Causes of Death after a Hospitalization with AKI.

Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI.

Association Between High Environmental Heat and Risk of Acute Kidney Injury Among Older Adults in a Northern Climate: A Matched Case-Control Study.

BACKGROUND: An association between high heat and acute kidney injury (AKI) has been reported in warm climates. However, whether this association generalizes to a northern climate, with more variable temperatures, is unknown. STUDY DESIGN: Matched case-control study. SETTING & PARTICIPANTS: Our study focused on older adults (mean age, 80 years) in the northern climate of Ontario, Canada. 52,913 case patients who had a hospital encounter with AKI in April through September 2005 to 2012 were matched with 174,222 controls for exact date, age, sex, rural residence, income, and history of chronic kidney disease. PREDICTOR: Heat periods were defined as 3 consecutive days exceeding the 95th percentile of area-specific maximum temperature. OUTCOMES: Hospital encounter (inpatient admission or emergency department visit) with a diagnosis of AKI. MEASUREMENTS: ORs (95% CIs) were used to assess the association between heat periods and AKI. To quantify the effect in absolute terms, we multiplied the population incidence rate of AKI in the absence of heat periods by our adjusted OR (an approximate of relative risk). RESULTS: Heat periods were significantly associated with higher risk for AKI (adjusted OR, 1.11; 95% CI, 1.00-1.23). Heat periods in absolute terms were associated with an additional 182 cases of AKI per 100,000 person-years during the warm season. LIMITATIONS: We did not know how long persons were outside or if they had access to air conditioning. CONCLUSIONS: In a northern climate, periods of higher environmental heat were associated with a modestly higher risk for hospital encounter with AKI among older adults.

The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis.

Background: It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). Methods: We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD. Results: Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies). Conclusion: Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful.

Perioperative aspirin and clonidine and risk of acute kidney injury: a randomized clinical trial.

IMPORTANCE: Acute kidney injury, a common complication of surgery, is associated with poor outcomes and high health care costs. Some studies suggest aspirin or clonidine administered during the perioperative period reduces the risk of acute kidney injury; however, these effects are uncertain and each intervention has the potential for harm. OBJECTIVE: To determine whether aspirin compared with placebo, and clonidine compared with placebo, alters the risk of perioperative acute kidney injury. DESIGN, SETTING, AND PARTICIPANTS: A 2 × 2 factorial randomized, blinded, clinical trial of 6905 patients undergoing noncardiac surgery from 88 centers in 22 countries with consecutive patients enrolled between January 2011 and December 2013. INTERVENTIONS: Patients were assigned to take aspirin (200 mg) or placebo 2 to 4 hours before surgery and then aspirin (100 mg) or placebo daily up to 30 days after surgery, and were assigned to take oral clonidine (0.2 mg) or placebo 2 to 4 hours before surgery, and then a transdermal clonidine patch (which provided clonidine at 0.2 mg/d) or placebo patch that remained until 72 hours after surgery. MAIN OUTCOMES AND MEASURES: Acute kidney injury was primarily defined as an increase in serum creatinine concentration from the preoperative concentration by either an increase of 0.3 mg/dL or greater (≥26.5 µmol/L) within 48 hours of surgery or an increase of 50% or greater within 7 days of surgery. RESULTS: Aspirin (n = 3443) vs placebo (n = 3462) did not alter the risk of acute kidney injury (13.4% vs 12.3%, respectively; adjusted relative risk, 1.10; 95% CI, 0.96-1.25). Clonidine (n = 3453) vs placebo (n = 3452) did not alter the risk of acute kidney injury (13.0% vs 12.7%, respectively; adjusted relative risk, 1.03; 95% CI, 0.90-1.18). Aspirin increased the risk of major bleeding. In a post hoc analysis, major bleeding was associated with a greater risk of subsequent acute kidney injury (23.3% when bleeding was present vs 12.3% when bleeding was absent; adjusted hazard ratio, 2.20; 95% CI, 1.72-2.83). Similarly, clonidine increased the risk of clinically important hypotension. In a post hoc analysis, clinically important hypotension was associated with a greater risk of subsequent acute kidney injury (14.3% when hypotension was present vs 11.8% when hypotension was absent; adjusted hazard ratio, 1.34; 95% CI, 1.14-1.58). CONCLUSIONS AND RELEVANCE: Among patients undergoing major noncardiac surgery, neither aspirin nor clonidine administered perioperatively reduced the risk of acute kidney injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01082874.

The risk of perioperative bleeding in patients with chronic kidney disease: a systematic review and meta-analysis.

BACKGROUND: Worldwide, millions of patients with chronic kidney disease undergo surgery each year. Although chronic kidney disease increases the risk of bleeding in nonoperative settings, the risk of perioperative bleeding is less clear. We conducted a systematic review and meta-analysis to summarize existing information and quantify the risk of perioperative bleeding from chronic kidney disease. METHODS: We screened 9376 citations from multiple databases for cohort studies published between 1990 and 2011. Studies that met our inclusion criteria included patients undergoing any major surgery, with a sample size of at least 100 patients with chronic kidney disease (as defined by the primary study authors with an elevated preoperative serum creatinine value or a low estimated glomerular filtration rate). Their outcomes had to be compared with a reference group of at least 100 patients without chronic kidney disease. Our primary outcomes were (1) receipt of perioperative blood transfusions and (2) need for reoperation for reasons of bleeding. RESULTS: Twenty-three studies met our criteria for review (20 cardiac surgery, 3 non-cardiac surgery). Chronic kidney disease was associated with a greater risk of requiring blood transfusion (7 studies in cardiac surgery, totaling 22,718 patients) and weighted incidence in patients with normal kidney function was 53% and in chronic kidney disease was 73%; pooled odds ratio, 2.7 (95% confidence interval, 2.1-3.4). After adjustment for relevant factors, the association remained statistically significant in 4 studies. Chronic kidney disease was associated with more reoperation for reasons of bleeding (14 studies in cardiac surgery, totaling 569,715 patients) and weighted incidence in patients with normal kidney function was 2.4% and in chronic kidney disease was 2.7%; pooled odds ratio, 1.6 (95% confidence interval, 1.3-1.8). However, after adjustment for relevant factors (as done in 5 studies), the association was no longer statistically significant. CONCLUSIONS: Chronic kidney disease is associated with perioperative bleeding but not bleeding that required reoperation. Further studies should stage chronic kidney disease with the modern system, better define bleeding outcomes, and guide intervention to improve the safety of surgery in this at-risk population.

Magnesium and Fracture Risk in the General Population and Patients Receiving Dialysis: A Narrative Review.

Purpose of Review: Magnesium is an essential mineral for bone metabolism, but little is known about how magnesium intake alters fracture risk. We conducted a narrative review to better understand how magnesium intake, through supplementation, diet, or altering the concentration of dialysate magnesium, affects mineral bone disease and the risk of fracture in individuals across the spectrum of kidney disease. Sources of Information: Peer-reviewed clinical trials and observational studies. Methods: We searched for relevant articles in MEDLINE and EMBASE databases. The methodologic quality of clinical trials was assessed using a modified version of the Downs and Black criteria checklist. Key Findings: The role of magnesium intake in fracture prevention is unclear in both the general population and in patients receiving maintenance dialysis. In those with normal kidney function, 2 meta-analyses showed higher bone mineral density in those with higher dietary magnesium, whereas 1 systematic review showed no effect on fracture risk. In patients receiving maintenance hemodialysis or peritoneal dialysis, a higher concentration of dialysate magnesium is associated with a lower concentration of parathyroid hormone, but little is known about other bone-related outcomes. In 2 observational studies of patients receiving hemodialysis, a higher concentration of serum magnesium was associated with a lower risk of hip fracture. Limitations: This narrative review included only articles written in English. Observed effects of magnesium intake in the general population may not be applicable to those with chronic kidney disease particularly in those receiving dialysis.

Justification: Le magnésium est un minéral essentiel pour le métabolisme osseux, mais on en sait peu sur la façon dont un apport en magnésium modifie le risque de fracture. Nous avons procédé à un examen narratif afin de mieux comprendre comment les maladies liées à la densité minérale osseuse et le risque de fracture sont affectés par un apport en magnésium (supplémentation, régime alimentaire ou modification de la concentration de dialysat de magnésium) chez les personnes atteintes d'insuffisance rénale. Sources: Essais cliniques et études observationnelles examinés par des pairs. Méthodologie: Nous avons répertorié les articles pertinents dans les bases de données MEDLINE et EMBASE. Une version modifiée des critères de contrôle de la qualité des études de Downs et Black a servi à évaluer la qualité méthodologique des essais cliniques retenus. Principaux résultats: Le rôle d'un apport en magnésium dans la prévention des fractures n'est pas clair, tant dans la population générale que chez les patients sous dialyse d'entretien. Chez les personnes ayant une fonction rénale normale, deux méta-analyses ont montré que les personnes dont le régime alimentaire est riche en magnésium présentent une densité minérale osseuse plus élevée; alors qu'une revue systématique n'a montré aucun effet sur le risque de fracture. Chez les patients sous hémodialyse d'entretien ou dialyse péritonéale, une concentration plus élevée de dialysat de magnésium est associée à une plus faible concentration d'hormone parathyroïdienne, mais on en sait peu sur les autres effets liés aux os. Dans deux études observationnelles portant sur des patients sous hémodialyse, une concentration plus élevée de magnésium sérique a été associée à un risque plus faible de fracture de la hanche. Limites: Cet examen narratif ne comprend que des articles rédigés en anglais. Il est possible que les effets d'un apport en magnésium observés dans la population générale ne puissent s'appliquer aux personnes atteintes d'une néphropathie chronique, en particulier aux personnes sous dialyse.

Predicting Myocardial Injury and Other Cardiac Complications After Elective Noncardiac Surgery with the Revised Cardiac Risk Index: The VISION Study.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is widely used to estimate risk of cardiac complications after noncardiac surgery; its estimates do not capture myocardial injury after noncardiac surgery (MINS). We evaluated the incidence of cardiac complications including MINS across RCRI risk classes and the RCRI's ability to discriminate, before surgery, between patients who will experience these complications and those who will not. METHODS: This was a secondary analysis of a prospective cohort study of 35,815 patients ≥ 45 years old who had elective inpatient noncardiac surgery from 2007 to 2013 at 28 centres in 14 countries. The primary outcome was a composite of MINS, myocardial infarction, nonfatal cardiac arrest, or cardiac death within 30 days after surgery. The secondary outcome was this composite without MINS. RESULTS: The primary outcome occurred in 4725 patients (13.2%); its incidences across RCRI classes I (no risk factors), II (1 risk factor), III (2 risk factors), and IV (≥ 3 risk factors) were, respectively, 8.2%, 15.4%, 26.6%, and 40.2% (C-statistic for discrimination 0.65 [95% confidence interval 0.62-0.68]). The secondary outcome occurred in 1174 patients (3.3%) with incidences of 1.6%, 4.0%, 7.9%, and 12.9%, respectively (C-statistic 0.69 [0.65-0.72]). Thirty-five percent of primary outcome events and 26.9% of secondary outcome events occurred in patients with no RCRI risk factors. CONCLUSION: The RCRI alone is not sufficient to guide postoperative cardiac monitoring because 1 in 12 patients ≥ 45 years of age without any RCRI risk factors have a cardiac complication after major noncardiac surgery, and most of them would be missed without systematic troponin testing.

A Higher Concentration of Dialysate Magnesium to Reduce the Frequency of Muscle Cramps: A Narrative Review.

PURPOSE OF REVIEW: Strategies to mitigate muscle cramps are a top research priority for patients receiving hemodialysis. As hypomagnesemia is a possible risk factor for cramping, we reviewed the literature to better understand the physiology of cramping as well as the epidemiology of hypomagnesemia and muscle cramps. We also sought to review the evidence from interventional studies on the effect of oral and dialysate magnesium-based therapies on muscle cramps. SOURCES OF INFORMATION: Peer-reviewed articles. METHODS: We searched for relevant articles in major bibliographic databases including MEDLINE and EMBASE. The methodological quality of interventional studies was assessed using a modified version of the Downs and Blacks criteria checklist. KEY FINDINGS: The etiology of muscle cramps in patients receiving hemodialysis is poorly understood and there are no clear evidence-based prevention or treatment strategies. Several factors may play a role including a low concentration of serum magnesium. The prevalence of hypomagnesemia (concentration of <0.7 mmol/L) in patients receiving hemodialysis ranges from 10% to 20%. Causes of hypomagnesemia include a low dietary intake of magnesium, use of medications that inhibit magnesium absorption (eg, proton pump inhibitors), increased magnesium excretion (eg, high-dose loop diuretics), and a low concentration of dialysate magnesium. Dialysate magnesium concentrations of ≤0.5 mmol/L may be associated with a decrease in serum magnesium concentration over time. Preliminary evidence from observational and interventional studies suggests a higher dialysate magnesium concentration will raise serum magnesium concentrations and may reduce the frequency and severity of muscle cramps. However, the quality of evidence supporting this benefit is limited, and larger, multicenter clinical trials are needed to further determine if magnesium-based therapy can reduce muscle cramps in patients receiving hemodialysis. In studies conducted to date, increasing the concentration of dialysate magnesium appears to be well-tolerated and is associated with a low risk of symptomatic hypermagnesemia. LIMITATIONS: Few interventional studies have examined the effect of magnesium-based therapy on muscle cramps in patients receiving hemodialysis and most were nonrandomized, pre-post study designs.

CONTEXTE MOTIVANT LA REVUE: Les stratégies visant à atténuer les crampes musculaires sont parmi les principales priorités de recherche des patients hémodialysés. L'hypomagnésémie étant un possible facteur de risque, nous avons procédé à une revue de la littérature afin de mieux en comprendre l'épidémiologie, et d'examiner la physiologie et l'épidémiologie des crampes musculaires. Nous souhaitions également examiner les données probantes issues d'études interventionnelles portant sur l'effet des thérapies à base de dialysat de magnésium et de magnésium oral sur les crampes musculaires. SOURCES: Articles examinés par les pairs. MÉTHODOLOGIE: Nous avons cherché les articles pertinents dans les principales bases de données bibliographiques, notamment MEDLINE et EMBASE. La qualité méthodologique a été évaluée à l'aide d'une version modifiée des critères de contrôle de la qualité des études de Downs et Black. PRINCIPAUX RÉSULTATS: L'étiologie des crampes musculaires chez les patients hémodialysés est mal comprise et il n'existe aucune stratégie de prévention ou traitement clairement fondé sur des données probantes. Plusieurs facteurs pourraient jouer un rôle, notamment de faibles concentrations sériques de magnésium. La prévalence de l'hypomagnésémie (concentration inférieure à 0,7 mmol/L) chez les patients hémodialysés variait de 10 à 20 %. Une faible consommation de magnésium dans l'alimentation, la prise de médicaments inhibant l'absorption du magnésium (ex. les inhibiteurs de la pompe à protons), l'excrétion accrue du magnésium (ex. dose élevée de diurétiques de l'anse) et une faible concentration de dialysat de magnésium figuraient parmi les causes d'hypomagnésémie. Un taux de dialysat de magnésium inférieur ou égal à 0,5 mmol/L pourrait être associé à une diminution de la concentration sérique de magnésium au fil du temps. Les résultats préliminaires de certaines études observationnelles et interventionnelles suggèrent qu'une concentration sérique plus élevée de magnésium dans le dialysat augmenterait les concentrations sériques de magnésium et pourrait réduire la fréquence et la sévérité des épisodes de crampes musculaires. La qualité des preuves appuyant ce bienfait est cependant limitée. Des essais multicentriques et à plus vaste échelle sont nécessaires pour juger si un traitement à base de magnésium peut véritablement réduire les crampes musculaires chez les patients hémodialysés. Dans les études menées jusqu'à maintenant, l'augmentation de la concentration de dialysat de magnésium semblait bien tolérée et a été associée à un faible risque d'hypermagnésémie symptomatique. LIMITES: Peu d'études interventionnelles ont examiné l'effet de la prise de magnésium sur les crampes musculaires des patients hémodialysés, et la plupart de celles-ci constituaient des plans pré- ou post-études non randomisées.

Cultivating Innovative Pragmatic Cluster-Randomized Registry Trials Embedded in Hemodialysis Care: Workshop Proceedings From 2018.

Hemodialysis is a life-sustaining treatment for persons with kidney failure. However, those on hemodialysis still face a poor quality of life and a short life expectancy. High-quality research evidence from large randomized controlled trials is needed to identify interventions that improve the experiences, outcomes, and health care of persons receiving hemodialysis. With the support of the Canadian Institutes of Health Research and its Strategy for Patient-Oriented Research, the Innovative Clinical Trials in Hemodialysis Centers initiative brought together Canadian and international kidney researchers, patients, health care providers, and health administrators to participate in a workshop held in Toronto, Canada, on June 2 and 3, 2018. The workshop served to increase knowledge and awareness about the conduct of innovative, pragmatic, cluster-randomized registry trials embedded into routine hemodialysis care and provided an opportunity to discuss and build support for new trial ideas. The workshop content included structured presentations, facilitated group discussions, and expert panel feedback. Partnerships and promising trial ideas borne out of the workshop will continue to be developed to support the implementation of future large-scale trials.

L'hémodialyse constitue un traitement essentiel au maintien de la vie pour les personnes atteintes d'insuffisance rénale. Les patients hémodialysés voient cependant leur qualité et leur espérance de vie réduites. Des données de recherches probantes, provenant de vastes essais cliniques contrôlés à répartition aléatoire, sont nécessaires pour améliorer l'expérience, les résultats et les soins des patients hémodialysés. Grâce au soutien des Instituts de recherche en santé du Canada (IRSC) et de leur Stratégie de recherche axée sur le patient (SRAP), l'initiative sur les essais cliniques novateurs (ECN) en centres d'hémodialyse a réuni divers intervenants en santé rénale (chercheurs, patients, fournisseurs de soins et administrateurs), du Canada et de partout dans le monde, lors d'un colloque qui s'est tenu à Toronto les 2 et 3 juin 2018. Ce colloque a permis d'accroître la sensibilisation et les connaissances sur la conduite d'essais cliniques novateurs, répartis en grappes, pragmatiques et intégrés aux soins d'hémodialyse de routine. Cette rencontre a également fourni une occasion de discuter de nouvelles idées d'essais cliniques et de susciter les appuis nécessaires à leur réalisation. Le colloque s'est déroulé sous forme de présentations structurées, de discussions animées en groupe et de rétroaction de la part d'un comité d'experts. Les idées de recherche prometteuses et les partenariats issus de ce colloque continueront d'être développés pour soutenir la réalisation d'essais cliniques futurs de grande envergure.

Hospital case volume and clinical outcomes in critically ill patients with acute kidney injury treated with dialysis.

PURPOSE: To determine whether patients with severe acute kidney injury who receive dialysis (AKI-D) experience better outcomes at centres that care for more patients with AKI-D. MATERIALS AND METHODS: Linked administrative datasets where used to perform a retrospective cohort study of all critically ill patients in Ontario, Canada, who had a first episode of AKI-D between 2002 and 2011. Centre volume for a given year, was designated by calculating the mean number of patients treated with acute dialysis at that centre during that year and the one preceding it. Patients treated at that centre were then assigned to a centre volume quartile for that year. RESULTS: We identified 19,658 critically ill patients with AKI-D treated at 54 Ontario hospitals. Mortality and dialysis dependence at 90-days were 46% and 31%, respectively. Centre volume was not associated with mortality at 90 days (with quartile 1 as the reference, adjusted odds ratio (aOR) 1.16 (95% CI, 0.87 - 1.54) in quartile 2, aOR 1.17 (95% CI, 0.91 - 1.50) in quartile 3, and aOR 1.06 (95% CI, 0.81 - 1.41) in quartile 4). CONCLUSIONS: There are no Centre volume survival associations in the management of AKI-D despite high mortality and dependence rate.

Comparative genomic analysis of Campylobacter jejuni associated with Guillain-Barré and Miller Fisher syndromes: neuropathogenic and enteritis-associated isolates can share high levels of genomic similarity.

BACKGROUND: Campylobacter jejuni infection represents the most frequent antecedent infection triggering the onset of the neuropathic disorders Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Although sialylated ganglioside-mimicking lipo-oligosaccharide (LOS) structures are the strongest neuropathogenic determinants in C. jejuni, they do not appear to be the only requirement for a neuropathic outcome since strains capable of their production have been isolated from patients with uncomplicated cases of enteritis. Consequently, other pathogen and/or host-related factors contribute to the onset of neurological complications. We have used comparative genomic hybridization to perform a detailed genomic comparison of strains isolated from GBS/MFS and enteritis-only patients. Our dataset, in which the gene conservation profile for 1712 genes was assayed in 102 strains, including 56 neuropathogenic isolates, represents the largest systematic search for C. jejuni factors associated with GBS/MFS to date and has allowed us to analyze the genetic background of neuropathogenic C. jejuni strains with an unprecedented level of resolution. RESULTS: The majority of GBS/MFS strains can be assigned to one of six major lineages, suggesting that several genetic backgrounds can result in a neuropathogenic phenotype. A statistical analysis of gene conservation rates revealed that although genes involved in the sialylation of LOS structures were significantly associated with neuropathogenic strains, still many enteritis-control strains both bear these genes and share remarkable levels of genomic similarity with their neuropathogenic counterparts. Two capsule biosynthesis genes (Cj1421c and Cj1428c) showed higher conservation rates among neuropathogenic strains compared to enteritis-control strains. Any potential involvement of these genes in neuropathogenesis must be assessed. A single gene (HS:3 Cj1135) had a higher conservation rate among enteritis-control strains. This gene encodes a glucosyltransferase that is found in some of the LOS classes that do not express ganglioside mimics. CONCLUSION: Our findings corroborate that neuropathogenic factors may be transferred between unrelated strains of different genetic background. Our results would also suggest that the failure of some strains isolated from uncomplicated cases of enteritis to elicit a neuropathic clinical outcome may be due to subtle genetic differences that silence their neuropathogenic potential and/or due to host-related factors.

30-Day Readmissions After an Acute Kidney Injury Hospitalization.

BACKGROUND: The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized within 30 days and identified characteristics associated with hospital readmission. METHODS: We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission. RESULTS: We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58). CONCLUSIONS: One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community.

Characteristics and Outcomes of Patients Discharged Home from an Emergency Department with AKI.

BACKGROUND AND OBJECTIVES: Patients discharged home from an emergency department with AKI are not well described. This study describes their characteristics and outcomes and compares these outcomes to two referent groups. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a population-based retrospective cohort study in Ontario, Canada from 2003 to 2012 of 6346 patients aged ≥40 years who were discharged from the emergency department with AKI (defined using serum creatinine values). We analyzed the risk of all-cause mortality, receipt of acute dialysis, and hospitalization within 30 days after discharge. We used propensity score methods to compare all-cause mortality to two referent groups. We matched 4379 discharged patients to 4379 patients who were hospitalized from the emergency department with similar AKI stage. We also matched 6188 discharged patients to 6188 patients who were discharged home from the emergency department with no AKI. RESULTS: There were 6346 emergency department discharges with AKI. The mean age was 69 years and 6012 (95%) had stage 1, 290 (5%) had stage 2, and 44 (0.7%) had stage 3 AKI. Within 30 days, 149 (2%) (AKI stage 1: 127 [2%]; stage 2: 15 [5%]; stage 3: seven [16%]) died, 22 (0.3%) received acute dialysis, and 1032 (16%) were hospitalized. An emergency department discharge versus hospitalization with AKI was associated with lower mortality (3% versus 12%; relative risk, 0.3; 95% confidence interval, 0.2 to 0.3). An emergency department discharge with AKI versus no AKI was associated with higher mortality (2% versus 1%; relative risk, 1.6; 95% confidence interval, 1.2 to 2.0). CONCLUSIONS: Patients discharged home from the emergency department with AKI are at risk of poor 30-day outcomes. A better understanding of care in this at-risk population is warranted, as are testing strategies to improve care.

External validation of the Revised Cardiac Risk Index and update of its renal variable to predict 30-day risk of major cardiac complications after non-cardiac surgery: rationale and plan for analyses of the VISION study.

INTRODUCTION: The Revised Cardiac Risk Index (RCRI) is a popular classification system to estimate patients' risk of postoperative cardiac complications based on preoperative risk factors. Renal impairment, defined as serum creatinine >2.0 mg/dL (177 µmol/L), is a component of the RCRI. The estimated glomerular filtration rate has become accepted as a more accurate indicator of renal function. We will externally validate the RCRI in a modern cohort of patients undergoing non-cardiac surgery and update its renal component. METHODS AND ANALYSIS: The Vascular Events in Non-cardiac Surgery Patients Cohort Evaluation (VISION) study is an international prospective cohort study. In this prespecified secondary analysis of VISION, we will test the risk estimation performance of the RCRI in ∼34 000 participants who underwent elective non-cardiac surgery between 2007 and 2013 from 29 hospitals in 15 countries. Using data from the first 20 000 eligible participants (the derivation set), we will derive an optimal threshold for dichotomising preoperative renal function quantified using the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) glomerular filtration rate estimating equation in a manner that preserves the original structure of the RCRI. We will also develop a continuous risk estimating equation integrating age and CKD-Epi with existing RCRI risk factors. In the remaining (approximately) 14 000 participants, we will compare the risk estimation for cardiac complications of the original RCRI to this modified version. Cardiac complications will include 30-day non-fatal myocardial infarction, non-fatal cardiac arrest and death due to cardiac causes. We have examined an early sample to estimate the number of events and the distribution of predictors and missing data, but have not seen the validation data at the time of writing. ETHICS AND DISSEMINATION: The research ethics board at each site approved the VISION protocol prior to recruitment. We will publish our results and make our models available online at http://www.perioperativerisk.com. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00512109.

Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura.

A 36-year-old man presented to hospital with gross haematuria and evidence of severe, refractory thrombotic thrombocytopenic purpura. Initial treatment with high-volume plasma exchange therapy and early administration of rituximab failed to achieve a sustained clinical response. His clinical course was complicated by left hemianopsia and despite an urgent splenectomy he developed a large right-sided stroke with malignant cerebral oedema that required an emergent decompressive craniotomy. He also had numerous infectious complications as a consequence of an aggressive immunosuppressive strategy. While the patient did not respond to cyclophosphamide, cyclosporine, N-acetylcysteine, and one course of bortezomib, he eventually responded to a second course of bortezomib. One year later, the patient remains in remission and maintains excellent cognitive function. However, he has not completely recovered from his stroke and continues to participate in rehabilitation for his residual physical deficits.

A new approach for the analysis of bacterial microarray-based Comparative Genomic Hybridization: insights from an empirical study.

BACKGROUND: Microarray-based Comparative Genomic Hybridization (M-CGH) has been used to characterize the extensive intraspecies genetic diversity found in bacteria at the whole-genome level. Although conventional microarray analytical procedures have proved adequate in handling M-CGH data, data interpretation using these methods is based on a continuous character model in which gene divergence and gene absence form a spectrum of decreasing gene conservation levels. However, whereas gene divergence may yet be accompanied by retention in gene function, gene absence invariably leads to loss of function. This distinction, if ignored, leads to a loss in the information to be gained from M-CGH data. We present here results from experiments in which two genome-sequenced strains of C. jejuni were compared against each other using M-CGH. Because the gene content of both strains was known a priori, we were able to closely examine the effects of sequence divergence and gene absence on M-CGH data in order to define analytical parameters for M-CGH data interpretation. This would facilitate the examination of the relative effects of sequence divergence or gene absence in comparative genomics analyses of multiple strains of any species for which genome sequence data and a DNA microarray are available. RESULTS: As a first step towards improving the analysis of M-CGH data, we estimated the degree of experimental error in a series of experiments in which identical samples were compared against each other by M-CGH. This variance estimate was used to validate a Log Ratio-based methodology for identification of outliers in M-CGH data. We compared two genome strains by M-CGH to examine the effect of probe/target identity on the Log Ratios of signal intensities using prior knowledge of gene divergence and gene absence to establish Log Ratio thresholds for the identification of absent and conserved genes. CONCLUSION: The results from this empirical study validate the Log Ratio thresholds that have been used in other studies to establish gene divergence/absence. Moreover, the analytical framework presented here enhances the information content derived from M-CGH data by shifting the focus from divergent/absent gene detection to accurate detection of conserved and absent genes. This approach closely aligns the technical limitations of M-CGH analysis with practical limitations on the biological interpretation of comparative genomics data.

Improving Care after Acute Kidney Injury: A Prospective Time Series Study.

BACKGROUND: Acute kidney injury (AKI) complicates 15-20% of hospitalizations, and AKI survivors are at increased risk of chronic kidney disease and death. However, less than 20% of patients see a nephrologist within 3 months of discharge, even though a nephrologist visit within 90 days of discharge is associated with enhanced survival. To address this, we established an AKI Follow-Up Clinic and characterized the patterns of care delivered. METHODS: We conducted a prospective time series study. All hospitalized patients who developed Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 AKI were eligible. The pre-intervention period consisted of electronic reminders to the nephrology consults and cardiovascular surgery services to refer to the AKI Follow-Up Clinic. In the post-intervention period, eligible patients were automatically scheduled into the AKI Follow-Up Clinic at discharge. The primary outcome was the percentage of KDIGO stages 2-3 AKI survivors assessed by a nephrologist within 30 days of discharge. RESULTS: In the pre-intervention period, 8 of 46 patients (17%) were seen by a nephrologist within 30 days after discharge, and no additional patients were seen for 90 days. In the post-intervention period, 17 of 69 patients (25%) were seen by a nephrologist within 30 days after discharge (p = 0.36), with an additional 30 patients seen in 90 days (47 of 69, 68%, p < 0.001). The mean serum creatinine was 99 (SD 35) µmol/l prior to hospitalization and 133 (58) µmol/l at 3 months. Fifty-five of 79 patients (70%) received at least 1 medical intervention at their first AKI Follow-Up Clinic visit. CONCLUSIONS: An AKI Follow-Up Clinic with an automatic referral process increased the proportion of patients seen at 90 days, but not 30 days post discharge. Being seen in the AKI Follow-Up Clinic was associated with interventions in most patients. Future research is needed to evaluate the effect of the AKI Follow-Up Clinic on patient-centered outcomes, but physicians should be aware that AKI survivors may benefit from close outpatient follow-up and a multipronged approach to care similarly for other high-risk populations.

Ambulatory care after acute kidney injury: an opportunity to improve patient outcomes.

PURPOSE OF REVIEW: Acute kidney injury (AKI) is an increasingly common problem among hospitalized patients. Patients who survive an AKI-associated hospitalization are at higher risk of de novo and worsening chronic kidney disease, end-stage kidney disease, cardiovascular disease, and death. For hospitalized patients with dialysis-requiring AKI, outpatient follow-up with a nephrologist within 90 days of hospital discharge has been associated with enhanced survival. However, most patients who survive an AKI episode do not receive any follow-up nephrology care. This narrative review describes the experience of two new clinical programs to care for AKI patients after hospital discharge: the Acute Kidney Injury Follow-up Clinic for adults (St. Michael's Hospital and University Health Network, Toronto, Canada) and the AKI Survivor Clinic for children (Cincinnati Children's Hospital, USA). SOURCES OF INFORMATION: MEDLINE, PubMed, ISI Web of Science. FINDINGS: These two ambulatory clinics have been in existence for close to two (adult) and four (pediatric) years, and were developed separately and independently in different populations and health systems. The components of both clinics are described, including the target population, referral process, medical interventions, patient education activities, and follow-up schedule. Common elements include targeting patients with KDIGO stage 2 or 3 AKI, regular audits of the inpatient nephrology census to track eligible patients, medication reconciliation, and education on the long-term consequences of AKI. LIMITATIONS: Despite the theoretical benefits of post-AKI follow-up and the clinic components described, there is no high quality evidence to prove that the interventions implemented in these clinics will reduce morbidity or mortality. Therefore, we also present a plan to evaluate the adult AKI Follow-up Clinic in order to determine if it can improve clinical outcomes compared to patients with AKI who do not receive follow-up care. IMPLICATIONS: Follow-up of AKI survivors is low, and this review describes two different clinics that care for patients who survive an AKI episode. We believe that sharing the experiences of the AKI Follow-up Clinic and AKI Survivor Clinic provide physicians with a feasible framework to implement their own clinics, which may help AKI patients receive outpatient care commensurate with their high risk status.

OBJECTIFS DE LA REVUE: L'insuffisance rénale aiguë (IRA) est un problème de plus en plus fréquent chez les patients hospitalisés. Ceux d'entre eux qui survivent à un épisode d'IRA courent un risque élevé de développer une insuffisance rénale chronique et des maladies cardiovasculaires ou d'aggraver leur état vers l'insuffisance rénale terminale et donc, la mort. Chez les patients hospitalisés pour insuffisance rénale aiguë nécessitant une hémodialyse, un taux de survie accru a été associé à un suivi par un néphrologue dans les 90 jours suivant la sortie de l'hôpital. Cependant, la majorité de ces patients ne bénéficient d'aucun suivi en néphrologie post-hospitalisation. La présente revue narrative s'attarde à décrire l'expérience de deux nouveaux programmes cliniques qui prennent en charge les patients après leur sortie de l'hôpital à la suite d'un épisode d'IRA. Il s'agit des programmes de l'« Acute Kidney Injury Follow-up Clinic ¼ des hôpitaux St. Micheal et UHN de Toronto, et de la clinique pédiatrique « AKI Survivor Clinic for children ¼ de l'hôpital pour enfants de Cincinnati, aux États-Unis. SOURCES: MEDLINE, PubMed, ISI le web des sciences. CONSTATATIONS: Ces cliniques ambulatoires, qui existent depuis près de deux ans (clinique pour adultes) et de quatre ans (clinique pédiatrique) se sont développées séparément et de façon indépendante pour des populations différentes, dans des systèmes de santé différents. Les constituants de ces deux cliniques se distinguent par l'identification de la population ciblée, le processus de présentation, les interventions médicales, les activités de sensibilisation auprès des patients et leur calendrier de suivi. Les parties communes incluent le recrutement de patients atteints d'IRA de stades 2 et 3 quant aux chances de l'amélioration globale de leurs résultats (KDIGO). Ce recrutement se fait par le passage en revue à intervalles réguliers des listes de patients hospitalisés aux unités néphrologiques afin d'identifier ceux qui sont admissibles au suivi. Ces parties communes incluent aussi un bilan comparatif des médicaments et la transmission d'informations sur les conséquences à long terme de l'insuffisance rénale aiguë. LIMITES DE L'ÉTUDE: Malgré les bienfaits escomptés d'un suivi post-IRA et, les éléments cliniques décrits plus haut, il n'existe aucune preuve concrète que les procédures mises en œuvre dans ces programmes réduiront la morbidité ou la mortalité associées à la maladie. Par conséquent, nous présentons également un plan d'évaluation de la clinique pour adultes en suivi post-IRA afin de déterminer si son programme peut améliorer les résultats cliniques de ses patients en comparaison avec les patients ne recevant pas ce suivi. CONSÉQUENCES: De façon générale, peu de patients ayant survécu à un épisode d'IRA reçoivent un suivi adéquat post-hospitalisation. Cette revue présente deux cliniques offrant ce suivi. Nous pensons que le partage de leurs expériences respectives peut poser un cadre réalisable aux médecins traitants qui souhaiteraient mettre sur pied leurs propres cliniques, afin d'offrir à leurs patients un suivi en externe répondant adéquatement à leur état de santé précaire.