Isometric Exercise Training and Arterial Hypertension: An Updated Review.

Hypertension is recognised as a leading attributable risk factor for cardiovascular disease and premature mortality. Global initiatives towards the prevention and treatment of arterial hypertension are centred around non-pharmacological lifestyle modification. Exercise recommendations differ between professional and scientific organisations, but are generally unanimous on the primary role of traditional aerobic and dynamic resistance exercise. In recent years, isometric exercise training (IET) has emerged as an effective novel exercise intervention with consistent evidence of reductions in blood pressure (BP) superior to that reported from traditional guideline-recommended exercise modes. Despite a wealth of emerging new data and endorsement by select governing bodies, IET remains underutilised and is not widely prescribed in clinical practice. This expert-informed review critically examines the role of IET as a potential adjuvant tool in the future clinical management of BP. We explore the efficacy, prescription protocols, evidence quality and certainty, acute cardiovascular stimulus, and physiological mechanisms underpinning its anti-hypertensive effects. We end the review with take-home suggestions regarding the direction of future IET research.

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Invasive Gastrointestinal Mucormycosis.

Invasive mucormycosis is an opportunistic fungal infection that can be devastating in immunosuppressed patients. Gastrointestinal infection is rare, but carries among the highest mortality rates of its major clinical presentations. We present a case of invasive gastrointestinal mucormycosis in a patient who underwent recent chemotherapy and autologous stem cell transplant. Initial histopathology revealed cytomegalovirus infection, which was treated before subsequent diagnosis of mucormycosis on repeat bowel biopsy. Our case highlights a myriad of risk factors that increase the potential for serious infection by this pervasive fungus.

Predicting lifespan-extending chemical compounds for C. elegans with machine learning and biologically interpretable features.

Recently, there has been a growing interest in the development of pharmacological interventions targeting ageing, as well as in the use of machine learning for analysing ageing-related data. In this work, we use machine learning methods to analyse data from DrugAge, a database of chemical compounds (including drugs) modulating lifespan in model organisms. To this end, we created four types of datasets for predicting whether or not a compound extends the lifespan of C. elegans (the most frequent model organism in DrugAge), using four different types of predictive biological features, based on: compound-protein interactions, interactions between compounds and proteins encoded by ageing-related genes, and two types of terms annotated for proteins targeted by the compounds, namely Gene Ontology (GO) terms and physiology terms from the WormBase's Phenotype Ontology. To analyse these datasets, we used a combination of feature selection methods in a data pre-processing phase and the well-established random forest algorithm for learning predictive models from the selected features. In addition, we interpreted the most important features in the two best models in light of the biology of ageing. One noteworthy feature was the GO term "Glutathione metabolic process", which plays an important role in cellular redox homeostasis and detoxification. We also predicted the most promising novel compounds for extending lifespan from a list of previously unlabelled compounds. These include nitroprusside, which is used as an antihypertensive medication. Overall, our work opens avenues for future work in employing machine learning to predict novel life-extending compounds.

Development of a multivariable gene-expression signature targeting T-cell-mediated rejection in peripheral blood of kidney transplant recipients validated in cross-sectional and longitudinal samples.

BACKGROUND: Acute T-cell mediated rejection (TCMR) is usually indicated by alteration in serum-creatinine measurements when considerable transplant damage has already occurred. There is, therefore, a need for non-invasive early detection of immune signals that would precede the onset of rejection, prior to transplant damage. METHODS: We examined the RT-qPCR expression of 22 literature-based genes in peripheral blood samples from 248 patients in the Kidney Allograft Immune Biomarkers of Rejection Episodes (KALIBRE) study. To account for post-transplantation changes unrelated to rejection, we generated time-adjusted gene-expression residuals from linear mixed-effects models in stable patients. To select genes, we used penalised logistic regression based on 27 stable patients and 27 rejectors with biopsy-proven T-cell-mediated rejection, fulfilling strict inclusion/exclusion criteria. We validated this signature in i) an independent group of stable patients and patients with concomitant T-cell and antibody-mediated-rejection, ii) patients from an independent study, iii) cross-sectional pre-biopsy samples from non-rejectors and iv) longitudinal follow-up samples covering the first post-transplant year from rejectors, non-rejectors and stable patients. FINDINGS: A parsimonious TCMR-signature (IFNG, IP-10, ITGA4, MARCH8, RORc, SEMA7A, WDR40A) showed cross-validated area-under-ROC curve 0.84 (0.77-0.88) (median, 2.5th-97.5th centile of fifty cross-validation cycles), sensitivity 0.67 (0.59-0.74) and specificity 0.85 (0.75-0.89). The estimated probability of TCMR increased seven weeks prior to the diagnostic biopsy and decreased after treatment. Gene expression in all patients showed pronounced variability, with up to 24% of the longitudinal samples in stable patients being TCMR-signature positive. In patients with borderline changes, up to 40% of pre-biopsy samples were TCMR-signature positive. INTERPRETATION: Molecular marker alterations in blood emerge well ahead of the time of clinically overt TCMR. Monitoring a TCMR-signature in peripheral blood could unravel T-cell-related pro-inflammatory activity and hidden immunological processes. This additional information could support clinical management decisions in cases of patients with stable but poor kidney function or with inconclusive biopsy results.

Symmetric dimethylarginine is a stronger predictor of mortality risk than asymmetric dimethylarginine among older people with kidney disease.

BACKGROUND: Circulating asymmetric dimethylarginine and symmetric dimethylarginine are increased in patients with kidney disease. Symmetric dimethylarginine is considered a good marker of glomerular filtration rate, while asymmetric dimethylarginine is a marker of cardiovascular risk. However, a link between symmetric dimethylarginine and all-cause mortality has been reported. In the present study, we evaluated both dimethylarginines as risk and glomerular filtration rate markers in a cohort of elderly white individuals, both with and without chronic kidney disease. METHODS: Glomerular filtration rate was measured in 394 individuals aged >74 years using an iohexol clearance method. Plasma asymmetric dimethylarginine, symmetric dimethylarginine and iohexol were measured simultaneously using isotope dilution tandem mass spectrometry. RESULTS: Plasma asymmetric dimethylarginine concentrations were increased ( P < 0.01) in people with glomerular filtration rate <60 mL/min/1.73 m2 compared with those with glomerular filtration rate ≥60 mL/min/1.73 m2, but did not differ ( P > 0.05) between those with glomerular filtration rate 30-59 mL/min/1.73 m2 and <30 mL/min/1.73 m2. Plasma symmetric dimethylarginine increased consistently across declining glomerular filtration rate categories ( P < 0.0001). Glomerular filtration rate had an independent effect on plasma asymmetric dimethylarginine concentration, while glomerular filtration rate, gender, body mass index and haemoglobin had independent effects on plasma symmetric dimethylarginine concentration. Participants were followed up for a median of 33 months. There were 65 deaths. High plasma asymmetric dimethylarginine ( P = 0.0412) and symmetric dimethylarginine ( P < 0.0001) concentrations were independently associated with reduced survival. CONCLUSIONS: Among elderly white individuals with a range of kidney function, symmetric dimethylarginine was a better marker of glomerular filtration rate and a stronger predictor of outcome than asymmetric dimethylarginine. Future studies should further evaluate the role of symmetric dimethylarginine as a marker of outcome and assess its potential value as a marker of glomerular filtration rate.

Biological Variation of Plasma and Urinary Markers of Acute Kidney Injury in Patients with Chronic Kidney Disease.

BACKGROUND: Identification of acute kidney injury (AKI) is predominantly based on changes in plasma creatinine concentration, an insensitive marker. Alternative biomarkers have been proposed. The reference change value (RCV), the point at which biomarker change can be inferred to have occurred with statistical certainty, provides an objective assessment of change in serial tests results in an individual. METHODS: In 80 patients with chronic kidney disease, weekly measurements of blood and urinary biomarker concentrations were undertaken over 6 weeks. Variability was determined and compared before and after adjustment for urinary creatinine and across subgroups stratified by level of kidney function, proteinuria, and presence or absence of diabetes. RESULTS: RCVs were determined for whole blood, plasma, and urinary neutrophil gelatinase-associated lipocalin (111%, 59%, and 693%, respectively), plasma cystatin C (14%), creatinine (17%), and urinary kidney injury molecule 1 (497%), tissue inhibitor of metalloproteinases 2 (454%), N-acetyl-ß-d-glucosaminidase (361%), interleukin-18 (819%), albumin (430%), and α1-microglobulin (216%). Blood biomarkers exhibited lower variability than urinary biomarkers. Generally, adjusting urinary biomarker concentrations for creatinine reduced (P < 0.05) within-subject biological variability (CVI). For some markers, variation differed (P < 0.05) between subgroups. CONCLUSIONS: These data can form a basis for application of these tests in clinical practice and research studies and are applicable across different levels of kidney function and proteinuria and in the presence or absence of diabetes. Most of the studied biomarkers have relatively high CVI (noise) but also have reported large concentration changes in response to renal insult (signal); thus progressive change should be detectable (high signal-to-noise ratio) when baseline data are available.

Acute kidney injury: an acceptable risk of treatment with renin-angiotensin system blockade in primary care?

BACKGROUND: Use of renin-angiotensin system (RAS) blockade has become increasingly widespread driven by evidence-based guidance. There is concern about the role of these agents in the genesis of avoidable acute kidney injury (AKI). OBJECTIVES: To investigate the association between AKI and use of RAS blockade. DESIGN: Multilevel hierarchical analysis of a large cohort of patients registered with UK general practitioners. SETTING: Primary care practices in East and West Kent, United Kingdom. PATIENTS: 244,715 patients from 27 practices. MEASUREMENTS: Demographic, clinical, biochemical and prescription data. METHODS: Analyses of data acquired between 02/3/2004 and 17/04/2012 using multilevel logistic regression to determine the relationship between AKI and use of RAS blockade; further analysed by indication for treatment with RAS blockade. RESULTS: Sufficient serum creatinine data were available to define AKI in 63,735 patients with 208,275 blood test instances. In 95,569 instances the patient was prescribed a RAS antagonist of which 5.4% fulfilled criteria for AKI. The unadjusted odds ratio (OR) for AKI in those prescribed RAS blockade was 1.93 (1.81-2.06, 95%CI) falling to 1.11 (1.02-1.20, 95%CI) when adjusted for age, gender, co-morbidity, GFR category, proteinuria, systolic blood pressure and diuretic therapy. In patients with an evidence-based indication there was no difference in absolute risk of AKI. However, prescription of RAS blockade in the absence of indication appeared to be associated with greater risk of AKI. When analysis was repeated with AKIN2/AKIN3 as the outcome, although risk of AKI remained significant when unadjusted (OR 1.73, 95%CI 1.42-2.11, p<0.001), after full adjustment there was no increased risk (OR 0.83, 95%CI 0.63-1.09) in those taking RAS antagonists. However, when analysed by indication AKIN2/AKIN3 was significantly more likely in those prescribed RAS antagonists without indication (OR 2.04, 95%CI 1.41-2.94, p<0.001). LIMITATIONS: Observational database study. No information concerning hospitalisation. Prescribing assumptions and potential inaccurate coding. Potential survival bias; patients surviving longer will contribute more data. CONCLUSIONS: Use of RAS antagonists increased the risk of AKI, independent of common confounding variables. After correction for confounders the risk fell away and became non-significant for moderate and severe AKI. However, where there was no evidence-based indication for RAS antagonists the risk of AKI, whether mild, moderate or severe, remained greater.

CONTEXTE: Vu l'abondance de données probantes en la matière, le recours aux inhibiteurs du système rénine-angiotensine-aldostérone (SRAA) est de plus en plus répandu. Il existe certaines préoccupations quant au rôle de ces agents dans la genèse de l'insuffisance rénale aiguë (IRA) évitable. OBJECTIF DE L'ÉTUDE: Examiner, au sein d'une cohorte en soins de santé primaires, la présence de liens entre l'IRA et l'utilisation d'inhibiteurs du SRAA. TYPE D'ÉTUDE: Une analyse hiérarchique multiniveaux d'une vaste cohorte de patients suivis par des médecins généralistes du Royaume-Uni. CONTEXTE: Cliniques de soins de santé primaires situées dans l'est et l'ouest du comté du Kent, au Royaume-Uni. PATIENTS: Les données ont été recueillies auprès d'une cohorte de 244 715 patients en soins primaires, provenant de 27 cliniques de soins primaires dans l'est et l'ouest du comté du Kent. MESURES: Données démographiques, cliniques, biochimiques et issues d'ordonnances. MÉTHODES: L'analyse des données recueillies entre le 2004/03/02 et le 2012/04/17 a été effectuée par régression logistique multiniveaux afin de déterminer la relation entre l'IRA et l'utilisation d'inhibiteurs du SRAA, et ensuite par indication de traitement avec des inhibiteurs du SRAA. RÉSULTATS: Une quantité suffisante de données relatives à la créatininémie était disponible pour évaluer l'IRA chez 63 735 patients, qui avaient eu au total 208 275 prélèvements sanguins. Chez 95 569 sujets, un inhibiteur du SRAA a été prescrit, et 5,4% (5 194) de ces derniers ont eu un épisode d'IRA. Chez les patientsrecevant un traitement fondé sur des indications probantes, 5,8% (4473 sur 76 517) ont eu un épisode d'IRA. Le risque relatif non ajusté (RR) d'IRA associé à l'utilisation d'un inhibiteur du SRAA était de 1,93 (1,81-2,06, 95% IC), diminuant à 1,11 (1,02-1,20, 95% IC) lorsqu'ajusté pour l' âge, le sexe, la comorbidité, la catégorie de débit de filtration glomérulaire, la protéinurie, la pression artérielle systolique et le traitement diurétique. Chez les patients recevant un traitement par inhibiteurs du SRAA fondé sur des indications probantes, il n'y avait aucune différence de risque absolu d'IRA. Par contre, il semblait y avoir un lien entre la prescription d'inhibiteurs du SRAA en l'absence d'indications probantes et un risque accru d'IRA. Lorsque l'analyse a été répétée avec l'AKIN2/AKIN3 comme critère de jugement, le risque d'IRA associé à l'utilisation d'un inhibiteur du SRAA restait significatif dans le modèle non ajusté (RR 1,73, 95% IC 1,42-2,11, p < 0,001), mais aucune augmentation de risque n'a été observée après ajustement (RR 0,83, 95% IC 0,63-1,09). Par contre, le risque d'AKIN2/AKIN3 lié à l'utilisation d'un inhibiteur du SRAA était significativement plus élevée chez les patients qui recevaient ces agents sans indications probantes (RR 2,04, 95% IC, 1,41-2,94, p < 0,001). LIMITES DE L'ÉTUDE: Étude par observation de données prises dans des cliniques de soins primaires. Aucune information d'hospitalisation disponible (base de données de soins primaires). Interprétation des prescriptions et possibilité de codes erronés. Biais de temps d'immortalité possible : les patients qui vivent plus longtemps contribuent davantage à l'analyse par les prélèvements sanguins. CONCLUSIONS: Notre analyse montre que l'utilisation d'inhibiteurs du SRAA augmente le risque d'IRA. Le risque est indépendant de diverses variables de confusion, dont l'âge, la mesure de base de la fonction rénale, la présence de comorbidité pertinente et la pression artérielle systolique. Après correction pour les variables confusionnelles, le risque diminuait toujours : il devenait non significatif pour l'IRA modérée et sévère. Par contre, le risque d'IRA légere, modérée ou sévère demeurait élevé lorsque l'utilisation d'inhibiteurs du SRAA ne s'appuyait sur aucune indication probante. Renin angiotensin system blockade is known to be associated with acute kidney injury. This is the first study to examine this association by evidence-based indication. Although renin angiotensin system blockade increases the risk of acute kidney injury overall, in those with an evidence-based indication the majority of the effect is explained by underlying co-morbidity. In people with no evidence-based indication prescription of renin angiotensin blockade is an independent predictor of acute kidney injury.

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

BACKGROUND: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. METHODS: The study cohort was identified by using hospital data bases over a six month period. INCLUSION CRITERIA: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy.The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed.Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. RESULTS: The total study population was 61,432. 57,300 subjects with 'no AKI', mean age 64.The number (mean age) of acute serum creatinine rises overall were, 'AKI 1' 3,798 (72), 'AKI 2' 232 (73), and 'AKI 3' 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with 'no AKI', compared to 98.6%, 90.1% and 82.3% in those with 'AKI 1', 'AKI 2' and 'AKI 3' respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. CONCLUSIONS: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function.

What is the real impact of acute kidney injury?

BACKGROUND: Acute kidney injury (AKI) is a common clinical problem. Studies have documented the incidence of AKI in a variety of populations but to date we do not believe the real incidence of AKI has been accurately documented in a district general hospital setting.The aim here was to describe the detected incidence of AKI in a typical general hospital setting in an unselected population, and describe associated short and long-term outcomes. METHODS: A retrospective observational database study from secondary care in East Kent (adult catchment population of 582,300). All adult patients (18 years or over) admitted between 1st February 2009 and 31st July 2009, were included. Patients receiving chronic renal replacement therapy (RRT), maternity and day case admissions were excluded. AKI was defined by the acute kidney injury network (AKIN) criteria. A time dependent risk analysis with logistic regression and Cox regression was used for the analysis of in-hospital mortality and survival. RESULTS: The incidence of AKI in the 6 month period was 15,325 pmp/yr (adults) (69% AKIN1, 18% AKIN2 and 13% AKIN3). In-hospital mortality, length of stay and ITU utilisation all increased with severity of AKI. Patients with AKI had an increase in care on discharge and an increase in hospital readmission within 30 days. CONCLUSIONS: This data comes closer to the real incidence and outcomes of AKI managed in-hospital than any study published in the literature to date. Fifteen percent of all admissions sustained an episode of AKI with increased subsequent short and long term morbidity and mortality, even in those with AKIN1. This confers an increased burden and cost to the healthcare economy, which can now be quantified. These results will furnish a baseline for quality improvement projects aimed at early identification, improved management, and where possible prevention, of AKI.

Coding errors in an analysis of the impact of pay-for-performance on the care for long-term cardiovascular disease: a case study.

OBJECTIVE: There is no standard method of publishing the code ranges in research using routine data. We report how code selection affects the reported prevalence and precision of results. DESIGN: We compared code ranges used to report the impact of pay-for-performance (P4P), with those specified in the P4P scheme, and those used by our informatics team to identify cases. We estimated the positive predictive values (PPV) of people with chronic conditions who were included in the study population, and compared the prevalence and blood pressure (BP) of people with hypertension (HT). SETTING: Routinely collected primary care data from the quality improvement in chronic kidney disease (QICKD-ISRCTN56023731) trial. MAIN OUTCOME MEASURES: The case study population represented roughly 85% of those in the HT P4P group (PPV = 0.842; 95%CI = 0.840-0.844; p < 0.001). We also found differences in the prevalence of stroke (PPV = 0.694; 95%CI = 0.687- 0.700) and coronary heart disease (PPV = 0.166; 95%CI = 0.162-0.170), where the paper restricted itself to myocardial infarction codes. RESULTS: We found that the long-term cardiovascular conditions and codes selected for these conditions were inconsistent with those in P4P or the QICKD trial. The prevalence of HT based on the case study codes was 10.3%, compared with 11.8% using the P4P codes; the mean BP was 138.3 mmHg (standard deviation (SD) 15.84 mmHg)/79.4 mmHg (SD 10.3 mmHg) and 137.3 mmHg (SD 15.31)/79.1 mmHg (SD 9.93 mmHg) for the case study and P4P populations, respectively (p < 0.001). CONCLUSION: The case study lacked precision, and excluded cases had a lower BP. Publishing code ranges made this comparison possible and should be mandated for publications based on routine data.

Urinary ATP and visualization of intracellular bacteria: a superior diagnostic marker for recurrent UTI in renal transplant recipients?

Renal transplant recipients (RTR) are highly susceptible to urinary tract infections (UTIs) with over 50% of patients having at least one UTI within the first year. Yet it is generally acknowledged that there is considerable insensitivity and inaccuracy in routine urinalysis when screening for UTIs. Thus a large number of transplant patients with genuine urine infections may go undiagnosed and develop chronic recalcitrant infections, which can be associated with graft loss and morbidity. Given a recent study demonstrating ATP is released by urothelial cells in response to bacteria exposure, possibly acting at metabotropic P2Y receptors mediating a proinflammatory response, we have investigated alternative, and possibly more appropriate, urinalysis techniques in a cohort of RTRs. Mid-stream urine (MSU) samples were collected from 53 outpatient RTRs. Conventional leukocyte esterase and nitrite dipstick tests, and microscopic pyuria counts (in 1 µl), ATP concentration measurements, and identification of intracellular bacteria in shed urothelial cells, were performed on fresh unspun samples and compared to 'gold-standard' bacterial culture results. Of the 53 RTRs, 22% were deemed to have a UTI by 'gold-standard' conventional bacteria culture, whereas 87%, 8% and 4% showed evidence of UTIs according to leukocyte esterase dipstick, nitrite dipstick, and a combination of both dipsticks, respectively. Intracellular bacteria were visualized in shed urothelial cells of 44% of RTRs, however only 1 of the 23 RTRs (44%) was deemed to have a UTI by conventional bacteria culture. A significant association of the 'gold-standard' test with urinary ATP concentration combined with visualization of intracellular bacteria in shed urothelial cells was determined using the Fisher's exact test. It is apparent that standard bedside tests for UTIs give variable results and that seemingly quiescent bacteria in urothelial cells are very common in RTRs and may represent a focus of subclinical infection. Furthermore, our results suggest urinary ATP concentration combined with detection of intracellular bacteria in shed urinary epithelial cells may be a sensitive means by which to detect 'occult' infection in RTRs.

Findings from the implementation of a validated readmission predictive tool in the discharge workflow of a medical intensive care unit.

RATIONALE: Provider decisions about patients to be discharged from the intensive care unit (ICU) are often based on subjective intuition, sometimes leading to premature discharge and early readmission. The Stability and Work Load Index for Transfer (SWIFT) score, as a risk stratification tool, has moderate ability to predict patients at risk of ICU readmission. OBJECTIVES: To describe findings following the incorporation of the SWIFT score into the discharge workflow of a medical ICU. METHODS: The study involved 5,293 consecutive patients discharged alive from the medical ICU of an academic medical center. The SWIFT score and associated percentage risk for readmission were incorporated into daily rounds for purpose of discharge decision-making. We measured readmission rates before and after implementation and observed changes in provider discharge decisions for individual patients after SWIFT discussions. MEASUREMENTS AND MAIN RESULTS: Baseline (n = 1,906) and implementation (n = 1,938) cohorts differed with respect to APACHE III scores (P = 0.03). In the implementation cohort, 26.2% of subjects had SWIFT scores greater than 15 and thus were predicted to have a higher risk of unplanned readmissions. In this high-risk group, 25% had SWIFT discussed in their discharge planning. There was modification of provider discharge decisions in 108 (30%) of cases in which the SWIFT was discussed. SWIFT score values above a prespecified cutoff of 15 were associated with physician tendency to prolong ICU stay or to discharge to a monitored setting (P < 0.001). There was no difference in 24-hour or 7-day readmission rates between the baseline and implementation cohorts (1.9 vs. 2.4%, P = 0.24; 6.5 vs. 7.4%, P = 0.26, respectively) even after adjustment for severity of illness. CONCLUSIONS: Using the SWIFT score as an adjunct to clinical judgment, physicians modified their discharge decisions in one-third of subjects. Introducing such tools into the discharge workflow may present change management challenges that limit the evaluation of their impact on readmission rates and other relevant ICU outcomes.

Chronic kidney disease: Psoriasis--a risk factor for chronic kidney disease?

A new study presents compelling evidence of an association between moderate to severe psoriasis and chronic kidney disease (CKD). This association seems to be independent of traditional CKD risk factors and indicates that monitoring of kidney function in patients with psoriasis is warranted.

Change in the estimated glomerular filtration rate over time and risk of all-cause mortality.

Using a community-based cohort we studied the association between changes in the estimated glomerular filtration rate (eGFR) over time and the risk of all-cause mortality. We identified 529,312 adults who had at least three outpatient eGFR measurements over a 4-year period from a provincial laboratory repository in Alberta, Canada. Two indices of change in eGFR were evaluated: the absolute annual rate of change (in ml/min per 1.73 m(2) per year) and the annual percentage change (percent/year). The adjusted mortality risk associated with each category of change in eGFR was assessed, using stable eGFR (no change) as the reference. Over a median follow-up of 2.5 years there were 32,372 deaths. Compared to the reference participants, those with the greatest absolute annual decline less than or equal to 5 ml/min per 1.73 m(2) per year had significantly increased mortality (hazard ratio of 1.52) adjusted for covariates and kidney function at baseline (last eGFR measurement). Participants with the greatest increase in eGFR of 5 ml/min per 1.73 m(2) per year or more also had significantly increased mortality (adjusted hazard ratio of 2.20). A similar pattern was found when change in eGFR was quantified as an annual percentage change. Thus, both declining and increasing eGFR were independently associated with mortality and underscore the importance of identifying change in eGFR over time to improve mortality risk prediction.

Accuracy of the MDRD (Modification of Diet in Renal Disease) study and CKD-EPI (CKD Epidemiology Collaboration) equations for estimation of GFR in the elderly.

BACKGROUND: Glomerular filtration rate (GFR) is a measure of kidney function, commonly estimated using equations that adjust serum creatinine concentration for age, race, and sex. The Modification of Diet in Renal Disease (MDRD) Study equation is widely used, but underestimates GFR at higher levels. The serum creatinine-based Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI(cr)) equation generally provides more accurate estimation at GFR >60 mL/min/1.73 m(2). Newer equations have been reported using cystatin C concentration either alone (CKD-EPI(cys)) or in combination with creatinine concentration (CKD-EPI(cr-cys)). None of these equations has been well validated in older people. We tested the accuracy of these equations in people 74 years or older compared with GFR measured by a reference method. STUDY DESIGN: Diagnostic test evaluation in a prospective cohort. SETTING & PARTICIPANTS: Participants (n = 394; median age, 80 [range, 74-97] years) recruited from nephrology clinics and the community. INDEX TEST: GFR estimated using the MDRD Study, CKD-EPI(cr), CKD-EPI(cys) and CKD-EPI(cr-cys) equations. REFERENCE TEST: GFR measured using an iohexol clearance method. RESULTS: Median measured GFR was 53.4 (range, 7.2-100.9) mL/min/1.73 m(2). MDRD Study-, CKD-EPI(cr)-, and CKD-EPI(cr-cys)-estimated GFRs overestimated GFR (median differences of 3.5 [P< 0.001], 1.7 [P < 0.001], and 0.8 [P = 0.02] mL/min/1.73 m(2), respectively); the CKD-EPI(cys) equation was unbiased. Accuracy (percentage of estimates within 30% of measured GFR [P(30)]) was 81%, 83%, 86%, and 86% for the MDRD Study, CKD-EPI(cr), CKD-EPI(cys), and CKD-EPI(cr-cys) equations, respectively. Accuracy of the MDRD Study equation was inferior (P = 0.004) to the CKD-EPI(cr) equation at GFR >60 mL/min/1.73 m(2). LIMITATIONS: Those of non-European ancestry were not included. For practical reasons, only a 4-hour sampling protocol was used for iohexol clearance. CONCLUSIONS: The CKD-EPI(cr) equation appeared less biased and was more accurate than the MDRD Study equation. No equation achieved an ideal P(30) in the overall population. Our data suggest that GFR estimation is as satisfactory in older people of European ancestry as it has been reported to be in younger individuals.

Engaging primary care in CKD initiatives: the UK experience.

Over the last decade, since the introduction of an international classification of chronic kidney disease (CKD) and the development of simple tools to detect people with CKD, primary care has had to adapt to a new paradigm of disease. Significantly, improved identification of CKD, and increased awareness and understanding of the potential associated adverse outcomes, has in turn required the development, implementation and integration of new policies, models and pathways of care. The UK health care system, including primary care, is uniquely positioned to respond to new initiatives. Despite early reservations, CKD has gone from an unheard of condition in primary care prior to 2006 to one where people with this condition are recorded in disease registers and increasingly managed in accordance with evidence-based guidance. National and local initiatives implemented together have contributed to the improved understanding and management of CKD in primary care in the UK and are showing signs of having made significant health gains in CKD.