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.

A real-world assessment of mycophenolate mofetil for remission induction in eosinophilic granulomatosis with polyangiitis.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of ANCA-associated vasculitis (AAV). Clinical trials demonstrating the efficacy of mycophenolate mofetil (MMF) for remission induction in AAV excluded patients with EGPA. Despite this, MMF is commonly used in these patients. The objective of this study was to evaluate, for the first time, the effectiveness and tolerance of MMF in EGPA remission induction. A retrospective, two-center, real-world study was conducted in patients with EGPA who received MMF in addition to prednisolone for newly diagnosed or relapsing disease between 2009 and 2019. Baseline, 3-, 6- and 12-month outcome data were extracted from electronic health records. The primary outcome was disease remission, defined as a Birmingham Vasculitis Activity Score of 0 at 6 months. Secondary outcomes included disease relapse, median prednisolone dose at 12 months and drug tolerance. In total, 15 patients (73% male, median age 57) with EGPA (11 newly diagnosed/4 relapsing) were identified. At 6 months, 67% had achieved disease remission. At 12 months, this was maintained (66.7%) and 4 patients had relapsed. All but one patient remained on MMF at study completion and all patients tolerated MMF. Our real-world data suggest that MMF is an effective and well-tolerated agent for achieving disease remission in EGPA. A future randomized controlled trial of MMF in this neglected orphan disease is now 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.

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.

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.

Acute kidney injury-how does automated detection perform?

BACKGROUND: Early detection of acute kidney injury (AKI) is important for safe clinical practice. NHS England is implementing a nationwide automated AKI detection system based on changes in blood creatinine. Little has been reported on the similarities and differences of AKI patients detected by this algorithm and other definitions of AKI in the literature. METHODS: We assessed the NHS England AKI algorithm and other definitions using routine biochemistry in our own health authority in Scotland in 2003 (adult population 438 332). Linked hospital episode codes (ICD-10) were used to identify patients where AKI was a major clinical diagnosis. We compared how well the algorithm detected this subset of AKI patients in comparison to other definitions of AKI. We also evaluated the potential 'alert burden' from using the NHS England algorithm in comparison to other AKI definitions. RESULTS: Of 127 851 patients with at least one blood test in 2003, the NHS England AKI algorithm identified 5565 patients. The combined NHS England algorithm criteria detected 91.2% (87.6-94.0) of patients who had an ICD-10 AKI code and this was better than any individual AKI definition. Some of those not captured could be identified by algorithm modifications to identify AKI in retrospect after recovery, but this would not be practical in real-time. Any modifications also increased the number of alerted patients (2-fold in the most sensitive model). CONCLUSIONS: The NHS England AKI algorithm performs well as a diagnostic adjunct in clinical practice. In those without baseline data, AKI may only be seen in biochemistry in retrospect, therefore proactive clinical care remains essential. An alternative algorithm could increase the diagnostic sensitivity, but this would also produce a much greater burden of patient alerts.

Fatigue: a principal contributor to impaired quality of life in ANCA-associated vasculitis.

OBJECTIVES: To describe quality of life (QoL) in an ANCA-associated vasculitis (AAV) cohort and make comparisons with a general population sample. In addition, we aimed to take preliminary steps to identify potential disease and psycho-social factors which may determine QoL impairment. METHODS: A population-based case-control study was designed. All AAV patients resident in Grampian, Scotland, were invited to participate as cases. Controls were identified from a random sample of persons registered with four local general practices. Participants completed a questionnaire comprising validated generic and symptom-specific tools in the assessment of QoL. In addition, all cases were clinically assessed and putative disease factors recorded. Cases and controls were compared and, in addition, disease and psycho-social associations were explored for identified QoL impairments. RESULTS: In total, 74/90 (82%) cases and 781/2000 (39%) controls participated. Cases reported a significant impairment in physical health (P < 0.0001), but not mental health (P = 0.85), compared with controls, as measured by Short Form-8 (SF-8). Following adjustment for age and sex, persons with AAV were more than twice as likely to report mild/moderate fatigue [odds ratio (OR) 2.0; 95% CI 1.1, 3.8] or severe fatigue (OR 2.5; 95% CI 1.4, 4.5) compared with controls. Furthermore, among cases, fatigue was found to be strongly associated with impaired physical health (P < 0.0001), while disease factors such as disease activity and damage were not (P = 0.60 and 0.27, respectively). CONCLUSIONS: Patients with AAV report impaired physical but not mental health. Specifically, fatigue is a principal complaint and appears to be a major determinant of impaired QoL.

Evaluation of adjunctive mycophenolate for large vessel giant cell arteritis.

OBJECTIVES: GCA patients with large vessel involvement (LV-GCA) experience greater CS requirements and higher relapse rates compared with classical cranial GCA. Despite the distinct disease course, interventions in LV-GCA have yet to be investigated specifically. This study aimed to evaluate the CS-sparing effect and tolerability of first-line mycophenolate in LV-GCA. METHODS: A retrospective cohort study was conducted in patients with LV-GCA identified from a regional clinical database between 2005 and 2019. All cases were prescribed mycophenolate derivatives (MYC; MMF or mycophenolic acid) at diagnosis and were followed up for ≥2 years. The primary outcome was the cumulative CS dose at 1 year. Secondary outcomes included MYC tolerance, relapse rates and CRP levels at 1 and 2 years. RESULTS: A total of 37 patients (65% female; mean age 69.4 years, SD 7.9 years) were identified. All cases demonstrated large vessel involvement via CT/PET (n = 34), CT angiography (n = 5) or magnetic resonance angiography (n = 2). After 2 years, 31 patients remained on MYC, whereas 6 had switched to MTX or tocilizumab owing to significant disease relapse. The mean (±SD) cumulative prednisolone dose at 1 year was 4960 (±1621) mg. Relapse rates at 1 and 2 years were 16.2 and 27%, respectively, and CRP levels at 1 and 2 years were 4 [interquartile range (IQR) 4-6] and 4 (IQR 4-4) mg/l, respectively. CONCLUSION: To our knowledge, this is the first attempt to assess the effectiveness of any specific agent in LV-GCA. MYC might be both effective in reducing CS exposure and well tolerated in this subpopulation. A future randomized controlled trial is warranted.

Hip fracture incidence and mortality in chronic kidney disease: the GLOMMS-II record linkage cohort study.

BACKGROUND: Individuals on renal replacement therapy (RRT) have increased fracture risk, but risk in less advanced chronic kidney disease (CKD) is unclear. OBJECTIVE: To investigate CKD associations with hip fracture incidence and mortality. DESIGN: Record linkage cohort study Grampian Laboratory Outcomes Mortality and Morbidity Study II. SETTING: Single health region in Scotland. PARTICIPANTS: All individuals (≥15 years) with sustained CKD stages 3-5 and those on RRT, and a 20% random sample of those with normal renal function, in the resident population in 2003. OUTCOME MEASURES: Outcomes were (1) incident hip fracture measured with (A) admissions or (B) deaths, with at least 5.5 years follow-up and (2) post-hip fracture mortality. Unadjusted and adjusted, incident rate ratios (IRRs) and mortality rate ratios were calculated using Poisson regression. RESULTS: Of 39 630 individuals identified in 2003 (41% males, mean age 63.3 years), 19 537 had CKD stages 3-5, 345 were on RRT and 19 748 had normal estimated glomerular filtration rate (eGFR). Hip fracture incidence, measured by admissions, was increased in CKD stages 3-5 (compared with normal eGFR), both overall (adjusted IRR 1.49 (95% CI 1.24 to 1.79)) and for individual CKD stages 3a, 3b and 4. Hip fracture incidence, measured using deaths, was increased in those with CKD stages 3b and 4. Post-hip fracture mortality was only increased in CKD stage 4. There was only a small number of individuals and events for CKD stage 5, resulting in insufficient statistical power. CONCLUSION: Hip fracture incidence was higher in CKD stages 3-5 compared with normal eGFR. Post-hip fracture mortality was only increased in CKD stage 4. Reducing hip fracture incidence in CKD through regular fall and fracture risk review should reduce overall deaths after hip fracture in the population.

Long-term prognosis after acute kidney injury (AKI): what is the role of baseline kidney function and recovery? A systematic review.

OBJECTIVES: To summarise the evidence from studies of acute kidney injury (AKI) with regard to the effect of pre-AKI renal function and post-AKI renal function recovery on long-term mortality and renal outcomes, and to assess whether these factors should be taken into account in future prognostic studies. DESIGN/SETTING: A systematic review of observational studies listed in Medline and EMBASE from 1990 to October 2012. PARTICIPANTS: All AKI studies in adults with data on baseline kidney function to identify AKI; with outcomes either stratified by pre-AKI and/or post-AKI kidney function, or described by the timing of the outcomes. OUTCOMES: Long-term mortality and worsening chronic kidney disease (CKD). RESULTS: Of 7385 citations, few studies met inclusion criteria, reported baseline kidney function and stratified by pre-AKI or post-AKI function. For mortality outcomes, three studies compared patients by pre-AKI renal function and six by post-AKI function. For CKD outcomes, two studies compared patients by pre-AKI function and two by post-AKI function. The presence of CKD pre-AKI (compared with AKI alone) was associated with doubling of mortality and a fourfold to fivefold increase in CKD outcomes. Non-recovery of kidney function was associated with greater mortality and CKD outcomes in some studies, but findings were inconsistent varying with study design. Two studies also reported that risk of poor outcome reduced over time post-AKI. Meta-analysis was precluded by variations in definitions for AKI, CKD and recovery. CONCLUSIONS: The long-term prognosis after AKI varies depending on cause and clinical setting, but it may also, in part, be explained by underlying pre-AKI and post-AKI renal function rather than the AKI episode itself. While carefully considered in clinical practice, few studies address these factors and with inconsistent study design. Future AKI studies should report pre-AKI and post-AKI function consistently as additional factors that may modify AKI prognosis.

Maximising Acute Kidney Injury Alerts--A Cross-Sectional Comparison with the Clinical Diagnosis.

BACKGROUND: Acute kidney injury (AKI) is serious and widespread across healthcare (1 in 7 hospital admissions) but recognition is often delayed causing avoidable harm. Nationwide automated biochemistry alerts for AKI stages 1-3 have been introduced in England to improve recognition. We explored how these alerts compared with clinical diagnosis in different hospital settings. METHODS: We used a large population cohort of 4464 patients with renal impairment. Each patient had case-note review by a nephrologist, using RIFLE criteria to diagnose AKI and chronic kidney disease (CKD). We identified and staged AKI alerts using the new national NHS England AKI algorithm and compared this with nephrologist diagnosis across hospital settings. RESULTS: Of 4464 patients, 525 had RIFLE AKI, 449 had mild AKI, 2185 had CKD (without AKI) and 1305 were of uncertain chronicity. NHS AKI algorithm criteria alerted for 90.5% of RIFLE AKI, 72.4% of mild AKI, 34.1% of uncertain cases and 14.0% of patients who actually had CKD.The algorithm identified AKI particularly well in intensive care (95.5%) and nephrology (94.6%), but less well on surgical wards (86.4%). Restricting the algorithm to stage 2 and 3 alerts reduced the over-diagnosis of AKI in CKD patients from 14.0% to 2.1%, but missed or delayed alerts in two-thirds of RIFLE AKI patients. CONCLUSION: Automated AKI detection performed well across hospital settings, but was less sensitive on surgical wards. Clinicians should be mindful that restricting alerts to stages 2-3 may identify fewer CKD patients, but including stage 1 provides more sensitive and timely alerting.