Regional variation of COVID-19 admissions, acute kidney injury and mortality in England - a national observational study using administrative data.

BACKGROUND: This study explores regional variations in COVID-19 hospitalization rates, in-hospital mortality, and acute kidney injury (AKI) in England. We investigated the influence of population demographic characteristics, viral strain changes, and therapeutic advances on clinical outcomes. METHODS: Using hospital episode statistics, we conducted a retrospective cohort study with 749,844 admissions in 337,029 adult patients with laboratory-confirmed COVID-19 infection (March 1, 2020, to March 31, 2021). Multivariable logistic regression identified factors predicting AKI and mortality in COVID-19 hospitalized patients. RESULTS: London had the highest number of COVID-19 admissions (131,338, 18%), followed by the North-west region (122,683, 16%). The North-west had the highest population incidence of COVID-19 hospital admissions (21,167 per million population, pmp), while the South-west had the lowest (9,292 admissions pmp). Patients in London were relatively younger (67.0 ± 17.7 years) than those in the East of England (72.2 ± 16.8 years). The shortest length of stay was in the North-east (12.2 ± 14.9 days), while the longest was in the North-west (15.2 ± 17.9 days). All eight regions had higher odds of death compared to London, ranging from OR 1.04 (95% CI 1.00, 1.07) in the South-west to OR 1.24 (95% CI 1.21, 1.28) in the North-west. Older age, Asian ethnicity, emergency admission, transfers from other hospitals, AKI presence, ITU admission, social deprivation, and comorbidity were associated with higher odds of death. AKI incidence was 30.3%, and all regions had lower odds of developing AKI compared to London. Increasing age, mixed and black ethnicity, emergency admission, transfers from other providers, ITU care, and different levels of comorbidity were associated with higher odds of developing AKI. CONCLUSIONS: London exhibited higher hospital admission numbers and AKI incidence, but lower odds of death compared to other regions in England. TRIAL REGISTRATION: Registered on National Library of Medicine website ( www. CLINICALTRIALS: gov ) with registration number NCT04579562 on 8/10/2020.

Determinants of change in arterial stiffness over 5 years in early chronic kidney disease.

BACKGROUND: Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care. METHODS: A total of 1741 persons with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device. RESULTS: 970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation). CONCLUSIONS: We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.

Acute kidney injury associated with COVID-19: A retrospective cohort study.

BACKGROUND: Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19-associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom. METHODS AND FINDINGS: We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19-negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19-positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19-negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region. CONCLUSIONS: We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407156.

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study.

BACKGROUND: Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3. METHODS AND FINDINGS: Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification. CONCLUSIONS: We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.

An Organizational-Level Program of Intervention for AKI: A Pragmatic Stepped Wedge Cluster Randomized Trial.

BACKGROUND: Variable standards of care may contribute to poor outcomes associated with AKI. We evaluated whether a multifaceted intervention (AKI e-alerts, an AKI care bundle, and an education program) would improve delivery of care and patient outcomes at an organizational level. METHODS: A multicenter, pragmatic, stepped-wedge cluster randomized trial was performed in five UK hospitals, involving patients with AKI aged ≥18 years. The intervention was introduced sequentially across fixed three-month periods according to a randomly determined schedule until all hospitals were exposed. The primary outcome was 30-day mortality, with pre-specified secondary endpoints and a nested evaluation of care process delivery. The nature of the intervention precluded blinding, but data collection and analysis were independent of project delivery teams. RESULTS: We studied 24,059 AKI episodes, finding an overall 30-day mortality of 24.5%, with no difference between control and intervention periods. Hospital length of stay was reduced with the intervention (decreases of 0.7, 1.1, and 1.3 days at the 0.5, 0.6, and 0.7 quantiles, respectively). AKI incidence increased and was mirrored by an increase in the proportion of patients with a coded diagnosis of AKI. Our assessment of process measures in 1048 patients showed improvements in several metrics including AKI recognition, medication optimization, and fluid assessment. CONCLUSIONS: A complex, hospital-wide intervention to reduce harm associated with AKI did not reduce 30-day AKI mortality but did result in reductions in hospital length of stay, accompanied by improvements in in quality of care. An increase in AKI incidence likely reflected improved recognition.

What is the value of multidisciplinary care for chronic kidney disease?

In a Persepctive, Richard Fluck and Maarten Taal discuss the potential value of implementing multidisciplinary care programs for chronic kidney disease.

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

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

Chronic Kidney Disease in Primary Care: Outcomes after Five Years in a Prospective Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is commonly managed in primary care, but most guidelines have a secondary care perspective emphasizing the risk of end-stage kidney disease (ESKD) and need for renal replacement therapy. In this prospective cohort study, we sought to study in detail the natural history of CKD in primary care to better inform the appropriate emphasis for future guidance. METHODS AND FINDINGS: In this study, 1,741 people with CKD stage 3 were individually recruited from 32 primary care practices in Derbyshire, United Kingdom. Study visits were undertaken at baseline, year 1, and year 5. Binomial logistic regression and Cox proportional hazards models were used to model progression, CKD remission, and all-cause mortality. We used Kidney Disease: Improving Global Outcomes (KDIGO) criteria to define CKD progression and defined CKD remission as the absence of diagnostic criteria (estimated glomerular filtration rate [eGFR] >60 ml/min/1.73 m2 and urine albumin-to-creatinine ratio [uACR] <3 mg/mmol) at any study visit. Participants were predominantly elderly (mean ± standard deviation (SD) age 72.9 ± 9.0 y), with relatively mild reduction in GFR (mean ± SD eGFR 53.5 ± 11.8 mL/min/1,73 m2) and a low prevalence of albuminuria (16.9%). After 5 y, 247 participants (14.2%) had died, most of cardiovascular causes. Only 4 (0.2%) developed ESKD, but 308 (17.7%) evidenced CKD progression by KDIGO criteria. Stable CKD was observed in 593 participants (34.1%), and 336 (19.3%) met the criteria for remission. Remission at baseline and year 1 was associated with a high likelihood of remission at year 5 (odds ratio [OR] = 23.6, 95% CI 16.5-33.9 relative to participants with no remission at baseline and year 1 study visits). Multivariable analyses confirmed eGFR and albuminuria as key risk factors for predicting adverse as well as positive outcomes. Limitations of this study include reliance on GFR estimated using the Modification of Diet in Renal Disease study (MDRD) equation for recruitment (but not subsequent analysis) and a study population that was predominantly elderly and white, implying that the results may not be directly applicable to younger populations of more diverse ethnicity. CONCLUSIONS: Management of CKD in primary care should focus principally on identifying the minority of people at high risk of adverse outcomes, to allow intervention to slow CKD progression and reduce cardiovascular events. Efforts should also be made to identify and reassure the majority who are at low risk of progression to ESKD. Consideration should be given to adopting an age-calibrated definition of CKD to avoid labelling a large group of people with age-related decline in GFR and low associated risk as having CKD.

International Criteria for Acute Kidney Injury: Advantages and Remaining Challenges.

Nicholas Selby and colleagues describe how the definition of acute kidney injury brings opportunities and challenges in identifying patients at higher risk of adverse outcomes.

Intensive Hemodialysis and Health-Related Quality of Life.

Diminished health-related quality of life (HRQoL) is common in dialysis patients and associated with increased risks for morbidity and mortality. Patients may present limitations in both physical and mental HRQoL. Poor physical HRQoL may be defined by limited physical function, role limitations due to physical health, dissatisfaction with physical ability, and impaired mobility. Sleep disorders such as obstructive sleep apnea, restless legs, and fatigue are typical manifestations of poor physical HRQoL in dialysis patients. Poor mental HRQoL may be defined by depressive thinking, lack of positive affect, anxiety, and feelings of social isolation. The prevalence of depression is high in dialysis patients. Intensive hemodialysis (HD) can positively address HRQoL. In 3 randomized clinical trials, relative to conventional HD, intensive HD increased physical and mental component summary scores from the 36-Item Short-Form Health Survey (SF-36), although individual treatment effects of daily nocturnal HD were not statistically significant. In another large prospective study, initiation of short daily HD therapy was followed after 12 months by improvements in all SF-36 domains, sleep quality, and restless legs symptoms. In a small study of nocturnal HD, apnea and hypopnea episodes per hour decreased by almost 70% after conversion from conventional HD. Intensive HD is also associated with a large reduction in postdialysis recovery time. In contrast, 2 randomized clinical trials failed to demonstrate statistically significant effects of intensive HD on the Beck Depression Inventory score despite a significant decrease in Beck Depression Inventory score in the prospective study of short daily HD. Furthermore, intensive HD may not improve objective physical performance and can increase burden on caregivers in the home setting. In conclusion, intensive HD potentially can address both physical and mental aspects of poor HRQoL relative to conventional HD. However, more studies are needed to understand the effects of intensive HD, including specific schedules, on HRQoL.

Intensive Hemodialysis and Treatment Complications and Tolerability.

Hemodialysis (HD) treatment can be difficult to tolerate. Common complications are intradialytic hypotension (IDH) and long time to recovery after an HD session. IDH, as defined by nadir systolic blood pressure < 90mmHg and intradialytic decline > 30mmHg, occurs in almost 8% of HD sessions. IDH may be caused by aggressive ultrafiltration in response to interdialytic weight gain, can lead to myocardial stunning and cardiac arrhythmias, and is associated with increased risk for death. Long recovery time after a treatment session is also common. In DOPPS (Dialysis Outcomes and Practice Patterns Study), recovery time was 2 to 6 hours for 41% of HD patients and longer than 6 hours for 27%; recovery time was linearly associated with increased risks for death and hospitalization. Importantly, both decreases in blood pressure and feeling washed out or drained have been identified by patients as more important outcomes than death or hospitalization. Intensive HD likely reduces the likelihood of IDH. In the Frequent Hemodialysis Network trial, short daily and nocturnal schedules reduced the per-session probability of IDH by 20% and 68%, respectively, relative to 3 sessions per week. Due to lower ultrafiltration volume and/or rate, intensive HD may reduce intradialytic blood pressure variability. In a cross-sectional study, short daily and nocturnal schedules were associated with slower ultrafiltration and less dialysis-induced myocardial stunning than 3 sessions per week. In FREEDOM (Following Rehabilitation, Economics, and Everyday-Dialysis Outcome Measurements), a prospective cohort study of short daily HD, recovery time was reduced after 12 months from 8 hours to 1 hour, according to per-protocol analysis. Recovery time after nocturnal HD may be minutes. In conclusion, intensive HD can improve the tolerability of HD treatment by reducing the risk for IDH and decreasing recovery time after HD. These changes may improve the patient centeredness of end-stage renal disease care.

Intensive Hemodialysis and Potential Risks With Increasing Treatment.

Although intensive hemodialysis (HD) can address important clinical problems, increasing treatment also introduces risks. In this review, we assess risks pertaining to 6 domains: vascular access complications, infection, mortality, loss of residual kidney function, solute balance, and patient and care partner burden. In the Frequent Hemodialysis Network (FHN) trials, short daily and nocturnal schedules increased the incidence of access complications, although the incidence of access loss was not statistically higher. Observational studies indicate that infection-related hospitalization is an ongoing challenge with short daily HD. Excess risk may be catalyzed by poor infection control practices in the home setting in which intensive HD is typically delivered, but with fixed probability of bacterial contamination per cannulation, greater treatment frequency necessarily increases the risk for infectious complications. Buttonhole cannulation may increase the risk for metastatic infections. However, intensive HD in the home setting is associated with lower risk for infection than peritoneal dialysis. Data regarding mortality are equivocal. With extended follow-up of individuals in the FHN trials, short daily HD was associated with lower risk relative to the usual schedule, whereas nocturnal HD was associated with higher risk. In many, but not all, observational studies, short daily HD has been associated with lower risk than both in-center HD and peritoneal dialysis; however, observational studies are subject to unmeasured confounding. Intensive HD can accelerate the loss of residual kidney function in new dialysis patients with substantial urine output and can deplete solutes (eg, phosphorus) to the extent that supplementation is necessary. Finally, intensive HD may increase burden on patients and caregivers, possibly leading to technique failure. Some of these problems might be addressed with careful monitoring, so that relevant interventions (eg, antibiotics, retraining, and respite care) can be delivered. Ultimately, intensive HD is not a panacea for end-stage renal disease. Potential benefits and risks of treatment should be jointly considered.

A simple care bundle for use in acute kidney injury: a propensity score-matched cohort study.

BACKGROUND: Consensus guidelines for acute kidney injury (AKI) have recommended prompt treatment including attention to fluid balance, drug dosing and avoidance of nephrotoxins. These simple measures can be incorporated in a care bundle to facilitate early implementation. The objective of this study was to assess the effect of compliance with the AKI care bundle (AKI-CB) on in-hospital case-fatality and AKI progression. METHODS: In this larger, propensity score-matched cohort of multifactorial AKI, we examined the impact of compliance with an AKI-CB in 3717 consecutive episodes of AKI in 3518 patients between 1 August 2013 and 31 January 2015. Propensity score matching was performed to match 939 AKI events where the AKI-CB was completed with 1823 AKI events where AKI-CB was not completed. RESULTS: The AKI-CB was completed in 25.6% of patients within 24 h. The unadjusted case-fatality was higher when the AKI-CB was not completed versus when the AKI-CB was completed (24.4 versus 20.4%, P = 0.017). In multivariable analysis, AKI-CB completion within 24 h was associated with lower odds for in-hospital death [odds ratio (OR): 0.76; 95% confidence interval (95% CI): 0.62-0.92]. Increasing age (OR: 1.04; 95% CI: 1.03-1.05), hospital-acquired AKI (OR: 1.28; 95% CI: 1.04-1.58), AKI stage 2 (OR: 1.91; 95% CI: 1.53-2.39) and increasing Charlson's comorbidity index (CCI) [OR: 3.31 (95% CI: 2.37-4.64) for CCI of more than 5 compared with zero] had higher odds for death, whereas AKI during elective admission was associated with lower odds for death (OR: 0.29; 95% CI: 0.16-0.52). Progression to higher AKI stages was lower when the AKI-CB was completed (4.2 versus 6.7%, P = 0.02). CONCLUSIONS: Compliance with an AKI-CB was associated with lower mortality and reduced progression of AKI to higher stages. The AKI-CB is simple and inexpensive, and could therefore be applied in all healthcare settings to improve outcomes.

National trends in acute kidney injury requiring dialysis in England between 1998 and 2013.

Acute kidney injury (AKI) severe enough to require dialysis is increasing and associated with high mortality, yet robust information about temporal epidemiology of AKI requiring dialysis in England is lacking. In this retrospective observational study of the Hospital Episode Statistics (HES) data set covering the entire English National Health Service, we identified all patients with a diagnosis of AKI requiring dialysis between 1998 and 2013. This incidence increased from 774 cases (15.9 per million people) in 1998-1999 to 11,164 cases (208.7 per million people) in 2012-2013. The unadjusted in-hospital case-fatality was 30.3% in 1998-2003 and 30.2% in 2003-2008, but significantly increased to 41.1% in 2008-2013. Compared with 2003-2008, the multivariable adjusted odds ratio for death was higher in 1998-2003 at 1.20 (95% CI: 1.10-1.30) and in 2008-2013 at 1.13 (1.07-1.18). Charlson comorbidity scores of more than five (odds ratio 2.35; 95% CI: 2.20-2.51) and emergency admissions (2.46 (2.32-2.61) had higher odds for death. The odds for death decreased in patients over 85 years from 4.83 (3.04-7.67) in 1998-2003 to 2.19 (1.99-2.41) in 2008-2013. AKI in secondary diagnosis and in other diagnoses codes had higher odds for death compared with AKI in primary diagnosis code in all three periods. Thus, the incidence of AKI requiring dialysis has increased progressively over 15 years in England. Improvement in case-fatality in 2003-2008 has not been sustained in the last 5 years.

Acute kidney: improving the pathway of care for patients and across healthcare.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is common, harmful and of global concern. There is a need to understand the pathway of the management of AKI in order to identify potential areas where care can be improved, for the individual and for healthcare systems. RECENT FINDINGS: There has been considerable focus on risk assessment and earlier detection using changes in serum creatinine. There is less understanding of optimal management, enhanced and long-term recovery, and education to support better care. Using Kidney Disease Improving Global Outcomes-based criteria to improve the detection of AKI improves its detection, but requires supportive training and education to deliver better outcomes.Policy makers need to understand the personal and economic burden that results from AKI. There is a need to provide commissioning support, improvement methodologies, and registry initiatives with research investment to sustain progress in overall management. SUMMARY: There is clear evidence of harm related to AKI and a need to improve the reliability of care. The prevalence is high, with the potential to significantly improve short-term and long-term care by addressing all the elements in the pathway, at both patient and system level, assessing risk, detection, treatment, and recovery.

Results from a safety cohort of patients with renal anemia receiving the biosimilar epoetinzeta: The PASCO I study.

BACKGROUND: Epoetin-zeta (epoetin-ζ) (sold as Retacrit™/Silapo™) is a biologic product that was approved by the European Medicines Agency in 2007 after demonstrating biosimilarity to its reference product epoetin-α (Eprex™), based on a comprehensive comparability exercise including extensive biophysical characterization and three double-blind randomized controlled trials. Since 2008, epoetin-ζ has been prescribed by physicians across Europe to treat anemia of renal disease in many thousands of patients. METHODS: Provided here are results of the PASCO I study (post-authorization safety cohort observation of silapo/retacrit (epoetin-ζ) administered intravenously for the treatment of renal anemia). The primary study endpoint was the frequency of adverse events of special interest (AESI) occurring in patients receiving epoetin-ζ over a 1-year study observation period. RESULTS: The safety set included 1,634 patients who received at least 1 dose of epoetin-ζ during the study period. These patients experienced AESI at these frequencies: clotting of artificial kidney 9.8%, lack of efficacy 2.3%, cerebrovascular events (including cerebrovascular accident, cerebral infarction, cerebral hemorrhage, and transient ischemic attack) 1.8%, myocardial infarction 1.7%, acute myocardial infarction 1.2%, clinically relevant hyperkalemia 0.4%, deep vein thrombosis 0.2%, convulsion 0.2%, hypertensive encephalopathy 0.1%, and pulmonary embolism 0.1%. No patients were reported as having anaphylactoid reactions, angioedema, erythropoietinneutralizing antibodies, or pure red cell aplasia. The median weekly follow-up dose of epoetin-ζ was 158.6 IU/kg. Mean hemoglobin concentration ranged between 11.3 and 11.7 g/dL. From the safety set, 228 patients died (14.0%), while 1,135 patients (74.9%; excluding 119 with data missing) continued treatment with epoetin-ζ following the 12-month observation. CONCLUSION: The PASCO I study contributes significantly to current knowledge about the frequency of adverse events associated with the use of epoetin-ζ for the treatment of renal anemia and demonstrates a pattern of adverse events comparable with data for other existing epoetin products in Europe.

The burden of comorbidity in people with chronic kidney disease stage 3: a cohort study.

BACKGROUND: Multimorbidity is a growing concern for healthcare systems, with many countries experiencing demographic transition to older population profiles. Chronic kidney disease (CKD) is common but often considered in isolation. The extent and prognostic significance of its comorbidities is not well understood. This study aimed to assess the extent and prognostic significance of 11 comorbidities in people with CKD stage 3. METHODS: A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling. Comorbidity was defined by self-reported doctor-diagnosed condition, disease-specific medication or blood results (hemoglobin), and treatment burden as number of ongoing medications. Logistic regression was used to identify associations with greater treatment burden (taking >5 medications) and greater multimorbidity (3 or more comorbidities). Kaplan Meier plots and multivariate Cox proportional hazards models were used to investigate associations between multimorbidity and all-cause mortality. RESULTS: One thousand seven hundred forty-one people were recruited, mean age 72.9 +/-9 years. Mean baseline eGFR was 52 ml/min/1.73 m(2). Only 78/1741 (4 %) had no comorbidities, 453/1741 (26 %) had one, 508/1741 (29 %) had two and 702/1741 (40 %) had >2. Hypertension was common (88 %), 30 % had 'painful condition', 24 % anemia, 23 %, ischaemic heart disease, 17 % diabetes and 12 % thyroid disorders. Median medication use was 5 medications (interquartile range 3-8) and increased with degree of comorbidity. Greater treatment burden and multimorbidity were independently associated with age, smoking, increasing body mass index and decreasing eGFR. Treatment burden was also independently associated with lower education status. After median 3.6 years follow-up, 175/1741 (10 %) died. Greater multimorbidity was independently associated with mortality (hazard ratio 2.81 (95 % confidence intervals 1.72-4.58), p < 0.001) for 3 or more comorbidities vs 0 or 1). CONCLUSIONS: Isolated CKD was rare and multimorbidity the norm in this cohort of people with moderate CKD. Increasing multimorbidity was associated with greater medication burden and poorer survival. CKD management should include consideration of comorbidities.

The impact of vitamin D status on the relative increase in fibroblast growth factor 23 and parathyroid hormone in chronic kidney disease.

Fibroblast growth factor (FGF) 23 is an important regulator of phosphaturia. Its serum level was found to increase before that of parathyroid hormone (PTH) in early chronic kidney disease (CKD) in some but not all previous studies. As vitamin D insufficiency is associated with elevated PTH, we determined the effect of vitamin D status on FGF23 and PTH levels in relation to glomerular filtration rate (GFR) in people with CKD stage 3. Serum intact FGF23, PTH, and 25(OH)vitamin D3 were measured in 1664 patients who were prospectively recruited from primary care. Mean or median values for key variables were an age of 73 years, estimated GFR (eGFR) of 53 ml/min per 1.73 m(2), PTH 46 pg/ml, FGF23 42 pg/ml, and 25(OH)vitamin D3 53 nmol/l. FGF23 and PTH concentrations were elevated in similar proportions of people with lower eGFR in the whole cohort. However, when 752 people with vitamin D insufficiency or deficiency were excluded, FGF23 was elevated in a greater proportion than PTH at all levels of eGFR. Conversely, among people with vitamin D insufficiency, PTH was elevated in a greater proportion than FGF23 at all GFR levels of ⩾40 ml/min per 1.73 m(2). In this cohort, we were able to triangulate the relationship between 25(OH)vitamin D3, PTH, and FGF23, showing that vitamin D status critically determines whether FGF23 or PTH becomes elevated first in the context of lower GFR. Future studies of FGF23 in people with CKD should routinely determine their vitamin D status.

Catheter-related infection and septicemia: impact of seasonality and modifiable practices from the DOPPS.

Hemodialysis (HD) catheter-related infection (CRI) and septicemia contribute to adverse outcomes. The impact of seasonality and prophylactic dialysis practices during high-risk periods remain unexplored. This multicenter study analyzed DOPPS data from 12,122 HD patients (from 442 facilities) to determine the association between seasonally related climatic variables and CRI and septicemia. Climatic variables were determined by linkage to National Climatic Data Center of National Oceanic and Atmospheric Administration data. Catheter care protocols were examined to determine if they could mitigate infection risk during high-risk seasons. Survival models were used to estimate the adjusted hazard ratio (AHR) of septicemia by season and by facility catheter dressing protocol. The overall catheter-related septicemia rate was 0.47 per 1000 catheter days. It varied by season, with an AHR for summer of 1.46 (95% CI: 1.19-1.80) compared with winter. Septicemia was associated with temperature (AHR = 1.07; 95% CI: 1.02-1.13; p < 0.001). Dressing protocols using chlorhexidine (AHR of septicemia = 0.55; 95% CI: 0.39-0.78) were associated with fewest episodes of CRI or septicemia. Higher catheter-related septicemia in summer may be due to seasonal conditions (e.g., heat, perspiration) that facilitate bacterial growth and compromise protective measures. Extra vigilance and use of chlorhexidine-based dressing protocols may provide prophylaxis against CRI and septicemia.