Drug stewardship in chronic kidney disease to achieve effective and safe medication use.

People living with chronic kidney disease (CKD) often experience multimorbidity and require polypharmacy. Kidney dysfunction can also alter the pharmacokinetics and pharmacodynamics of medications, which can modify their risks and benefits; the extent of these changes is not well understood for all situations or medications. The principle of drug stewardship is aimed at maximizing medication safety and effectiveness in a population of patients through a variety of processes including medication reconciliation, medication selection, dose adjustment, monitoring for effectiveness and safety, and discontinuation (deprescribing) when no longer necessary. This Review is aimed at serving as a resource for achieving optimal drug stewardship for patients with CKD. We describe special considerations for medication use during pregnancy and lactation, during acute illness and in patients with cancer, as well as guidance for the responsible use of over-the-counter drugs, herbal remedies, supplements and sick-day rules. We also highlight inequities in medication access worldwide and suggest policies to improve access to quality and essential medications for all persons with CKD. Further strategies to promote drug stewardship include patient education and engagement, the use of digital health tools, shared decision-making and collaboration within interdisciplinary teams. Throughout, we position the person with CKD at the centre of all drug stewardship efforts.

Implementation of a One-Day Living Kidney Donor Assessment Clinic to Improve the Efficiency of the Living Kidney Donor Evaluation: Program Report.

Purpose of program: A key barrier to becoming a living kidney donor is an inefficient evaluation process, requiring more than 30 tests (eg, laboratory and diagnostic tests), questionnaires, and specialist consultations. Donor candidates make several trips to hospitals and clinics, and often spend months waiting for appointments and test results. The median evaluation time for a donor candidate in Ontario, Canada, is nearly 1 year. Longer wait times are associated with poorer outcomes for the kidney transplant recipient and higher health care costs. A shorter, more efficient donor evaluation process may help more patients with kidney failure receive a transplant, including a pre-emptive kidney transplant (ie, avoiding the need for dialysis). In this report, we describe the development of a quality improvement intervention to improve the efficiency, effectiveness, and patient-centeredness of the donor candidate evaluation process. We developed a One-Day Living Kidney Donor Assessment Clinic, a condensed clinic where interested donor candidates complete all testing and consultations within 1 day. Sources of information: The One-Day Living Kidney Donor Assessment Clinic was developed after performing a comprehensive review of the literature, receiving feedback from patients who have successfully donated, and meetings with transplant program leadership from St. Joseph's Healthcare Hamilton. A multistakeholder team was formed that included health care staff from nephrology, transplant surgery, radiology, cardiology, social work, nuclear medicine, and patients with the prior lived experience of kidney donation. In the planning stages, the team met regularly to determine the objectives of the clinic, criteria for participation, clinic schedule, patient flow, and clinic metrics. Methods: Donor candidates entered the One-Day Clinic if they completed initial laboratory testing and agreed to an expedited process. If additional testing was required, it was completed on a different day. Donor candidates were reviewed by the nephrologist, transplant surgeon, and donor coordinator approximately 2 weeks after the clinic for final approval. The team continues to meet regularly to review donor feedback, discuss challenges, and brainstorm solutions. Key findings: The One-Day Clinic was implemented in March 2019, and has now been running for 4 years, making iterative improvements through continuous patient and provider feedback. To date, we have evaluated more than 150 donor candidates in this clinic. Feedback from donors has been uniformly positive (98% of donors stated they were very satisfied with the clinic), with most noting that the clinic was efficient and minimally impacted work and family obligations. Hospital leadership, including the health care professionals from each participating department, continue to show support and collaborate to create a seamless experience for donor candidates attending the One-Day Clinic. Limitations: Clinic spots are limited, meaning some interested donor candidates may not be able to enter a One-Day Clinic the same month they come forward. Implications: This patient-centered quality improvement intervention is designed to improve the efficiency and experience of the living kidney donor evaluation, result in better outcomes for kidney transplant recipients, and potentially increase living donation. Our next step is to conduct a formal evaluation of the clinic, measuring qualitative feedback from health care professionals working in the clinic and donor candidates attending the clinic, and measuring key process and outcome measures in donor candidates who completed the one-day assessment compared with those who underwent the usual care assessment. This program evaluation will provide reliable, regionally relevant evidence that will inform transplant centers across the country as they consider incorporating a similar one-day assessment model.

Objectifs du programme: Devenir donneur de rein vivant est difficile, le principal obstacle étant le processus d'évaluation inefficace auquel les candidats doivent se soumettre. Ce processus comporte plus de 30 examens (p. ex. tests de laboratoire et tests diagnostiques), questionnaires et consultations avec des spécialistes. Les candidats donneurs font plusieurs visites dans les hôpitaux et cliniques, et passent souvent plusieurs mois à attendre des rendez-vous et des résultats de tests. En Ontario (Canada), le délai médian pour l'évaluation d'un candidat au don est de près d'un an. Les temps d'attente plus longs sont associés à de moins bons résultats pour les receveurs d'une greffe rénale, ainsi qu'à des coûts de soins de santé plus élevés. Un processus d'évaluation plus court et plus efficace des donneurs potentiels permettrait à un plus grand nombre de patients atteints d'insuffisance rénale de recevoir une greffe, y compris une greffe préventive (c.-à-d. permettant d'éviter la dialyse). Cet article décrit une intervention d'amélioration de la qualité visant à augmenter l'efficience, l'efficacité et la personnalisation du processus d'évaluation des candidats au don. Nous avons développé une clinique d'un jour pour l'évaluation des donneurs de reins vivants (One-Day Living Kidney Donor Assessment Clinic), soit une clinique condensée où les candidats passent tous les tests et consultent un spécialiste dans la même journée. Sources de l'information: La clinique d'un jour pour l'évaluation des donneurs de reins vivants a été développée à la suite d'un examen approfondi de la littérature, de la consultation des commentaires de patients ayant donné avec succès et de rencontres avec les dirigeants du programme de transplantation du St Joseph's Healthcare d'Hamilton. Une équipe multipartite a été formée; celle-ci réunit du personnel soignant en néphrologie, chirurgie de transplantation, radiologie, cardiologie, travail social et médecine nucléaire, ainsi que des patients ayant une expérience vécue du don de rein. L'équipe s'est réunie régulièrement pendant les étapes de planification pour déterminer les objectifs, les paramètres et le calendrier de la clinique, ainsi que les critères de participation et le flux de patients. Méthodologie: Les donneurs potentiels qui avaient complété les tests de laboratoire initiaux et qui acceptaient de se soumettre à un processus accéléré ont été évalués à la clinique d'un jour. Si des tests supplémentaires étaient nécessaires, ceux-ci étaient effectués un autre jour. Les candidats ont été rencontrés par le néphrologue, le chirurgien de transplantation et le coordonnateur des dons environ deux semaines après leur visite à la clinique pour l'approbation finale. L'équipe multipartite continue de se réunir régulièrement pour examiner les commentaires des donneurs, discuter des défis et trouver des solutions. Principaux résultats: La clinique d'un jour, mise sur pied en mars 2019, est en activité depuis quatre ans et permet des améliorations itératives grâce à la rétroaction continue des patients et des soignants. À ce jour, plus de 150 candidats au don ont été évalués à la clinique. Les commentaires des donneurs sont quasi unanimement positifs (98 % des candidats ont déclaré être très satisfaits de la clinique), la plupart soulignant l'efficacité de la clinique et les conséquences minimes du processus sur les obligations professionnelles et familiales. La direction de l'hôpital, tout comme les professionnels de la santé des services participants, continue d'appuyer la clinique d'un jour et de collaborer à la création d'une expérience fluide pour les donneurs potentiels qui la fréquentent. Limites: Les places à la clinique sont limitées; ainsi, certains candidats au don d'un rein vivant pourraient ne pas pouvoir être admis dans le mois où ils se présentent à la clinique. Conclusion: Cette intervention d'amélioration de la qualité axée sur les patients est conçue pour augmenter l'efficacité du processus d'évaluation et bonifier l'expérience des donneurs de rein vivants. Elle vise également à améliorer les résultats des receveurs d'une greffe rénale et, potentiellement, augmenter le don vivant. La prochaine étape sera une évaluation formelle de la clinique, c'est-à-dire la mesure de la rétroaction qualitative des professionnels de la santé qui y travaillent et des candidats au don qui la fréquentent, et l'analyse des processus clés et des résultats des candidats évalués à la clinique d'un jour par rapport à ceux qui suivent le processus d'évaluation habituel. Cette évaluation du programme fournira des données probantes fiables et propres à la région qui pourront informer les centres de transplantation de tout le pays qui envisagent d'intégrer un processus d'évaluation similaire.

Association of Clonal Hematopoiesis of Indeterminate Potential with Worse Kidney Function and Anemia in Two Cohorts of Patients with Advanced Chronic Kidney Disease.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown. METHODS: We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR<60 ml/min per 1.73m2. We also assessed kidney function, hematologic, and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over the following 5-year period. RESULTS: At baseline, CHIP was detected in 18 of 87 (21%) and 25 of 85 (29%) cohort participants. Participants with CHIP were at higher risk of kidney failure, as predicted by the Kidney Failure Risk Equation (KFRE), compared with those without CHIP. Individuals with CHIP manifested a 2.2-fold increased risk of a 50% decline in eGFR or ESKD over 5 years of follow-up (hazard ratio 2.2; 95% confidence interval, 1.2 to 3.8) in a Cox proportional hazard model adjusted for age, sex, and baseline eGFR. The addition of CHIP to 2-year and 5-year calibrated KFRE risk models improved ESKD predictions. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume versus those without CHIP. CONCLUSIONS: In this exploratory analysis of individuals with preexisting CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.

Modifiable Lifestyle Factors for Primary Prevention of CKD: A Systematic Review and Meta-Analysis.

BACKGROUND: Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. METHODS: To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR<60 ml/min per 1.73 m2). Secondary outcomes included other CKD surrogate measures (RRT, GFR decline, and albuminuria). RESULTS: We identified 104 studies of 2,755,719 participants with generally a low risk of bias. Higher dietary potassium intake associated with significantly decreased odds of CKD (odds ratio [OR], 0.78; 95% confidence interval [95% CI], 0.65 to 0.94), as did higher vegetable intake (OR, 0.79; 95% CI, 0.70 to 0.90); higher salt intake associated with significantly increased odds of CKD (OR, 1.21; 95% CI, 1.06 to 1.38). Being physically active versus sedentary associated with lower odds of CKD (OR, 0.82; 95% CI, 0.69 to 0.98). Current and former smokers had significantly increased odds of CKD compared with never smokers (OR, 1.18; 95% CI, 1.10 to 1.27). Compared with no consumption, moderate consumption of alcohol associated with reduced risk of CKD (relative risk, 0.86; 95% CI, 0.79 to 0.93). These associations were consistent, but evidence was predominantly of low to very low certainty. Results for secondary outcomes were consistent with the primary finding. CONCLUSIONS: These findings identify modifiable lifestyle factors that consistently predict the incidence of CKD in the community and may inform both public health recommendations and clinical practice.

Canadian Society of Nephrology Commentary on the Kidney Disease Improving Global Outcomes 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

PURPOSE OF REVIEW: (1) To provide commentary on the 2017 update to the Kidney Disease Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD); (2) to apply the evidence-based guideline update for implementation within the Canadian health care system; (3) to provide comment on the care of children with chronic kidney disease (CKD); and (4) to identify research priorities for Canadian patients. SOURCES OF INFORMATION: The KDIGO 2017 Clinical Practice Guideline Update for the Diagnosis, Evaluation, Prevention, and Treatment of CKD-MBD. METHODS: The commentary committee co-chairs selected potential members based on their knowledge of the Canadian kidney community, aiming for wide representation from relevant disciplines, academic and community centers, and different geographical regions. KEY FINDINGS: We agreed with many of the recommendations in the clinical practice guideline on the diagnosis, evaluation, prevention, and treatment of CKD-MBD. However, based on the uncommon occurrence of abnormalities in calcium and phosphate and the low likelihood of severe abnormalities in parathyroid hormone (PTH), we recommend against screening and monitoring levels of calcium, phosphate, PTH, and alkaline phosphatase in adults with CKD G3. We suggest and recommend monitoring these parameters in adults with CKD G4 and G5, respectively. In children, we agree that monitoring for CKD-MBD should begin in CKD G2, but we suggest measuring ionized calcium, rather than total calcium or calcium adjusted for albumin. With regard to vitamin D, we suggest against routine screening for vitamin D deficiency in adults with CKD G3-G5 and G1T-G5T and suggest following population health recommendations for adequate vitamin D intake. We recommend that the measurement and management of bone mineral density (BMD) be according to general population guidelines in CKD G3 and G3T, but we suggest against routine BMD testing in CKD G4-G5, CKD G4T-5T, and in children with CKD. Based on insufficient data, we also recommend against routine bone biopsy in clinical practice for adults with CKD or CKD-T, or in children with CKD, although we consider it an important research tool. LIMITATIONS: The committee relied on the evidence summaries produced by KDIGO. The CSN committee did not replicate or update the systematic reviews.

JUSTIFICATION: (1) Commenter les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC); (2) appliquer les lignes directrices actualisées et fondées sur les données probantes en vue de leur mise en œuvre dans le système de soins de santé canadien; (3) commenter les soins prodigués aux enfants atteints d'insuffisance rénale chronique (IRC) et (4) définir les priorités de recherche des patients Canadiens. SOURCES: Les recommandations du KDIGO 2017 (Kidney Disease Improving Global Outcomes) sur les bonnes pratiques cliniques pour le diagnostic, l'évaluation et le traitement des troubles du métabolisme minéral osseux associés aux maladies rénales chroniques (TMO-MRC). MÉTHODOLOGIE: Les coprésidents du comité ont sélectionné les membres potentiels sur la base de leur connaissance du secteur de la santé rénale au Canada, tout en visant une bonne représentation de toutes les disciplines concernées, des centres universitaires et communautaires et des différentes régions géographiques. PRINCIPAUX COMMENTAIRES: Nous approuvons un grand nombre des recommandations du KDIGO. Cependant, compte tenu de la rareté des anomalies du calcium et du phosphate et de la faible probabilité d'anomalies graves de la PTH (hormone parathyroïde), nous déconseillons le dépistage et la surveillance des taux de calcium, de phosphate, de PTH et de phosphatase alcaline chez les adultes atteints d'IRC de stade G3. Nous suggérons de mesurer ces paramètres chez les adultes de stade G4 et nous le recommandons pour les patients de stade G5. Chez les enfants, nous appuyons la recommandation de commencer la surveillance des TMO-MRC dès le stade G2, mais nous suggérons de mesurer le calcium ionisé plutôt que les taux de calcium total ou de calcium corrigé en fonction de l'albumine. En ce qui concerne la vitamine D, nous déconseillons le dépistage de routine des carences chez les adultes atteints d'IRC de stade G3 à G5 et G1T à G5T; nous suggérons plutôt de suivre les recommandations visant la population générale pour un apport adéquat en vitamine D. Nous recommandons que la mesure et la prise en charge de la densité minérale osseuse (DMO) se fassent en suivant les recommandations pour la population générale chez les adultes atteints d'IRC de stade G3 et G3T, mais nous déconseillons les tests de DMO de routine chez les adultes de stades G4-G5 et G4T-G5T, de même que chez les enfants atteints d'IRC. En raison de données insuffisantes, nous déconseillons également la pratique systématique d'une biopsie osseuse chez les adultes atteints d'IRC ou d'IRC-TMO, ainsi que chez les enfants atteints d'IRC, bien que nous la considérions comme un important outil de recherche. LIMITES: Le comité s'est appuyé sur le résumé des preuves rédigé par le KDIGO. Le comité de la SCN n'a pas reproduit ou mis à jour les revues systématiques.

Population-Attributable Fractions of Modifiable Lifestyle Factors for CKD and Mortality in Individuals With Type 2 Diabetes: A Cohort Study.

BACKGROUND: We quantified the impact of lifestyle and dietary modifications on chronic kidney disease (CKD) by estimating population-attributable fractions (PAFs). STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: Middle-aged adults with type 2 diabetes but without severe albuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET; n=6,916). FACTORS: Modifiable lifestyle/dietary risk factors, such as physical activity, size of social network, alcohol intake, tobacco use, diet, and intake of various food items. OUTCOMES: The primary outcome was CKD, ascertained as moderate to severe albuminuria or ≥5% annual decline in estimated glomerular filtration rate (eGFR) after 5.5 years. The competing risk for death was considered. PAF was defined as the proportional reduction in CKD or mortality (within 5.5 years) that would occur if exposure to a risk factor was changed to an optimal level. RESULTS: At baseline, median urinary albumin-creatinine ratio and eGFR were 6.6 (IQR, 2.9-25.0) mg/mmol and 71.5 (IQR, 58.1-85.9) mL/min/1.73m(2), respectively. After 5.5 years, 704 (32.5%) participants developed albuminuria, 1,194 (55.2%) had a ≥5% annual eGFR decline, 267 (12.3%) had both, and 1,022 (14.8%) had died. Being physically active every day has PAFs of 5.1% (95% CI, 0.5%-9.6%) for CKD and 12.3% (95% CI, 4.9%-19.1%) for death. Among food items, increasing vegetable intake would have the largest impact on population health. Considering diet, weight, physical activity, tobacco use, and size of social network, exposure to less than optimum levels gives PAFs of 13.3% (95% CI, 5.5%-20.9%) for CKD and 37.5% (95% CI, 27.8%-46.7%) for death. For the 17.8 million middle-aged Americans with diabetes, improving 1 of these lifestyle behaviors to the optimal range could reduce the incidence or progression of CKD after 5.5 years by 274,000 and the number of deaths within 5.5 years by 405,000. LIMITATIONS: Ascertainment of changes in kidney measures does not precisely match the definitions for incidence or progression of CKD. CONCLUSIONS: Healthy lifestyle and diet are associated with less CKD and mortality and may have a substantial impact on population kidney health.

Urate lowering therapy to improve renal outcomes in patients with chronic kidney disease: systematic review and meta-analysis.

BACKGROUND: Hyperuricemia may contribute to renal injury. We do not know whether use of treatments that lower urate reduce the progression of chronic kidney disease (CKD) and cardiovascular disease. We performed a systematic review and meta-analysis of randomized controlled trials to assess the benefits and risks of treatments that lower urate in patients with stages 3-5 CKD. METHODS: We searched MEDLINE, EMBASE, CENTRAL, Web of Science and trial registers for randomized controlled trials (RCTs) without language restriction. Two authors independently screened articles, assessed risk of bias and extracted data. Data obtained included serum uric acid, serum creatinine or other estimates of glomerular filtration rate, incidence of end-stage renal disease (ESRD), systolic and diastolic blood pressure, proteinuria, cardiovascular disease and adverse events. RESULTS: From the 5497 citations screened, 19 RCTs enrolling 992 participants met our inclusion criteria. Given significant heterogeneity in duration of follow-up and study comparators, only trials greater than 3 months comparing allopurinol and inactive control were meta-analyzed using random effects models. Pooled estimate for eGFR was in favour of allopurinol with a mean difference (MD) of 3.2 ml/min/1.73 m(2), 95% CI 0.16-6.2 ml/min/1.73 m(2), p = 0.039 and this was consistent with results for serum creatinine. Statistically significant reductions in serum uric acid, systolic and diastolic blood pressure were found, favouring allopurinol. There were insufficient data on adverse events, incidence of ESRD and cardiovascular disease for analysis. CONCLUSIONS: Adequately powered RCTs are needed to establish whether treatments that lower urate have beneficial renal and cardiovascular effects.

Biomarkers of inflammation, fibrosis, cardiac stretch and injury predict death but not renal replacement therapy at 1 year in a Canadian chronic kidney disease cohort.

BACKGROUND: Newer biomarkers, reflective of biological processes, such as inflammation and fibrosis, cardiac stretch or damage and vascular health may be useful in understanding clinical events in chronic kidney disease (CKD). We assessed whether these newer biomarkers, alone or as a panel, improve risk prediction for renal replacement therapy or death, over and above conventional clinical, demographic and laboratory variables. METHODS: We conducted a prospective observational Canadian cohort study in 2544 CKD patients with estimated glomerular filtration rate (eGFR) of 15-45 mL/min/1.73 m(2), under nephrology care, in urban and rural centers. We measured traditional clinical and laboratory risk factors, as well as newer biomarkers: cystatin C, high sensitivity c-reactive protein (hsCRP), interleukin 6 (IL6), transforming growth factor ß1 (TGFß1), fibroblast growth factor 23 (FGF23), N-terminal probrain natriuretic peptide (NT-proBNP), troponin I and asymmetric dimethylarginine (ADMA). Key outcomes were renal replacement therapy (RRT, dialysis or transplantation) and death, during the first year follow-up after enrollment: a time point important for clinical decision-making for patients and providers. RESULTS: Newer biomarkers do not improve the prediction of RRT, when added to conventional risk factors such as eGFR, urine albumin to creatinine ratio, hemoglobin, phosphate and albumin. However, in predicting death within 1 year, cystatin C, NT-proBNP, hsCRP and FGF23 values significantly improved model discrimination and reclassification: c statistic increased by absolute 4.3% and Net Reclassification Improvement for categories of low, intermediate and high risk at 11.2%. CONCLUSIONS: Our findings suggest that the addition of newer biomarkers may be useful in predicting death in patients with established CKD within a 1-year timeframe. This information may be useful in informing prognosis and redirect resources to serve patients at higher risk to improve outcomes and sustainability of the nephrology care system.

Cohort profile: Canadian study of prediction of death, dialysis and interim cardiovascular events (CanPREDDICT).

BACKGROUND: The Canadian Study of Prediction of Death, Dialysis and Interim Cardiovascular Events (CanPREDDICT) is a large, prospective, pan-Canadian, cohort study designed to improve our understanding of determinants of renal and cardiovascular (CV) disease progression in patients with chronic kidney disease (CKD). The primary objective is to clarify the associations between traditional and newer biomarkers in the prediction of specific renal and CV events, and of death in patients with CKD managed by nephrologists. This information could then be used to better understand biological variation in outcomes, to develop clinical prediction models and to inform enrolment into interventional studies which may lead to novel treatments. METHODS/DESIGNS: Commenced in 2008, 2546 patients have been enrolled with eGFR between 15 and 45 ml/min 1.73m2 from a representative sample in 25 rural, urban, academic and non academic centres across Canada. Patients are to be followed for an initial 3 years at 6 monthly intervals, and subsequently annually. Traditional biomarkers include eGFR, urine albumin creatinine ratio (uACR), hemoglobin (Hgb), phosphate and albumin. Newer biomarkers of interest were selected on the basis of biological relevance to important processes, commercial availability and assay reproducibility. They include asymmetric dimethylarginine (ADMA), N-terminal pro-brain natriuretic peptide (NT-pro-BNP), troponin I, cystatin C, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL6) and transforming growth factor beta 1 (TGFß1). Blood and urine samples are collected at baseline, and every 6 monthly, and stored at -80°C. Outcomes of interest include renal replacement therapy, CV events and death, the latter two of which are adjudicated by an independent panel. DISCUSSION: The baseline distribution of newer biomarkers does not appear to track to markers of kidney function and therefore may offer some discriminatory value in predicting future outcomes. The granularity of the data presented at baseline may foster additional questions.The value of the cohort as a unique resource to understand outcomes of patients under the care of nephrologists in a single payer healthcare system cannot be overstated. Systematic collection of demographic, laboratory and event data should lead to new insights. The mean age of the cohort was 68 years, 90% were Caucasian, 62% were male, and 48% had diabetes. Forty percent of the cohort had eGFR between 30-45 mL/min/1.73m², 22% had eGFR values below 20 mL/min/1.73m²; 61% had uACR < 30. Serum albumin, hemoglobin, calcium and 25-hydroxyvitamin D (25(OH)D) levels were progressively lower in the lower eGFR strata, while parathyroid hormone (PTH) levels increased. Cystatin C, ADMA, NT-proBNP, hsCRP, troponin I and IL-6 were significantly higher in the lower GFR strata, whereas 25(OH)D and TGFß1 values were lower at lower GFR. These distributions of each of the newer biomarkers by eGFR and uACR categories were variable.

Mercury-associated nephrotic syndrome: a case report and systematic review of the literature.

Kidney injury from mercury is known to cause dose-related tubular dysfunction and idiosyncratic nephrotic syndrome according to various case reports. Motivated by a patient with subacute-onset nephrotic syndrome, histologic features of secondary focal segmental glomerulosclerosis, and concurrent mercury toxicity, we conducted a systematic review to explore renal histologic changes in patients with toxic mercury exposures and nephrotic syndrome. Data were extracted from a patient's clinical record. MEDLINE/Ovid was searched from 1950 to November 2010 using a prespecified search strategy. Two nephrology textbooks and the UpToDate online database also were searched. Inclusion criteria were studies of humans with nephrotic syndrome, nephrotic-range proteinuria, or kidney biopsy results reported. There were no exclusion criteria. We identified 27 other reports of 42 patients with nephrotic syndrome or nephrotic-range proteinuria. Of the 26 individuals, including our patient, who underwent kidney biopsy, histology showed glomerular disease in 21. Of these 20 biopsies, 4 showed minimal change disease and 15 showed membranous glomerulonephritis. Mercury exposure can lead to various glomerular lesions; we emphasize the importance of a careful occupational and dietary history in elucidating a cause for the undetermined nephrotic syndrome.

Waist-to-Hip Ratio, Cardiovascular Outcomes, and Death in Peritoneal Dialysis Patients.

Objectives. The primary objective of this study was to determine the relationship between waist-to-hip ratio (WHR), cardiovascular (CV) events, and mortality in peritoneal dialysis (PD) patients. A secondary objective was to investigate the association between abdominal obesity and systemic inflammatory markers. Methods. This is a prospective study of 22 prevalent PD patients. WHR was measured at baseline. C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Main outcomes were first CV event and death from all causes. Survival analysis was used to examine the relationship between anthropomorphic measures and clinical outcomes. Results. Mean follow-up period was 3.1 years. In Kaplan-Meier analysis, survival was lower in those with higher WHR (P = .002). In Cox regression, WHR independently predicted mortality and first CV event after adjustment for known ischemic heart disease (hazard ratio [HR] 1.17, confidence interval [CI] 1.05-1.30 for death; HR 1.13, CI 1.01-1.26 for CV event). WHR correlated with serum TNF-α (r = 0.45; P = .05). Conclusion. The results of this study suggest WHR may be a risk factor for increased CV events and mortality in PD patients. Abdominal obesity is also associated with inflammatory markers. Larger studies are warranted to confirm these findings.

Progression of internal carotid artery stenosis in patients with peripheral arterial occlusive disease.

OBJECTIVES: To study the risk factors and rate of progression of asymptomatic carotid stenosis in patients with peripheral arterial occlusive disease. METHODS: Between July 1999 and September 2003, we studied consecutive patients referred to a vascular laboratory for peripheral arterial occlusive disease who had not experienced neurologic symptoms within the previous 3 years. Carotid duplex ultrasound scan (DUS) was performed at baseline and at 6 to 12-month intervals. The internal carotid artery peak systolic velocity (PSV) was used to determine severity of carotid stenosis. Multilevel linear regression modeling (MLM) was used to identify the rate of progression and risk factors for progression. RESULTS: For 614 consecutive patients, median follow-up by DUS was 30 (2-42) months. Patients were 73 +/- 10-years-old, and 62% were men. Mean ankle-brachial index (ABI) was 0.79 +/- 0.24. The baseline prevalence of carotid stenosis >or=50% (PSV >or=125 cm/second) was 22%. During follow-up, ipsilateral amaurosis fugax, transient ischemic attacks, and strokes occurred in 3 (0.4%), 7 (1.1%), and 5 (0.8%) patients, respectively. Overall, there was little progression in carotid stenosis. Female gender, low ABI, and smoking were risk factors for progression of disease regardless of severity of carotid stenosis. Patients with >or=50% carotid stenosis were at greatest risk of progression if they continued smoking and were diabetic. Prediction models for progression of carotid stenosis given a baseline PSV and patient risk factors were constructed. CONCLUSION: There are few neurologic events in patients with asymptomatic carotid stenosis. The average rate of progression of stenosis over 2 years is not significant but greater in diabetic patients with baseline stenosis >50% who continue smoking. Rescreening by serial DUS should be limited to high-grade stenosis and follow-up performed at an interval of 1-2 years.

Open versus endovascular repair of abdominal aortic aneurysm: a survey of Canadian vascular surgeons.

OBJECTIVE: The aim of this survey was to determine Canadian vascular surgeons' experience with elective endovascular aortic repair (EVAR) and traditional open repair and their interest in participating in an expertise- based randomized controlled trial (RCT) as opposed to a conventional RCT comparing these 2 procedures. METHODS: A single-page questionnaire was developed and sent by fax, email or post to all vascular surgeons in Canada. Nonresponders were recontacted on 2 additional occasions to improve the response rate. The questionnaire had 2 sections. The first inquired about current and past practice patterns, including experience in both open and endovascular techniques. The second investigated the surgeons' belief in the value of open as opposed to endovascular repair and the value of expertise-based RCT methodology; it also canvassed their interest in participating in a future trial. Definitions of expertise in open and endovascular repair were drawn from the published literature. Criteria to determine the feasibility of conducting an expertise-based RCT were established a priori. RESULTS: The questionnaire was sent to 259 surgeons who appeared in multiple vascular surgery databases, and the overall response rate was 56% (95% confidence interval [CI] 50%-62%). The mean career experience was 406 cases (standard deviation [SD] 359) for conventional open abdominal aortic aneurysm (AAA) repair and 24 cases (SD 48) for endovascular repair. Of the responding surgeons, 51% (95% CI 41%-60%) ranked conventional open repair as "probably superior." Respondents were equally interested in participating in an RCT using either expertise-based methodology (54%, 95% CI 44%-63%) or conventional design (51%, 95% CI 41%-60%). CONCLUSION: Uncertainty exists among vascular surgeons in Canada as to the role of endovascular surgery in the repair of AAA. A national RCT comparing open with endovascular repair in the elective setting is potentially feasible with either expertise-based or conventional design. Increases in the number of surgeons who are willing to participate and have expertise in EVAR, in addition to high recruitment rates among eligible patients, will be necessary to make such a trial feasible in Canada.

Endovascular repair of ruptured abdominal aortic aneurysms: a systematic review and meta-analysis.

OBJECTIVES: The perioperative mortality for people with ruptured abdominal aortic aneurysms (RAAA) has not changed for two decades. Of patients who survive long enough to undergo open repair for ruptured aneurysms, half die (48%; 95% confidence interval [CI] 46 to 50). Randomized trials have shown that endovascular aneurysm repair (EVAR) for nonruptured abdominal aortic aneurysms decreases perioperative mortality compared with open repair. EVAR may similarly benefit patients with RAAA. We aimed to summarize studies of patients undergoing EVAR for ruptured aneurysms. METHODS: Two reviewers searched Medline and EMBASE databases from 1994 to July 2006, Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effectiveness, the Cochrane Central Register of Controlled Trials, Best Evidence 1994 to 2006, reference lists, clinical trial registries, and conference proceedings; we also contacted authors. All published and unpublished studies in which a group of people with ruptured aneurysms, assessed objectively by imaging, was treated with EVAR (REVAR) were eligible. We used the generic inverse variance function of the REVMAN software to pool results for death in hospital. Sensitivity analyses, using prespecified subgroups, explored heterogeneity between studies. RESULTS: Pooled mortality in 18 observational studies describing 436 people who underwent REVAR was 21% (95% CI 13 to 29); however, 90% of the heterogeneity between studies was not explained by chance alone. Surgical volume explained substantial heterogeneity. According to study-specific criteria, 47% (95% CI 39 to 55) of people with ruptured aneurysms were potentially eligible for REVAR. CONCLUSIONS: Mortality in people who underwent REVAR is lower than that in historical reports of unselected people undergoing open repair. Further investigation is needed to determine whether the difference in mortality is attributable to patient selection alone or to this new approach to treatment.

Relationship between glomerular filtration rate and the prevalence of metabolic abnormalities: results from the Third National Health and Nutrition Examination Survey (NHANES III).

BACKGROUND AND AIMS: National Kidney Foundation Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines recommend that all people with a glomerular filtration rate (GFR) <60 ml/min/1.73 m(2) undergo evaluation for anaemia and metabolic bone disease. We aim to report the prevalence of metabolic complications in adults with low GFR. METHODS: Analysis of 15,802 non-institutionalised adult participants in the Third National Health and Nutrition Survey (NHANES III), a cross-sectional population-based survey conducted in the United States between 1986 and 1994. Renal function was estimated according the modification of diet in renal disease equation 7 (MDRD GFR), the Cockcroft-Gault formula and by the serum creatinine cut-off points described by Couchoud and colleagues. Haemoglobin <110 g/l occurred in 42.2% [95% confidence interval (CI) 28.3-56.0] of patients with MDRD GFR <30 ml/min/1.73 m(2) [stage 3 chronic kidney disease (CKD)] and 3.5% (95% CI 2.4-4.7) of patients with MDRD GFR between 30 and 60 ml/min/1.73 m(2) (stage 4-5 CKD). Corresponding prevalences for calcium <2.15 mmol/l were 8.2 (95% CI 1.6-14.8) and 3.4 (95% CI 1.7-5.2); for phosphate >1.6 mmol/l, 15.1 (95% CI 5.0-25.3) and 0.3 (95% CI 0-0.6); and for bicarbonate <23 mmol/l, 32.7 (95% CI 19.6-45.9) and 5.7 (95% CI 3.3-8.2), respectively. Similar results were obtained when patients were categorised by the Cockcroft-Gault formula or Couchoud's cut-off points. CONCLUSIONS: The prevalence of complications in stage 3 CKD is low. These data do not support the recommendation for routine screening for metabolic complications of renal insufficiency in adults seen in primary care settings whose GFR exceeds 30 ml/min/1.73 m(2).

Outcomes of acute coronary syndrome in a large Canadian cohort: impact of chronic renal insufficiency, cardiac interventions, and anemia.

BACKGROUND: Chronic renal insufficiency (CRI) has been identified as an important risk factor for cardiac events. Studies in the United States reported decreased survival and decreased use of surgical and medical interventions after myocardial infarction in patients with CRI. METHODS: We studied the impact of renal function on health outcomes in a Canadian cohort of consecutive patients admitted with acute coronary syndrome (ACS) between October 1997 and October 1999. The study design is an observational cohort of 5,549 adult patients who survived to discharge with a discharge diagnosis of ACS. Renal function is classified into 4 levels: (1) normal, glomerular filtration rate (GFR) greater than 80 mL/min/1.73 m2 (>1.33 mL/s); (2) mild CRI, GFR of 60 to 80 mL/min/1.73 m2 (1.00 to 1.33 mL/s); (3) moderate CRI, GFR of 30 to 59 mL/min/1.73 m2 (0.50 to 0.98 mL/s); and (4) severe CRI, GFR less than 30 mL/min/1.73 m2 (<0.50 mL/s). The primary outcome is death. RESULTS: Advanced and moderate CRI independently predicted death (hazard ratio, 1.06; 95% confidence interval [CI], 1.01 to 1.12; and hazard ratio, 1.23; 95% CI, 1.18 to 1.29). Severe anemia (hemoglobin level < 9.0 g/dL [<90 g/L]) also was an independent risk factor for death (hazard ratio, 1.38; 95% CI, 1.18 to 1.61). Use of beta-blockers (hazard ratio, 0.91; 95% CI, 0.86 to 0.97), acetylsalicylic acid (hazard ratio, 0.90; 95% CI, 0.84 to 0.97), lipid-lowering therapy (hazard ratio, 0.84; 95% CI, 0.78 to 0.89), and medical thrombolysis (hazard ratio, 0.89; 95% CI, 0.81 to 0.97) were associated with reduced risk for death. Medical interventions with beta-blockers, acetylsalicylic acid, lipid-lowering therapy, and thrombolysis and surgical intervention were significantly less likely to be used in patients with CRI. CONCLUSION: Despite universal access to health care, Canadian patients with CRI are more likely to die after a cardiac event and less likely to receive important interventions.