Is health-related quality of life trajectory associated with dialysis modality choice in advanced chronic kidney disease?

BACKGROUND: Patients with advanced chronic kidney disease have lower health-related quality of life (HRQOL) than the general population. There is uncertainty regarding patterns of HRQOL changes before dialysis initiation. This study aimed to characterise HRQOL trajectory and assess its potential association with intended dialysis modality. METHODS: This prospective single-centre cohort study followed adults with an estimated glomerular filtration rate ≤15 mL/min/1.73 m2 for one year. Patients were allocated into one of two groups based on their intended treatment modality, 'home dialysis' (peritoneal dialysis or home haemodialysis (HD)) and 'other' (in-centre HD or conservative care). Follow-up was for up to 1 year or earlier if initiated on kidney replacement therapy or died. Kidney Disease Quality of Life - Short Form (KDQOL-SF) was completed every 6 months. Predictors of changes in KDQOL-SF components were modelled using mixed effect multivariable linear regressions. RESULTS: One hundred and nine patients were included. At baseline, crude physical composite summary (PCS) (45 ± 10 vs. 39 ± 8) was higher in patients choosing home dialysis (n = 41), while mental composite summary (MCS) was similar in both groups. After adjustment, patients choosing home dialysis had an increase in MCS (B = 8.4 per year, p = 0.007) compared to those selecting in-centre HD/conservative care. This translates into an annual increase in MSC by 3 points for the 'home dialysis' group, compared to an annual decline by 5.4 points in the 'other' group. There was no difference in PCS trajectory through time. CONCLUSIONS: Patients choosing home dialysis had improved MCS over time compared to those not selecting home dialysis. More work is needed to determine how differences in processes of care and/or unmeasured patient characteristics modulate this association.

Older age, kidney concordant diseases and the dilemma of adherence to guidelines: A narrative review.

Evidence-based medicine is pivotal to contemporary clinical practice, and the excellence of a healthcare institution is measured by the adherence of its clinical staff to the clinical practice guidelines (CPGs) among other standards and policies. Following the recommendations of CPGs in older adults poses different challenges to prescribers. In this narrative review we explore research studies that assessed clinicians' adherence to CPGs when prescribing to older adults with chronic kidney disease and its concordant disorders, and to discuss the potential barriers and facilitators to better adherence to CPGs. Our review of the literature found that the adherence level to CPGs differed according to country, disease condition and healthcare setting. Clinicians' attitudes toward older adults and the CPGs, the unfamiliarity with the CPGs, and the lack of time, were commonly cited barriers. Interventions suggested to improve adherence to CPGs include direct mentoring, educational activities, and the integration of CPGs recommendations within hospital protocols and policies.

Determining Factors Influencing RAS Inhibitors Re-Initiation in ICU: A Modified Delphi Method.

Background: Renin-angiotensin system inhibitors (RASi) are not re-initiated for almost a quarter of patients who suffered acute kidney injury 6 months after discharge. This discontinuation might be partly explained by the nephrotoxicity of these medications, yet they remain of benefit, especially for patients with heart failure. Objective: To determine the factors deemed by clinicians to influence RASi re-initiation and set threshold values for important safety parameters. Design: Three-round modified online Delphi survey. Setting: The study was conducted in Quebec, Canada. Participants: Twenty clinicians from nephrology, intensive care medicine, and internal medicine. Measurements: The factors' importance was rated on 4-point Likert-type scale, ranging from "not important" to "very important" by the panelists. Methods: We conducted a brief literature review to uncover possible influencing factors followed by a 3-round modified Delphi survey to establish a consensus on the importance of these factors. Results: We recruited 20 clinicians (7 nephrologists, 3 internists, and 10 intensive care physicians). We created a list of 25 factors, 15 of which met consensus. Eleven of these factors, including serum creatinine, glomerular filtration rate, and acute kidney injury (AKI) stage, were deemed as important while 4, such as responsibility ambiguity and absence of feedback, were deemed as not important. The majority of the 10 factors which did not meet consensus were related to the clinical setting, such as a pharmacist follow-up and the required time to ensure optimal RASi re-initiation. Limitations: Quebec clinicians' agreement might not reflect the opinion of the rest of Canada. The survey measures clinicians' belief rather than their actual practice. Conclusion: Renin-angiotensin system inhibitors re-initiation is a rather complex concept which encompasses several factors. Our research uncovered some of these factors which may be used to develop guidelines on optimal RASi re-initiation.

Contexte: Six mois après avoir reçu leur congé de l'hôpital, près du quart des patients ayant vécu un épisode d'insuffisance rénale aiguë n'ont toujours pas réamorcé les inhibiteurs du système rénine-angiotensine (iSRA). Cette interruption pourrait s'expliquer en partie par la néphrotoxicité de ces médicaments, bien qu'ils soient bénéfiques, particulièrement pour les patients souffrant d'insuffisance cardiaque. Objectifs: Déterminer les facteurs jugés par les cliniciens comme exerçant une influence sur la reprise des iSRA et définir des valeurs de seuil pour les paramètres de sécurité considérés comme importants. Conception: Une version modifiée de l'enquête Delphi menée en ligne, en trois étapes. Cadre: Étude menée au Québec (Canada). Participants: 20 cliniciens en néphrologie, en médecine de soins intensifs ou en médecine interne. Mesures: L'importance des facteurs a été évaluée par les panélistes sur une échelle de type Likert à quatre points allant de « pas important ¼ à « très important ¼. Méthodologie: Nous avons procédé à une brève revue de la littérature pour repérer les possibles facteurs influençant la reprise des iSRA. Une enquête Delphi modifiée a ensuite été menée en trois étapes afin d'établir un consensus sur l'importance de ces facteurs. Résultats: Nous avons recruté 20 cliniciens (7 néphrologues, 3 internistes et 10 intensivistes). Nous avons créé une liste de 25 facteurs, dont 15 faisaient consensus. De ceux-ci, 11 ont été jugés importants, notamment la créatinine sérique, le débit de filtration glomérulaire et le stade de l'insuffisance rénale aigüe (IRA); alors que 4, notamment l'ambiguïté de la responsabilité et l'absence de rétroaction, ont été jugés non importants. La majorité des 10 facteurs qui ne faisaient pas consensus étaient liés au milieu clinique, notamment le suivi du pharmacien et le temps nécessaire pour assurer une reprise optimale des iSRA. Limites: L'accord des cliniciens du Québec pourrait ne pas refléter l'opinion des cliniciens du reste du Canada. L'enquête mesure les croyances des cliniciens plutôt que leur pratique réelle. Conclusion: La reprise des iSRA est un concept assez complexe qui englobe plusieurs facteurs. Notre recherche a révélé certains facteurs qui peuvent être utilisés pour élaborer des lignes directrices sur la reprise optimale des iSRA après un épisode d'insuffisance rénale aigüe.

The effect of renin-angiotensin-aldosterone system inhibitors on continuous and binary kidney outcomes in subgroups of patients with diabetes: a meta-analysis of randomized clinical trials.

INTRODUCTION: Diabetic nephropathy is the leading cause of kidney failure. Clinical practice guidelines recommend prescribing renin-angiotensin aldosterone system inhibitors (RAASi) to prevent diabetic nephropathy at any stage. We conducted this systematic review and meta-analysis to compare the effects of RAASi with placebo and other antihypertensive agents in adults with diabetes on continuous and binary kidney outcomes to provide a comprehensive review of the class effect of RAASi on several subgroups. METHODS: A systematic electronic search to identify randomized clinical trials of a duration of ≥ 12 months that recruited ≥ 50 adult participants with type 1 or 2 diabetes with any stage of chronic kidney disease and proteinuria was conducted in MEDLINE, CINAHL, EMBASE, and Cochrane library with no language restriction. Studies were screened against the inclusion and exclusion criteria by two reviewers independently. RESULTS: In this meta-analysis, evidence was drawn from 26,551 patients with diabetes from 46 studies. Our analysis shows that RAASi were better than placebo in reducing SrCr (the raw mean difference [RMD] = -13.4 µmol/L; 95%CI: -16.78; -10.01) and albuminuria levels (standardized mean difference [SMD] = -1; 95%CI: -1.57, -0.44, I2 = 96%). When compared to other active treatments, RAASi did not reduce SrCr (RMD = 0.03 µmol/L; 95%CI: -6.4, 6.10, I2 = 76%), caused a non-significant reduction of GFR levels (RMD = -1.21 mL/min; 95%CI: -4.52, 2.09, I2 = 86%), and resulted in modest reduction of albuminuria levels (SMD = -0.55; 95%CI: -0.95, -0.16, I2 = 90%). RAASi were superior to placebo in reducing the risks of kidney failure (OR = 0.74; 95%CI: 0.56, 0.97) and doubling of serum creatinine levels (SrCr; OR = 0.71; 95%CI: 0.55, 0.91), but not in promoting the regression of albuminuria (OR = 3.00; 95%CI: 0.96, 9.37). RAASi, however, were not superior to other antihypertensives in reducing the risks of these outcomes. Patients with type 2 diabetes, macroalbuminuria and longer duration of diabetes had less risk of developing kidney failure in placebo-controlled trials, while longer duration of diabetes, normal kidney function, and hypertension increased the probability of achieving regression of albuminuria in active-controlled trials. CONCLUSION: While our findings revealed the non-superiority of RAASi over other antihypertensives and portrayed a class effect on several subgroups of study participants, it raised a challenging question on whether RAASi deserve their place as first-line therapy in managing diabetic nephropathy.

The Impact of Hypoglycemia on Productivity Loss and Utility in Patients With Type 2 Diabetes Treated With Insulin in Real-world Canadian Practice: Protocol for a Prospective Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) imposes a substantial burden owing to its increasing prevalence and life-threatening complications. In patients who do not achieve glycemic targets with oral antidiabetic drugs, the initiation of insulin is recommended. However, a serious concern regarding insulin is drug-induced hypoglycemia. Hypoglycemia is known to affect quality of life and the use of health care resources. However, health economics and outcomes research (HEOR) data for economic modelling are limited, particularly regarding utility values and productivity losses. OBJECTIVE: This real-world prospective study aims to assess the impact of hypoglycemia on productivity and utility in insulin-treated adults with T2DM from Ontario and Quebec, Canada. METHODS: This noninterventional, multicenter, 3-month prospective study will recruit patients from 4 medical clinics and 2 endocrinology or diabetes clinics. Patients will be identified using appointment lists and enrolled through consecutive sampling during routinely scheduled consultations. To be eligible, patients must be aged ≥18 years, diagnosed with T2DM, and treated with insulin. Utility and productivity will be measured using the EQ-5D-5L questionnaire and Institute for Medical Technology Assessment Productivity Cost Questionnaire, respectively. Questionnaires will be completed 4, 8, and 12 weeks after recruitment. Generalized estimating equation models will be used to investigate productivity losses and utility decrements associated with incident hypoglycemic events while controlling for individual patient characteristics. A total of 500 patients will be enrolled to ensure the precision of HEOR estimates. RESULTS: This study is designed to fill a gap in the Canadian evidence on the impact of hypoglycemia on HEOR outcomes. More specifically, it will generate productivity and utility inputs for the economic modeling of T2DM. CONCLUSIONS: Insulin therapy is expensive, and hypoglycemia is a significant component of economic evaluation. Robust HEOR data may help health technology assessment agencies in future reimbursement decision-making. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/35461.

Real-world evidence: a practical toolbox for collecting health state utilities.

Health state utilities (HSU) data collected in real-world evidence studies are at risk of bias. Although numerous guidance documents are available, practical advice to avoid bias in HSU studies is limited. Thus, the objective of this article was to develop a concise toolbox intended for investigators seeking to collect HSU in a real-world setting. The proposed toolbox builds on existing guidance and provides practical steps to help investigators perform good quality research. The toolbox aims at increasing the credibility of HSU data for future reimbursement decision making.

Qualitative and Quantitative Dosage of the Anti M-Type Phospholipase A2 Receptor Autoantibody: One-Year Experience in Quebec's Reference Center.

BACKGROUND: Quantification of the M-type phospholipase A2 receptor antibodies (anti-PLA2R) is now an essential tool for diagnosis and management of primary membranous nephropathy (MN). Since October 2018, Hôpital Maisonneuve-Rosemont (HMR) has been designated as Quebec's reference center for serum anti-PLA2R antibody testing by the Institut National d'Excellence en Santé et Services Sociaux (INESSS), the regulatory body on drugs and tests usage in Quebec. OBJECTIVES: To describe the 2-step method of serum qualitative and quantitative anti-PLA2R antibody testing during its first year of use in Quebec and analyze its diagnostic value in the province's population. DESIGN: Retrospective cohort study. SETTING: Single-center academic teaching hospital in Quebec, Canada. PATIENTS: All patients who had a serum anti-PLA2R antibody test analyzed at HMR from October 1, 2018, to October 1, 2019, were included in the study. MEASUREMENTS: Serum anti-PLA2R antibodies were screened by indirect immunofluorescence tests. If results were positive or undetermined, it was followed by a quantitative enzyme-linked immunosorbent assay (ELISA) test. Both tests were based on a commercial kit developed by the same company. METHODS: We calculated sensitivity, specificity, predictive value, and likelihood ratio for both tests, using kidney biopsy findings performed at HMR as the gold standard. RESULTS: In Quebec, a total of 1690 tests were performed among 1025 patients during the study year. A small proportion of these patients (8%) were followed at HMR. Patients tested at HMR and in the rest of Quebec had similar characteristics. Test validity was only characterized for patients tested at HMR. Sensitivity and specificity were, respectively, 58% and 100% for the qualitative test, and 71% and 100% for the quantitative test. The combined net sensitivity was 42% and the net specificity 100%. The net positive and negative predictive value were 100% and 84% respectively, whereas the net negative likelihood ratio was 0.58. LIMITATIONS: As the detailed analysis was only possible in the small proportion of patients clinically followed at HMR, there is a possible selection bias. Another potential selection bias was the focus on patients who were selected to have a kidney biopsy, probably because of more severe disease, higher probability of glomerulonephritis, or lesser number of comorbidities. Given the retrospective nature of this study, there was no systematic kidney biopsy or serum PLA2R antibody testing performed. Finally, we were unable to provide detailed information on the timing between immunosuppressive therapy and anti-PLA2R results. CONCLUSIONS: Serum anti-PLA2R antibody testing was widely used in Quebec during its first year of availability. A 2-step approach, using a qualitative test first, followed by a quantitative test if the results are positive or undetermined, appears efficient to avoid useless quantitative testing in negative patients and to better characterize undetermined results on immunofluorescence. TRIAL REGISTRATION: Due to the retrospective nature of this study, no trial registration was performed.

CONTEXTE: La quantification des anticorps des récepteurs de la phospholipase A2 de type M (anti-PLA2R) est désormais un outil essentiel pour le diagnostic et la prise en charge de la glomérulonéphrite extra-membraneuse primaire (GEMp). Depuis octobre 2018, l'Hôpital Maisonneuve-Rosemont (HMR) a été désigné par l'Institut National d'Excellence en Santé et Services Sociaux (INESSS)­l'organisme règlementant l'usage des médicaments et des tests au Québec­comme le centre hospitalier de référence dans la province pour le dépistage des anticorps sériques anti-PLA2R. OBJECTIFS: Décrire la méthode en deux étapes du test qualitatif et quantitatif des anticorps anti-PLA2R sériques au cours de sa première année d'utilisation au Québec et évaluer sa valeur diagnostique dans la population de la province. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Un centre hospitalier universitaire du Québec (Canada). SUJETS: Ont été inclus tous les patients dont le test des anticorps sériques anti-PLA2R a été analysé à HMR entre le 1er octobre 2018 et le 1er octobre 2019. MESURES: Les anticorps sériques anti-PLA2R ont été détectés par immunofluorescence indirecte. Les résultats positifs ou indéterminés ont été suivis d'un test ELISA quantitatif. Les deux tests ont été réalisés à l'aide de trousses commerciales développées par la même entreprise. MÉTHODOLOGIE: Nous avons analysé la sensibilité, la spécificité, la valeur prédictive et le rapport de vraisemblance des deux tests avec comme référence des résultats de biopsie rénale obtenus à HMR. RÉSULTATS: Au Québec, au cours de l'année de l'étude, 1 690 tests ont été effectués sur 1 025 patients; une faible proportion de ces patients (8 %) étaient suivis à HMR. Les patients, qu'ils aient été testés à HMR et ailleurs au Québec, présentaient des caractéristiques semblables. La validité du test n'a été caractérisée que pour les patients testés à HMR. La sensibilité et la spécificité s'établissaient respectivement à 58 % et à 100 % pour le test qualitatif, et à 71 % et 100 % pour le test quantitatif. La sensibilité nette combinée était de 42 % et la spécificité nette, de 100 %. Les valeurs prédictives nettes, positive et négative, étaient respectivement de 100 % et de 84 %, alors que le ratio net de probabilité négative était de 0,58. LIMITES: L'étude présente un possible biais de sélection puisque l'analyse détaillée n'était possible que pour la faible proportion de patients suivis à HMR. L'accent mis sur les patients sélectionnés pour une biopsie rénale, probablement en raison d'une maladie plus grave, d'une probabilité plus élevée de glomérulonéphrite ou d'un moins grand nombre de comorbidités, constitue un autre possible biais de sélection. Aucune biopsie rénale ou test d'anticorps de PLA2R sérique systématique n'a été effectué puisque l'étude est rétrospective. Enfin, il n'a pas été possible de fournir des informations détaillées sur le temps écoulé entre le traitement immunosuppresseur et les résultats du test d'anticorps anti-PLA2R. CONCLUSION: Le test d'anticorps sériques anti-PLA2R a été largement utilisé au Québec au cours de sa première année de disponibilité. Une approche en deux étapes, constituée d'un test qualitatif suivi d'un test quantitatif si le résultat est positif ou indéterminé, semble efficace pour éviter de procéder inutilement à des tests quantitatifs chez les patients négatifs et pour caractériser plus précisément les résultats indéterminés par immunofluorescence. ENREGISTREMENT DE L'ESSAI: L'essai n'a pas été enregistré puisqu'il s'agit d'une étude rétrospective.

Impact of using concomitant conventional DMARDs on adherence to biologic DMARD treatment in rheumatoid arthritis: Multi-centre, population-based cohort study.

PURPOSE: To evaluate the impact of concomitant use of conventional synthetic DMARDs (csCMARD) on adherence, switching and dose of biologic disease modifying antirheumatic drugs (bDMARD) in rheumatoid arthritis (RA) patients treated with bDMARDs. PATIENTS AND METHODS: This was a population-based cohort study conducted in five provinces of Canada (Alberta, Manitoba, Ontario, Quebec, and Saskatchewan), and one American database (IBM® MarketScan® Databases). Adult RA patients entered the study after a 3-month initiation period of bDMARDs between 1 January 2007, and 30 March 2014. Concomitant csDMARD exposure was compared to non-csDMARD exposure on the following outcomes: discontinuation of bDMARD therapy, switching of bDMARDs, and percent change in dose of bDMARD compared to initial dose. The effect of the time-varying changes in csDMARD exposure was analyzed using marginal structural models. Dose change was analyzed using linear regression. Results from each participating site were combined using likelihood ratio meta-analysis. RESULTS: The study population comprised 20,221 new users of bDMARDs: adalimumab (7609), etanercept (9809), abatacept (1024), infliximab (1779). Concomitant use of csDMARD therapy was not significantly associated with reduced discontinuation of bDMARD treatment (hazard ratio 0.90, 95% intrinsic confidence interval 0.79 to 1.02) or reduced switching of bDMARDs (hazard ratio 0.95, 95% intrinsic confidence interval 0.80 to 1.11), but was associated with a small increase in bDMARD dose compared to the mean dose over the first three months of treatment (mean percentage change in dose +0.56% mg/day, 95% intrinsic confidence interval +0.14% to +0.97%). CONCLUSION: In this large study of RA patients using bDMARDs in Canada and the United States, we found no clear evidence that patients who received concomitant csDMARD therapy were less likely to discontinue, switch or increase their dose of bDMARD.

Association of pediatric cardiac surgery-associated acute kidney injury with post-discharge healthcare utilization, mortality and kidney outcomes.

BACKGROUND: Acute kidney Injury (AKI) in children undergoing cardiac surgery (CS) is strongly associated with hospital morbidity. Post-discharge CS AKI outcomes are less clear. We evaluated associations between AKI and post-discharge (a) healthcare utilization, (b) chronic kidney disease (CKD) or hypertension and (c) mortality. METHODS: This is a retrospective two-centre cohort study of children surviving to hospital discharge after CS. Primary exposures were post-operative ≥Stage 1 AKI and ≥Stage 2 AKI defined by Kidney Disease Impoving Global Outcomes. Association of AKI with time to outcomes was determined using multivariable Cox-Proportional Hazards analysis. RESULTS: Of 350 participants included (age 3.1 (4.5) years), 180 [51.4%] developed AKI and 60 [17.1%] developed ≥Stage 2 AKI. Twenty-eight (9%) participants developed CKD or hypertension (composite outcome), and 17 (5%) died within 5 years of discharge. Post-operative ≥Stage 1 and ≥Stage 2 AKI were not associated with post-discharge hospitalizations, emergency room (ER) visits, physician visits or CKD or hypertension in adjusted analyses. A trend was observed between ≥Stage 2 AKI and mortality but was not statistically significant. In unadjusted stratified analyses, AKI was associated with post-discharge hospitalizations in children with RACHS-1 score ≥3, complex chronic disease classification and children living in urban areas. CONCLUSIONS: Post-CS AKI is not associated with post-discharge healthcare utilization, death and CKD or hypertension, though it may be associated with healthcare utilization in more complex paediatric CS children. Studies should aim to better understand post-CS healthcare utilization patterns and non-AKI risk factors for CKD, hypertension and mortality, to reduce adverse long-term outcomes after CS.

Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study).

BACKGROUND AND OBJECTIVES: There is a renewed interest in the successful use of aminoglycosides due to increasing resistance in gram-negative infections. Few studies to date have examined the pharmacokinetics (PK) of intradialytic infusions of tobramycin. This study sought to characterize the pharmacokinetic profile of intradialytically administered tobramycin in infected patients receiving chronic intermittent hemodialysis and to determine whether it is possible to achieve favorable PK targets. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: In this prospective pharmacokinetic study, a single dose (5 mg/kg) of tobramycin was administered intradialytically to 11 noncritically ill patients undergoing chronic intermittent hemodialysis. Blood samples were collected at selected time to determine tobramycin serum concentrations. The PK analysis was performed using Phoenix™ NLME. The efficacy exposure outcome for nonsevere gram-negative infections sensitive to tobramycin with a minimum inhibitory concentration ≤1 were maximum concentration (Cmax ≥ 10 mg/L) and area under the curve (AUC24 h > 30 mg⋅h/L). For toxicity, the goal was to identify plasma trough concentrations <2 mg/L. RESULTS: Tobramycin disposition was best described by a one-compartment model using a total clearance composed of the systemic clearance and a transitory hemodialysis clearance. Tobramycin mean (SD) Cmax, trough levels, and AUC24h were 13.1 (1.3) mg/L, 1.32 (0.47) mg/L, and 61 (23) mg⋅h/L, respectively. Monte Carlo simulation run with 1000 virtual patients showed that a 5 mg/kg dose of tobramycin administered intradialytically can outperformed the usual low-dose postdialysis dosing (80% meeting all targets versus <1%, respectively). CONCLUSIONS: A single high dose of tobramycin can achieve favorable PK outcome when administered using intradialytic infusions in hemodialysis patients. This practical dosing regimen may represent an effective and safer alternative to the usual dosing in the treatment of nonsevere gram-negative infections.

CONTEXTE ET OBJECTIFS: La résistance croissante des infections à Gram négatif suscite un regain d'intérêt pour l'utilisation efficace des aminoglycosides. À ce jour, peu d'études ont examiné la pharmacocinétique (PK) des infusions intradialytiques de tobramycine. La présente étude a tenté de caractériser le profil pharmacocinétique de la tobramycine administrée par infusion intradialytique chez des patients malades recevant des traitements intermittents d'hémodialyse de façon chronique. L'étude visait également à déterminer s'il est possible d'atteindre des objectifs de pharmacocinétique favorables. MÉTHODOLOGIE: Pour cette étude de pharmacocinétique prospective, une dose unique (5 mg/kg) de tobramycine a été administrée par infusion intradialytique à onze patients suivant des traitements d'hémodialyse intermittente de façon chronique ne nécessitant pas une admission aux soins intensifs. Des échantillons de sang ont été prélevés à des moments précis afin de mesurer les concentrations sériques de tobramycine. L'analyse de la PK a été effectuée à l'aide du PhoenixMC NLME. Les issues d'exposition d'efficacité avec une concentration minimale inhibitrice inférieure ou égale à 1 pour les infections à Gram négatifs non graves sensibles à la tobramycine étaient la concentration maximum (Cmax: ≥10 mg/L) et la surface sous la courbe (SSC24h: >30 mg⋅h/L). Quant à la toxicité, l'objectif était l'observation de concentrations plasmatiques inférieures à 2 mg/L. RÉSULTATS: La disponibilité de la tobramycine a été mieux décrite par un modèle à un compartiment utilisant une clairance totale composée de la clairance systémique et de la clairance transitoire de l'hémodialyse. La Cmax moyenne, la concentration minimale et la SSC24h de la tobramycine (écart-type) s'établissaient respectivement à 13,1 (1,3) mg/L, à 1,32 (0,47) mg/L et à 61 (23) mg⋅h/L. Une simulation de Monte Carlo réalisée avec 1 000 patients virtuels a montré qu'une dose unique de 5 mg/kg de tobramycine administrée par infusion intradialytique surpasse la faible dose normalement administrée après la dialyse (80 % des objectifs atteints pour la dose unique contre moins de 1 %, respectivement). CONCLUSIONS: Une dose unique élevée de tobramycine permet d'atteindre des paramètres pharmacocinétiques favorables si elle est administrée par infusion intradialytique chez les patients hémodialysés. Ce schéma posologique peut représenter une solution de remplacement efficace et plus sûre au dosage normalement administré pour le traitement des infections à Gram négatifs non graves.

Successful surgical weight loss with laparoscopic sleeve gastrectomy for morbid obesity prior to kidney transplantation.

Morbid obesity in kidney transplant (KT) candidates is associated with increased complications and graft failure. Multiple series have demonstrated rapid and significant weight loss after laparoscopic sleeve gastrectomy (LSG) in this population. Long-term and post-transplant weight evolutions are still largely unknown. A retrospective review was performed in eighty patients with end-stage kidney disease (ESKD) who underwent LSG in preparation for KT. From a median initial BMI of 43.7 kg/m2 , the median change at 1-year was -10.0 kg/m2 . Successful surgical weight loss (achieving a BMI < 35 kg/m2 or an excess body weight loss >50%) was attained in 76.3% and was associated with male gender, predialysis status, lower obesity class and lack of coronary artery disease. Thirty-one patients subsequently received a KT with a median delay of 16.7 months. Weight regain (increase in BMI of 5 kg/m2 postnadir) and recurrent obesity (weight regain + BMI > 35) remain a concern, occurring post-KT in 35.7% and 17.9%, respectively. Early LSG should be considered for morbidly obese patients with ESKD for improved weight loss outcomes. Early KT after LSG does not appear to affect short-term surgical weight loss. Candidates with a BMI of up to 45 kg/m2 can have a reasonable expectation to achieve the limit within 1 year.

Arteriovenous Fistula Creation and Estimated Glomerular Filtration Rate Decline in Advanced CKD: A Matched Cohort Study.

Background: Kidney failure is associated with a high burden of morbidity and mortality. Previous studies have raised the possibility that arteriovenous fistula (AVF) creation may attenuate eGFR decline. This study aimed to compare eGFR decline in predialysis patients with an AVF, matched to patients oriented toward peritoneal dialysis (PD). Methods: Predialysis patients with an AVF and those oriented toward PD were retrospectively matched using a propensity score. Time zero was defined as the "AVF creation date" for the AVF group and the "date when eGFR was closest to the matched patient's eGFR at AVF creation" for the PD group. Crude and predicted eGFR decline in AVF and PD groups were compared before and after time zero using mixed-effect linear regressions. Results: In total, 61 pairs were matched. Crude annual eGFR decline before AVF creation/time zero was -4.1 ml/min per m2 per year in the AVF group versus -5.3 ml/min per m2 per year in the PD group (P=0.75) and after time zero, -2.5 ml/min per m2 per year in the AVF group versus -4.5 ml/min per m2 per year in the PD group (P=0.02). The predicted annual decline decreased from -5.1 ml/min per m2 per year in the AVF group before AVF creation to -2.8 ml/min per m2 per year after (P<0.01), whereas there was no difference in the PD group (-5.5 versus -5.1 ml/min per m2 per year respectively, P=0.41). Conclusions: In this matched study, AVF creation was associated with a deceleration of kidney function decline compared with a control PD-oriented group. Prospective studies are needed to assess the potential mechanisms between vascular access creation and eGFR slope attenuation.

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.

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.

Use of Desmopressin Prior to Kidney Biopsy in Patients With High Bleeding Risk.

INTRODUCTION: To prevent bleeding after native kidney biopsy (NKB), nephrologists often prescribe desmopressin, especially for patients with reduced estimated glomerular filtration rate (eGFR) at risk of uremia-related platelet dysfunction. However, only 1 randomized study has suggested a beneficial effect for desmopressin in patients with eGFR ≥60 ml/min per 1.73 m2. This retrospective cohort study aimed to evaluate desmopressin effect on postbiopsy bleeding in all patients, regardless of eGFR and other comorbidities. METHODS: In this retrospective cohort study, all adult patients who underwent an NKB from April 1, 2013, to April 30, 2018, in a tertiary hospital were identified. The association between desmopressin use and bleeding complications, including hemoglobin fall, transfusion, hematoma, symptomatic hematoma, urgent radiologic study, and hypotension, was analyzed using multivariable logistic regression models. RESULTS: A total of 413 native kidney biopsies were studied, 79% of which were performed after receiving desmopressin. Patients receiving desmopressin had worse chronic kidney disease (eGFR 28 vs. 45 ml/min per 1.73 m2; P < 0.001) and were more often hospitalized (48% vs. 32%; P = 0.009). Despite higher bleeding risk, patients using desmopressin had a similar likelihood of symptomatic hematomas (odds ratio [OR], 0.39; 95% confidence interval [CI], 0.13-1.14) and a lower need for urgent radiologic studies (OR, 0.33; 95% CI, 0.11-0.98). CONCLUSION: Patients at higher risk of bleeding using desmopressin before kidney biopsy had bleeding complications similar to those not using desmopressin. These results highlight potential important clinical and financial benefits of desmopressin use before kidney biopsy.

Osteoporotic fracture rates in chronic hemodialysis and effect of heparin exposure: a retrospective cohort study.

BACKGROUND: Patients receiving chronic hemodialysis treatments are at a higher risk of fracture compared to the general population. While the use of heparin during dialysis is crucial to avoid thrombosis of the extracorporeal circuit, the association of unfractionated heparin (UFH) and the risk of osteoporotic fracture has been shown for many years. However, this association was not as clear for low-molecular-weight heparin (LMWH) and the few collected data originated from studies among pregnant women. Our aim was to measure osteoporotic fracture rate among hemodialysis patients and to evaluate the association of LMWH compared to UFH in hemodialysis. METHODS: A retrospective cohort study was conducted on data extracted from the RAMQ and Med-Echo databases from January 2007 to March 2013 with patients chronically hemodialyzed in 21 participating centers. Incidence rates for each fracture sites were measured per 1000 patient-year (p-y) and their 95% confidence intervals (CI). Osteoporotic fracture risk for a first event with LMWH compared to UFH was estimated using a cox proportional hazard model using demographics, comorbidities and drug use as covariates. RESULTS: 4796 patients undergoing chronic hemodialysis were identified. The incidence rate for all fracture sites was 22.7 /1000 p-y (95% CI: 19.6-26.1) and 12.8 /1000 p-y (95% CI: 10.5-15.4) for hip and femur fractures. We found a similar risk of osteoporotic fracture for LMWH compared to UFH (adjusted HR = 1.01; 95%CI: 0.72-1.42). Age and malignancy increased the risk of fracture while cerebrovascular disease decreased the risk of fracture. CONCLUSIONS: Compared to UFH, LMWH did not change the risk of osteoporotic fracture when used for the extracorporeal circuit anticoagulation in chronic hemodialysis.

Review of real-world evidence studies in type 2 diabetes mellitus: Lack of good practices.

OBJECTIVES: Unlike randomized controlled trials, lack of methodological rigor is a concern about real-world evidence (RWE) studies. The objective of this study was to characterize methodological practices of studies collecting pharmacoeconomic data in a real-world setting for the management of type 2 diabetes mellitus (T2DM). METHODS: A systematic literature review was performed using the PICO framework: population consisted of T2DM patients, interventions and comparators were any intervention for T2DM care or absence of intervention, and outcomes were resource utilization, productivity loss or utility. Only RWE studies were included, defined as studies that were not clinical trials and that collected de novo data (no retrospective analysis). RESULTS: The literature search identified 1,158 potentially relevant studies, among which sixty were included in the literature review. Many studies showed a lack of transparency by not mentioning the source for outcome and exposure measurement, source for patient selection, number of study sites, recruitment duration, sample size calculation, sampling method, missing data, approbation by an ethics committee, obtaining patient's consent, conflicts of interest, and funding. A significant proportion of studies had poor quality scores and was at high risk of bias. CONCLUSIONS: RWE from T2DM studies lacks transparency and credibility. There is a need for good procedural practices that can increase confidence in RWE studies. Standardized methodologies specifically adapted for RWE studies collecting pharmacoeconomic data for the management of T2DM could help future reimbursement decision making in this major public health problem.

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.