Gordon Prescott

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.

Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study

Abstract Objective: To examine the association between hypertensive diseases of pregnancy (gestational hypertension and pre-eclampsia) and the development of circulatory diseases in later life. Design: Cohort study of women who had pre-eclampsia during their first singleton pregnancy. Two comparison groups were matched for age and year of delivery, one with gestational hypertension and one with no history of raised blood pressure. Setting: Maternity services in the Grampian region of Scotland. Participants: Women selected from the Aberdeen maternity and neonatal databank who were resident in Aberdeen and who delivered a first, live singleton from 1951 to 1970. Main outcome measures: Current vital and cardiovascular health status ascertained through postal questionnaire survey, clinical examination, linkage to hospital discharge, and mortality data. Results: There were significant positive associations between pre-eclampsia/eclampsia or gestational hypertension and later hypertension in all measures. The adjusted relative risks varied from 1.13-3.72 for gestational hypertension and 1.40-3.98 for pre-eclampsia or eclampsia. The adjusted incident rate ratio for death from stroke for the pre-eclampsia/eclampsia group was 3.59 (95% confidence interval 1.04 to 12.4). Conclusions: Hypertensive diseases of pregnancy seem to be associated in later life with diseases related to hypertension. If greater awareness of this association leads to earlier diagnosis and improved management, there may be scope for reducing a proportion of the morbidity and mortality from such diseases. What is already known on this topic Much is known about the effect of cardiovascular risks factors that are shared by men and women, but less on those specific to women Retrospective studies, based on patient recall, suggest that hypertension in pregnancy may be associated with increased risk of cardiovascular diseases in later life What this study adds Prospective recording of blood pressure and proteinuria shows that women who experienced raised blood pressure in pregnancy have a long term risk of hypertension Women who experience raise blood pressure in pregnancy have an increased risk of stroke and, to a lesser extent, an increased risk of ischaemic heart disease Long term cardiovascular risks are greater for women who had pre-eclampsia than those who experienced gestational hypertension (hypertension without proteinuria)

Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Renal Function and Outcome From Coronary Artery Bypass Grafting: Impact on Mortality After a 2.3-Year Follow-Up

Background— Severe renal dysfunction is associated with a worse outcome after coronary artery bypass graft surgery (CABG). Less is known about the effects of milder degrees of renal impairment, and previous studies have relied on levels of serum creatinine, an insensitive indicator of renal function. Recent studies have suggested that estimated glomerular filtration rate (eGFR) is a more discriminatory measure. However, data on the utility of eGFR in predicting outcome from CABG are limited. Methods and Results— We studied 2067 consecutive patients undergoing CABG. Demographic and clinical data were collected preoperatively, and patients were followed up a median of 2.3 years after surgery. Estimated GFR was calculated from the Modification of Diet in Renal Disease equation. The primary outcome was all-cause mortality. Mean±SD eGFR was 57.9±17.6 mL/min per 1.73 m2 in the 158 patients who died during follow-up compared with 64.7±13.8 mL/min per 1.73 m2 in survivors (hazard ratio [HR], 0.71 per 10 mL/min per 1.73 m2; 95% CI, 0.64 to 0.80; P<0.001). Estimated GFR was an independent predictor of mortality in both models with other individual univariable predictors (HR, 0.80 per 10 mL/min per 1.73 m2; 95% CI, 0.72 to 0.89; P<0.001) and the European system for cardiac operative risk evaluation (HR, 0.88 per 10 mL/min per 1.73 m2; 95% CI, 0.78 to 0.98; P=0.02). Conclusions— Estimated GFR is a powerful and independent predictor of mortality after CABG.

Can physiological variables and early warning scoring systems allow early recognition of the deteriorating surgical patient

Objective:Early warning scoring systems are widely used in clinical practice to allow early recognition of the deteriorating patient, but they lack validation. We aimed to test the ability of physiologic variables, either alone or in existing early scoring systems, to predict major deterioration in a patient’s condition and attempt to derive functions with superior accuracy. Design:A comparative cohort study. Setting:A teaching hospital in Scotland. Patients:Two cohorts of general surgical high-dependency patients. The cohorts are a group of surgical high-dependency care patients who did not require intensive care admission and another group of patients who did require admission. Interventions:None. Measurements and Main Results:Prospective physiologic data on consecutive surgical high-dependency unit patients were collected and compared with physiologic data on patients admitted to the intensive care unit from the same surgical high-dependency units. Data were quality checked and summarized, and discriminant analysis and receiver operator curves were used to discriminate between the groups. There were significant physiologic differences between groups with regard to heart rate (p < .001, area under the receiver operating characteristic curve [AUC] 0.7), respiratory rate (p < .001, AUC 0.71), and oxygen saturation (p < .001, AUC 0.78) across time points. This was not present for systolic blood pressure or temperature. Existing early warning scoring systems had good discriminatory power (AUC 0.83–0.86). We derived discriminant functions, which have a high predictive ability to determine differences between groups (p < .0001, AUC 0.86–0.90). We found that heart rate and respiratory rate could detect differences between groups at 6 and 8 hrs before ICU admission, but oxygen saturation and the discriminant function 2 could detect differences 48 hrs before ICU admission. Conclusions:Some commonly used physiologic variables have reasonable power in determining the difference between patients requiring intensive care unit admission, but others are poor. Existing early warning scores have comparatively good discriminatory power. We have derived functions with excellent predictive power in this derivation cohort.

The changing pattern of referral in acute kidney injury

BACKGROUNDnAcute kidney injury (AKI) is not only managed by nephrologists, but also by several other subspecialists. The referral rate to nephrologists and the factors influencing it are unknown.nnnAIMSnTo determine the referral rate, factors affecting referral and outcomes across the spectrum of AKI in a population based study.nnnMETHODSnWe identified all patients with serum creatinine concentrations ≥150 µmol/l (male) or ≥130 µmol/l (female) over a 6-month period. AKI was defined according to the RIFLE classification (risk, injury, failure, loss, end stage renal disease [ESRD]). Clinical information and outcomes were obtained from each patients case records.nnnRESULTSnA total of 562 patients were identified as having AKI (incidence 2147 per million population/year [pmp/y]). One hundred and sixty-four patients (29%) were referred to nephrologists-referral rate 627 pmp/y. Forty-nine percent of patients whose serum creatinine rose to >300 µmol/l were referred compared with 22% in our previous study of 1997. Forty-eight patients required renal replacement therapy-incidence 184 pmp/y in comparison to 50 pmp/y in our previous study of 1997. Patients had higher odds of referral if they were male, of younger age and were in the F category of the RIFLE classification. Patients had lower odds of referral if they had multiple co-morbid conditions or if they were managed in a hospital without a nephrology service.nnnCONCLUSIONnThere has been a significant rise in the referral rate of patients with AKI to nephrologists but even during our period of study only one-third of such patients were being referred. With rising incidence and increased awareness, the referral rate will certainly rise putting a significant burden on the nephrology services.

Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data

BACKGROUNDnSome evidence suggests that chronic kidney disease is a risk factor for lower-extremity peripheral artery disease. We aimed to quantify the independent and joint associations of two measures of chronic kidney disease (estimated glomerular filtration rate [eGFR] and albuminuria) with the incidence of peripheral artery disease.nnnMETHODSnIn this collaborative meta-analysis of international cohorts included in the Chronic Kidney Disease Prognosis Consortium (baseline measurements obtained between 1972 and 2014) with baseline measurements of eGFR and albuminuria, at least 1000 participants (this criterion not applied to cohorts exclusively enrolling patients with chronic kidney disease), and at least 50 peripheral artery disease events, we analysed adult participants without peripheral artery disease at baseline at the individual patient level with Cox proportional hazards models to quantify associations of creatinine-based eGFR, urine albumin-to-creatinine ratio (ACR), and dipstick proteinuria with the incidence of peripheral artery disease (including hospitalisation with a diagnosis of peripheral artery disease, intermittent claudication, leg revascularisation, and leg amputation). We assessed discrimination improvement through c-statistics.nnnFINDINGSnWe analysed 817u2008084 individuals without a history of peripheral artery disease at baseline from 21 cohorts. 18u2008261 cases of peripheral artery disease were recorded during follow-up across cohorts (median follow-up was 7·4 years [IQR 5·7-8·9], range 2·0-15·8 years across cohorts). Both chronic kidney disease measures were independently associated with the incidence of peripheral artery disease. Compared with an eGFR of 95 mL/min per 1·73 m2, adjusted hazard ratios (HRs) for incident study-specific peripheral artery disease was 1·22 (95% CI 1·14-1·30) at an eGFR of 45 mL/min per 1·73 m2 and 2·06 (1·70-2·48) at an eGFR of 15 mL/min per 1·73 m2. Compared with an ACR of 5 mg/g, the adjusted HR for incident study-specific peripheral artery disease was 1·50 (1·41-1·59) at an ACR of 30 mg/g and 2·28 (2·12-2·44) at an ACR of 300 mg/g. The adjusted HR at an ACR of 300 mg/g versus 5 mg/g was 3·68 (95% CI 3·00-4·52) for leg amputation. eGFR and albuminuria contributed multiplicatively (eg, adjusted HR 5·76 [4·90-6·77] for incident peripheral artery disease and 10·61 [5·70-19·77] for amputation in eGFR <30 mL/min per 1·73 m2 plus ACR ≥300 mg/g or dipstick proteinuria 2+ or higher vs eGFR ≥90 mL/min per 1·73 m2 plus ACR <10 mg/g or dipstick proteinuria negative). Both eGFR and ACR significantly improved peripheral artery disease risk discrimination beyond traditional predictors, with a substantial improvement prediction of amputation with ACR (difference in c-statistic 0·058, 95% CI 0·045-0·070). Patterns were consistent across clinical subgroups.nnnINTERPRETATIONnEven mild-to-moderate chronic kidney disease conferred increased risk of incident peripheral artery disease, with a strong association between albuminuria and amputation. Clinical attention should be paid to the development of peripheral artery disease symptoms and signs in people with any stage of chronic kidney disease.nnnFUNDINGnAmerican Heart Association, US National Kidney Foundation, and US National Institute of Diabetes and Digestive and Kidney Diseases.

A randomised controlled trial (RCT) of telephone delivered cognitive behaviour therapy (TCBT) and exercise in the management of chronic widespread pain (CWP): Identifying long-term outcome and who benefits from which treatment

SUPPLEMENTSex Bias In Autoimmune Diseases : Increased Risk Of 47,XXX In Systemic Lupus Erythematosus (SLE) and Sjogrens Syndrome (SS) Supports The Gene Dose HypothesisBackground/Purpose: Human FoxP3+ Th-cells are heterogeneous in function and include not only suppressive cells (TRegs) but also nonsuppressive cells that abundantly secrete proinflammatory cytokines. We have previously shown that FoxP3+ Th-cells were increased in GPA-patients during remission as compared to healthy controls (HCs). In this group of patients, however, we observed a defective suppressor function of TRegs, and an increase in the percentage of Th-17 cells. These observations make it tempting to investigate whether increased FoxP3+ Th-cells in GPA-patients are attributed to an increase in the cytokine-secreting non-suppressive FoxP3+Th-cells. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 46 GPA-patients in remission and from 22 age- and sex-matched HCs. Expression of CD4, CD45RO, and FoxP3 were determined by flow cytometric analysis. The expression levels of FoxP3 and CD45RO were used for distinction between activated suppressor TRegs (FoxP3HighCD45RO+; ASTReg), resting suppressor TRegs (FoxP3LowCD45RO-; RSTReg), and cytokine-secreting non-suppressor TRegs (FoxP3LowCD45RO+; NONTReg) cells. Intracellular expression of IFNg, IL-17, and IL-21 were determined in the various FoxP3+ Th-cell subsets after in vitro activation of PBMCs by PMA and Ca-Ionophore. Results: A significant increase in the frequency of NONTReg cells was observed in GPA-patients as compared with HCs, whereas no differences were detected in RSTReg- and ASTReg cells between GPA-patients and HCs. The distribution of RSTReg- and NONTReg cells did not differ between ANCA-negative and ANCA-positive patients, whereas lower percentages of ASTReg cells were observed in ANCA-positive patients as compared to ANCA-negative patients and HCs. Importantly, a significant increase in the percentage of IL-17+ and IL-21+ cells was seen within the NONTRegcells from ANCA-positive patients (n= 9) when compared to ANCA-negative (n= 10) and HCs (n= 12), whereas no differences were found between ANCA-negative and HCs. Conclusion: Increased FoxP3 expression in Th-cells from GPA-patients is related to an increase in a subset of non-suppressive Th-cells. Increased production of IL-17 and IL-21 cytokines, in NONTReg cells from ANCApositive patients points towards FoxP3+ effector cells and decrease in suppressive TReg cells in relation to ANCA production.Complex Functional Effects Within The HLA Contribute To Sjogrens Syndrome Pathogenesis and May Influence Both Transcriptional Regulation and Peptide Binding

W15.1 Pregnancy induced hypertension and subsequent health and mortality of women: a record linkage study

Hypertensive disease recurred in 94 (50%) of the 189 women with a subsequent pregnancy, of whom 17 (18%) delivered again before 37 weeks. In contrast, 95 women (50%) had an uneventful subsequent pregnancy. Chronic hypertension and maternal age were significantly associated with the recurrence risk. Women undergoing recurrence had an 8-fold chance of developing chronic hypertension (31% versus 4% RR 8.1). Conclusions: Women with hypertensive disorders resulting in delivery near term in the index pregnancy have a 1 in 2 chance of recurrence of a hypertensive disorder, but only a 1 in 5 chance of recurrence and delivery before 37 weeks. Women with a recurrence are prone for developing chronic hypertension.