACR categories and the mean annual per-patient costs ranged from £4966 (A1) to £9196 (A3) and from £4997 (G2) to £7595 (G5), demonstrating that a large healthcare burden can be attributed to a relatively small number of patients with later stage CKD, including those with kidney failure and/or albuminuria. Conclusions: HCRU and costs associated with CKD impose a substantial burden on the healthcare system, particularly in the more advanced stages of CKD. New interventions that can delay the progression of CKD to kidney failure may not only prolong the patient's life, but would also provide significant resource and cost savings to healthcare providers.