Estimating glomerular filtration rate in patients with acute kidney injury: a prospective multicenter study of diagnostic accuracy.

BACKGROUND: Estimating glomerular filtration rate (GFR) in acute kidney injury (AKI) is challenging, with limited data comparing estimated and gold standard methods to assess GFR. The objective of our study was to assess the performance of the kinetic estimated GFR (KeGFR) and Jelliffe equations to estimate GFR in AKI, using a radioisotopic method (technetium-diethylenetriaminepentaacetic acid) as a reference measure. METHODS: We conducted a prospective multicenter observational study in hospitalized patients with AKI. We computed the Jelliffe and KeGFR equations to estimate GFR and compared these estimations to measured GFR (mGFR) by a radioisotopic method. The performances were assessed by correlation, Bland-Altman plots and smoothed and linear regressions. We conducted stratified analyses by age and chronic kidney disease (CKD). RESULTS: The study included 119 patients with AKI, mostly from the intensive care unit (63%) and with Stage 1 AKI (71%). The eGFR obtained from the Jelliffe and KeGFR equations showed a good correlation with mGFR (r = 0.73 and 0.68, respectively). The median eGFR by the Jelliffe and KeGFR equations was less than the median mGFR, indicating that these equations underestimated the mGFR. On Bland-Altman plots, the Jelliffe and KeGFR equations displayed a considerable lack of agreement with mGFR, with limits of agreement >40 mL/min/1.73 m2. Both equations performed better in CKD and the KeGFR performed better in older patients. Results were similar across AKI stages. CONCLUSIONS: In our study, the Jelliffe and KeGFR equations had good correlations with mGFR; however, they had wide limits of agreement. Further studies are needed to optimize the prediction of mGFR with estimatation equations.

Acute kidney injury in critically ill children and 5-year hypertension.

BACKGROUND: To develop a pediatric-specific hypertension algorithm using administrative data and use it to evaluate the association between acute kidney injury (AKI) in the intensive care unit (ICU) and hypertension diagnosis 5 years post-discharge. METHODS: Two-center retrospective cohort study of children (≤ 18 years old) admitted to the pediatric ICU in Montreal, Canada, between 2003 and 2005 and followed until 2010. Patients with a valid healthcare number and without end-stage renal disease were included. Patients who could not be merged with the provincial database, did not survive admission, underwent cardiac surgery, had pre-existing renal disease associated with hypertension or a prior diagnosis of hypertension were excluded. AKI defined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Using diagnostic codes and medications from administrative data, novel pediatric-specific hypertension definitions were designed. Both the evaluation of the prevalence of hypertension diagnosis and the association between AKI and hypertension occurred. RESULTS: Nineteen hundred and seventy eight patients were included (median age at admission [interquartile range] 4.3 years [1.1-11.8], 44% female, 325 (16.4%) developed AKI). Of these patients, 130 (7%) had a hypertension diagnosis 5 years after discharge. Patients with AKI had a higher prevalence of hypertension diagnosis [non-AKI: 84/1653 (5.1%) vs. AKI: 46/325 (14.2%), p < .001]. Children with AKI had a higher adjusted risk of hypertension diagnosis (hazard ratio [95% confidence interval] 2.19 [1.47-3.26]). CONCLUSIONS: Children admitted to the ICU have a high prevalence of hypertension post-discharge and children with AKI have over two times higher risk of hypertension compared to those with no AKI.

Association Between Metformin Adherence and All-Cause Mortality Among New Users of Metformin: A Nested Case-Control Study.

BACKGROUND: Metformin presents better survival rates than other oral antidiabetics in the treatment of type 2 diabetes. However, these benefits may be dampened by inadequate treatment adherence. OBJECTIVE: We aimed to investigate the relationship between adherence level to metformin therapy and all-cause mortality over 10 years in incident metformin users. METHODS: A nested case-control study was conducted using a large cohort of beneficiaries of the Quebec public drug insurance plan, aged 45 to 85 years, who initiated metformin between 2000 and 2009. Each case of all-cause death during follow-up was matched with up to 10 controls. Adherence to metformin was measured using the medication possession ratio (MPR). Conditional logistic regression models were used to estimate rate ratios (RRs) for mortality between adherent (MPR ≥ 80%) and nonadherent patients (MPR < 80%). Subgroup analyses were conducted according to age (45-64 and 65-85 years) and comedication use (antihypertensive/cardiovascular drugs and statins). RESULTS: The cohort included 82 720 incident metformin users, followed up for 2.4 [0.8-4.4] years (median [interquartile range]) and 4747 cases of all-cause deaths. Analyses revealed decreased mortality risks after long-term adherence to metformin. Specifically, RRs were 0.84 (95% CI = [0.71-0.98]) and 0.69 [0.57-0.85] after 4 to 6 and ≥6 years of adherence to metformin, respectively. Survival benefits of long-term adherence (≥4 years) were also observed across most subgroups and particularly in patients using neither antihypertensive/cardiovascular drugs nor statins (0.57 [0.41-0.77]). CONCLUSIONS: Long-term adherence to metformin is associated with decreased risks of all-cause mortality in incident metformin users. Further research should investigate whether survival benefits vary according to the comorbidity burden of patients.

A stepwise approach for the management of poisoning with extracorporeal treatments.

The use of an extracorporeal treatment (ECTR) in a poisoned patient may be life-saving in a limited number of scenarios. The decision-processes surrounding the use of ECTR in poisoning is complex: most nephrologists are not trained to assess a poisoned patient while clinical toxicologists rarely prescribe ECTRs. Deciding on which ECTR is most appropriate for a poison requires a good understanding of the poison's physicochemical and pharmacokinetic properties. Further, a detailed understanding of the capabilities and limitations of the different ECTRs can be useful to select the most appropriate ECTR for a given clinical situation. This manuscript provides a stepwise approach to assess the usefulness of ECTRs in poisoning.

Principles and operational parameters to optimize poison removal with extracorporeal treatments.

A role for nephrologists in the management of a poisoned patient involves evaluating the indications for, and methods of, enhancing the elimination of a poison. Nephrologists are familiar with the various extracorporeal treatments (ECTRs) used in the management of impaired kidney function, and their respective advantages and disadvantages. However, these same skills and knowledge may not always be considered, or applicable, when prescribing ECTR for the treatment of a poisoned patient. Maximizing solute elimination is a key aim of such treatments, perhaps more so than in the treatment of uremia, because ECTR has the potential to reverse clinical toxicity and shorten the duration of poisoning. This manuscript reviews the various principles that govern poison elimination by ECTR (diffusion, convection, adsorption, and centrifugation) and how components of the ECTR can be adjusted to maximize clearance. Data supporting these recommendations will be presented, whenever available.

Nonpharmacologic approaches for pain management during labor compared with usual care: a meta-analysis.

OBJECTIVES: To assess the effects of nonpharmacologic approaches to pain relief during labor, according to their endogenous mechanism of action, on obstetric interventions, maternal, and neonatal outcomes. DATA SOURCE: Cochrane library, Medline, Embase, CINAHL and the MRCT databases were used to screen studies from January 1990 to December 2012. STUDY SELECTION: According to Cochrane criteria, we selected randomized controlled trials that compared nonpharmacologic approaches for pain relief during labor to usual care, using intention-to-treat method. RESULTS: Nonpharmacologic approaches, based on Gate Control (water immersion, massage, ambulation, positions) and Diffuse Noxious Inhibitory Control (acupressure, acupuncture, electrical stimulation, water injections), are associated with a reduction in epidural analgesia and a higher maternal satisfaction with childbirth. When compared with nonpharmacologic approaches based on Central Nervous System Control (education, attention deviation, support), usual care is associated with increased odds of epidural OR 1.13 (95% CI 1.05-1.23), cesarean delivery OR 1.60 (95% CI 1.18-2.18), instrumental delivery OR 1.21 (95% CI 1.03-1.44), use of oxytocin OR 1.20 (95% CI 1.01-1.43), labor duration (29.7 min, 95% CI 4.5-54.8), and a lesser satisfaction with childbirth. Tailored nonpharmacologic approaches, based on continuous support, were the most effective for reducing obstetric interventions. CONCLUSION: Nonpharmacologic approaches to relieve pain during labor, when used as a part of hospital pain relief strategies, provide significant benefits to women and their infants without causing additional harm.

Adherence to antihypertensive agents improves risk reduction of end-stage renal disease.

Uncontrolled hypertension is associated with an increased risk of end-stage renal disease (ESRD). Intensified blood pressure control may slow progression of chronic kidney disease; however, the impact of antihypertensive agent adherence on the prevention of ESRD has never been evaluated. Here we assessed the impact of antihypertensive agent adherence on the risk of ESRD in 185,476 patients in the RAMQ databases age 45 to 85 and newly diagnosed/treated for hypertension between 1999 and 2007. A case cohort study design was used to assess the risk of and multivariate Cox proportional models were used to estimate the adjusted hazard ratio of ESRD. Adherence level was reported as a medication possession ratio. Mean patient age was 63 years, 42.2% male, 14.0% diabetic, 30.3% dyslipidemic, and mean follow-up was 5.1 years. A high adherence level of 80% or more to antihypertensive agent(s) compared to a lower one was related to a risk reduction of ESRD (hazard ratio 0.67; 95% confidence intervals 0.54-0.83). Sensitivity analysis revealed that the effect is mainly in those without chronic kidney disease. Risk factors for ESRD were male, diabetes, peripheral artery disease, chronic heart failure, gout, previous chronic kidney disease, and use of more than one agent. Thus, our study suggests that a better adherence to antihypertensive agents is related to a risk reduction of ESRD and this adherence needs to be improved to optimize benefits.

Population pharmacokinetic and pharmacodynamic modeling of acetazolamide in peritoneal dialysis patients and healthy volunteers.

PURPOSE: To characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of acetazolamide (ACTZ) in peritoneal dialysis patients, ACTZ 500 mg was administered intravenously to 7 healthy subjects (HV) and 8 peritoneal dialysis patients (CAPD). METHODS: Population PK/PD modeling was performed with ACTZ serum (total and unbound), urine and dialysate concentrations, intra-ocular pressure (IOP) and covariates. A multi-compartment PK model (accounting for non-linear protein binding) and an inhibitory Emax (maximal change in IOP) PD model were selected. RESULTS: As expected, renal clearance (which almost equals total body clearance) was severely decreased in CAPD (1.2 vs 80.3 L/h) and the elimination half-life of total ACTZ was prolonged (20.6 vs 3.4 hours). The protein binding was significantly altered with a mean free fraction 4.2% in HV and 8.6% in CAPD. Moreover protein binding of ACTZ was concentration dependent in both HV and CAPD. Despite a higher free fraction of ACTZ, the Emax was lower in CAPD: 4.4±1.4 vs 7.4±2.8 mmHg. CONCLUSION: Both PK and PD are significantly altered in dialysis patients.

Effect of cinacalcet availability and formulary listing on parathyroidectomy rate trends.

BACKGROUND: Recent trends in parathyroidectomy rates are not known. Our objective was to investigate the trend in parathyroidectomy rates between 2001 and 2010, and to evaluate if the availability and reimbursement of cinacalcet modified that trend. METHODS: Using a provincial administrative database, we included all adult patients receiving chronic dialysis treatments between 2001 and 2010 (incident and prevalent) in a time series analysis. The effect of cinacalcet availability on parathyroidectomy bimonthly rates was modeled using an ARIMA intervention model using different cut-off dates: September 2004 (Health Canada cinacalcet approval), January 2005, June 2005, January 2006, June 2006 (date of cinacalcet provincial reimbursement), and January 2007. RESULTS: A total of 12 795 chronic dialysis patients (mean age 64 years, 39% female, 82% hemodialysis) were followed for a mean follow-up of 3.3 years. During follow-up, 267 parathyroidectomies were identified, translating to an average rate of 7.0 per 1000 person-years. The average parathyroidectomy rate before cinacalcet availability was 11.4 /1000 person-years, and 3.6 /1000 person-years after cinacalcet public formulary listing. Only January 2006 as an intervention date in the ARIMA model was associated with a change in parathyroidectomy rates (estimate: -5.58, p = 0.03). Other intervention dates were not associated with lower parathyroidectomy rates. CONCLUSIONS: A reduction in rates of parathyroidectomy was found after January 2006, corresponding to cinacalcet availability. However, decreased rates may be due to other factors occurring simultaneously with cinacalcet introduction and further studies are needed to confirm these findings.

Association of Phlebotomy on Blood Product Transfusion Requirements During Liver Transplantation: An Observational Cohort Study on 1000 Cases.

Background: During the past 2 decades, transfusion requirements have decreased drastically during orthotopic liver transplantation (OLT), and transfusion-free transplantation is nowadays increasingly common. Understanding that liberal intravenous volume loading in cirrhotic patients may have detrimental consequences is key. In contrast, phlebotomy is a method to lower central venous pressure and portal venous pressure. The objective of this study was to determine the effectiveness and safety of phlebotomy in the early phase of blood transfusion, blood loss, renal function, and mortality. Methods: The present study evaluated the impact of phlebotomy on bleeding, transfusion rate, renal dysfunction, and mortality in 1000 consecutive OLTs. Two groups were defined and compared using phlebotomy. Multivariate logistic and linear regression models were used to determine predictors of bleeding, red blood cell (RBC) transfusion, renal dysfunction, and mortality. Results: A mean of 0.7 ± 1.5 RBC units was transfused per patient for 1000 OLTs, 75% did not receive any RBCs, and the median and interquartile range (25-75) were 0 for all blood products transfused. The phlebotomy was associated with decreased transfusion (RBCs, plasma, platelets, cryoprecipitate, albumin), with less bleeding, and with an increased survival rate, both 1 mo and 1 y. Phlebotomy was not associated with renal dysfunction. Conclusions: The practice of phlebotomy to lower portal venous pressure was associated with reduced blood product transfusions and blood loss during liver dissection without deleterious effect on renal function.

Impact of adherence to antihypertensive agents on clinical outcomes and hospitalization costs.

BACKGROUND: Cardiovascular diseases (CVD) represent a heavy economic burden on individuals, health services, and society. Low adherence to antihypertensive (AH) agents is acknowledged as a major contributor to the lack of blood pressure control, and may have a significant impact on clinical outcomes and healthcare costs. OBJECTIVES: To evaluate the impact of low adherence to AH agents on cardiovascular outcomes and hospitalization costs. METHODS: A cohort of 59,647 patients with essential hypertension was reconstructed from the Régie de l'assurance maladie du Québec and Med-Echo databases. Subjects included were between 45 and 85 years of age, without any evidence for symptomatic CVD, newly treated with AH agents between 1999 and 2002 and followed-up for a 3-year period. Adherence to AH agents was categorized as >or=80% or <80%. The adjusted odds ratio (OR) for CVD events between the 2 adherence groups was estimated using a polytomous logistic analysis. A 2-part model was applied for hospitalization costs. RESULTS: Patients with low adherence were more likely to have coronary disease (OR, 1.07; 95% confidence interval [CI], 1.00-1.13), cerebrovascular disease (OR, 1.13; 95% CI, 1.03-1.25), and chronic heart failure (OR, 1.42; 95% CI, 1.27-1.58) within the 3-year follow-up period. Among hospitalized patients, low adherence to AH therapy was associated with increased costs by approximately $3574 (95% CI, $2897-$4249) per person within a 3-year period. CONCLUSIONS: Low adherence to AH agents is correlated with a higher risk of vascular events, hospitalization, and greater healthcare costs. An increased level of adherence to AH agents should provide a better health status for individuals and a net economic gain.

Adherence level of antihypertensive agents in coronary artery disease.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * Non-adherence is probably an important source of preventable cardiovascular morbidity and mortality. * However, until now there have been very few large effectiveness studies assessing the relationship between adherence levels to antihypertensive medication and major cardiovascular outcomes for primary prevention of cardiovascular disease. WHAT THIS STUDY ADDS: * The study results suggest that there is an association between better adherence to antihypertensive agents and a relative risk reduction of coronary artery disease. * Adherence to antihypertensive agents needs to be improved so that patients can benefit from the full protective effects of antihypertensive therapies. AIMS: Antihypertensive (AH) agents have been shown to reduce the risk of cardiovascular events, including coronary artery disease (CAD). Previous surveys have shown that a substantial number of patients with diagnosed hypertension remain uncontrolled. Non-adherence to AH agents may reduce the effectiveness. The aim was to evaluate the impact of better adherence to AH agents on the occurrence of CAD in a real clinical setting. METHODS: A cohort of 83 267 patients was reconstructed using the Régie de l'assurance maladie du Québec databases. Patients were eligible if they were between 45 and 85 years of age without indication of cardiovascular disease, and had been newly treated with AH agents between 1999 and 2004. A nested case-control design was used to study the incidence of CAD. Every case of CAD was matched for age and duration of follow-up to up to 15 randomly selected controls. The adherence level was measured by calculating the medication possession ratio. Cases' adherence was calculated from the start of follow-up to the time of the CAD (index date). For controls, adherence was calculated from the start of follow-up to the time of selection (index date). Rate ratios of CAD were estimated by conditional logistic regression adjusting for covariables. RESULTS: The mean patient age was 65 years, 37% were male, 8% had diabetes and 18% had dyslipidaemia. High adherence level (96%) to AH therapy compared with lower adherence level (59%) was associated with a relative risk reduction of CAD events (rate ratios 0.90; 0.84, 0.95). Risk factors for CAD were male gender, diabetes, dyslipidaemia and developing a cardiovascular condition disease during follow-up. CONCLUSION: Our study suggests that better adherence to AH agents is associated with a risk reduction of CAD. Adherence to AH agents needs to be improved so that patients can benefit from the full protective effects of AH therapies.

Agreement Between Administrative Database and Medical Chart Review for the Prediction of Chronic Kidney Disease G category.

BACKGROUND: Chronic kidney disease (CKD) is a major health issue and cardiovascular risk factor. Validity assessment of administrative data for the detection of CKD in research for drug benefit and risk using real-world data is important. Existing algorithms have limitations and we need to develop new algorithms using administrative data, giving the importance of drug benefit/risk ratio in real world. OBJECTIVE: The aim of this study was to validate a predictive algorithm for CKD GFR category 4-5 (eGFR < 30 mL/min/1.73 m2 but not receiving dialysis or CKD G4-5ND) using the administrative databases of the province of Quebec relative to estimated glomerular filtration rate (eGFR) as a reference standard. DESIGN: This is a retrospective cohort study using chart collection and administrative databases. SETTING: The study was conducted in a community outpatient medical clinic and pre-dialysis outpatient clinic in downtown Montreal and rural area. PATIENTS: Patient medical files with at least 2 serum creatinine measures (up to 1 year apart) between September 1, 2013, and June 30, 2015, were reviewed consecutively (going back in time from the day we started the study). We excluded patients with end-stage renal disease on dialysis. The study was started in September 2013. MEASUREMENT: Glomerular filtration rate was estimated using the CKD Epidemiological Collaboration (CKD-EPI) from each patient's file. Several algorithms were developed using 3 administrative databases with different combinations of physician claims (diagnostics and number of visits) and hospital discharge data in the 5 years prior to the cohort entry, as well as specific drug use and medical intervention in preparation for dialysis in the 2 years prior to the cohort entry. METHODS: Chart data were used to assess eGFR. The validity of various algorithms for detection of CKD groups was assessed with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: A total of 434 medical files were reviewed; mean age of patients was 74.2 ± 10.6 years, and 83% were older than 65 years. Sensitivity of algorithm #3 (diagnosis within 2-5 years and/or specific drug use within 2 years and nephrologist visit ≥4 within 2-5 years) in identification of CKD G4-5ND ranged from 82.5% to 89.0%, specificity from 97.1% to 98.9% with PPV and NPV ranging from 94.5% to 97.7% and 91.1% to 94.2%, respectively. The subsequent subgroup analysis (diabetes, hypertension, and <65 and ≥65 years) and also the comparisons of predicted prevalence in a cohort of older adults relative to published data emphasized the accuracy of our algorithm for patients with severe CKD (CKD G4-5ND). LIMITATIONS: Our cohort comprised mostly older adults, and results may not be generalizable to all adults. Participants with CKD without 2 serum creatinine measurements up to 1 year apart were excluded. CONCLUSIONS: The case definition of severe CKD G4-5ND derived from an algorithm using diagnosis code, drug use, and nephrologist visits from administrative databases is a valid algorithm compared with medical chart reviews in older adults.

CONTEXTE: L'insuffisance rénale chronique (IRC) est un problème de santé majeur et un facteur de risque cardiovasculaire. La validité de la détection de l'IRC à partir des bases de données administratives est importante pour les études évaluant en situation réelle les bénéfices et les risques des médicaments. Les algorithmes existants comportent des limites et, compte tenu de l'importance revêtue par ce rapport bénéfices/risques, le développement de nouveaux algorithmes utilisant les bases de données administratives s'avère essentiel. OBJECTIF: Valider le pouvoir prédictif d'un algorithme pour détecter l'insuffisance rénale chronique sévère (DFGe <30 mL/min/1.73 m2, patient non-dialysé ou CKD G4-5ND) à partir des banques de données administratives de la province de Québec, avec le débit de filtration glomérulaire estimé (DFGe) comme point de référence. TYPE D'ÉTUDE: Étude de cohorte rétrospective réalisée à partir des dossiers médicaux et de données administratives. CADRE: Des cliniques médicales communautaires et de protection rénale de Montréal et des régions rurales périphériques. SUJETS: Les dossiers médicaux de patients avec au moins deux mesures de la créatinine sérique (en moins d'un an) entre le 1er septembre 2013 et le 30 juin 2015 ont été revus consécutivement, en reculant dans le temps. Les patients avec insuffisance rénale terminale et dialysés ont été exclus. L'étude a débuté en septembre 2013. MESURES: Le DFG a été estimé à l'aide de la formule CKD Epidemiological Collaboration (CKD-EPI) à partir du dossier médical de chaque patient. Nous avons développé différents algorithmes en utilisant trois banques de données administratives avec différentes combinaisons de facturations médicales (diagnostics et nombre de visites en néphrologie) et de données colligées au congé de l'hôpital dans les cinq ans précédant l'entrée dans la cohorte, de même qu'avec la consommation de certains médicaments et les interventions médicales subies en préparation à la dialyse dans les deux ans précédant l'entrée dans la cohorte. MÉTHODOLOGIE: Les données des dossiers médicaux ont été utilisées pour définir le DFGe. La validité des algorithmes développés a été évaluée en utilisant la sensibilité, la spécificité, la valeur prédictive positive (VPP) et la valeur prédictive négative (VPN). RÉSULTATS: En tout, 434 dossiers médicaux ont été revus; l'âge moyen des patients était de 74.2 ± 10.6 ans et 83% avaient plus de 65 ans. La sensibilité de l'algorithme no.3 (diagnostic dans un délai de 2 à 5 ans et/ou l'usage de médicaments spécifiques dans un délai de 2 ans, et au moins quatre visites médicales en néphrologie dans les 2 à 5 ans précédant la date d'entrée dans la cohorte) dans l'identification d'une insuffisance rénale sévère (CKD G4-5ND) variait de 82.5% à 89.0%. La spécificité de ce même algorithme variait de 97.1% à 98.9% avec une PPV et une NPV allant respectivement de 94.5.% à 97.7% et de 91.1% à 94.2%. L'analyse de sous-groupes (patients diabétiques, hypertendus, âgés de moins de 65 ans ou âgés de 65 ans et plus) ainsi que la comparaison de la prévalence prédite dans une cohorte de patients âgés par rapport aux données de la littérature font valoir la précision de notre algorithme pour les patients avec insuffisance rénale sévère (CKD G4-5ND). LIMITES: Notre cohorte était composée essentiellement de sujets âgées, les résultats pourraient ne pas s'appliquer à tous les adultes. Les patients n'ayant pas eu deux mesures de la créatinine sérique à l'intérieur d'un an ont été exclus. CONCLUSION: Chez les personnes âgées, la définition de cas pour une insuffisance chronique rénale sévère (CKD G4-5ND) estimée par un algorithme utilisant les codes diagnostic, la consommation de médicaments spécifiques et les services médicaux de néphrologie tirés des données administratives s'avère un algorithme valide comparativement à l'examen du dossier médical.

Impact of a better adherence to antihypertensive agents on cerebrovascular disease for primary prevention.

BACKGROUND AND PURPOSE: The benefits of antihypertensive (AH) drugs on the risks of major cardiovascular outcomes have been demonstrated in clinical trials. However, approximately half of hypertensive patients do not adhere well to their prescribed AH therapy in actual practice. The purpose of this study was to assess the impact of adherence to AH agents on the incidence of cerebrovascular disease (CD) in real-world practice. METHODS: A cohort of 83 267 hypertensive patients was reconstructed from the Régie de l'assurance maladie du Québec databases. Subjects included were between 45 and 85 years old, initially free of cardiovascular disease, and newly treated for hypertension with AH agents between 1999 and 2004. A nested case-control design was conducted to study CD occurrence. Every case was matched for age and duration of follow-up with up to 15 randomly selected control subjects. The adherence to AH drugs was measured by calculating the medication possession ratio. Conditional logistic regression models were performed to assess the association between adherence to AH agents and CD adjusting for various potential confounders. RESULTS: At cohort entry, the mean patient age was 65 years, 37.3% were male, 8.6% had diabetes, and 19.5% had dyslipidemia. High adherence (>/=80%) to AH drugs significantly decreased the risk of CD by 22% (rate ratio, 0.78; 95% CI, 0.70 to 0.87) compared with lower adherence. Male gender, occurrence of cardiovascular disease during follow-up, and dyslipidemia were risk factors for CD. CONCLUSIONS: High adherence to AH therapy is associated with a reduced risk of CD outside the context of clinical trials in primary prevention.

Acute Kidney Injury in Critically Ill Children and Subsequent Chronic Kidney Disease.

BACKGROUND: The progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children. OBJECTIVES: We aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge. DESIGN: Retrospective cohort study using chart collection and administrative data. SETTING: Two-center study in Montreal, Canada. PATIENTS: Children (≤18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease. MEASUREMENTS: Acute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ≥1 CKD diagnostic code or ≥1 CKD-specific medication prescription. METHODS: Chart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association. RESULTS: A total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively (P < .001). LIMITATIONS: Results may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further. CONCLUSIONS: Acute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.

CONTEXTE: Chez l'enfant, la progression de l'insuffisance rénale aigüe (IRA) vers l'insuffisance rénale chronique (IRC) est encore mal connue. OBJECTIFS: Nous souhaitions élaborer une définition de l'IRC pédiatrique à partir des données administratives, et l'employer pour évaluer l'association entre l'IRA chez les enfants gravement malades et un diagnostic d'IRC cinq ans après leur sortie de l'hôpital. TYPE D'ÉTUDE: Étude de cohorte rétrospective réalisée à partir des dossiers médicaux et des données administratives. CADRE: Deux centres hospitaliers de Montréal (Canada). SUJETS: L'étude porte sur des enfants (≤18 ans) admis à deux unités de soins intensifs (USI) pédiatriques entre 2003 et 2005. Les patients atteints d'insuffisance rénale terminale ou sans numéro d'assurance-maladie ont été exclus d'emblée. Seule la première admission survenue au cours de l'étude a été retenue. Les patients n'ayant pu être reliés aux données administratives, n'ayant pas survécu à l'hospitalisation ou souffrant d'une néphropathie préexistante ont été exclus. MESURES: L'IRA a été définie selon les critères KDIGO (Kidney Disease: Improving Global Outcomes) et l'IRC cinq ans après la sortie de l'hôpital par la présence d'au moins un code diagnostique pour l'IRC ou la prise d'au moins un médicament spécifique au traitement de l'IRC. MÉTHODOLOGIE: Les données des dossiers médicaux, utilisées pour définir l'exposition (IRA), ont été couplées aux données administratives provinciales, utilisées pour définir le résultat (IRC). Un modèle de régression de Cox a servi à établir l'association entre IRA et IRC. RÉSULTATS: Ont été inclus 2 235 patients (56 % de garçons), dont l'âge médian à l'admission était de 3,7 ans. De ce nombre, 464 (21 %) ont développé une IRA en cours d'hospitalisation à l'USI pédiatrique. Cinq ans après leur sortie de l'hôpital, 43 patients (2 %) avaient reçu un diagnostic d'IRC. Les patients atteints d'une IRA de stade 1 et de stade 2-3 ont présenté un plus grand risque de progresser vers l'IRC (rapport de risque ajusté [IC à 95 %] 2,2 [1,1 ­ 4,5] et 2,5 [1,1 ­ 5,7] respectivement, P < 0,001). LIMITES: Les résultats pourraient ne pas s'appliquer aux patients non admis aux USI pédiatriques. Nous n'avons pu ajuster les résultats avec les variables après la sortie de l'hôpital. Des études futures devraient examiner plus attentivement ces potentiels facteurs de risque supplémentaires. CONCLUSION: L'IRA chez l'enfant a été associée à une progression vers l'IRC cinq ans après la sortie de l'hôpital, telle que définie par les données administratives de santé.

A Validation Study of Administrative Health Care Data to Detect Acute Kidney Injury in the Pediatric Intensive Care Unit.

BACKGROUND: Large studies evaluating pediatric acute kidney injury (AKI) epidemiology and outcomes are lacking, partially due to underuse of large administrative health care data. OBJECTIVE: To assess the diagnostic accuracy of administrative health care data-defined AKI in children admitted to the pediatric intensive care unit (PICU). DESIGN: Retrospective cohort study utilizing chart and administrative data. SETTING: Children admitted to the PICU at 2 centers in Montreal, QC. PATIENTS: Patients between 0 and 18 years old with a provincial health insurance number, without end-stage renal disease and admitted to the PICU between January 1, 2003, and March 31, 2005, were included. MEASUREMENTS: The AKI was defined from chart data using the Kidney Disease: Improving Global Outcomes (KDIGO) definition (Chart-AKI). The AKI defined using administrative health data (Admin-AKI) was based on International Classification of Disease, Ninth Revision (ICD-9) AKI codes. METHODS: Data available from retrospective chart review, including baseline and PICU patient characteristics, and serum creatinine (SCr) and urine output (UO) values during PICU admission, were merged with provincial administrative health care data containing diagnostic and procedure codes used for ascertaining Admin-AKI. Sensitivity, specificity, positive, and negative predictive value of Admin-AKI compared with Chart-AKI (reference standard) were calculated. Univariable associations between Admin-AKI and hospital mortality were evaluated. RESULTS: A total of 2051 patients (55% male, mean age at admission 6.1 ± 5.8 years, 355 cardiac surgery, 1696 noncardiac surgery) were included. The AKI defined by SCr or UO criteria occurred in 52% of cardiac surgery patients and 24% of noncardiac surgery patients. Overall, Admin-AKI detected Chart-AKI with low sensitivity, but high specificity in cardiac and noncardiac surgery patients. Sensitivity increased by 1.5 to 2 fold with each increase in AKI severity stage. Admin-AKI was associated with hospital mortality (13% in Admin-AKI vs 2% in non-AKI, P < .001). LIMITATIONS: These data were generated in a PICU population; future research should study non-PICU populations. CONCLUSIONS: Use of administrative health care data to define AKI in children leads to AKI incidence underestimation. However, for detecting more severe AKI, sensitivity is higher, while maintaining high specificity.

CONTEXTE: On dispose de peu d'études à grande échelle évaluant l'épidémiologie et l'évolution de l'insuffisance rénale aigüe (IRA) chez les enfants, notamment en raison d'une sous-utilisation des données administratives du système de santé. OBJECTIF: Évaluer la précision diagnostique de l'IRA définie à partir des données administratives en santé chez des enfants admis aux unités de soins intensifs pédiatriques (USIP). TYPE D'ÉTUDE: Une étude de cohorte rétrospective utilisant des données administratives et les données provenant des dossiers médicaux. CADRE: Les USIP de deux centres hospitaliers de Montréal, au Canada. SUJETS: Ont été inclus les patients âgés de 0 à 18 ans possédant un numéro d'assurance-maladie provincial qui ont été admis aux USIP entre le 1er janvier 2003 et le 31 mars 2005 avec une insuffisance rénale non terminale. MESURES: L'IRA-Dos a été définie à partir des dossiers médicaux en utilisant les critères du KDIGO (Kidney Disease: Improving Global Outcomes). L'IRA-Admin a été définie à partir des données administratives en santé avec les codes d'IRA de la neuvième révision de la Classification internationale des maladies (CIM-9). MÉTHODOLOGIE: Les données tirées de l'examen rétrospectif des dossiers médicaux, soit les valeurs de créatinine sérique (SCr) et de diurèse pendant le séjour aux USIP et les caractéristiques des patients, initiales et à l'admission, ont été fusionnées aux données administratives provinciales en santé contenant les codes de diagnostic et de procédure utilisés pour établir l'IRA-Admin. La sensibilité, la spécificité et les valeurs prédictives négative et positive de l'IRA-Admin, en comparaison à l'IRA-Dos (standard de référence), ont été calculées. L'association univariée entre l'IRA-Admin et la mortalité à l'hôpital a également été évaluée. RÉSULTATS: Un total de 2 051 patients ont été inclus (355 ayant subi une cardiochirurgie et 1 696 non opérés). L'âge moyen des sujets à l'admission était de 6,1 ± 5,8 ans et 55 % étaient des garçons. L'IRA définie par les critères de SCr et de diurèse a été diagnostiquée chez 52 % des patients opérés et chez 24 % des patients non opérés. Pour l'ensemble de la cohorte (patients opérés ou non), l'IRA-Admin a détecté l'IRA-Dos avec une faible sensibilité, mais avec une spécificité élevée. La sensibilité s'est accrue de 1,5 à 2 fois pour chaque passage à un stade supérieur de gravité de l'IRA. Enfin, l'IRA-Admin a été associée à un taux plus élevé de mortalité à l'hôpital (13 % des patients IRA-Admin contre 2 % des patients sans IRA, p<0,001). LIMITATIONS: Ces résultats concernent une population de patients hospitalisés aux USIP. Des études futures devraient inclure des populations non admises aux USIP. CONCLUSIONS: L'utilisation des données administratives en santé pour définir l'IRA chez les enfants a mené à une sous-estimation de son incidence. Cependant, la méthode montre une plus grande sensibilité dans la détection des cas plus graves d'IRA, tout en conservant une spécificité élevée.

Healthcare Utilization after Acute Kidney Injury in the Pediatric Intensive Care Unit.

BACKGROUND AND OBJECTIVES: Little is known about the long-term burden of AKI in the pediatric intensive care unit. We aim to evaluate if pediatric AKI is associated with higher health service use post-hospital discharge. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective cohort study of children (≤18 years old) admitted to two tertiary centers in Montreal, Canada. Only the first admission per patient was included. AKI was defined in two ways: serum creatinine alone or serum creatinine and/or urine output. The outcomes were 30-day, 1-year, and 5-year hospitalizations, emergency room visits, and physician visits per person-time using provincial administrative data. Univariable and multivariable Poisson regression were used to evaluate AKI associations with outcomes. RESULTS: A total of 2041 children were included (56% male, mean admission age 6.5±5.8 years); 299 of 1575 (19%) developed AKI defined using serum creatinine alone, and when urine output was included in the AKI definition 355 of 1622 (22%) children developed AKI. AKI defined using serum creatinine alone and AKI defined using serum creatinine and urine output were both associated with higher 1- and 5-year hospitalization risk (AKI by serum creatinine alone adjusted relative risk, 1.42; 95% confidence interval, 1.12 to 1.82; and 1.80; 1.54 to 2.11, respectively [similar when urine output was included]) and higher 5-year physician visits (adjusted relative risk, 1.26; 95% confidence interval, 1.14 to 1.39). AKI was not associated with emergency room use after adjustments. CONCLUSIONS: AKI is independently associated with higher hospitalizations and physician visits postdischarge.

Long-term Mortality After Acute Kidney Injury in the Pediatric ICU.

OBJECTIVES: (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)-defined AKI alters the association. METHODS: A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS: The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46-6.57] and 3.38 [1.63-7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS: AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships.

An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).

BACKGROUND: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice. OBJECTIVE: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week. DESIGN: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016. SETTING: Ten sites in Canada. PATIENTS: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week. MEASUREMENTS: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation. METHODS: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits. RESULTS: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation. LIMITATIONS: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d. CONCLUSIONS: Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01879618, registered June 13, 2013.

CONTEXTE: La daltéparine sodique, une héparine de faible poids moléculaire, est indiquée pour prévenir la formation de caillots dans le circuit extracorporel durant l'hémodialyse (HD). Pour une séance de dialyse d'une durée maximale de quatre heures, l'étiquette du produit recommande une dose fixe de 5 000 unités internationales (U.I.) administrée en bolus. Cependant, il est possible qu'il puisse être bénéfique d'ajuster la dose en pratique. OBJECTIF: Le but de l'étude PARROT était d'analyser l'innocuité et l'efficacité d'une dose ajustable de daltéparine chez des patients atteints d'insuffisance rénale terminale (IRT) et nécessitant trois à quatre séances d'HD par semaine. TYPE D'ÉTUDE: Il s'agit d'une étude ouverte et multicentrique à traitement unique d'une durée de sept semaines couvrant la période entre octobre 2013 et mars 2016. CADRE: L'étude a eu lieu dans dix centres de dialyse au Canada. SUJETS: L'étude a inclus 152 patients atteints d'IRT et nécessitant trois à quatre séances d'HD par semaine. MESURES: Le résultat principal était la proportion de séances d'HD complétées, non interrompues de manière prématurée en raison d'une anticoagulation inadéquate. MÉTHODOLOGIE: Tous les participants ont initialement reçu 5000 U.I. de daltéparine, dose qui a pu être ajustée lors des séances subséquentes, lorsqu'indiqué par le contexte clinique, à raison d'augmentation ou de réduction de 500 ou 1 000 U.I., sans spécification quant aux doses limites. RÉSULTATS: Les patients ont été suivis sur une période de 256 mois-patients. Pratiquement toutes les séances d'HD évaluables (99,9 %; IC 95 % : 99,7-100) ont été complétées sans coagulation prématurée. La dose de daltéparine a été ajustée pour plus de la moitié (52,3 %) des participants, essentiellement en raison de coagulation ou d'un besoin de procéder à une compression de l'accès vasculaire au-delà de 10 minutes. La dose médiane de daltéparine était de 5 000 U.I. (entre 500 et 13 000 U.I.). Aucune hémorragie majeure n'a été rapportée, mais une hémorragie mineure est survenue dans 2,3 % de toutes les séances d'HD analysées. Aucune bioaccumulation n'a été détectée. LIMITES: Cette étude de courte durée à traitement unique a été conçue pour optimiser le dosage de daltéparine à l'aide d'un schéma de posologie flexible. Elle ne visait pas à évaluer spécifiquement la minimisation de la dose ou à fournir des informations sur l'innocuité à long terme d'une posologie flexible pour la daltéparine. Également, les patients à haut risque d'hémorragie ont été exclus de l'étude, notamment ceux qui prenaient des anticoagulants ou des antiplaquettaires autres qu'une dose quotidienne de moins de 100 mg d'aspirine. CONCLUSION: Dans l'ensemble, un schéma posologique flexible pour la daltéparine sodique a permis de compléter les séances d'HD de façon sécuritaire, en plus de fournir des avantages cliniques par rapport à une dose fixe.