Recovery of kidney function after acute kidney disease-a multi-cohort analysis.

BACKGROUND: There are no consensus definitions for evaluating kidney function recovery after acute kidney injury (AKI) and acute kidney disease (AKD), nor is it clear how recovery varies across populations and clinical subsets. We present a federated analysis of four population-based cohorts from Canada, Denmark and Scotland, 2011-18. METHODS: We identified incident AKD defined by serum creatinine changes within 48 h, 7 days and 90 days based on KDIGO AKI and AKD criteria. Separately, we applied changes up to 365 days to address widely used e-alert implementations that extend beyond the KDIGO AKI and AKD timeframes. Kidney recovery was based on resolution of AKD and a subsequent creatinine measurement below 1.2× baseline. We evaluated transitions between non-recovery, recovery and death up to 1 year; within age, sex and comorbidity subgroups; between subset AKD definitions; and across cohorts. RESULTS: There were 464 868 incident cases, median age 67-75 years. At 1 year, results were consistent across cohorts, with pooled mortalities for creatinine changes within 48 h, 7 days, 90 days and 365 days (and 95% confidence interval) of 40% (34%-45%), 40% (34%-46%), 37% (31%-42%) and 22% (16%-29%) respectively, and non-recovery of kidney function of 19% (15%-23%), 30% (24%-35%), 25% (21%-29%) and 37% (30%-43%), respectively. Recovery by 14 and 90 days was frequently not sustained at 1 year. Older males and those with heart failure or cancer were more likely to die than to experience sustained non-recovery, whereas the converse was true for younger females and those with diabetes. CONCLUSION: Consistently across multiple cohorts, based on 1-year mortality and non-recovery, KDIGO AKD (up to 90 days) is at least prognostically similar to KDIGO AKI (7 days), and covers more people. Outcomes associated with AKD vary by age, sex and comorbidities such that older males are more likely to die, and younger females are less likely to recover.

Care processes and outcomes of deprivation across the clinical course of kidney disease: findings from a high-income country with universal healthcare.

BACKGROUND: No single study contrasts the extent and consequences of inequity of kidney care across the clinical course of kidney disease. METHODS: This population study of Grampian (UK) followed incident presentations of acute kidney injury (AKI) and incident estimated glomerular filtration rate (eGFR) thresholds of <60, <45 and <30 mL/min/1.73 m2 in separate cohorts (2011-2021). The key exposure was area-level deprivation (lowest quintile of the Scottish Index of Multiple Deprivation). Outcomes were care processes (monitoring, prescribing, appointments, unscheduled care), long-term mortality and kidney failure. Modelling involved multivariable logistic regression, negative binomial regression and cause-specific Cox models with and without adjustment of comorbidities. RESULTS: There were 41 313, 51 190, 32 171 and 17 781 new presentations of AKI and eGFR thresholds <60, <45 and <30  mL/min/1.73 m2. A total of 6.1-7.8% of the population was from deprived areas and (versus all others) presented on average 5 years younger, with more diabetes and pulmonary and liver disease. Those from deprived areas were more likely to present initially in hospital, less likely to receive community monitoring, less likely to attend appointments and more likely to have an unplanned emergency department or hospital admission episode. Deprivation had the greatest association with long-term kidney failure at the eGFR <60 mL/min/1.73 m2 threshold {adjusted hazard ratio [HR] 1.48 [95% confidence interval (CI) 1.17-1.87]} and this association decreased with advancing disease severity [HR 1.09 (95% CI 0.93-1.28) at eGFR <30 mL/min/1.73 m2), with a similar pattern for mortality. Across all analyses the most detrimental associations of deprivation were an eGFR threshold <60 mL/min/1.73 m2, AKI, males and those <65 years of age. CONCLUSIONS: Even in a high-income country with universal healthcare, serious and consistent inequities in kidney care exist. The poorer care and outcomes with area-level deprivation were greater earlier in the disease course.

Inequalities in children's mental health care: analysis of routinely collected data on prescribing and referrals to secondary care.

BACKGROUND: One in eight children in the United Kingdom are estimated to have a mental health condition, and many do not receive support or treatment. The COVID-19 pandemic has negatively impacted mental health and disrupted the delivery of care. Prevalence of poor mental health is not evenly distributed across age groups, by sex or socioeconomic groups. Equity in access to mental health care is a policy priority but detailed socio-demographic trends are relatively under-researched. METHODS: We analysed records for all mental health prescriptions and referrals to specialist mental health outpatient care between the years of 2015 and 2021 for children aged 2 to 17 years in a single NHS Scotland health board region. We analysed trends in prescribing, referrals, and acceptance to out-patient treatment over time, and measured differences in treatment and service use rates by age, sex, and area deprivation. RESULTS: We identified 18,732 children with 178,657 mental health prescriptions and 21,874 referrals to specialist outpatient care. Prescriptions increased by 59% over the study period. Boys received double the prescriptions of girls and the rate of prescribing in the most deprived areas was double that in the least deprived. Mean age at first mental health prescription was almost 1 year younger in the most deprived areas than in the least. Referrals increased 9% overall. Initially, boys and girls both had an annual referral rate of 2.7 per 1000, but this fell 6% for boys and rose 25% for girls. Referral rate for the youngest decreased 67% but increased 21% for the oldest. The proportion of rejected referrals increased steeply since 2020 from 17 to 30%. The proportion of accepted referrals that were for girls rose to 62% and the mean age increased 1.5 years. CONCLUSIONS: The large increase in mental health prescribing and changes in referrals to specialist outpatient care aligns with emerging evidence of increasing poor mental health, particularly since the start of the COVID-19 pandemic. The static size of the population accepted for specialist treatment amid greater demand, and the changing demographics of those accepted, indicate clinical prioritisation and unmet need. Persistent inequities in mental health prescribing and referrals require urgent action.

Harmonization of epidemiology of acute kidney injury and acute kidney disease produces comparable findings across four geographic populations.

There is substantial variability in the reported incidence and outcomes of acute kidney injury (AKI). The extent to which this is attributable to differences in source populations versus methodological differences between studies is uncertain. We used 4 population-based datasets from Canada, Denmark, and the United Kingdom to measure the annual incidence and prognosis of AKI and acute kidney disease (AKD), using a homogenous analytical approach that incorporated KDIGO creatinine-based definitions and subsets of the AKI/AKD criteria. The cohorts included 7 million adults ≥18 years of age between 2011 and 2014; median age 59-68 years, 51.9-54.4% female sex. Age- and sex-standardised incidence rates for AKI or AKD were similar between regions and years; range 134.3-162.4 events/10,000 person years. Among patients who met either KDIGO 48-hour or 7-day AKI creatinine criteria, the standardised 1-year mortality was similar (30.4%-38.5%) across the cohorts, which was comparable to standardised 1-year mortality among patients who met AKI/AKD criteria using a baseline creatinine within 8-90 days prior (32.0%-37.4%). Standardised 1-year mortality was lower (21.0%-25.5% across cohorts) among patients with AKI/AKD ascertained using a baseline creatinine >90 days prior. These findings illustrate that the incidence and prognosis of AKI and AKD based on KDIGO criteria are consistent across 3 high-income countries when capture of laboratory tests is complete, creatinine-based definitions are implemented consistently within but not beyond a 90-day period, and adjustment is made for population age and sex. These approaches should be consistently applied to improve the generalizability and comparability of AKI research and clinical reporting.

Validation of Risk Prediction Models to Inform Clinical Decisions After Acute Kidney Injury.

RATIONALE & OBJECTIVE: There is limited evidence to guide follow-up after acute kidney injury (AKI). Knowledge gaps include which patients to prioritize, at what time point, and for mitigation of which outcomes. In this study, we sought to compare the net benefit of risk model-based clinical decisions following AKI. STUDY DESIGN: External validation of 2 risk models of AKI outcomes: the Grampian -Aberdeen (United Kingdom) AKI readmissions model and the Alberta (Canada) kidney disease risk model of chronic kidney disease (CKD) glomerular (G) filtration rate categories 4 and 5 (CKD G4 and G5). Process mining to delineate existing care pathways. SETTING & PARTICIPANTS: Validation was based on data from adult hospital survivors of AKI from Grampian, 2011-2013. PREDICTORS: KDIGO-based measures of AKI severity and comorbidities specified in the original models. OUTCOMES: Death or readmission within 90 days for all hospital survivors. Progression to new CKD G4-G5 for patients surviving at least 90 days after AKI. ANALYTICAL APPROACH: Decision curve analysis to assess the "net benefit" of use of risk models to guide clinical care compared to alternative approaches (eg, prioritizing all AKI, severe AKI, or only those without kidney recovery). RESULTS: 26,575 of 105,461 hospital survivors in Grampian (mean age, 60.9 ± 19.8 [SD] years) were included for validation of the death or readmission model, and 9,382 patients (mean age, 60.9 ± 19.8 years) for the CKD G4-G5 model. Both models discriminated well (area under the curve [AUC], 0.77 and 0.86, respectively). Decision curve analysis showed greater net benefit for follow up of all AKI than only severe AKI in most cases. Both original and refitted models provided net benefit superior to any other decision strategy. In process mining of all hospital discharges, 41% of readmissions and deaths occurred among people recovering after AKI. 1,464 of 3,776 people (39%) readmitted after AKI had received no intervening monitoring. LIMITATIONS: Both original models overstated risks, indicating a need for regular updating. CONCLUSIONS: Follow up after AKI has potential net benefit for preempting readmissions, death, and subsequent CKD progression. Decisions could be improved by using risk models and by focusing on AKI across a full spectrum of severity. The current lack of monitoring among many with poor outcomes indicates possible opportunities for implementation of decision support.

The long-term health effects of attending a selective school: a natural experiment.

BACKGROUND: Education is widely associated with better physical and mental health, but isolating its causal effect is difficult because education is linked with many socioeconomic advantages. One way to isolate education's effect is to consider environments where similar students are assigned to different educational experiences based on objective criteria. Here we measure the health effects of assignment to selective schooling based on test score, a widely debated educational policy. METHODS: In 1960s Britain, children were assigned to secondary schools via a test taken at age 11. We used regression discontinuity analysis to measure health differences in 5039 people who were separated into selective and non-selective schools this way. We measured selective schooling's effect on six outcomes: mid-life self-reports of health, mental health, and life limitation due to health, as well as chronic disease burden derived from hospital records in mid-life and later life, and the likelihood of dying prematurely. The analysis plan was accepted as a registered report while we were blind to the health outcome data. RESULTS: Effect estimates for selective schooling were as follows: self-reported health, 0.1 worse on a 4-point scale (95%CI - 0.2 to 0); mental health, 0.2 worse on a 16-point scale (- 0.5 to 0.1); likelihood of life limitation due to health, 5 percentage points higher (- 1 to 10); mid-life chronic disease diagnoses, 3 fewer/100 people (- 9 to + 4); late-life chronic disease diagnoses, 9 more/100 people (- 3 to + 20); and risk of dying before age 60, no difference (- 2 to 3 percentage points). Extensive sensitivity analyses gave estimates consistent with these results. In summary, effects ranged from 0.10-0.15 standard deviations worse for self-reported health, and from 0.02 standard deviations better to 0.07 worse for records-derived health. However, they were too imprecise to allow the conclusion that selective schooling was detrimental. CONCLUSIONS: We found that people who attended selective secondary school had more advantaged economic backgrounds, higher IQs, higher likelihood of getting a university degree, and better health. However, we did not find that selective schooling itself improved health. This lack of a positive influence of selective secondary schooling on health was consistent despite varying a wide range of model assumptions.

Characterizing infection in anti-neutrophil cytoplasmic antibody-associated vasculitis: results from a longitudinal, matched-cohort data linkage study.

OBJECTIVES: Infection exerts a major burden in ANCA-associated vasculitis (AAV), however, its precise extent and nature remains unclear. In this national study we aimed to longitudinally quantify, characterize and contextualize infection risk in AAV. METHODS: We conducted a multicentre matched cohort study of AAV. Complementary data on infections were retrieved via data linkage with the population-based Scottish microbiological laboratory, hospitalization and primary care prescribing registries. RESULTS: A total of 379 AAV patients and 1859 controls were followed up for a median of 3.5 years (interquartile range 1.9-5.7). During follow-up, the proportions of AAV patients with at least one laboratory-confirmed infection, severe infection and primary care antibiotic prescription were 55.4%, 35.6% and 74.6%, respectively. The risk of infection was higher in AAV than in matched controls {laboratory-confirmed infections: incidence rate ratio [IRR] 7.3 [95% confidence interval (CI) 5.6, 9.6]; severe infections: IRR 4.4 [95% CI 3.3, 5.7]; antibiotic prescriptions: IRR 2.2 [95% CI 1.9, 2.6]}. Temporal trend analysis showed that AAV patients remained at a higher risk of infections throughout the follow-up period, especially year 1. Although the Escherichia genus was the most commonly identified pathogen (16.6% of AAV, 5.5% of controls; P < 0.0001), AAV patients had the highest risk for Herpes [IRR 12.5 (95% CI 3.7, 42.6)] and Candida [IRR 11.4 (95% CI 2.4, 55.4)]. CONCLUSION: AAV patients have up to seven times higher risk of infection than the general population and the overall risk remains significant after 8 years of follow-up. The testing of enhanced short- to medium-term prophylactic antibiotic regimes should be considered.

Predicting kidney failure risk after acute kidney injury among people receiving nephrology clinic care.

BACKGROUND: Outcomes after acute kidney injury (AKI) are well described, but not for those already under nephrology clinic care. This is where discussions about kidney failure risk are commonplace. We evaluated whether the established kidney failure risk equation (KFRE) should account for previous AKI episodes when used in this setting. METHODS: This observational cohort study included 7491 people referred for nephrology clinic care in British Columbia in 2003-09 followed to 2016. Predictors were previous Kidney Disease: Improving Global Outcomes-based AKI, age, sex, proteinuria, estimated glomerular filtration rate (eGFR) and renal diagnosis. Outcomes were 5-year kidney failure and death. We developed cause-specific Cox models (AKI versus no AKI) for kidney failure and death, stratified by eGFR (

Risk factors associated with biochemically detected and hospitalised acute kidney injury in patients prescribed renin angiotensin system inhibitors.

AIMS: Therapy with angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) is a mainstay of treatment for heart failure (HF), diabetes mellitus (DM) and chronic kidney disease (CKD). These agents have been associated with development of acute kidney injury (AKI) during intercurrent illness. Risk factors for AKI in patients prescribed ACEi/ARB therapy are not well described. METHODS: We captured the incidence of AKI in patients commencing ACEi/ARB during 2009-2015 using anonymised patient records. Hospital-coded AKI was defined from hospital episode statistics; biochemical AKI was ascertained from laboratory data. Risk factors for biochemically detected and hospitalised AKI were investigated. RESULTS: Of 61,318 patients prescribed ACEi/ARB, with 132 885 person years (py) follow-up, there were 1070 hospitalisations with AKI as a diagnosis recorded and a total of 4645 AKI events, including AKI episodes indicated by biochemical KDIGO-based creatinine change criteria. Incidence of any AKI event was 35.0 per 1000-py, hospital-coded AKI was 7.8 per 1000-py and biochemical AKI was 33.7 per 1000-py. Independent risk factors in a multivariable model for hospital-coded AKI events were age, male gender, HF, diabetes, cerebrovascular disease, lower estimated glomerular filtration rate, socioeconomic deprivation, diuretic or non-steroidal anti-inflammatory use (all P < 0.001). CONCLUSION: In patients prescribed ACEi/ARB, the highest risk of AKI is associated with conditions which are considered strong evidence-based indications for their prescription. Socio-economic status is an under-reported risk factor for AKI with these agents. Strategies targeted at prevention of AKI may be of benefit, such as enhanced awareness based on higher risk comorbidities.

Defining and measuring multimorbidity: a systematic review of systematic reviews.

Background: Multimorbidity, the coexistence of multiple health conditions, is a growing public health challenge. Research and intervention development are hampered by the lack of consensus regarding defining and measuring multimorbidity. The aim of this systematic review was to pool the findings of systematic reviews examining definitions and measures of multimorbidity. Methods: Medline, Embase, PubMed and Cochrane were searched from database inception to February 2017. Two authors independently screened titles, abstracts and full texts and extracted data from the included papers. Disagreements were resolved with a third author. Reviews were quality assessed. Results: Of six reviews, two focussed on definitions and four on measures. Multimorbidity was commonly defined as the presence of multiple diseases or conditions, often with a cut-off of two or more. One review developed a holistic definition including biopsychosocial and somatic factors as well as disease. Reviews recommended using measures validated for the outcome of interest. Disease counts are an alternative if no validated measure exists. Conclusions: To enable comparison between studies and settings, researchers and practitioners should be explicit about their choice of definition and measure. Using a cut-off of two or more conditions as part of the definition is widely adopted. Measure selection should be based on tools validated for the outcome being considered. Where there is no validated measure, or where multiple outcomes or populations are being considered, disease counts are appropriate.

Models of care for chronic kidney disease: A systematic review.

AIM: Chronic kidney disease (CKD) is common and presents an increasing burden to patients and health services. However, the optimal model of care for patients with CKD is unclear. We systematically reviewed the clinical effectiveness of different models of care for the management of CKD. METHODS: A comprehensive search of eight databases was undertaken for articles published from 1992 to 2016. We included randomized controlled trials that assessed any model of care in the management of adults with pre-dialysis CKD, reporting renal, cardiovascular, mortality and other outcomes. Data extraction and quality assessment was carried out independently by two authors. RESULTS: Results were summarized narratively. Nine articles (seven studies) were included. Four models of care were identified: nurse-led, multidisciplinary specialist team, pharmacist-led and self-management. Nurse and pharmacist-led care reported improved rates of prescribing of drugs relevant to CKD. Heterogeneity was high between studies and all studies were at high risk of bias. Nurse-led care and multidisciplinary specialist care were associated with small improvements in blood pressure control. CONCLUSION: Evidence of long term improvements in renal, cardiovascular or mortality endpoints was limited by short follow up. We found little published evidence about the effectiveness of different models of care to guide best practice for service design, although there was some evidence that models of care where health professionals deliver care according to a structured protocol or guideline may improve adherence to treatment targets.

Life-course determinants of cognitive reserve (CR) in cognitive aging and dementia - a systematic literature review.

OBJECTIVES: The concept of cognitive reserve (CR) is defined as a moderator, which allows an individual to preserve cognition despite underlying brain pathology. There is no consensus of what potentially modifiable CR determinants are of greatest importance. The aim of this review was to identify life-course factors which protect older individuals from expressing cognitive decline despite the presence of brain pathology. METHOD: A systematic review search was performed in MEDLINE (1946-06/09/13), EMBASE (1947-06/09/13), and PsycheInfo (1967-06/09/13). We included studies examining CR in the context of the four commonest subtypes of dementia, mild cognitive impairment or healthy aging. Studies which combined measurement of underlying dementia-related neuropathology, cognitive function, and factors providing CR in a single model were accepted. We performed a qualitative synthesis of the results. RESULTS: Thirty-four studies out of 9229 screened records met our inclusion criteria and were therefore quality assessed and data extracted. Variation in CR definition made comparison across studies difficult. One hundred and forty-four out of 156 models examined education and occupation: overall, 58% of eligible models classified education and 60% occupation as a CR determinant, with 12% and 44% of those, respectively, being of high quality. Within healthy population suitable to inform preventative interventions, there was consistent evidence for education having a protective effect on general cognition in the face of multiple brain burden measures, while occupation presented inconclusive results within cognitive groups. CONCLUSIONS: Further research on modifiable determinants of CR beyond education/occupation including early-life factors and consensus on CR definition are warranted.

Post-discharge kidney function is associated with subsequent ten-year renal progression risk among survivors of acute kidney injury.

The extent to which renal progression after acute kidney injury (AKI) arises from an initial step drop in kidney function (incomplete recovery), or from a long-term trajectory of subsequent decline, is unclear. This makes it challenging to plan or time post-discharge follow-up. This study of 14651 hospital survivors in 2003 (1966 with AKI, 12685 no AKI) separates incomplete recovery from subsequent renal decline by using the post-discharge estimated glomerular filtration rate (eGFR) rather than the pre-admission as a new reference point for determining subsequent renal outcomes. Outcomes were sustained 30% renal decline and de novo CKD stage 4, followed from 2003-2013. Death was a competing risk. Overall, death was more common than subsequent renal decline (37.5% vs 11.3%) and CKD stage 4 (4.5%). Overall, 25.7% of AKI patients had non-recovery. Subsequent renal decline was greater after AKI (vs no AKI) (14.8% vs 10.8%). Renal decline after AKI (vs no AKI) was greatest among those with higher post-discharge eGFRs with multivariable hazard ratios of 2.29 (1.88-2.78); 1.50 (1.13-2.00); 0.94 (0.68-1.32) and 0.95 (0.64-1.41) at eGFRs of 60 or more; 45-59; 30-44 and under 30, respectively. The excess risk after AKI persisted over ten years of study, irrespective of AKI severity, or post-episode proteinuria. Thus, even if post-discharge kidney function returns to normal, hospital admission with AKI is associated with increased renal progression that persists for up to ten years. Follow-up plans should avoid false reassurance when eGFR after AKI returns to normal.

A cancer geography paradox? Poorer cancer outcomes with longer travelling times to healthcare facilities despite prompter diagnosis and treatment: a data-linkage study.

BACKGROUND: Rurality and distance from cancer treatment centres have been shown to negatively impact cancer outcomes, but the mechanisms remain obscure. METHODS: We analysed the impact of travel time to key healthcare facilities and mainland/island residency on the cancer diagnostic pathway (treatment within 62 days of referral, and within 31 days of diagnosis) and 1-year mortality using a data-linkage study with 12 339 patients. RESULTS: After controlling for important confounders, mainland patients with more than 60 min of travelling time to their cancer treatment centre ((OR 1.42; 95% CI 1.25-1.61) and island dwellers (OR 1.32; 95% CI 1.09-1.59) were more likely to commence cancer treatment within 62 days of general practitioner (GP) referral and within 31 days of their cancer diagnosis compared with those living within 15 min. Island-dweller patients were more likely to have their diagnosis and treatment started on the same or next day (OR 1.72; 95% CI 1.31-2.25). Increased travelling time to a cancer treatment centre was associated with increased mortality to 1 year (30-59 min (HR 1.21; 95% CI 1.05-1.41), >60 min (HR 1.18; 95% CI 1.03-1.36), island dweller (HR 1.17; 95% CI 0.97-1.41). CONCLUSIONS: Island dwelling and greater mainland travel burden was associated with more rapid cancer diagnosis and treatment following GP referral even after adjustment for advanced disease; however, these patients also experienced a survival disadvantage compared with those living nearer. Cancer services may need to be better configured to suit the different needs of dispersed populations.

Intermediate and Long-term Outcomes of Survivors of Acute Kidney Injury Episodes: A Large Population-Based Cohort Study.

BACKGROUND: The long-term prognosis after acute kidney injury (AKI) is variable. It is unclear how the prognosis of AKI and its relationship to prognostic factors (baseline kidney function, AKI severity, prior AKI episodes, and recovery of kidney function) change as follow-up progresses. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: The Grampian Laboratory Outcomes Morbidity and Mortality Study II (GLOMMS-II) is a large regional population cohort with complete serial biochemistry and outcome data capture through data linkage. From GLOMMS-II, we followed up 17,630 patients hospitalized in 2003 through to 2013. PREDICTORS: AKI identified using KDIGO (Kidney Disease: Improving Global Outcomes) serum creatinine criteria, characterized by baseline kidney function (estimated glomerular filtration rate [eGFR] ≥ 60, 45-59, 30-44, and <30mL/min/1.73m2), AKI severity (KDIGO stage), 90-day recovery of kidney function, and prior AKI episodes. OUTCOMES: Intermediate- (30-364 days) and long-term (1-10 years) mortality and long-term renal replacement therapy. MEASUREMENTS: Poisson regression in time discrete intervals. Multivariable Cox regression for those at risk in the intermediate and long term, adjusted for age, sex, baseline comorbid conditions, and acute admission circumstances. RESULTS: Of 17,630 patients followed up for a median of 9.0 years, 9,251 died. Estimated incidences of hospital AKI were 8.4% and 17.6% for baseline eGFRs≥60 and <60mL/min/1.73m2, respectively. Intermediate-term (30-364 days) adjusted mortality HRs for AKI versus no AKI were 2.48 (95% CI, 2.15-2.88), 2.50 (95% CI, 2.04-3.06), 1.90 (95% CI, 1.51-2.39), and 1.63 (95% CI, 1.20-2.22) for eGFRs≥60, 45 to 59, 30 to 44, and <30mL/min/1.73m2, respectively. Among 1-year survivors, long-term HRs were attenuated: 1.44 (95% CI, 1.31-1.58), 1.25 (95% CI, 1.09-1.43), 1.21 (95% CI, 1.03-1.42), and 1.08 (95% CI, 0.85-1.36), respectively. The excess long-term hazards in AKI were lower for lower baseline eGFRs (P for interaction = 0.01). LIMITATIONS: Nonprotocolized observational data. No adjustment for albuminuria. CONCLUSIONS: The prognostic importance of a discrete AKI episode lessens over time. Baseline kidney function is of greater long-term importance.

Acute kidney injury as an independent risk factor for unplanned 90-day hospital readmissions.

BACKGROUND: Reducing readmissions is an international priority in healthcare. Acute kidney injury (AKI) is common, serious and also a global concern. This analysis evaluates AKI as a candidate risk factor for unplanned readmissions and determines the reasons for readmissions. METHODS: GLOMMS-II is a large population cohort from one health authority in Scotland, combining hospital episode data and complete serial biochemistry results through data-linkage. 16453 people (2623 with AKI and 13830 without AKI) from GLOMMS-II who survived an index hospital admission in 2003 were used to identify the causes of and predict readmissions. The main outcome was "unplanned readmission or death" within 90 days of discharge. In a secondary analysis, the outcome was limited to readmissions with acute pulmonary oedema. 26 candidate predictors during the index admission included AKI (defined and staged 1-3 using an automated e-alert algorithm), prior AKI episodes, baseline kidney function, index admission circumstances and comorbidities. Prediction models were developed and assessed using multivariable logistic regression (stepwise variable selection), C statistics, bootstrap validation and decision curve analysis. RESULTS: Three thousand sixty-five (18.6%) patients had the main outcome (2702 readmitted, 363 died without readmission). The outcome was strongly predicted by AKI. Multivariable odds ratios for AKI stage 3; 2 and 1 (vs no AKI) were 2.80 (2.22-3.53); 2.23 (1.85-2.68) and 1.50 (1.33-1.70). Acute pulmonary oedema was the reason for readmission in 26.6% with AKI and eGFR < 60; and 4.0% with no AKI and eGFR ≥ 60. The best stepwise model from all candidate predictors had a C statistic of 0.698 for the main outcome. In a secondary analysis, a model for readmission with acute pulmonary oedema had a C statistic of 0.853. In decision curve analysis, AKI improved clinical utility when added to any model, although the incremental benefit was small when predicting the main outcome. CONCLUSIONS: AKI is a strong, consistent and independent risk factor for unplanned readmissions - particularly readmissions with acute pulmonary oedema. Pre-emptive planning at discharge should be considered to minimise avoidable readmissions in this high risk group.

Past Decline Versus Current eGFR and Subsequent Mortality Risk.

A single determination of eGFR associates with subsequent mortality risk. Prior decline in eGFR indicates loss of kidney function, but the relationship to mortality risk is uncertain. We conducted an individual-level meta-analysis of the risk of mortality associated with antecedent eGFR slope, adjusting for established risk factors, including last eGFR, among 1.2 million subjects from 12 CKD and 22 other cohorts within the CKD Prognosis Consortium. Over a 3-year antecedent period, 12% of participants in the CKD cohorts and 11% in the other cohorts had an eGFR slope <-5 ml/min per 1.73 m(2) per year, whereas 7% and 4% had a slope >5 ml/min per 1.73 m(2) per year, respectively. Compared with a slope of 0 ml/min per 1.73 m(2) per year, a slope of -6 ml/min per 1.73 m(2) per year associated with adjusted hazard ratios for all-cause mortality of 1.25 (95% confidence interval [95% CI], 1.09 to 1.44) among CKD cohorts and 1.15 (95% CI, 1.01 to 1.31) among other cohorts during a follow-up of 3.2 years. A slope of +6 ml/min per 1.73 m(2) per year also associated with higher all-cause mortality risk, with adjusted hazard ratios of 1.58 (95% CI, 1.29 to 1.95) among CKD cohorts and 1.43 (95% CI, 1.11 to 1.84) among other cohorts. Results were similar for cardiovascular and noncardiovascular causes of death and stronger for longer antecedent periods (3 versus <3 years). We conclude that prior decline or rise in eGFR associates with an increased risk of mortality, independent of current eGFR.

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

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

Late-life deficits in cognitive, physical and emotional functions, childhood intelligence and occupational profile: a life-course examination of the Aberdeen 1936 Birth Cohort (ABC1936).

OBJECTIVES: the 'triad of impairment' phenomenon describes the co-occurrence of age-related cognitive, emotional and physical functioning deficits. We investigated how occupational profile and childhood intelligence contribute to the triad of impairment in late life. METHODS: we analysed data of a subsample of the Aberdeen Birth Cohort of 1936 (n = 346). Data were collected on participants' childhood intelligence, late-life cognitive ability, physical functioning, depressive symptoms and main lifetime occupation. We summarised the various occupational and impairment measures into two latent variables, 'occupational profile' and the 'triad of impairment'. We used a series of data reduction approaches and structural equation models (SEMs) of increasing complexity to test both the validity of the models and to understand causal relationships between the life-course risks for the triad of impairment. RESULTS: occupational profile had a significant effect on the triad of impairment independent of childhood intelligence. Childhood intelligence was the predominant influence on the triad of impairment and exerted its effect directly and indirectly via its influence on occupation. The direct effect of childhood intelligence exceeded the independent influence of the occupational profile on impairment by a factor of 1.7-1.8 and was greater by a factor of ∼4 from the indirect pathway (via occupation). CONCLUSIONS: childhood intelligence was the predominant influence on the triad of impairment in late life, independently of the occupational profile. Efforts to reduce impairment in older adults should be informed by a life-course approach with special attention to the early-life environment.

Looking to the future: predicting renal replacement outcomes in a large community cohort with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is common and important due to poor outcomes. An ability to stratify CKD care based on outcome risk should improve care for all. Our objective was to develop and validate 5-year outcome prediction tools in a large population-based CKD cohort. Model performance was compared with the recently reported 'kidney failure risk equation' (KFRE) models. METHODS: Those with CKD in the Grampian Laboratory Outcomes Mortality and Morbidity Study-I (3396) and -II (18 687) cohorts were used to develop and validate a renal replacement therapy (RRT) prediction tool. The discrimination, calibration and overall performance were assessed. The net reclassification index compared performance of the developed model and the 3- and 4-variable KFRE model to predict RRT in the validation cohort. RESULTS: The developed model (with measures of age, sex, excretory renal function and proteinuria) performed well with a C-statistic of 0.938 (0.918-0.957) and Hosmer-Lemeshow (HL) χ(2) statistic 4.6. In the validation cohort (18 687), the developed model falsely identified fewer as high risk (414 versus 3278 individuals) compared with the KFRE 3-variable model (measures of age, sex and excretory renal function), but had more false negatives (58 versus 21 individuals). The KFRE 4-variable model could only be applied to 2274 individuals because of a lack of baseline urinary albumin creatinine ratio data, thus limiting its use in routine clinical practice. CONCLUSIONS: CKD outcome prediction tools have been developed by ourselves and others. These tools could be used to stratify care, but identify both false positives and -negatives. Further refinement should optimize the balance between identifying those at increased risk with clinical utility for stratifying care.