Focused Jurisdictional Scan of Glomerulonephritis Medication Access in Canada: A Program Report.

Purpose of Program: Glomerulonephritis (GN) is a group of rare kidney diseases that is increasingly being managed with higher cost immunosuppressive (IS) agents in Canada. Ontario Health's Ontario Renal Network (ORN) oversees the management and delivery of GN services in the province. Stakeholder surveys previously conducted by ORN identified that both clinicians and patients do not perceive access to GN medications as comprehensive or timely. The program conducted a focused jurisdictional scan among 7 provinces to inform ORN initiatives to improve access to GN medications. Specifically, the program examined clinician experience with GN access, public drug coverage criteria, and timelines for public coverage for select IS agents (ie, tacrolimus, cyclosporine, mycophenolate mofetil [MMF], mycophenolate sodium, rituximab, and eculizumab) used to manage GN in adults who live in Canada. Methods: For the selected IS agents, a focused jurisdictional scan on medication access was conducted by ORN in 2018 and updated in July 2022. Information was obtained by searching the gray literature and/or credible online sources for public funding policies and eligibility criteria. Findings were supplemented by personal communications with provincial drug programs and consulting GN clinical experts from 7 provinces (ie, Alberta, British Columbia, Saskatchewan, Manitoba, Ontario, Nova Scotia, and Quebec). Key Findings: Clinicians from different provinces prescribe IS agents similarly for GN indications, despite distinctions in public drug funding policies. While patients can obtain public funding for many IS agents, for GN, most provinces rely on case-by-case review processes. In addition, provinces can vary in their funding criteria and which IS agents are listed on the public formulary. For IS agents that require prior authorization or case-by-case review, timelines vary by province with decisions taking a few days to weeks. British Columbia, with a GN-specific drug formulary, had the most integrated and efficient system for patients and prescribers. Limitations: This scan primarily relied on publicly available information for drug coverage criteria and clinician experience with access in their province. Since this scan was conducted, public drug coverage criteria and/or application processes may have changed. Implications: While patients in most provinces have similar needs and nephrologists similar prescribing patterns, gaps still exist for publicly funded GN medications. Interprovincial differences in the drugs funded, funding criteria, and application process may affect timely and equitable access to GN medications across Canada. Given the rarity of GN, a pan-Canadian funding approach may be warranted to improve the current state.

Objectif du programme: Les glomérulonéphrites (GN) sont un groupe de néphropathies rares qui sont de plus en plus fréquemment traitées avec les agents immunosuppresseurs (IS) coûteux au Canada. Le Réseau rénal de l'Ontario (ORN­Ontario Renal Network) de Santé Ontario supervise la gestion et la prestation des services liés à la GN dans cette province. Des enquêtes menées précédemment par l'ORN auprès des parties prenantes ont révélé que tant les cliniciens que les patients ne percevaient pas l'accès aux médicaments pour traiter la GN comme complet ou opportun. Le programme a mené une analyse ciblée des territoires de compétences dans sept provinces afin d'orienter les initiatives de l'ORN ayant pour objectif d'améliorer l'accès aux médicaments pour traiter la GN. Plus précisément, le programme a examiné l'expérience des cliniciens en matière d'accès aux médicaments pour traiter la GN, les critères d'admissibilité au régime public d'assurance-médicaments et les délais de couverture publique de certains agents IS (p. ex., tacrolimus, cyclosporine, mycophénolate mofétil [MMF], mycophénolate sodique, Rituximab, éculizumab) utilisés pour traiter la GN chez les adultes canadiens. Méthodologie: Une analyse ciblée des territoires de compétences quant à l'accès aux médicaments a été réalisée par l'ORN en 2018 et mise à jour en juillet 2022. L'information quant aux politiques de financement public et aux critères d'admissibilité a été obtenue en effectuant une recherche dans la littérature grise et des sources crédibles en ligne. Les résultats ont été complétés par des communications directes avec les régimes provinciaux d'assurance-médicaments et des experts cliniques de la GN de sept provinces (Alberta, Colombie-Britannique, Saskatchewan, Manitoba, Ontario, Nouvelle-Écosse et Québec). Principaux résultats: Les cliniciens des différentes provinces prescrivent des agents IS de façon similaire pour les indications liées à la GN, malgré des distinctions dans les politiques publiques de financement des médicaments. Bien que les patients bénéficient d'une couverture publique pour de nombreux agents IS, pour le traitement de la GN, la plupart des provinces s'appuient sur des processus d'examen au cas par cas. De plus, il peut exister des différences entre les provinces en ce qui concerne les critères de financement et les agents IS qui figurent sur leur formulaire public. Dans le cas des agents IS nécessitant une autorisation au préalable ou un examen au cas par cas, les délais varient d'une province à l'autre; les décisions pouvant prendre de quelques jours à quelques semaines. La Colombie-Britannique, qui dispose d'un formulaire de médicaments pour traiter spécifiquement la GN, présente le système le plus intégré et le plus efficace pour les patients et les prescripteurs. Limites: Cette analyse s'est principalement appuyée sur des renseignements accessibles au public en ce qui concerne les critères de couverture des médicaments et l'expérience des cliniciens en matière d'accès dans leur province. Les critères de couverture des médicaments publics et les processus de demande pourraient avoir changé depuis que cette analyse a été effectuée. Conclusion: Bien que les patients de la plupart des provinces aient des besoins similaires et que les néphrologues aient des habitudes de prescription similaires, des lacunes subsistent en ce qui concerne le financement public des médicaments pour traiter la GN. Les différences interprovinciales entre les médicaments financés, les critères de financement et le processus de demande peuvent avoir une incidence sur l'accès opportun et équitable aux médicaments pour traiter la GN à travers le Canada. Étant donné la rareté de cette maladie, une approche de financement pancanadienne pourrait être justifiée afin d'améliorer l'état actuel.

The Canadian Glomerulonephritis Registry (CGNR) and Translational Research Initiative: Rationale and Clinical Research Protocol.

Background: Glomerulonephritis (GN) is a leading cause of kidney failure and accounts for 20% of incident cases of end-stage kidney disease (ESKD) in Canada annually. Reversal of kidney injury and prevention of progression to kidney failure is possible; however, limited knowledge of underlying disease mechanisms and lack of noninvasive biomarkers and therapeutic targets are major barriers to successful therapeutic intervention. Multicenter approaches that link longitudinal clinical and outcomes data with serial biologic specimen collection would help bridge this gap. Objective: To establish a national, patient-centered, multidimensional web-based clinical database and federated virtual biobank to conduct human-based molecular and clinical research in GN in Canada. Design: Multicenter, prospective observational registry, starting in 2019. Setting: Nine participating Canadian tertiary care centers. Patients: Adult patients with a histopathologic pattern of injury consistent with IgA nephropathy, focal and segmental glomerulosclerosis, minimal change disease, membranous nephropathy, C3 glomerulopathy, and membranoproliferative GN recruited within 24 months of biopsy. Measurements: Initial visits include detailed clinical, histopathological, and laboratory data collection, blood, urine, and tonsil swab biospecimen collection, and a self-administered quality of life questionnaire. Follow-up clinical and laboratory data collection, biospecimen collection, and questionnaires are obtained every 6 months thereafter. Methods: Patients receive care as defined by their physician, with study visits scheduled every 6 months. Patients are followed until death, dialysis, transplantation, or withdrawal from the study. Key outcomes include a composite of ESKD or a 40% decline in estimated glomerular filtration rate (eGFR) at 2 years, rate of kidney function decline, and remission of proteinuria. Clinical and molecular phenotypical data will be analyzed by GN subtype to identify disease predictors and discover therapeutic targets. Limitations: Given the relative rarity of individual glomerular diseases, one of the major challenges is patient recruitment. Initial registry studies may be underpowered to detect small differences in clinically meaningful outcomes such as ESKD or death due to small sample sizes and short duration of follow-up in the initial 2-year phase of the study. Conclusions: The Canadian Glomerulonephritis Registry (CGNR) supports national collaborative efforts to study glomerular disease patients and their outcomes. Trial registration: NCT03460054.

Contexte: Les glomérulonéphrites (GN) sont des causes importantes d'insuffisance rénale; elles représentent 20 % des cas incidents d'insuffisance rénale terminale (IRT) au Canada chaque année. Inverser la néphropathie et prévenir la progression vers l'insuffisance rénale est possible, mais deux obstacles majeurs freinent la réussite de l'intervention thérapeutique: une compréhension limitée des mécanismes sous-jacents de la maladie, de même que l'absence de biomarqueurs non invasifs et de cibles thérapeutiques. Les approches multicentriques reliant les données cliniques longitudinales et les résultats de santé à la collecte d'échantillons biologiques en série permettraient de combler cette lacune. Objectif: Créer une base de données cliniques nationale en ligne, multidimensionnelle et axée sur le patient, de même qu'une biobanque virtuelle fédérée pour permettre de mener des recherches moléculaires et cliniques humaines sur les GN au Canada. Type d'étude: Registre d'observation prospectif multicentrique débuté en 2019. Cadre: Neuf centres de soins tertiaires canadiens. Sujets: Des patients adultes recrutés dans les 24 mois suivant la biopsie et présentant un profil histopathologique de lésion compatible avec une néphropathie à IgA, une hyalinose segmentaire et focale, une maladie à changement minime, une glomérulonéphrite extra-membraneuse, une glomérulopathie à C3 et une glomérulonéphrite membranoproliférative. Mesures: La première visite comporte une collecte détaillée des données cliniques, histopathologiques et de laboratoire, la collecte d'échantillons biologiques (sang, urine et écouvillonnage des amygdales), ainsi qu'un questionnaire autoadministré sur la qualité de vie. Pour le suivi, la collecte des données cliniques et de laboratoire, la collecte des échantillons biologiques et les questionnaires s'effectuent tous les six mois. Méthodologie: Les patients reçoivent des soins comme établi par leur médecin, et les visites d'étude sont programmées tous les six mois. Les patients sont suivis jusqu'au décès ou jusqu'à la dialyse, à la transplantation ou au retrait de l'étude. Un critère de jugement combiné (IRT, ou diminution de 40 % du débit de filtration glomérulaire estimé après deux ans), ainsi que le taux de déclin de la fonction rénale et la rémission de la protéinurie sont les principaux critères de jugement. Les données phénotypiques cliniques et moléculaires seront analysées par sous-types de GN afin d'identifier les prédicteurs de la maladie et de découvrir de nouvelles cibles thérapeutiques. Limites: Le recrutement des sujets demeure un des principaux défis puisque les maladies glomérulaires prises individuellement sont relativement rares. La faible taille des échantillons et la courte durée du suivi pendant les deux ans de la phase initiale de l'étude pourraient faire en sorte que les études initiales issues du registre ne soient pas assez puissantes pour détecter de légères différences dans les résultats cliniquement significatifs comme l'IRT ou le décès. Conclusion: Le Canadian Glomerulonephritis Registry (CGNR) appuie les efforts de collaboration nationale visant à étudier les patients atteints de maladies glomérulaires et leur évolution clinique. Enregistrement de l'essai: NCT03460054.

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

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

Trends in Biopsy-Based Diagnosis of Kidney Disease: A Population Study.

BACKGROUND: Kidney biopsy is considered the gold standard for diagnosis of renal disease. It is increasingly performed in cases of diagnostic uncertainty, including in patients with coexistent diabetes and hypertension, for which a presumptive clinical diagnosis can be made. Little is known about the incidence and distribution of biopsy-proven kidney diseases. Changes in the distribution of biopsy diagnoses over time may have significant implications for resource allocation and future research. OBJECTIVE: We studied the relative frequency of kidney diseases in Southern Alberta over the past 30 years, to determine whether the population-standardized annual biopsy rate and incidence of selected diagnostic categories have changed. We hypothesized an increasing incidence of renal biopsies and a growing proportion of nonglomerular diseases (eg, tubulointerstitial disorders) likely due to evolving indications for biopsy. Given the rise in obesity, diabetes, and aging population with chronic kidney disease (CKD), we anticipated a rise in nephroangiosclerosis and diabetic nephropathy over time. DESIGN: Retrospective population-based cohort study using the Biobank for the Molecular Classification of Kidney Disease (BMCKD). SETTING: Southern Alberta, Canada. PATIENTS: All patients who underwent renal biopsy between 1985 and 2015 in our database. MEASUREMENTS: We used descriptive and quantitative analysis to characterize demographics and biopsy-based diagnoses. METHODS: We conducted a retrospective population-based cohort study to analyze all consecutive patients who underwent at least one kidney biopsy over a 30-year period in Southern Alberta (1985-2015). We considered the first adequate biopsy. We described the annual standardized incidence of biopsy-proven kidney diseases over time and summarized associated patient characteristics. We assumed a Poisson distribution for biopsy counts and used provincial demographic information to standardize rates. RESULTS: During the study period, 6434 people (58% male; mean age: 47.9 years) underwent a kidney biopsy. The population-standardized annual biopsy rate increased from 10.8 biopsies per 100 000 person-years in the first 5 years of the study (1985-1989) to 18.2 biopsies per 100 000 person-years in the last 5 years (2010-2014). The mean age at the time of biopsy increased from 42.5 years (1985-1989) to 51.4 years (2010-2014). Glomerular diseases remained the most prevalent histopathological group, with a growing representation of diabetic kidney disease from 3.69% to 16.18%, and a relative decrease in the proportion of other glomerular diseases from 72.32% to 62.92% of glomerular diagnoses. Tubulointerstitial diseases increased from 5.87% to 7.36% of total diagnoses. LIMITATIONS: Classification schemes have changed over time, so recently recognized conditions may have been misclassified in earlier data. There was a changing group of pathologists and nephrologists over this period. Variations in interpretation and application of biopsy indications by physician may influence recorded prevalence of certain diagnoses. We do not yet have complete information on indications or patient outcomes linked to the database. CONCLUSIONS: In Southern Alberta, kidney biopsy is being utilized more frequently and in older people. Diabetic nephropathy is increasingly diagnosed, which may reflect either or both changes in the prevalence of causative factors and local biopsy practices.

CONTEXTE: La biopsie rénale est considérée comme la méthode par excellence pour diagnostiquer des néphropathies. Elle est de plus en plus pratiquée dans les cas de diagnostics incertains, notamment chez les patients souffrant également de diabète et d'hypertension, et pour lesquels un diagnostic clinique présomptif peut être posé. On en sait encore peu sur l'incidence et la distribution statistique des néphropathies avérées par biopsie. Des variations dans la distribution statistique des diagnostics par biopsie au fil du temps pourraient avoir des répercussions significatives sur l'affectation des ressources et sur les recherches futures. OBJECTIFS: Nous voulions savoir si le taux de biopsies annuel normalisé selon la population et l'incidence des catégories de diagnostic sélectionnées avaient varié. Nous avions émis l'hypothèse d'une incidence croissante des biopsies rénales et d'une proportion croissante d'affections non glomérulaires (notamment les troubles tubulo-interstitiels) susceptibles d'être attribuables à une demande croissante pour des biopsies. Compte tenu de l'augmentation des cas d'obésité et de diabète, et du vieillissement de la population atteinte de néphropathies chroniques, nous avions anticipé une augmentation des cas de néphroangiosclérose et de néphropathie diabétique au fil du temps. TYPE D'ÉTUDE: Une étude de cohorte rétrospective sur des données provenant de la biobanque BMCKD (Biobank for the Molecular Classification of Kidney Disease). CADRE DE L'ÉTUDE: Le sud de la province de l'Alberta, au Canada. SUJETS: Tous les patients répertoriés dans notre base de données en raison d'une biopsie rénale subie entre 1985 et 2015. MESURES: Nous avons employé l'analyse descriptive et quantitative pour caractériser les données démographiques des patients et le diagnostic posé à la suite d'une biopsie. MÉTHODOLOGIE: Nous avons mené une étude de cohorte rétrospective pour examiner tous les patients consécutifs ayant subi au moins une biopsie rénale sur une période de 30 ans (1985 à 2015) dans le sud de l'Alberta. Nous avons tenu compte de la première biopsie satisfaisante. Nous avons mesuré l'incidence annuelle normalisée des néphropathies avérées par biopsie au fil du temps et nous avons résumé les caractéristiques des patients qui y étaient associés. Une distribution de Poisson a permis d'établir le nombre de biopsies, alors que les données démographiques provinciales ont servi à la normalisation des taux. RÉSULTATS: Au cours de la période étudiée, 6 434 personnes (âge moyen : 47,9 ans), dont 58 % étaient des hommes, ont subi une biopsie rénale. Entre les cinq premières années (1985-1989) et les cinq dernières années de l'étude (2010-2014), le taux de biopsies annuel normalisé selon la population est passé de 10,8 par 100 000 années-personnes à 12,8 par 100 000 années-personnes; l'âge moyen au moment de subir la biopsie est passé de 42,5 ans à 51,4 ans. Le groupe histopathologique des atteintes glomérulaires est demeuré le plus prévalent des diagnostics glomérulaires avec une représentation croissante des cas de néphropathies diabétiques (de 3,69 % à 16,18 %) et une diminution relative de la proportion des autres atteintes glomérulaires (de 72,32 % à 62,92 %). Quant aux affections tubulo-insterstitielles, elles sont passées de 5,87 % à 7,36 % de tous les diagnostics posés au cours de la période étudiée. LIMITES: Plusieurs variables ont évolué au cours de la période étudiée : les équipes de pathologistes et de néphrologues ont changé, et les systèmes de classification ont été modifiés; de sorte que certaines affections diagnostiquées récemment pourraient avoir été mal classées dans les données antérieures. De plus, des différences dans l'interprétation et l'application des biopsies de la part des médecins pourraient avoir influencé la prévalence consignée pour certains diagnostics. Nous ne disposons toujours pas d'informations complètes sur les indications et les résultats des patients liés à la base de données. CONCLUSION: Dans le sud de l'Alberta, la biopsie rénale est de plus pratiquée, et ce, chez des patients plus âgés. La néphropathie diabétique est de plus en plus diagnostiquée; ce qui pourrait indiquer des variations dans la prévalence des facteurs en cause et/ou des changements dans les pratiques locales quant à l'usage de la biopsie.

A matched case-control study to assess the association between non-steroidal anti-inflammatory drug use and thrombotic microangiopathy.

Several case reports suggest that non-steroidal anti-inflammatory drug (NSAID) use is associated with development of thrombotic microangiopathy (TMA). We conducted a matched population-based case-control study using linked administrative healthcare data in Ontario, Canada to assess the relationship between TMA hospitalization and recent exposure to prescription NSAIDs versus acetaminophen (acetaminophen was chosen as the referent drug because it has no known association with TMA). Cases and controls were drawn from a source population of adults who filled a prescription for either NSAIDs or acetaminophen between 1991 and 2015 (restricted to adults with prescription drug benefits [n = 3.6 million]). We identified 44 eligible cases with a hospital admission for incident TMA and a recent prescription for NSAIDs or acetaminophen. We successfully matched 38 cases (1:4) to 152 controls without TMA on demographics, risk factors for TMA, and indications for NSAID use. Cases and controls were similar with respect to age (71 years) and sex (63% women); however, on average, cases had more comorbidities than controls (12 vs. 14; p<0.05) and more primary care visits in the year before the index date (19 vs. 12; p<0.05). Cases were significantly less likely than controls to have received a recent prescription for NSAIDs (19/38 [50%] vs. 115/152 [76%], respectively; adjusted odds ratio 0.37, 95% confidence interval: 0.16 to 0.84). Results were similar in several sensitivity analyses. Overall, the results of this study do not support a harmful association between NSAID use and the development of TMA.

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

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

Plasmapheresis for the treatment of kidney diseases.

The purpose of this review is to examine the evidence supporting the application of plasma exchange in renal disease. Our review focuses on the following 6 most common renal indications for plasma exchange based on 2014 registry data from the Canadian Apheresis Group: (i) thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome; (ii) renal transplantation, (iii) anti-neutrophil cytoplasm antibodies-associated vasculitis, (iv) cryoglobulinemia, (v) focal segmental glomerulosclerosis, and (vi) Goodpasture syndrome. The rarity of these diseases and their rapid, often fatal course mean that randomized controlled studies of plasma exchange are rarely conducted. Although evidence from an adequately powered randomized controlled trial supports the use of plasma exchange to treat thrombotic thrombocytopenic purpura, the use of plasma exchange to treat other renal diseases is only supported by observational and mechanistic studies. Larger well-designed trials are needed to clarify the potential role of plasma exchange in renal disease. Growing international collaboration will improve the quality of future studies in this area.

Long-term outcomes of thrombotic microangiopathy treated with plasma exchange: A systematic review.

With the adoption of plasma exchange as standard treatment for thrombotic microangiopathy (TMA), more patients are surviving and long-term outcomes have greater relevance. We conducted a systematic review to synthesize and evaluate the quality of evidence on long-term outcomes of TMA among adults treated with plasma exchange and to identify factors that may be associated with a worse long-term prognosis. We searched databases from 1980 to 2013 for eligible articles published in any language. We included studies that reported outcomes in at least ten adults with a history of TMA treated with plasma exchange and at least 6 months of follow-up. We abstracted data in duplicate and assessed the methodological quality of each study using an assessment tool developed based on recommended validity criteria. We screened 6672 articles, reviewed 213, and included 34 studies totaling 1182 patients (study median [range], 24 [10-118]). The mean (or median) follow-up ranged from 6 months to 13 years. The cumulative incidence of relapse and mortality was highly variable and ranged from 3 to 84 and 0 to 61%, respectively. The incidence of other outcomes across 10 studies also varied (outcomes included hypertension, kidney disease, preeclampsia, stroke, seizure, severe cognitive impairment, and depression); in three other studies, long-term neurocognitive function and health-related quality of life were significantly lower than in the general population. Patients who survive an episode of TMA may be susceptible to long-term vascular complications, but the magnitude of this risk and how to mitigate it remains unclear. Am. J. Hematol. 91:623-630, 2016. © 2016 Wiley Periodicals, Inc.

Characteristics and Outcomes of AKI Treated with Dialysis during Pregnancy and the Postpartum Period.

Acute kidney injury (AKI) is a rare complication of pregnancy, but may be associated with significant morbidity and mortality in young and often otherwise healthy women. We conducted a retrospective population-based cohort study of all consecutive pregnancies over a 15-year period (1997-2011) in Ontario, Canada, and describe the incidence and outcomes of AKI treated with dialysis during pregnancy or within 12 weeks of delivery. Of 1,918,789 pregnancies, 188 were complicated by AKI treated with dialysis (incidence: 1 per 10,000 [95% confidence interval, 0.8 to 1.1]). Only 21 of 188 (11.2%) women had record of a preexisting medical condition; however, 130 (69.2%) women experienced a major pregnancy-related complication, including preeclampsia, thrombotic microangiopathy, heart failure, sepsis, or postpartum hemorrhage. Eight women died (4.3% versus 0.01% in the general population), and seven (3.9%) women remained dialysis dependent 4 months after delivery. Low birth weight (<2500 g), small for gestational age, or preterm birth (<37 weeks' gestation) were more common in pregnancies in which dialysis was initiated (35.6% versus 14.0%; relative risk, 3.40; 95% confidence interval, 2.52 to 4.58). There were no stillbirths and fewer than five neonatal deaths (<2.7%) in affected pregnancies compared with 0.1% and 0.8%, respectively, in the general population. In conclusion, AKI treated with dialysis during pregnancy is rare and typically occurs in healthy women who acquire a major pregnancy-related medical condition such as preeclampsia. Many affected women and their babies have good short-term outcomes.

High-performance information search filters for CKD content in PubMed, Ovid MEDLINE, and EMBASE.

BACKGROUND: Finding relevant articles in large bibliographic databases such as PubMed, Ovid MEDLINE, and EMBASE to inform care and future research is challenging. Articles relevant to chronic kidney disease (CKD) are particularly difficult to find because they are often published under different terminology and are found across a wide range of journal types. STUDY DESIGN: We used computer automation within a diagnostic test assessment framework to develop and validate information search filters to identify CKD articles in large bibliographic databases. SETTING & PARTICIPANTS: 22,992 full-text articles in PubMed, Ovid MEDLINE, or EMBASE. INDEX TEST: 1,374,148 unique search filters. REFERENCE TEST: We established the reference standard of article relevance to CKD by manual review of all full-text articles using prespecified criteria to determine whether each article contained CKD content or not. We then assessed filter performance by calculating sensitivity, specificity, and positive predictive value for the retrieval of CKD articles. Filters with high sensitivity and specificity for the identification of CKD articles in the development phase (two-thirds of the sample) were then retested in the validation phase (remaining one-third of the sample). RESULTS: We developed and validated high-performance CKD search filters for each bibliographic database. Filters optimized for sensitivity reached at least 99% sensitivity, and filters optimized for specificity reached at least 97% specificity. The filters were complex; for example, one PubMed filter included more than 89 terms used in combination, including "chronic kidney disease," "renal insufficiency," and "renal fibrosis." In proof-of-concept searches, physicians found more articles relevant to the topic of CKD with the use of these filters. LIMITATIONS: As knowledge of the pathogenesis of CKD grows and definitions change, these filters will need to be updated to incorporate new terminology used to index relevant articles. CONCLUSIONS: PubMed, Ovid MEDLINE, and EMBASE can be filtered reliably for articles relevant to CKD. These high-performance information filters are now available online and can be used to better identify CKD content in large bibliographic databases.

Gestational hypertension and preeclampsia in living kidney donors.

BACKGROUND: Young women wishing to become living kidney donors frequently ask whether nephrectomy will affect their future pregnancies. METHODS: We conducted a retrospective cohort study of living kidney donors involving 85 women (131 pregnancies after cohort entry) who were matched in a 1:6 ratio with 510 healthy nondonors from the general population (788 pregnancies after cohort entry). Kidney donations occurred between 1992 and 2009 in Ontario, Canada, with follow-up through linked health care databases until March 2013. Donors and nondonors were matched with respect to age, year of cohort entry, residency (urban or rural), income, number of pregnancies before cohort entry, and the time to the first pregnancy after cohort entry. The primary outcome was a hospital diagnosis of gestational hypertension or preeclampsia. Secondary outcomes were each component of the primary outcome examined separately and other maternal and fetal outcomes. RESULTS: Gestational hypertension or preeclampsia was more common among living kidney donors than among nondonors (occurring in 15 of 131 pregnancies [11%] vs. 38 of 788 pregnancies [5%]; odds ratio for donors, 2.4; 95% confidence interval, 1.2 to 5.0; P=0.01). Each component of the primary outcome was also more common among donors (odds ratio, 2.5 for gestational hypertension and 2.4 for preeclampsia). There were no significant differences between donors and nondonors with respect to rates of preterm birth (8% and 7%, respectively) or low birth weight (6% and 4%, respectively). There were no reports of maternal death, stillbirth, or neonatal death among the donors. Most women had uncomplicated pregnancies after donation. CONCLUSIONS: Gestational hypertension or preeclampsia was more likely to be diagnosed in kidney donors than in matched nondonors with similar indicators of baseline health. (Funded by the Canadian Institutes of Health Research and others.).

Adherence to prescribing recommendations made on a provincial formulary.

Guidance regarding appropriate and cost-effective use of prescription drugs is published in the Ontario Drug Benefit Formulary in the form of "therapeutic notes." We conducted a cross-sectional study of all residents of Ontario aged 66 and older who received a new prescription for one of two drugs, aliskiren or sitagliptin, between December 1, 2008 and March 31, 2012 to determine how frequently such guidance is followed. Approximately half of initial prescriptions for aliskiren and sitagliptin were prescribed in a manner that did not conform to the therapeutic note recommendations (51.4% and 49.3%, respectively). Given this high rate of non-conformance, policy makers may wish to use other mechanisms to influence prescriber behaviour to improve the quality and efficiency of healthcare.

Plasma exchange for kidney disease: what is the best evidence?

Therapeutic plasma exchange (TPE) has been used as adjunctive therapy for various kidney diseases dating back to the 1970s. In many cases, support for TPE was on mechanistic grounds given the potential to remove unwanted large molecular-weight substances such as autoantibodies, immune complexes, myeloma light chains, and cryoglobulins. More recently, growing evidence from randomized controlled trials, meta-analyses, and prospective studies has provided insights into more rational use of this therapy. This report describes the role of TPE for the 6 most common kidney indications in the 2013 Canadian Apheresis Group (CAG) registry and the evidence that underpins current recommendations and practice. These kidney indications include thrombotic microangiopathy, antiglomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated vasculitis, cryoglobulinemia, recurrence of focal and segmental glomerulosclerosis in the kidney allograft, and kidney transplantation.

High-performance information search filters for acute kidney injury content in PubMed, Ovid Medline and Embase.

BACKGROUND: We frequently fail to identify articles relevant to the subject of acute kidney injury (AKI) when searching the large bibliographic databases such as PubMed, Ovid Medline or Embase. To address this issue, we used computer automation to create information search filters to better identify articles relevant to AKI in these databases. METHODS: We first manually reviewed a sample of 22 992 full-text articles and used prespecified criteria to determine whether each article contained AKI content or not. In the development phase (two-thirds of the sample), we developed and tested the performance of >1.3-million unique filters. Filters with high sensitivity and high specificity for the identification of AKI articles were then retested in the validation phase (remaining third of the sample). RESULTS: We succeeded in developing and validating high-performance AKI search filters for each bibliographic database with sensitivities and specificities in excess of 90%. Filters optimized for sensitivity reached at least 97.2% sensitivity, and filters optimized for specificity reached at least 99.5% specificity. The filters were complex; for example one PubMed filter included >140 terms used in combination, including 'acute kidney injury', 'tubular necrosis', 'azotemia' and 'ischemic injury'. In proof-of-concept searches, physicians found more articles relevant to topics in AKI with the use of the filters. CONCLUSIONS: PubMed, Ovid Medline and Embase can be filtered for articles relevant to AKI in a reliable manner. These high-performance information filters are now available online and can be used to better identify AKI content in large bibliographic databases.

Glomerular disease search filters for Pubmed, Ovid Medline, and Embase: a development and validation study.

BACKGROUND: Tools to enhance physician searches of Medline and other bibliographic databases have potential to improve the application of new knowledge in patient care. This is particularly true for articles about glomerular disease, which are published across multiple disciplines and are often difficult to track down. Our objective was to develop and test search filters for PubMed, Ovid Medline, and Embase that allow physicians to search within a subset of the database to retrieve articles relevant to glomerular disease. METHODS: We used a diagnostic test assessment framework with development and validation phases. We read a total of 22,992 full text articles for relevance and assigned them to the development or validation set to define the reference standard. We then used combinations of search terms to develop 997,298 unique glomerular disease filters. Outcome measures for each filter included sensitivity, specificity, precision, and accuracy. We selected optimal sensitive and specific search filters for each database and applied them to the validation set to test performance. RESULTS: High performance filters achieved at least 93.8% sensitivity and specificity in the development set. Filters optimized for sensitivity reached at least 96.7% sensitivity and filters optimized for specificity reached at least 98.4% specificity. Performance of these filters was consistent in the validation set and similar among all three databases. CONCLUSIONS: PubMed, Ovid Medline, and Embase can be filtered for articles relevant to glomerular disease in a reliable manner. These filters can now be used to facilitate physician searching.

Myocardial siderosis due to hemochromatosis in an individual with hypertrophic cardiomyopathy.

A patient with hypertrophic cardiomyopathy (HCM) and transfusion-dependent sideroblastic anemia, who presented with decompensated heart failure, is described. The present case demonstrates the usefulness of cardiac magnetic resonance imaging as a noninvasive imaging modality to assess the etiology of new systolic dysfunction in the setting of HCM. Cardiac magnetic resonance imaging is able to differentiate between the dilated 'burned-out' phase of HCM and a concomitant dilated cardiomyopathy secondary to myocarditis or hemosiderosis.