William G. Simpson

Incidence and Outcomes in Acute Kidney Injury: A Comprehensive Population-Based Study

Epidemiological studies of acute kidney injury (AKI) and acute-on-chronic renal failure (ACRF) are surprisingly sparse and confounded by differences in definition. Reported incidences vary, with few studies being population-based. Given this and our aging population, the incidence of AKI may be much higher than currently thought. We tested the hypothesis that the incidence is higher by including all patients with AKI (in a geographical population base of 523,390) regardless of whether they required renal replacement therapy irrespective of the hospital setting in which they were treated. We also tested the hypothesis that the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE) classification predicts outcomes. We identified all patients with serum creatinine concentrations > or =150 micromol/L (male) or > or =130 micromol/L (female) over a 6-mo period in 2003. Clinical outcomes were obtained from each patients case records. The incidences of AKI and ACRF were 1811 and 336 per million population, respectively. Median age was 76 yr for AKI and 80.5 yr for ACRF. Sepsis was a precipitating factor in 47% of patients. The RIFLE classification was useful for predicting full recovery of renal function (P < 0.001), renal replacement therapy requirement (P < 0.001), length of hospital stay [excluding those who died during admission (P < 0.001)], and in-hospital mortality (P = 0.035). RIFLE did not predict mortality at 90 d or 6 mo. Thus the incidence of AKI is much higher than previously thought, with implications for service planning and providing information to colleagues about methods to prevent deterioration of renal function. The RIFLE classification is useful for identifying patients at greatest risk of adverse short-term outcomes.

Effect of increased consumption of whole-grain foods on blood pressure and other cardiovascular risk markers in healthy middle-aged persons: a randomized controlled trial

BACKGROUND Three daily portions of whole-grain foods could lower cardiovascular disease risk, but a comprehensive intervention trial was needed to confirm this recommendation. OBJECTIVES We aimed to assess the effects of consumption of 3 daily portions of whole-grain foods (provided as only wheat or a mixture of wheat and oats) on markers of cardiovascular disease risk in relatively high-risk individuals. DESIGN This was a randomized controlled dietary trial in middle-aged healthy individuals. After a 4-wk run-in period with a refined diet, we randomly allocated volunteers to a control (refined diet), wheat, or wheat + oats group for 12 wk. The primary outcome was a reduction of cardiovascular disease risk factors by dietary intervention with whole grains, which included lipid and inflammatory marker concentrations, insulin sensitivity, and blood pressure. RESULTS We recruited a total of 233 volunteers; 24 volunteers withdrew, and 3 volunteers were excluded. Systolic blood pressure and pulse pressure were significantly reduced by 6 and 3 mm Hg, respectively, in the whole-grain foods groups compared with the control group. Systemic markers of cardiovascular disease risk remained unchanged apart from cholesterol concentrations, which decreased slightly but significantly in the refined group. CONCLUSIONS Daily consumption of 3 portions of whole-grain foods can significantly reduce cardiovascular disease risk in middle-aged people mainly through blood pressure-lowering mechanisms. The observed decrease in systolic blood pressure could decrease the incidence of coronary artery disease and stroke by ≥15% and 25%, respectively. This trial was registered at clinicaltrials.gov as ISRCTN27657880.

Effect of a tomato-rich diet on markers of cardiovascular disease risk in moderately overweight, disease-free, middle-aged adults: a randomized controlled trial

BACKGROUND Cardiovascular disease (CVD) is a major cause of mortality in the United Kingdom. Epidemiologic studies suggest that consumption of tomato-based foods may lower CVD risk. Such potential benefits have been ascribed in part to high concentrations of lycopene in the tomatoes. However, these findings have not yet been validated by comprehensive intervention trials. OBJECTIVE The aim of this study was to conduct a single-blind, randomized controlled intervention trial with healthy middle-aged volunteers to assess whether the consumption of tomato-based foods affects recognized biomarkers of CVD risk. DESIGN After a 4-wk run-in period with a low-tomato diet, 225 volunteers (94 men and 131 women) aged 40-65 y were randomly assigned into 1 of 3 dietary intervention groups and asked to consume a control diet (low in tomato-based foods), a high-tomato-based diet, or a control diet supplemented with lycopene capsules (10 mg/d) for 12 wk. Blood samples were collected at baseline, at 6 wk, and after the intervention and were analyzed for carotenoid and lipid profiles and inflammatory markers. Blood pressure, weight, and arterial stiffness were also measured. Dietary intake was also determined during the intervention. RESULTS None of the systemic markers (inflammatory markers, markers of insulin resistance and sensitivity) changed significantly after the dietary intervention. Moreover, lipid concentrations and arterial stiffness were also unaffected by the interventions. CONCLUSION These data indicate that a relatively high daily consumption of tomato-based products (equivalent to 32-50 mg lycopene/d) or lycopene supplements (10 mg/d) is ineffective at reducing conventional CVD risk markers in moderately overweight, healthy, middle-aged individuals. This trial was registered at isrctn.org as ISRCTN34203810.

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.

Fluvastatin does not prevent the acute-phase response to intravenous zoledronic acid in post-menopausal women.

The acute-phase response (APR) to aminobisphosphonates is triggered by activation of γδ T cells, resulting in pro-inflammatory cytokine release. Statins prevent aminobisphosphonate-induced γδ T cell activation in vitro, raising the possibility that statins might prevent the APR in vivo. The objective of this study was to determine whether fluvastatin prevents the APR to zoledronic acid in post-menopausal women. A double-blind, randomised, placebo-controlled study was conducted in 60 healthy, post-menopausal, female volunteers (mean age 60.6 ± 4.0). Volunteers received 5 mg zoledronic acid by intravenous infusion, and either three times 40 mg fluvastatin (0 hr, 24 hr and 48 hr), 40 mg fluvastatin (0 hr) plus placebo (24 hr and 48 hr), or placebo (0 hr, 24 hr and 48 hr), orally. Post-infusion symptoms were assessed by questionnaire. Changes in γδ T cell levels, pro-inflammatory cytokines (TNFα, IFNγ, IL-6) and C-reactive protein (CRP) were measured in peripheral blood at various time-points post-infusion. Zoledronic acid administration triggered increased serum levels of TNFα, IFNγ, IL-6 and CRP in ≥70% of study volunteers, whilst characteristic APR symptoms were observed in >50% of participants. Zoledronic acid also induced a transient fall in circulating Vγ9Vδ2 T cell levels at 48 hr, consistent with Vγ9Vδ2 T cell activation. Concurrent fluvastatin administration did not prevent zoledronic acid-induced cytokine release, alter circulating Vγ9Vδ2 T cell levels, nor diminish the frequency or severity of APR symptoms. In conclusion, intravenous zoledronic acid induced pro-inflammatory cytokine release and APR symptoms in the majority of study participants, which was not prevented by co-administration of fluvastatin.

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.

Is routine hospital episode data sufficient for identifying individuals with chronic kidney disease? A comparison study with laboratory data

Internationally, investment in the availability of routine health care data for improving health, health surveillance and health care is increasing. We assessed the validity of hospital episode data for identifying individuals with chronic kidney disease compared to biochemistry data in a large population-based cohort, the Grampian Laboratory Outcomes, Morbidity and Mortality Study-II (n = 70,435). Grampian Laboratory Outcomes, Morbidity and Mortality Study-II links hospital episode data to biochemistry data for all adults in a health region with impaired kidney function and random samples of individuals with normal and unmeasured kidney function in 2003. We compared identification of individuals with chronic kidney disease by hospital episode data (based on International Classification of Diseases-10 codes) to the reference standard of biochemistry data (at least two estimated glomerular filtration rates <60 mL/min/1.73 m2 at least 90 days apart). Hospital episode data, compared to biochemistry data, identified a lower prevalence of chronic kidney disease and had low sensitivity (<10%) but high specificity (>97%). Using routine health care data from multiple sources offers the best opportunity to identify individuals with chronic kidney disease.