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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.

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. Graphical Abstract Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-02010-3.

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.

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.

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 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 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.

Background Real-world data for patients with chronic kidney disease (CKD), specifically pertaining to clinical management, metabolic control, treatment patterns, quality of life (QoL) and dietary patterns, are limited. Understanding these gaps using real-world, routine care data will improve our understanding of the challenges and consequences faced by patients with CKD, and will facilitate the long-term goal of improving their management and prognosis. Methods DISCOVER CKD follows an enriched hybrid study design, with both retrospective and prospective patient cohorts, integrating primary and secondary data from patients with CKD from China, Italy, Japan, Sweden, the UK and the USA. Data will be prospectively captured over a 3-year period from >1000 patients with CKD who will be followed up for at least 1 year via electronic case report form entry during routine clinical visits and also via a mobile/tablet-based application, enabling the capture of patient-reported outcomes (PROs). In-depth interviews will be conducted in a subset of ∼100 patients. Separately, secondary data will be retrospectively captured from >2 000 000 patients with CKD, extracted from existing datasets and registries. Results The DISCOVER CKD program captures and will report on patient demographics, biomarker and laboratory measurements, medical histories, clinical outcomes, healthcare resource utilization, medications, dietary patterns, physical activity and PROs (including QoL and qualitative interviews). Conclusions The DISCOVER CKD program will provide contemporary real-world insight to inform clinical practice and improve our understanding of the epidemiology and clinical and economic burden of CKD, as well as determinants of clinical outcomes and PROs from a range of geographical regions in a real-world CKD setting.

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.

Background Attaining the narrow haemoglobin (Hb) range recommended by European Renal Best Practice Guidelines renal anaemia guidelines may be difficult, and whether this leads to better outcomes following dialysis initiation is not known. Methods This was an observational study from the Swedish Renal Registry 2012–16, including all patients with non-dialysis-dependent chronic kidney disease (CKD) initiating renal anaemia treatment. We evaluated factors associated with off-target Hb attainment (12 g/dL). For those who initiated dialysis, we explored associations between the pre-end-stage kidney disease (pre-ESKD) time in which Hb was within or above range, and pre-ESKD Erythropoietin Resistance Index (ERI) with the 1-year risk of death or major adverse cardiovascular events + (MACE+). Results About 5000 patients initiated anaemia treatment, contributing to 25 431 consecutive visits over time. Patients with polycystic kidney disease, diabetic nephropathy and nephrosclerosis, with recent bleeding/transfusion, with higher C-reactive protein or abnormal phosphate had higher odds of maintaining Hb below range. Conversely, patients with older age, CKD Stages 3b–4, pyelonephritis, kidney transplant, iron medication, higher ESA doses or abnormal serum calcium and albumin had higher odds of maintaining Hb above range. A total of 1361 patients initiated dialysis, among whom 220 deaths and 453 MACE+ occurred. A greater time spent with a pre-ESKD Hb >12 g/dL was associated with a lower risk of MACE+ (hazard ratio = 0.76; 95% confidence interval 0.61–0.94) after dialysis initiation, and a lower pre-ESKD Erythropoietin Resistance Index (ERI) was associated with improved survival (1.39; 1.02–1.90). Conclusions Our study identified populations that require additional efforts to control their Hb. Our outcome analysis supports the value of pre-ESKD anaemia care while illustrating the problems of ESA hyporesponsiveness in clinical practice.

Background Users of guideline-recommended renin–angiotensin–aldosterone system (RAAS) inhibitors may experience disruptions to their treatment, e.g. due to hyperkalaemia, hypotension or acute kidney injury. The risks associated with treatment disruption have not been comprehensively assessed; therefore, we evaluated the risk of adverse clinical outcomes in RAAS inhibitor users experiencing treatment disruptions in a large population-wide database. Methods This exploratory, retrospective analysis utilized data from the UK’s Clinical Practice Research Datalink, linked to Hospital Episodes Statistics and the Office for National Statistics databases. Adults (≥18 years) with first RAAS inhibitor use (defined as angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) between 1 January 2009 and 31 December 2014 were eligible for inclusion. Time to the first occurrence of adverse clinical outcomes [all-cause mortality, all-cause hospitalization, cardiac arrhythmia, heart failure hospitalization, cardiac arrest, advancement in chronic kidney disease (CKD) stage and acute kidney injury] was compared between RAAS inhibitor users with and without interruptions or cessations to treatment during follow-up. Associations between baseline characteristics and adverse clinical outcomes were also assessed. Results Among 434 027 RAAS inhibitor users, the risk of the first occurrence of all clinical outcomes, except advancement in CKD stage, was 8–75% lower in patients without interruptions or cessations versus patients with interruptions/cessations. Baseline characteristics independently associated with increased risk of clinical outcomes included increasing age, smoking, CKD, diabetes and heart failure. Conclusions These findings highlight the need for effective management of factors associated with RAAS inhibitor interruptions or cessations in patients for whom guideline-recommended RAAS inhibitor treatment is indicated.

Background Hyperkalemia is common among hemodialysis (HD) patients and has been associated with adverse clinical outcomes. Previous studies considered a single serum potassium (K) measurement or time-averaged values, but serum K excursions out of the target range may be more reflective of true hyperkalemia events. We assessed whether hyperkalemia excursions lead to an elevated risk of adverse clinical outcomes. Methods Using data from 21 countries in Phases 4–6 (2009–18) of the Dialysis Outcomes and Practice Patterns Study (DOPPS), we investigated the associations between peak serum K level, measured monthly predialysis, over a 4-month period (‘peak K’) and clinical outcomes over the subsequent 4 months using Cox regression, adjusted for potential confounders. Results The analysis included 62 070 patients contributing a median of 3 (interquartile range 2–6) 4-month periods. The prevalence of hyperkalemia based on peak K was 58% for >5.0, 30% for >5.5 and 12% for >6.0 mEq/L. The all-cause mortality hazard ratio for peak K (reference ≤5.0 mEq/L) was 1.15 [95% confidence interval (CI) 1.09, 1.21] for 5.1–5.5 mEq/L, 1.19 (1.12, 1.26) for 5.6–6.0 mEq/L and 1.33 (1.23, 1.43) for >6.0 mEq/L. Results were qualitatively consistent when analyzing hospitalizations and a cardiovascular composite outcome. Conclusions Among HD patients, we identified a lower K threshold (peak K 5.1–5.5 mEq/L) than previously reported for increased risk of hospitalization and mortality, with the implication that a greater proportion (>50%) of the HD population may be at risk. A reassessment of hyperkalemia severity ranges is needed, as well as an exploration of new strategies for effective management of chronic hyperkalemia.

Introduction The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines recommend classifying patients by glomerular filtration rate (GFR) and albuminuria to predict chronic kidney disease (CKD) prognosis. The aim of this systematic review was to explore the epidemiological burden of CKD stratified by the KDIGO 2012 categories. Methods MEDLINE® and Embase were searched for observational studies of patients with CKD with results stratified according to the KDIGO 2012 classification. Investigated outcomes were prevalence, incidence, and risk factors and complications of CKD, including mortality. Results The review included ten observational studies with 3033 to 46,949 participants, conducted in the USA, China, France, Italy and Spain. The most frequently reported outcome was the prevalence of CKD (GFR categories G3–5), ranging from 2% to 17%. Most participants were normoalbuminuric, with 0.4–3.2% macroalbuminuric, and most fell within the KDIGO 2012 low-risk or moderate-risk groups, with 0.9–5.6% in the high-risk and 0.3–4.8% in the very high-risk groups. Although scarce, data on the prevalence of comorbidities in CKD according to the KDIGO classification suggest that they increase with albuminuria severity. Conclusions Patients with CKD frequently have complications, but only a small proportion have severely increased albuminuria or fall within the KDIGO high-risk or very high-risk groups. These groups, however, are associated with the highest burden of disease, as comorbidities are more prevalent with increasing albuminuria severity. New studies framed by the KDIGO 2012 classification are needed to address key gaps in the understanding of CKD burden and outcomes. Electronic supplementary material The online version of this article (10.1007/s12325-020-01568-8) contains supplementary material, which is available to authorized users.

Purpose Anemia is prevalent in patients with chronic kidney disease (CKD), but the longitudinal risk of anemia in patients with newly identified CKD is unknown. We therefore examined the risks of experiencing anemia in persons with newly identified CKD. Patients and Methods This cohort study included adult patients with newly identified CKD stages 3-5 defined by an estimated glomerular filtration rate (eGFR) level

International audience; 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, eGFR12 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.

Rationale & Objective Previous studies of inflammation and anemia management in hemodialysis (HD) patients may be biased due to patient differences. We used a self-matched longitudinal design to test whether new inflammation, defined as an acute increase in C-reactive protein (CRP) level, reduces hemoglobin response to erythropoiesis-stimulating agent (ESA) treatment. Study Design Self-matched longitudinal design. Setting & Participants 3,568 new inflammation events, defined as CRP level > 10 mg/L following a 3-month period with CRP level ≤ 5 mg/L, were identified from 12,389 HD patients in the Dialysis Outcomes and Practice Patterns Study (DOPPS) phases 4 to 6 (2009-2018) in 10 countries in which CRP is routinely measured. Predictor “After” (vs “before”) observing a high CRP level. Outcomes Within-patient changes in hemoglobin level, ESA dose, and ESA hyporesponsiveness (hemoglobin 6,000 [Japan] or >8,000 [Europe] U/wk). Analytical Approach Linear mixed models and modified Poisson regression. Results Comparing before with after periods, mean hemoglobin level decreased from 11.2 to 10.9 g/dL (adjusted mean change, −0.26 g/dL), while mean ESA dose increased from 6,320 to 6,960 U/wk (adjusted relative change, 8.4%). The prevalence of ESA hyporesponsiveness increased from 7.6% to 12.3%. Both the unadjusted and adjusted prevalence ratios of ESA hyporesponsiveness were 1.68 (95% CI, 1.48-1.91). These associations were consistent in sensitivity analyses varying CRP thresholds and were stronger when the CRP level increase was sustained over the 3-month after period. Limitations Residual confounding by unmeasured time-varying risk factors for ESA hyporesponsiveness. Conclusions In the 3 months after HD patients experienced an increase in CRP levels, hemoglobin levels declined quickly, ESA doses increased, and the prevalence of ESA hyporesponsiveness increased appreciably. Routine CRP measurement could identify inflammation as a cause of worsened anemia. In turn, these findings speak to a potentially important role for anemia therapies that are less susceptible to the effects of inflammation., Graphical Abstract

Lumbosacral transitional vertebrae (LSTV) are defined as congenital anatomical variations, observed unilaterally or bilaterally, in which the transverse process of the last lumbar vertebra exhibits signs of dysplasia evident as increased craniocaudal height, with varying degrees of articulation or fusion to the ‘first' sacral vertebra. Such variations give rise to vertebral morphology that may display lumbar or sacral characteristics at the terminal lumbar spine, together with subsequent enumeration variation. The purpose of this study was to establish baseline data on the prevalence rates of LSTV and to describe the morphological characteristics (Type, subtype, frequency of side and spinal enumeration) of LSTV in the South African population. This study was subdivided into two main sections, namely Part 1: medical imaging appraisal and Part 2: osteological morphology appraisal. In Part 1, both retrospective and prospective cohort randomised sampling methods of data collection of medical images were used. The appraisal of the medical images included radiographs, magnetic resonance imagers and computerised tomography scans. Prevalence rates, utilising the Castellvi et al. (1984) classification, were established via radiographs only. Additionally, lumbar spine enumeration, namely lumbarisation and sacralisation, was made through the appraisal of lumbar radiographs. Images were obtained from medical radiology practices located at Groote Schuur Hospital in Cape Town, Western Cape Province and Charlotte Maxeke Johannesburg Academic Hospital in Johannesburg, Gauteng Province. The total imaging cohort included 3096 individuals of which 308 individuals (10%) were found to contain LSTV. Prevalence rates were further evaluated by subdivision of the three largest ancestries in South Africa. Ancestries were classified as African (n=1032), Mixed (n=1032) and European (n=1032). The prevalence of LSTV in the three ancestral groups was 10.5%, 9.3% and 9.9% respectively and the sex distribution was greater in females (52.1%) then in males (47.9%). The morphological assessment found the prevalence of LSTV by Type was Type II (67.9%) followed by Types III (27.6%) and IV (4.5%). The most frequent subtype by prevalence was Type IIA (41.9%) followed by Type IIB (26%), Type IIIB (21.8%), and Type IV (5.8%). Additionally, the frequency of side was bilateral (47.7%), left (26.6%), right (21.1%), and other (4.5%). Comparison of ancestry and spinal enumeration analyses established statistical significance for individuals of African-ancestry (67.0%) and Mixed-ancestry (72.9%) both of which demonstrated a greater affinity of prevalence for sacralisation (p=0.008), with a small effect size (V=0.178) over the European-ancestry subgroup (52.4%). Furthermore, a statistical significance with a medium effect size (V=0.256) was found in males (p=0.010) when comparing ancestry and spinal enumeration between sexes. In Part 2, a systematic search of the total cadaveric skeletal collection housed at the University of Witwatersrand (the Dart Collection of skeletons) yielded 1797 human skeletal specimens of between 21 and 65 years of age at time of death. One-hundred and fourteen skeletal remains were identified as containing LSTV. Damage and loss of vertebral elements resulted in a subset of 91 LSTV for study. A sex balanced control group cohort of 30 males and 30 females was selected at random from the Dart Collection for comparative analyses. A number of osteometric measurements were evaluated comparing the LSTV and control group cohorts. Numerous osteometric comparisons were statistically significant highlighting the many changes in lumbar and sacral morphology associated with LSTV. There are several original findings to emerge. Thisis the first study to establish the prevalence of LSTV in a large sample from the South African population, subdivided into the three largest ancestral groups. Novel findings associated with LSTV include iliolumbar articulation, bipartition of the sacral foramen, intra-articular vacuum phenomenon of accessory articulations of LSTV, enlargement of the contralateral TVP associated with Types III and IV LSTV, lumbar ossified bridging syndrome and a novel complex named by the researcher as the transverso-sacro-iliac articulation. Furthermore, the researcher has proposed three modifications to the Castellvi et al. (1984) classification, namely (1) that there should be a sub-classification of the Type IV LSTV into right and left nomenclature, (2) the inclusion of a new subtype of Type II LSTV morphology, a unilateral right or left iliolumbar articulation associated with contralateral Type IIA morphology, and (3) a modified morphological classification of LSTV based on the presence of an extended sacroiliac articulation either directly or via the transverso-sacro-iliac articulation. The latter effectively increases the size of the sacroiliac joint and is thought to increase spinopelvic stability. The transverso-sacroiliac articulation was demonstrated for all clinically significant LSTV Types (II-IV), both unilateral (right or left) and bilateral. Finally, this is the first study to incorporate an in situ and an ex situ study in the same population by examining spinal morphology of LSTV using medical images and skeletal remains for descriptive analyses.

Delaying disease progression and reducing the risk of mortality are key goals in the treatment of chronic kidney disease (CKD). New drug classes to augment renin–angiotensin–aldosterone system (RAAS) inhibitors as the standard of care have scarcely met their primary endpoints until recently. This systematic literature review explored treatments evaluated in patients with CKD since 1990 to understand what contemporary data add to the treatment landscape. Eighty-nine clinical trials were identified that had enrolled patients with estimated glomerular filtration rate 13.9–102.8 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 29.9–2911.0 mg/g, with (75.5%) and without (20.6%) type 2 diabetes (T2D). Clinically objective outcomes of kidney failure and all-cause mortality (ACM) were reported in 32 and 64 trials, respectively. Significant reductions (P 300–5000 mg/g) and dapagliflozin (in patients with or without T2D and UACR 200–5000 mg/g) added to a background of RAAS inhibition. Significant reductions in ACM were observed with dapagliflozin in the DAPA-CKD trial. Contemporary data therefore suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD. Supplementary Information The online version contains supplementary material available at 10.1007/s12325-021-02006-z.

Introduction: Kidney Disease: Improving Global Outcomes (KDIGO) 2012 guidelines classify chronic kidney disease (CKD) risk or prognosis using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR). We assessed patient characteristics and outcomes according to the KDIGO classification, using data from DISCOVER CKD (NCT04034992). Methods: Data were extracted from the US integrated Limited Claims and Electronic Health Record Dataset and TriNetX databases, and the UK Clinical Practice Research Datalink linked to Hospital Episode Statistics and Office for National Statistics databases. Eligible patients were aged ≥18 years with CKD, and identified by 2 consecutive eGFR measures (5 to 2; ≥90 days apart [maximum 730]) from January 2008. Index date was the second eGFR measurement; patients were categorized using the UACR measure closest to the index. Outcomes included patient characteristics, eGFR or UACR measurement frequency, and clinical outcomes per baseline KDIGO classification. Results: Across databases, only 8.6% of patients with 2 eGFR measures had ≥1 UACR measures. Among 123,807 eligible patients, prevalence of heart failure, hypertension, and type 2 diabetes increased with increasing albuminuria. Incidence rates of mortality and adverse cardiovascular and renal outcomes increased with declining baseline eGFR, and particularly with increasing albuminuria. Median number of eGFR and UACR tests per year post-index ranged from 1.6 to 2.5 and 0.5 to 0.6, respectively, across databases; there was no clear increase in UACR testing frequency following the KDIGO 2012 guidelines. Conclusion: Albuminuria monitoring is critical for optimal risk stratification in CKD, and our findings highlight an imperative for more regular UACR testing in clinical practice.

IntroductionGeneric multiattribute utility instruments (MAUIs) are efficient tools for determining and enumerating health-related quality of life. MAUIs accomplish this by generating health state utilities (HSUs) via algorithms. Minimal important differences (MIDs) assist with the interpretation of HSUs by estimating minimum changes that are clinically significant. The overall goal of the proposed systematic review and meta-analysis is the development of comprehensive guidelines for MID estimation.Methods and analysisThis protocol defines a systematic review and meta-analysis of MIDs for generic MAUIs. The proposed research will involve a comprehensive investigation of 10 databases (EconLit, IDEAs database, INAHTA database, Medline, PsycINFO, Embase, Emcare, JBIEBP and CINAHL) from 1 June 2022 to 7 June 2022, and will be performed and reported in accordance with several validated guidelines, principally the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The quality of papers, considered for inclusion in the review, will be appraised using the COnsensus-based Standards for the selection of health Measurement INstruments, inter alia.Narrative analysis will involve identifying the characteristics of MIDs including methods of calculation, sources of heterogeneity, and validation. Meta-analysis will also be conducted. The descriptive element of meta-analysis will involve the generation of I2statistics and Galbraith plots of MID heterogeneity. Together with narrative analysis, this will allow sources of MID heterogeniety to be identified. A multilevel mixed model, estimated via restricted maximum likelihood estimation, will be constructed for the purposes of meta-regression. Meta-regression will attempt to enumerate the effects of sources of heterogeneity on MID estimates. Meta-analysis will be concluded with pooling of MIDs via a linear random-effects model.Ethics and disseminationEthics approval is not required for this review, as it will aggregate data from published literature. Methods of dissemination will include publication in a peer-reviewed journal, as well as presentation at conferences and seminars.PROSPERO registration numberCRD42021261821.

Funder: AstraZeneca, 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.

Introduction: Further understanding of adverse clinical events in patients with chronic kidney disease (CKD) is needed. This study aimed to describe characteristics of patients with nondialysis-dependent (NDD) and dialysis-dependent (DD) CKD and to assess incidence rates of uncommon adverse clinical events of interest in these patients. Methods: This retrospective study used electronic medical record data from USA CKD patients (≥18 years) with estimated glomerular filtration rate (eGFR) 2 between January 1, 2010, and December 31, 2018, obtained from the USA-based TriNetX database. NDD-CKD and DD-CKD were diagnosed and staged from ≥2 consecutive eGFR readings, recorded ≥90 days apart. Dialysis was identified using procedure codes for renal replacement therapy. Outcomes assessed were select uncommon adverse clinical events, defined by International Classification of Disease, 9th and 10th Revision codes. Results: Incidence rates of adverse clinical events per 100 person-years (95% confidence interval) were generally higher in patients with DD-CKD versus NDD-CKD. Differences were particularly pronounced for hyperkalemia (26.9 [26.2–27.6] vs. 4.5 [4.5–4.6]), acidosis (15.1 [14.7–15.6] vs. 3.4 [3.4–3.4]), and sepsis (14.6 [14.2–15.1] vs. 3.3 [3.3–3.4]). Among DD-CKD patients, incidence rates of adverse events were particularly high during the first 3 months following dialysis initiation. Incidence of adverse clinical events generally increased with decreasing eGFR among patients with NDD-CKD and with hemoglobin Conclusions: Our results help establish baseline rates of uncommon adverse clinical events and provide additional evidence of increased morbidity for patients with DD-CKD versus NDD-CKD.

Background Serum potassium (SK+) is a vital electrolyte, which level is maintained by adjusting renal K+ excretion. Variability in SK+ has been linked to increased risk of mortality and other adverse clinical events in patients in intensive care and/or receiving haemodialysis, prompting a similar investigation in cardiovascular patients. Purpose To examine the effect of SK+ variability on all-cause mortality (ACM) and the incidence of major adverse cardiovascular events (MACE), comprising arrhythmia, [subsequent records of] HF, myocardial infarction, or stroke, in patients with heart failure (HF) or resistant hypertension (RHTN). Methods Patients aged ≥18 years with HF or RHTN were identified from the UK Clinical Practice Research Datalink (CPRD, primary care data) and linked Hospital Episode Statistics (HES, secondary care data). HF and RHTN were defined through READ codes recorded during the study period (2008-June 2018) or the five-year look-back period (2003–2007). Index date was set to 1st January 2008 or initial diagnosis; whichever occurred later. Mean SK+ and variability of measurements (quantified as standard deviation [SD] and each patient categorised as low or highly variable based on the median SD of the cohort), and crude incidence rates of ACM and MACE were estimated over a follow-up period from index date to event or end of follow-up (death, loss to follow-up or end of study, whichever was earlier). Results The eligible population included 317,135 RHTN patients and 84,210 HF patients with a mean follow-up of 6.37 (SD 3.06) and 5.01 (SD 3.20) years, respectively. In both cohorts, higher mean SK+ ≥5.0 mmol/L was associated with increased rates of ACM and MACE relative to a mean SK+ of 3.5–5 mmol/L (Table 1). High SK+ variability was associated with increased incidence of adverse outcomes, with rates consistently higher in the high SK+ variability group compared to low-variability patients with the same diagnosis and mean SK+ category (Table 1); all comparisons were statistically significant except for ACM in HF patients with mean SK+ ≥5 mmol/L. Conclusion Independently of mean SK+, increased variability in SK+ levels was associated with an increased rate of mortality and MACE in patients with RHTN or HF. Careful SK+ monitoring and management to maintain SK+ concentrations may improve the outcomes of patients with RHTN and HF. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Background Hyper- and hypokalaemia are frequent complications in patients with heart failure (HF). The association between all-cause mortality (ACM), major adverse cardiovascular events (MACE) and serum potassium (K+) has previously been characterised in a UK incident HF population, with hypo- and hyperkalaemic patients being at increased risk of adverse clinical outcomes. Purpose This study aimed to assess the generalisability and findings of previously published risk equations in a broader HF population, spanning both incident and prevalent HF cases regardless of chronic kidney disease (CKD), and to explore the relationship between duration of HF and elevated risk associated with hypo- or hyperkalaemia. Methods A retrospective cohort study was conducted using linked UK Clinical Practice Research Datalink (CPRD) GOLD and Hospital Episode Statistics (HES) data. Eligible patients included individuals ≥18 years with HF (identified using READ codes) during the study period (January 2008 to June 2018) or five-year lookback period (2003 to 2007). Patients' index date was set to 1st January 2008 for prevalent patients or date of HF diagnosis for incident patients. Adverse clinical outcomes included ACM and MACE, a composite of arrhythmia, HF, myocardial infarction and stroke. Published risk equations for ACM and MACE for incident HF without CKD were refitted to this broader study population using original covariates and model forms. Coefficient values were adjusted for the inclusion of HF duration (≤5 and >5 years). Incidence rate ratios (IRRs) were recalculated with K+ concentration 4.5 to Results The HF cohort consisted of 84,210 patients with a mean follow-up of 5.01 years. The cohort was predominantly male (53.0%), with a mean age of 77.3 years at index. Ischaemic heart disease, hypertension, atrial fibrillation and type 2 diabetes were present in 42.24%, 61.39%, 40.89% and 20.38% of the population, respectively. CKD stage 3+ was present in 39.13% of patients, with a cohort mean estimated glomerular filtration rate of 56.9 mL/min/1.73m2 at index. Crude ACM and MACE event rates were 159.5 (95% confidence interval (CI): 157.9–161.0) and 575.8 (95% CI: 572.8–578.7) per 1,000 patient years, respectively. Hypo- and hyperkalaemia were generally associated with increased risk of ACM and MACE in comparison with patients with K+ concentrations of 4.5 to Conclusion A real-world analysis of UK patients suggests that previously published associations between hypo- and hyperkalaemia and increased risk of adverse clinical outcomes in an incident HF population are generalisable to a cohort of incident and prevalent HF patients, irrespective of HF duration and the presence of comorbid CKD. Improved monitoring and management of K+ may have the potential to improve outcomes in these patients. Figure 1. IRRs of ACM and MACE Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

Background Patients with chronic kidney disease (CKD), heart failure (HF), resistant hypertension (RHTN) and diabetes are at an increased risk of hyperkalaemia (HK) which can be potentially life-threatening, as a result of cardiac arrhythmias, cardiac arrest leading to sudden death. In these patients, renin-angiotensin-aldosterone system inhibitors (RAASi), are used to manage several cardiovascular and renal conditions, and are associated with an increased risk of HK. Assessing the burden of HK in real-world clinical practice may concentrate relevant care on those patients most in need, potentially improving patient outcomes and efficiency of the healthcare system. Purpose To assess the burden of HK in a real-world population of UK patients with at least one of: RHTN, Type I or II diabetes, CKD stage 3+, dialysis, HF, or in receipt of a prescription for RAASi. Methods Primary and secondary care data for this retrospective study were obtained from the UK Clinical Practice Research Datalink (CPRD) and linked Hospital Episode Statistics (HES). Eligible patients were identified using READ codes defining the relevant diagnosis, receipt of indication-specific medication, or, in the case of CKD, an estimated glomerular filtration rate (eGFR) ≤60 ml/min/1.73m2 within the study period (01 January 2008 to 30 June 2018) or in the five-year lookback period (2003–2007). The index date was defined as 01 January 2008 or first diagnosis of an eligible condition or RAASi prescription, whichever occurred latest. HK was defined as K+ ≥5.0 mmol/L; thresholds of ≥5.5 mmol/L and ≥6.0 mmol/L were explored as sensitivity analyses. Incidence rates of HK were calculated with 95% confidence intervals (CI). Results The total eligible population across all cohorts was 931,460 patients. RHTN was the most prevalent comorbidity (n=317,135; 34.0%) and dialysis the least prevalent (n=4,415; 0.5%). The majority of the eligible population were prescribed RAASi during follow-up (n=754,523; 81.0%). At a K+ threshold of ≥5.0 mmol/L, the dialysis cohort had the highest rate of HK (501.0 events per 1,000 patient-years), followed by HF (490.9), CKD (410.9), diabetes (355.0), RHTN (261.4) and the RAASi cohort (211.2) (Figure 1). This pattern was still observed at alternative threshold definitions of HK. Conclusion This large real-world study of UK patients demonstrates the burden of hyperkalaemia in high-risk patient populations from the UK. There is a need for effective prevention and treatment of HK, particularly in patients with CKD, dialysis or HF where increased incidence rates are observed which in turn will improve patient outcomes and healthcare resource usage. Figure 1. Rates of HK by condition Funding Acknowledgement Type of funding source: Private company. Main funding source(s): AstraZeneca

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.

BackgroundChronic 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.ObjectiveThe 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.MethodsAdult 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.ResultsThe 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.ConclusionsThis 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.

Previously lacking in the literature, we describe longitudinal patterns of anemia prescriptions for non-dialysis-dependent chronic kidney disease (NDD-CKD) patients under nephrologist care. We analyzed data from 2818 Stage 3-5 NDD-CKD patients from Brazil, Germany, and the US, naïve to anemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrollment in the CKDopps. We report the cumulative incidence function (CIF) of medication initiation stratified by baseline characteristics. Even in patients with hemoglobin (Hb)

Background and Aims Previously lacking in the literature, this analysis aims to comprehensively describe longitudinal patterns of anaemia management, including prescriptions of ESA and iron replacement, for non-dialysis dependent chronic kidney disease (NDD-CKD) stage 3 to 5 patients under nephrologist care. Method We analysed data from a prospective cohort of 2455 NDD-CKD patients from Brazil, Germany and the US, who were not using anaemia medications (oral iron, intravenous [IV] iron, or erythropoiesis stimulating agent [ESA]) at enrolment in the Chronic Kidney Disease Outcomes and Practice Patterns Study (CKDOPPS). We excluded 26% (N=862) of patients who were using any anaemia treatment from the source population at CKDOPPS study entry; we further excluded patients with (a) missing data for demographics and/or clinical history, or (b) no laboratory and medication data during follow-up. We reported the cumulative incidence (CI) of anaemia treatment initiation, stratified by biochemical parameters and patient characteristics. For patients that started therapy, we report the frequency of medication type at the moment of initiation, as well as switches and discontinuation over 12 months. Results The CI of any anaemia treatment initiation at 12 months was 18% for the whole sample, and 54% for patients with haemoglobin (Hb) Conclusion Anaemia treatment is initiated in a limited number of NDD-CKD patients with clinical signs that would indicate to do so, and many patients discontinue treatment, for reasons yet to be clarified. Although haemoglobin was the main factor associated with prescriptions, only about half of patients with Hb

Background and Aims Attaining the narrow hemoglobin range (10-12 g/dL) recommended by current ERBP renal anemia guidelines may be difficult, and whether this leads to better outcomes is not well known. This study aimed to identify patient and clinical factors associated with difficulties in maintaining hemoglobin target ranges in routine non-dialysis nephrologist care. We also evaluated whether adherence to ERBP hemoglobin recommendations during pre-dialysis care predicted early post-dialysis outcomes. Method Observational study from the Swedish Renal Registry including all patients with non-dialysis dependent CKD stages 3b-5 developing renal anemia or initiating treatment (iron, ESA or both) between 2012-2016. Through multinomial logistic regression with clustered variance, we identified clinical conditions associated to serum hemoglobin values outside the ERBP recommended range (12 g/dL) throughout all recorded patient visits until death, dialysis or end of follow-up. For those who initiated dialysis, we calculated the proportion of patient-time in which hemoglobin was maintained within range (time in range [TIR]). We then explored associations between TIR and subsequent one-year risk of death or MACE (composite of death caused by CVD and non-fatal MI, stroke, heart failure) with Cox proportional hazards regression. Results A total 8106 patients with CKD 3b-5 developed incident anemia in Sweden during 2012-2016, contributing with 37422 nephrology visits during median 2 years of follow up. In multinomial logistic regression, being a man and having received iron or higher ESA doses was associated with hemoglobin values outside target range. Patients with CKD 3b and 4, ongoing transplant, history of CVD, or with higher serum calcium and albumin levels had higher odds of maintaining hemoglobin values above range. Conversely, recent bleeding or transfusions, nephrosclerosis, inflammation (CRP>5 mg/dl), and higher phosphate levels increased the odds of having hemoglobin values below range. A total 2435 patients initiated maintenance dialysis during the study period. Of those, 327 died and 701 developed MACE during the subsequent year. Their median TIR during their pre-dialysis period was 44% (IQR: 34-50). On a continuous scale (FIGURE), we observed worse outcomes for patients with poor guideline recommendation adherence (low percentage TIR), although the association was judged weak. On a categorical scale, patients that spent more than 40% of their pre-dialysis TIR had lower hazards of death (0.57, 95% CI 0.41-0.80) and MACE (0.67, 95% CI, 0.54-0.84) compared to those with Conclusion This nationwide study reports that greater adherence to ERBP anemia guidelines during pre-dialysis care, using existing conventional therapeutic approaches, is associated with better post-dialysis outcomes. Whether active interaction by healthcare practitioners affected the observed relationship needs to be further explored.

Background and Aims Patients with chronic kidney disease (CKD) are at increased risk of hyperkalaemia, HK (high serum potassium concentration) due to impaired renal function. This medical condition is potentially life threatening if untreated or poorly managed. This study describes the characteristics of CKD patients in the UK who experience HK and assessed the frequency of recurrent HK and time between first (index) and subsequent events. Method A retrospective cohort study was conducted using linked Clinical Practice Research Datalink (CPRD) and Hospital Episode Statistics (HES) data from 01 January 2008 to 30 June 2018, with a five-year lookback period (2003-2007). Patients were included if they were diagnosed with CKD stage 3+ (READ code or eGFR 18 years at diagnosis (index). Patient demographics, clinical history and baseline medication use were described. HK was defined as serum K+ ≥5.0 mmol/L. HK events occurring during the study period, but after diagnosis of CKD, were assessed. Recurrent HK was defined as any event subsequent to the first event. Time to recurrence was calculated using Kaplan-Meier. Results In total, 297,702 CKD patients (mean age 74.7 years [standard deviation: 11.3], male [41.4%]) met eligibility criteria. At time of CKD diagnosis, 30.6% of the population had resistant hypertension. Other prominent comorbidities included diabetes (22.24%), CKD (7.9%) and cancer (7.8%). Approximately half of patients were in receipt of diuretics at baseline (49.2%), while 32.5% and 32.0% were in receipt of beta blockers and calcium channel blockers, respectively. During follow up, 67.0% of patients received a renin-angiotensin aldosterone system inhibitor (RAASi). 147,215 patients (49.5%) experienced at least one HK event, of which 53,695 (36.5%) had only one HK event, 93,250 (63.5%) had two or more HK events and 29,413 (20.0%) had six or more events. HK event incidence was predictive of subsequent events, with the probability of experiencing a HK event increasing from 49.5% to 63.5%, 70.7%, 74.1%, 76.5% and 78.6% for patients experiencing 2-6 events, respectively. There was an inverse relationship between the number of recurrent events and time to next event, with less time between the next event for those experiencing multiple events (Figure 1). Conclusion This study shows that approximately half of CKD patients experienced a HK event. Furthermore, patients who experienced a HK event were at increased risk of subsequent events. Frequent monitoring of serum potassium may help reduce the burden of HK in patients with CKD.