Prescribing patterns and medications costs in patients on maintenance hemodialysis and peritoneal dialysis.

BACKGROUND AND HYPOTHESIS: Polypharmacy is a significant clinical issue for patients on dialysis but has been incompletely studied. We investigated the prevalence and costs of polypharmacy in a population-based cohort of participants treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: We studied adults aged ≥ 20 years in Alberta, Canada receiving maintenance HD or PD as of March 31, 2019. We characterized participants as users of 0-29 drug categories of interest and those aged ≥ 65 as users/non-users of potentially inappropriate medications (PIM). We calculated the number of drug categories, daily pill burden, total annual cost, and annual cost per participant, and compared this to an age- and sex-matched cohort from the general Alberta population. RESULTS: Among 2 248 participants (mean age 63 years; 39% female) on HD (n = 1 781) or PD (n = 467), the median number of prescribed drug categories was 6 [interquartile range (IQR) 4, 8]; median daily pill burden was 8.0 (IQR 4.6, 12.6) pills/day, with 5% prescribed ≥ 21.7 pills/day, and 16.5% prescribed ≥ 15 pills/day. Twelve % were prescribed at least one drug that is contraindicated in kidney failure. The median annual per participant cost was ${\$}$3,831, totaling approximately ${\$}$11.6 million annually for all participants. When restricting to the 1 063 participants aged ≥ 65, the median number of PIM categories was 2 (IQR 1, 2), with a median PIM pill burden of 1.2 pills/day (IQR 0.5, 2.4). Compared to PD participants, HD participants had similar daily pill burden, higher use of PIM, and higher annual per participant cost. Pill burden and associated costs for participants on dialysis were more than 3-fold and 10-fold higher, respectively, compared to the matched participants from the general population. CONCLUSION: Participants on dialysis have markedly higher use of prescription medications and associated costs than the general population. Effective methods to de-prescribe in the dialysis population are needed.

Frailty and Clinical Outcomes in Patients Treated With Hemodialysis: A Prospective Cohort Study.

Rationale and Objective: Frailty is common among people with kidney failure treated with hemodialysis (HD). The objective was to describe how frailty evolves over time in people treated by HD, how improvements in frailty and frailty markers are associate with clinical outcomes, and the characteristics that are associated with improvement in frailty. Study Design: Prospective cohort study. Setting and Participants: Adults initiating thrice weekly in-center HD in Canada. Exposure: We classified frailty using a 5-point score (3 or more indicates frailty) based on physical inactivity, slowness or weakness, poor endurance or exhaustion, and malnutrition. We categorized the frailty trajectory as never present, improving, deteriorating, and always present. Outcomes: All-cause death, hospitalizations, and placement into long-term care. Analytical Approach: We examined the association between time-varying frailty measures and these outcomes using Cox and negative binomial models, after adjustment for potential confounders. Results: 985 participants were included and followed up for a median of 33 months; 507 (51%) died, 761 (77%) experienced ≥1 hospitalization and 115 (12%) entered long-term care. Overall, 760 (77%) reported frailty during follow-up. Three-quarters (78%) of those with frailty at baseline remained frail throughout the follow-up, 46% without baseline frailty became frail, and 23% with baseline frailty became nonfrail. Higher frailty scores were associated with an increased risk of mortality (fully adjusted HR, 1.58 per unit; 95% CI, 1.39-1.80) and an increased rate of hospitalization (RR, 1.16 per unit; 95% CI, 1.09-1.23). Compared with those who were frail throughout the follow-up, participants with frailty at baseline but improving during follow-up showed a lower mortality (HR, 0.59; 95% CI, 0.42-0.81), and a lower rate of hospitalization (RR, 0.70; 95% CI, 0.56-0.87). Limitations: There was missing data on frailty at baseline and during follow-up. Conclusions: Frailty was associated with a higher risk of poor outcomes compared with those without frailty, and participants whose status improved from frail to nonfrail showed better clinical outcomes than those who remained frail. These findings emphasize the importance of identifying and implementing effective treatments for frailty in patients receiving maintenance HD.

Associations between body mass index and all-cause mortality: A systematic review and meta-analysis.

Fasting insulin and c-reactive protein confound the association between mortality and body mass index. An increase in fat mass may mediate the associations between hyperinsulinemia, hyperinflammation, and mortality. The objective of this study was to describe the "average" associations between body mass index and the risk of mortality and to explore how adjusting for fasting insulin and markers of inflammation might modify the association of BMI with mortality. MEDLINE and EMBASE were searched for studies published in 2020. Studies with adult participants where BMI and vital status was assessed were included. BMI was required to be categorized into groups or parametrized as non-first order polynomials or splines. All-cause mortality was regressed against mean BMI squared within seven broad clinical populations. Study was modeled as a random intercept. ß coefficients and 95% confidence intervals are reported along with estimates of mortality risk by BMIs of 20, 30, and 40 kg/m2 . Bubble plots with regression lines are drawn, showing the associations between mortality and BMI. Splines results were summarized. There were 154 included studies with 6,685,979 participants. Only five (3.2%) studies adjusted for a marker of inflammation, and no studies adjusted for fasting insulin. There were significant associations between higher BMIs and lower mortality risk in cardiovascular (unadjusted ß -0.829 [95% CI -1.313, -0.345] and adjusted ß -0.746 [95% CI -1.471, -0.021]), Covid-19 (unadjusted ß -0.333 [95% CI -0.650, -0.015]), critically ill (adjusted ß -0.550 [95% CI -1.091, -0.010]), and surgical (unadjusted ß -0.415 [95% CI -0.824, -0.006]) populations. The associations for general, cancer, and non-communicable disease populations were not significant. Heterogeneity was very large (I2 ≥ 97%). The role of obesity as a driver of excess mortality should be critically re-examined, in parallel with increased efforts to determine the harms of hyperinsulinemia and chronic inflammation.

Long-Term Outcomes for Living Kidney Donors With Early Guideline-Concordant Follow-up Care: A Retrospective Cohort Study.

Background: Current guidelines recommend that living kidney donors receive lifelong annual follow-up care to monitor kidney health. In the United States, the reporting of complete clinical and laboratory data for kidney donors has been mandated for the first 2 years post-donation; however, the long-term impact of early guideline-concordant care remains unclear. Objective: The primary objective of this study was to compare long-term post-donation follow-up care and clinical outcomes of living kidney donors with and without early guideline-concordant follow-up care. Design: Retrospective, population-based cohort study. Setting: Linked health care databases were used to identify kidney donors in Alberta, Canada. Patients: Four hundred sixty living kidney donors who underwent nephrectomy between 2002 and 2013. Measurements: The primary outcome was continued annual follow-up at 5 and 10 years (adjusted odds ratio with 95% confidence interval, LCLaORUCL). Secondary outcomes included mean change in estimated glomerular filtration rate (eGFR) over time and rates of all-cause hospitalization. Methods: We compared long-term follow-up and clinical outcomes for donors with and without early guideline-concordant care, defined as annual physician visit and serum creatinine and albuminuria measurement for the first 2 years post-donation. Results: Of the 460 donors included in this study, 187 (41%) had clinical and laboratory evidence of guideline-concordant follow-up care throughout the first 2 years post-donation. The odds of receiving annual follow-up for donors without early guideline-concordant care were 76% lower at 5 years (aOR 0.180.240.32) and 68% lower at 10 years (aOR 0.230.320.46) compared with donors with early care. The odds of continuing follow-up remained stable over time for both groups. Early guideline-concordant follow-up care did not appear to substantially influence eGFR or hospitalization rates over the longer term. Limitations: We were unable to confirm whether the lack of physician visits or laboratory data in certain donors was due to physician or patient decisions. Conclusions: Although policies directed toward improving early donor follow-up may encourage continued follow-up, additional strategies may be necessary to mitigate long-term donor risks.

Contexte: Les lignes directrices actuelles recommandent que les donneurs de rein vivants soient suivis annuellement, et ce, à vie, afin de surveiller leur santé rénale. Aux États-Unis, la déclaration des données cliniques et des données de laboratoire complètes pour les donneurs de rein est exigée pour les deux premières années suivant le don. On ignore cependant les répercussions à long terme pour ceux qui reçoivent des soins précoces conformes aux lignes directrices. Objectif: Le principal objectif de cette étude était de comparer les soins de suivi post-don à long terme et les résultats cliniques des donneurs de rein vivants, selon qu'ils avaient reçu ou non des soins de suivi précoces conformes aux recommandations. Type d'étude: Étude de cohorte rétrospective basée sur une population. Cadre: Les banques de données couplées du système de santé ont été utilisées pour identifier les donneurs de rein de l'Alberta (Canada). Sujets: L'étude porte sur 460 donneurs de rein vivants ayant subi leur néphrectomie entre 2002 et 2013. Mesures: Le principal critère d'évaluation était un suivi annuel continu à 5 et à 10 ans post-don (rapport de cotes corrigé avec intervalle de confiance de 95 % [LICRRcLSC]). Les résultats secondaires comprenaient la variation moyenne du débit de filtration glomérulaire estimé (DFGe) au fil du temps et les taux d'hospitalisation toutes causes confondues. Méthodologie: Nous avons comparé le suivi à long terme et les résultats cliniques de donneurs qui avaient reçu ou non des soins précoces conformes aux directives, définis par une visite annuelle chez le médecin et des mesures de la créatinine sérique et de l'albuminurie pour les deux premières années post-don. Résultats: Des 460 donneurs inclus à l'étude, 187 (41 %) disposaient de preuves de suivi conformes aux directives, soit de données cliniques et de laboratoire, pour les deux premières années post-don. Les chances d'avoir un suivi annuel pour les donneurs qui n'avaient pas reçu de soins précoces conformes aux directives étaient de 76 % inférieures à 5 ans (RRc: 0,180,240,32) et de 68 % inférieures à 10 ans (RRc: 0,230,320,46) par rapport aux donneurs qui en avaient reçu. Les chances de poursuivre le suivi sont demeurées stables au fil du temps pour les deux groupes. Le fait d'avoir reçu des soins de suivi précoces conformes aux recommandations ne semble pas avoir eu d'incidence importante sur les mesures de DFGe ou les taux d'hospitalisation à long terme. Limites: Nous n'avons pas été en mesure de confirmer si l'absence de visites chez le médecin ou le manque de données de laboratoire chez certains donneurs était dû à des décisions du médecin ou du patient. Conclusion: Bien que les politiques visant à améliorer le suivi précoce des donneurs d'organes puissent encourager la poursuite du suivi, des stratégies supplémentaires pourraient être nécessaires pour atténuer les risques à long terme pour ces personnes.

Mortality and Resource Use Among Individuals With Chronic Kidney Disease or Cancer in Alberta, Canada, 2004-2015.

Importance: Although the public is aware that cancer is associated with excess mortality and adverse outcomes, the clinical consequences of chronic kidney disease (CKD) are not well understood. Objective: To compare the clinical consequences of incident severe CKD and the first diagnosis with a malignant tumor, focusing on the 10 leading causes of cancer in men and women residing in Canada. Design, Setting, and Participants: This population-based cohort study enrolled individuals aged 19 years and older with severe CKD or certain types of cancer between 2004 and 2015 in Alberta, Canada. Data were analyzed in November 2021. Exposures: Individuals were categorized as having severe CKD (based on estimated glomerular filtration rate <30 mL/min/1.73 m2 or nephrotic albuminuria without dialysis or kidney transplantation) or nonmetastatic or metastatic cancer (defined by a diagnosis of lung, breast, colorectal, prostate, bladder, thyroid, kidney or renal pelvis, uterus, pancreas, or oral cancer). Main Outcomes and Measures: All-cause mortality, number of hospitalizations, total number of hospital days, and placement into long-term care were calculated after diagnosis. Results: Of 200 494 individuals in the cohort (104 559 women [52.2%]; median [IQR] age, 66.8 [55.9-77.7] years), 51 159 (25.5%) had incident severe CKD, 115 504 (57.6%) had nonmetastatic cancer, and 33 831 (16.9%) had metastatic cancer. Kaplan-Meier 1-year survival was 83.3% (95% CI, 83.0%-83.6%) for patients with CKD, 91.2% (95% CI, 91.0%-91.4%) for patients with nonmetastatic cancer, and 52.8% (95% CI, 52.2%-53.3%) for patients with metastatic cancer. Kaplan-Meier 5-year survival was 54.6% (95% CI, 54.2%-55.1%) for patients with CKD, 76.6% (95% CI, 76.3%-76.8%) for patients with nonmetastatic cancer, and 33.9% (95% CI, 33.3%-34.4%) for patients with metastatic cancer. Compared with nonmetastatic cancer, the age-, sex-, and comorbidity-adjusted relative rate of death was similar for CKD (adjusted relative rate, 1.00; 95% CI, 0.97-1.03; P = .92) during the first year of follow-up and was higher for CKD at years 1 to 5 (adjusted relative rate 1.23; 95% CI, 1.19-1.26). During the first year of follow-up, for patients with CKD, adjusted rates of placement in long-term care (adjusted relative rate, 0.88; 95% CI, 0.82-0.94) and hospitalization (adjusted relative rate, 0.65; 95% CI, 0.64-0.66) were lower than rates for patients with nonmetastatic cancer; however, those rates were higher for the CKD group than for the nonmetastatic cancer group during years 1 to 5 (long-term care placement, adjusted relative rate, 1.36; 95% CI, 1.29-1.43; hospitalization, adjusted relative rate, 1.55; 95% CI, 1.52-1.58). As expected, adjusted rates of long-term care placement and hospitalization were higher for patients with metastatic cancer than for the other 2 groups. Conclusions and Relevance: In this study, mortality, hospitalization, and likelihood of placement into long-term care were similar for CKD and nonmetastatic cancer. These data highlight the importance of CKD as a public health problem.

Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials.

OBJECTIVE: To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. DESIGN: Network meta-analysis. DATA SOURCES: Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. MAIN OUTCOME MEASURES: Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. RESULTS: 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 3 to 40 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes. CONCLUSIONS: In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with some differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019153180.

Development and Validation of Nine Deprescribing Algorithms for Patients on Hemodialysis to Decrease Polypharmacy.

BACKGROUND: Polypharmacy is ubiquitous in patients on hemodialysis (HD), and increases risk of adverse events, medication interactions, nonadherence, and mortality. Appropriately applied deprescribing can potentially minimize polypharmacy risks. Existing guidelines are unsuitable for nephrology clinicians as they lack specific instructions on how to deprescribe and which safety parameters to monitor. OBJECTIVE: To develop and validate deprescribing algorithms for nine medication classes to decrease polypharmacy in patients on HD. DESIGN: Questionnaires and materials sent electronically. PARTICIPANTS: Nephrology practitioners across Canada (nephrologists, nurse practitioners, renal pharmacists). METHODS: A literature search was performed to develop the initial algorithms via Lynn's method for development of content-valid clinical tools. Content and face validity of the algorithms was evaluated over three interview rounds using Lynn's method for determining content validity. Canadian nephrology clinicians each evaluated three algorithms (15 clinicians per round, 45 clinicians in total) by rating each algorithm component on a four-point Likert scale for relevance; face validity was rated on a five-point scale. After each round, content validity index of each component was calculated and revisions made based on feedback. If content validity was not achieved after three rounds, additional rounds were completed until content validity was achieved. RESULTS: After three rounds of validation, six algorithms achieved content validity. After an additional round, the remaining three algorithms achieved content validity. The proportion of clinicians rating each face validity statement as "Agree" or "Strongly Agree" ranged from 84% to 95% (average of all five questions, across three rounds). LIMITATIONS: Algorithm development was guided by existing deprescribing protocols intended for the general population and the expert opinions of our study team, due to a lack of background literature on HD-specific deprescribing protocols. There is no universally accepted method for the validation of clinical decision-making tools. CONCLUSIONS: Nine medication-specific deprescribing algorithms for patients on HD were developed and validated by clinician review. Our algorithms are the first medication-specific, patient-centric deprescribing guidelines developed and validated for patients on HD.

CONTEXTE: La polypharmacie est très répandue chez les patients hémodialysés et augmente le risque d'événements indésirables, d'interactions médicamenteuses, d'inobservance au traitement et de mortalité. La déprescription, appliquée de façon appropriée, peut réduire les risques associés à la polypharmacie. Les directives de déprescription existantes ne conviennent cependant pas aux cliniciens en néphrologie puisqu'elles ne renferment aucune indication spécifique sur la manière de procéder ni sur les paramètres de sécurité à surveiller. OBJECTIF: Développer et valider des algorithmes de déprescription pour neuf classes de médicaments en vue de réduire la polypharmacie chez les patients hémodialysés. CONCEPTION: Des questionnaires et des documents envoyés par voie électronique. PARTICIPANTS: Des praticiens en néphrologies de partout au Canada (néphrologues, infirmières-praticiennes, pharmaciens spécialisés en néphrologie). MÉTHODOLOGIE: Une recherche bibliographique a été effectuée pour développer les algorithmes initiaux avec la méthode de Lynn pour le développement d'outils cliniques à contenu validé. Le contenu et la validité apparente des algorithmes ont été évalués au cours de trois cycles d'interviews par la méthode de Lynn pour déterminer la validité d'un contenu. Les praticiens interviewés (15 par cycle, pour un total de 45) ont chacun évalué trois algorithmes en classant la pertinence de leurs composants sur une échelle de Likert en quatre points, et en classant leur validité apparente sur une échelle en cinq points. Après chaque cycle, l'indice de validité du contenu a été calculé pour chaque composant et des correctifs ont été apportés en fonction de la rétroaction. Si la validité du contenu n'était pas atteinte après trois cycles, des cycles supplémentaires étaient effectués jusqu'à ce que celle-ci soit atteinte. RÉSULTATS: Six algorithmes ont atteint la validité après trois cycles de validation. Les trois algorithmes restants l'ont atteint après un cycle supplémentaire. La proportion de cliniciens ayant attribué la mention de validité apparente « d'accord ¼ ou « tout à fait d'accord ¼ se situait entre 84 et 95 % (moyenne des cinq questions, sur trois cycles). LIMITES: Le développement des algorithmes repose sur les protocoles de déprescription existants, destinés à la population générale, et sur l'avis des experts de notre équipe d'étude puisque la documentation portant sur des protocoles de déprescription spécifiques aux patients hémodialysés est insuffisante. Il n'existe aucune méthode universellement acceptée pour valider les outils de décision clinique. CONCLUSION: Neuf algorithmes de déprescription spécifiques aux patients hémodialysés ont été développés et validés par révision des cliniciens. Nos algorithmes sont les premiers guides de déprescription développés et validés spécifiquement pour les médicaments des patients hémodialysés. ENREGISTREMENT DE L'ESSAI: Sans objet ­ il s'agit d'une série de questionnaires.

Changes in kidney function follow living donor nephrectomy.

Better understanding of kidney function after living donor nephrectomy and how it differs by donor characteristics can inform patient selection, counselling, and follow-up care. To evaluate this, we conducted a retrospective matched cohort study of living kidney donors in Alberta, Canada between 2002-2016, using linked healthcare administrative databases. We matched 604 donors to 2,414 healthy non-donors from the general population based on age, sex, year of cohort entry, urban residence and the estimated glomerular filtration rate (eGFR) before cohort entry (nephrectomy date for donors and randomly assigned date for non-donors). The primary outcome was the rate of eGFR change over time (median follow-up seven years; maximum 15 years). The median age of the cohort was 43 years, 64% women, and the baseline (pre-donation) eGFR was 100 mL/min/1.73 m2. Overall, from six weeks onwards, the eGFR increased by +0.35 mL/min/1.73 m2 per year (95% confidence interval +0.21 to +0.48) in donors and significantly decreased by -0.85 mL/min/1.73 m2 per year (-0.94 to -0.75) in the matched healthy non-donors. The change in eGFR between six weeks to two years, two to five years, and over five years among donors was +1.06, +0.64, and -0.06 mL/min/1.73 m2 per year, respectively. In contrast to the steady age-related decline in kidney function in non-donors, post-donation kidney function on average initially increased by 1 mL/min/1.73 m2 per year attributable to glomerular hyperfiltration, which began to plateau by five years post-donation. Thus, the average change in eGFR over time is significantly different between donors and non-donors.

Impact of Ramadan fasting on kidney function and related outcomes in patients with chronic kidney disease: a systematic review protocol.

INTRODUCTION: Fasting during the month of Ramadan is a significant Islamic religious practice that involves abstinence from food, drink and medication from dawn to dusk. As just under a quarter of the world's population identifies as Muslim, the effect of fasting on chronic conditions, such as chronic kidney disease (CKD) is a topic of broad relevance. To date, the information in this area has been mixed, with many limitations of previous studies. This study aims to synthesise the evidence of the effect of Ramadan fasting on changes on kidney function, risk factors, episodes of acute kidney injury and impact on the quality of life in patients with CKD or kidney transplant. METHODS AND ANALYSIS: A systematic review of the literature will be conducted, using electronic databases such as MEDLINE, Embase, Global Health, CINAHL and Scopus. Original research and grey literature on the effect of Ramadan fasting in adult patients with CKD or renal transplantation will be included. Two reviewers will independently screen articles for inclusion in the review and independently assess the methodology of included studies using a customised checklist. Mean difference or risk ratio will be reported for continuous or dichotomous outcomes and results will be pooled using a random-effects model where heterogeneity is reasonable. If possible, subgroups (CKD status, setting, season and risk of bias) will be analysed for effect modification with fasting and the outcomes of interest. Risk of bias will be assessed using the Downs and Black checklist. ETHICS AND DISSEMINATION: The results will be disseminated using a multifaceted approach to engage all stakeholders (patients, practitioners and community leaders). Research ethics board approval is not required as this is a systematic review of previously published research. PROSPERO REGISTRATION NUMBER: CRD42018088973.

Outcomes Following Macrolide Use in Kidney Transplant Recipients.

BACKGROUND: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. OBJECTIVE: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. DESIGN: Retrospective cohort study. SETTING: We used linked health care databases in Alberta, Canada. PATIENTS: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. MEASUREMENTS: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. METHODS: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). RESULTS: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (-5.4 vs -1.9 mL/min/1.73 m2, P < .05). LIMITATIONS: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. CONCLUSION: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.

CONTEXTE: Les inhibiteurs de la calcineurine (CNI : cyclosporine, tacrolimus) sont essentiels à l'immunosuppression suivant une transplantation rénale. Ils présentent toutefois de nombreux risques d'interactions médicamenteuses avec les antibiotiques macrolides (clarithromycine, érythromycine et azithromycine) employés couramment pour traiter les infections atypiques. La clarithromycine et l'érythromycine inhibent le métabolisme des CNI et augmentent leurs risques de néphrotoxicité, ce qui n'est pas le cas de l'azithromycine. OBJECTIFS: Déterminer la fréquence de co-prescription d'un CNI et d'un macrolide chez les receveurs d'une greffe rénale, la proportion de patients ayant fait l'objet d'un suivi post-prescription et le risque d'effets indésirables attribuables aux médicaments. TYPE D'ÉTUDE: Une étude de cohorte rétrospective. CADRE: Les banques de données couplées du système de santé de l'Alberta (Canada). SUJETS: Nous avons inclus 293 adultes receveurs d'un rein entre 2008 et 2015 et à qui on avait co-prescrit un CNI et un macrolide. MESURES: Le principal résultat attendu était une combinaison d'hospitalisation toutes causes, d'insuffisance rénale aigüe (hausse minimale de 0,3 mg/dL de la créatinine sérique ou équivalente à 1,5 fois la valeur mesurée initialement), ou de décès du patient dans les 30 jours suivant la prescription d'un macrolide. MÉTHODOLOGIE: Nous avons répertorié les co-prescriptions CNI-macrolide et comparé les résultats des patients traités par clarithromycine/érythromycine à ceux traités avec l'azithromycine. Nous avons employé un modèle linéaire à effets mixtes pour établir les variations moyennes dans les mesures de créatinine sérique et de DFGe. RÉSULTATS: Des 293 receveurs d'un rein ayant reçu une co-prescription CNI-macrolide, 38 % (n = 112) ont été traités avec la clarithromycine/érythromycine et 62 % (n = 181) avec l'azithromycine. Les patients ayant reçu de la clarithromycine/érythromycine étaient moins susceptibles de faire l'objet d'un suivi ambulatoire du taux de créatinine sérique post-prescription (56 % contre 69 % pour l'azithromycine, p = 0,03). Aucune différence significative n'a été observée entre les deux groupes quant au principal résultat attendu (17 % contre 11 %; p = 0,11). Cependant, les patients traités par clarithromycine/érythromycine présentaient un risque supérieur d'hospitalisation toutes causes (10 % contre 3 %; p = 0,02), et la moyenne de décroissance du DFGe pour ces patients était significativement supérieure (-5,4 mL/min/1,73 m2 contre -1,9 mL/min/1,73 m2 pour l'azithromycine; p < 0,05). LIMITES: Nous n'avions pas les niveaux de CNI corrélés avec le moment de la co-prescription CNI-macrolide, ni les indications justifiant l'ordonnance de macrolide. CONCLUSION: La clarithromycine et l'érythromycine ont été fréquemment co-prescrites aux receveurs d'une greffe rénale traités avec des CNI, malgré la connaissance des interactions médicamenteuses. Les patients recevant de la clarithromycine/érythromycine sont plus susceptibles d'être hospitalisés que ceux recevant de l'azithromycine. L'adoption de pratiques de prescription plus sûres est justifiée chez les receveurs d'une greffe rénale.

Statin use and the risk of acute kidney injury in older adults.

BACKGROUND: As more patients at lower cardiovascular (CV) risk are treated with statins, the balance between cardiovascular benefits and the risk of adverse events becomes increasingly important. METHODS: We did a population-based cohort study (May 1, 2002 to March 30, 2013) using province-wide laboratory and administrative data in Alberta. We studied new statin users aged 66 years of age and older who were not receiving renal replacement therapy at baseline. We assessed statin use at 30-day intervals to allow time-varying assessment of statin exposure in Cox proportional hazards models that examined the relation between statin use and hospitalization with acute kidney injury (AKI). RESULTS: Of the 128,140 new statin users, 47 and 46% were prescribed high- and medium-intensity regimens at the index date. During median follow-up of 4.6 years (interquartile range 2.2, 7.4), 9118 individuals were hospitalized for AKI. Compared to non-use, the use of high- and medium-intensity statin regimens was associated with significant increases in the adjusted risks of hospitalization with AKI: hazard ratios 1.16 [95% confidence interval (CI) 1.10, 1.23] and 1.07 (95% CI 1.01, 1.13), respectively. Risks of AKI were higher among women than men, and among users of angiotensin converting enzyme inhibitors/angiotensin receptor blockers than non-users, and among diuretic users (p for interaction 0.002, 0.01, and 0.04 respectively). CONCLUSIONS: We found a graded, independent association between the intensity of statin use and the risk of hospitalization with AKI, although the absolute magnitude of the excess risk was small.

Follow-up Care of Living Kidney Donors in Alberta, Canada.

BACKGROUND: Previous guidelines recommend that living kidney donors receive lifelong annual follow-up care to assess renal health. OBJECTIVE: To determine whether these best practice recommendations are currently being followed. DESIGN: Retrospective cohort study using linked health care databases. SETTING: Alberta, Canada (2002-2014). PATIENTS: Living kidney donors. MEASUREMENTS: We determined the proportion of donors who had annual outpatient physician visits and laboratory measurements for serum creatinine and albuminuria. RESULTS: There were 534 living kidney donors with a median follow-up of 7 years (maximum 13 years). The median age at the time of donation was 41 years and 62% were women. Overall, 25% of donors had all 3 markers of care (physician visit, serum creatinine, albuminuria measurement) in each year of follow-up. Adherence to physician visits was higher than serum creatinine or albuminuria measurements (67% vs 31% vs 28% of donors, respectively). Donors with guideline-concordant care were more likely to be older, reside closer to the transplant center, and receive their nephrectomy in more recent years. LIMITATIONS: Our results may not be generalizable to other countries that do not have a similar universal health care system. CONCLUSIONS: These findings suggest significant evidence-practice gaps, in that the majority of donors saw a physician, but the minority had measurements of kidney function or albuminuria. Future interventions should target improving follow-up care for all donors.

CONTEXTE: Des recommandations émises antérieurement préconisaient de faire le suivi médical à vie, sur une base annuelle, des donneurs de rein vivants afin d'évaluer leur santé rénale. OBJECTIF DE L'ÉTUDE: L'étude visait à vérifier si ces recommandations de bonnes pratiques étaient suivies. TYPE D'ÉTUDE: Une étude de cohorte rétrospective pour laquelle on a utilisé les bases de données interreliées en soins de santé. CADRE DE L'ÉTUDE: L'étude concerne des patients de la province de l'Alberta, au Canada, et couvre la période allant de 2002 à 2014. PATIENTS: Des donneurs de rein vivants. MESURES: Nous avons établi la proportion de donneurs qui avaient été vus par un médecin en consultation externe et pour qui des mesures de la créatinine et de l'albuminurie avaient été faites. RÉSULTATS: Nous avons répertorié 534 donneurs de rein vivants dont la durée médiane du suivi médical était de sept ans (treize ans maximum). L'âge médian au moment du don d'organe était de 41 ans et la cohorte était constituée à 62 % de donneuses. Dans l'ensemble, 25 % des donneurs montraient les trois indicateurs recherchés (visite chez le médecin, mesure de la créatinine et de l'albuminurie) pour chaque année de suivi. La proportion des donneurs qui voyaient un médecin annuellement s'est avérée nettement supérieure (67 %) à celle des donneurs présentant des mesures de la créatinine (31 %) et de l'albuminurie (28 %). Enfin, on a observé que les donneurs qui suivaient les recommandations étaient plus susceptibles d'être plus âgés, de résider près du centre de greffe et d'avoir subi leur néphrectomie plus récemment. LIMITES DE L'ÉTUDE: Nos résultats pourraient ne pas être généralisables aux pays n'ayant pas un système universel des soins de santé similaire à celui du Canada. CONCLUSION: Ces constatations laissent entrevoir des écarts significatifs entre les données probantes et la pratique, en ce sens que la majorité des donneurs avaient consulté un médecin, mais que peu d'entre eux présentaient des mesures de la fonction rénale ou de l'albuminurie. Dès lors, les prochaines interventions devraient cibler l'amélioration du suivi médical de tous les donneurs.

Extracellular fluid management and hypertension in urban dwelling versus rural dwelling hemodialysis patients.

BACKGROUND: Rural-dwelling hemodialysis patients have less frequent contact with nephrologists than urban-dwelling patients, and are known to have higher mortality. We hypothesized that rural-dwelling hemodialysis patients would have more evidence of poorly controlled extracellular fluid volume (ECVF) than otherwise similar urban-dwellers. METHODS: We studied prevalent hemodialysis patients within a single renal program in Alberta, Canada and assessed ECFV using bioimpedance spectroscopy (BIS). Our primary outcome was impedance vector length (ohm/m) as assessed by BIS using the Xitron Hydra 4200 device, where shorter vector length indicated poorer ECFV control. Because poor ECFV control can lead to hypertension, we also assessed pre- and post-dialysis blood pressure. We measured outcomes at baseline. RESULTS: We studied 228 hemodialysis patients, of whom 115 (50.4 %) and 113 (49.6 %) were urban- and rural-dwelling, respectively. There were no differences in volume control in urban versus rural participants; odds ratio (OR) for vector length in the lowest sex-specific quartile of vector length was 0.93 (95 % CI 0.54, 1.59) after adjusting for age, sex, diabetic status, years since dialysis initiation and phase angle. The odds of very poor blood pressure control (pre-dialysis blood pressure ≥180/100) did not differ between urban and rural participants [fully adjusted OR 0.96 (0.36, 2.60)]. CONCLUSIONS: Differences in ECFV control do not appear to explain higher mortality among remote- and rural- dwelling hemodialysis patients, compared to urban-dwellers.

In-Center Nocturnal Hemodialysis Versus Conventional Hemodialysis: A Systematic Review of the Evidence.

BACKGROUND: Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better understand the evidence for in-center nocturnal HD, we sought to systematically review the literature to determine the effects of in-center nocturnal HD versus conventional HD on clinically relevant outcomes. STUDY DESIGN: We searched MEDLINE, Embase, Evidence-Based Medicine Reviews (EBMR), Web of Science, and Scopus from the earliest date in the database to November 2016. SETTING & POPULATION: Adults receiving in-center nocturnal HD compared with those receiving conventional HD. SELECTION CRITERIA FOR STUDIES: All quasi-experimental and observational studies were considered; randomized trials were sought but not found. PREDICTOR: Nocturnal vs conventional in-center HD. OUTCOMES: Indexes of blood pressure and left ventricular hypertrophy, markers of anemia, measures of bone mineral metabolism, nutrition, quality of life, sleep quality, episodes of intradialytic hypotension, hospitalization, and mortality. RESULTS: Of 2,086 identified citations, 21 met the inclusion criteria, comprising a total of 1,165 in-center nocturnal HD patients and 15,865 conventional HD patients. Although there was substantial heterogeneity in reporting of outcomes, we pooled data for measures of blood pressure, anemia, and mineral metabolism. Though heterogeneity was generally high, in-center nocturnal HD was associated with improved systolic blood pressure (-3.18 [95% CI, -5.58 to -0.78) mm Hg, increased hemoglobin levels (0.53 [95% CI, 0.11-0.94] g/dL), and lower serum phosphate levels (-0.97 [95% CI, -1.48 to -0.46] mg/dL). LIMITATIONS: No randomized trials have been conducted to address the clinical effects of in-center nocturnal HD. The quality of the observational literature contributing to the results of this review was generally poor to moderate. Confounded outcomes are a significant concern. Publication bias and outcome reporting bias remain possibilities. CONCLUSIONS: Relative to conventional HD, in-center nocturnal HD was associated with improvements in several clinically relevant outcomes. Other benefits may not have been detected due to small sample sizes of included studies; no prespecified outcome was worse with in-center nocturnal HD.

Impact of using two dialyzers in parallel on phosphate clearance in hemodialysis patients: a randomized trial.

BACKGROUND: Dietary restriction and phosphate binders are the main interventions used to manage hyperphosphatemia in people on hemodialysis, but have limited efficacy. Modifying conventional dialysis regimens to enhance phosphate clearance as an alternative approach remains relatively unstudied. METHODS: This was a 10-week, 2-arm, randomized crossover study. Participants were prevalent dialysis patients ( n = 32) with consecutive serum phosphate levels >1.6 mmol/L and on stable doses of a phosphate binder. Following a 2-week run-in period, participants were randomized to initiate dialysis using two high flux dialyzers in parallel (blood flow ≥350 mL/min, dialysate flow 800 mL/min) or standard dialysis using one high flux dialyzer (blood flow ≥350 mL/min, dialysate flow of 800 mL/min). Each regimen was 3 weeks in duration. After a 2-week washout period, participants received the alternate regimen. The primary outcome was the mean difference in phosphate clearance by dialyzer strategy. Secondary outcomes were phosphate removal and pre-dialysis serum phosphate. RESULTS: Phosphate clearance for the double dialyzer strategy did not differ significantly from the single dialyzer strategy [mean difference 7.5 mL/min (95% confidence interval, 95% CI, -6.1, 21.0), P = 0.28]. There was no difference in total phosphate removal and pre-dialysis phosphate between the double and single dialyzer strategies [total phosphate removal mean difference -0.2 mmol (95% CI -4.1, 3.7), P = 0.93; pre-dialysis mean difference 0.01 mmol/L (95% CI -0.18, 0.21), P = 0.88]. There was no difference in the proportion of participants who experienced at least one episode of intradialytic hypotension (32 versus 47%, P = 0.13). A limitation of the study was frequent protocol deviations in the dialysis prescription. CONCLUSIONS: In this study, the use of two dialyzers in parallel did not increase phosphate clearance, phosphate removal or pre-dialysis serum phosphorus when compared with a standard dialysis treatment strategy. Future studies should continue to evaluate novel methods of phosphate removal using conventional hemodialysis.

Randomised factorial mixed method pilot study of aerobic and resistance exercise in haemodialysis patients: DIALY-SIZE!

OBJECTIVES: For people with end-stage renal disease requiring haemodialysis, exercise can improve aspects of quality of life (QoL). However, the relative benefits and risks of different types of exercise in this population are unknown. Therefore, this pilot study aimed to evaluate the feasibility of a main study evaluating the efficacy of cycling and resistance exercise each performed during the haemodialysis treatment on QoL. METHODS: In this factorial (2×2) pilot trial, 31 haemodialysis patients were randomised to cycling, resistance, cycling and resistance, or an attention control. Feasibility was defined a priori by criteria on recruitment, fidelity to the protocol and patient response to the intervention. To better understand feasibility, we conducted interviews with dialysis unit staff and trial participants. As secondary outcomes, we estimated the main effect of cycling and weights each compared with control on QoL, physical function and strength. FINDINGS: We exceeded the target accrual of 28 participants over 12 weeks. Irrespective of exercise group allocation, adherence was high; of the 1038 training sessions offered, 87% were initiated and over 80% of exercise sessions were performed as per protocol. Progression based on perceived exertion, individual instruction and interactions with the kinesiologist facilitated acceptability across exercise groups. Using an attention control, measures of contamination and attrition were low. Important barriers to unit staff readiness for the intervention were initial safety and workflow concerns, unit workload and onerous data collection. Secondary outcomes were not statistically significant. Adverse events were low and did not increase with a higher volume of exercise. CONCLUSIONS: The main study is feasible with minor modifications. In addition to practical assistance, involvement from unit staff could increase patient participation and improve trial implementation. Strategies to increase acceptability of the intervention for staff include improving workflow integration and using a prestudy demonstration phase to introduce the intervention. TRIAL REGISTRATION NUMBER: NCT02234232.

Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes: A Meta-analysis.

IMPORTANCE: Numerous glucose-lowering drugs are used to treat type 2 diabetes. OBJECTIVE: To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin. DATA SOURCES: Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016. STUDY SELECTION: Randomized clinical trials of 24 weeks' or longer duration. DATA EXTRACTION AND SYNTHESIS: Random-effects network meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight. RESULTS: A total of 301 clinical trials (1,417,367 patient-months) were included; 177 trials (56,598 patients) of drugs given as monotherapy; 109 trials (53,030 patients) of drugs added to metformin (dual therapy); and 29 trials (10,598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, -22% [-27% to -18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, -10% [95% CI, -18% to -2%]). CONCLUSIONS AND RELEVANCE: Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

Impact of age on the association between CKD and the risk of future coronary events.

BACKGROUND: Elucidation of the relationship between age, kidney function, and absolute coronary risk would facilitate efforts to promote chronic kidney disease (CKD) as a high-risk state for future vascular events and justify current recommendations for statin treatment in CKD. STUDY DESIGN: Population-based study. SETTING & PARTICIPANTS: 1,268,538 people with data for estimated glomerular filtration rate and albuminuria who were treated in a single Canadian province. PREDICTORS: CKD risk groups (G1, G2, G3a, G3b, and G4 had estimated glomerular filtration rate ≥90, 60-89.9, 45-59.9, 30-44.9, and 15-29.9 mL/min/1.73 m2, respectively; A1, A2, and A3 had albuminuria with albumin-creatinine ratio [ACR]<30 mg/g or dipstick urinalysis negative, ACR of 30-300 mg/g or dipstick trace or 1+, and ACR >300 mg/g or dipstick ≥ 2+, respectively) and age (<40, 40-49, ≥50 years). OUTCOMES: Rates of coronary death or nonfatal myocardial infarction (expressed per 1,000 person-years), stratified by age, sex, and CKD stage. MEASUREMENTS: The first available serum creatinine value and the corresponding date were set as the index serum creatinine value and index date, respectively. ACR or dipstick urinalysis data were obtained from the periods defined by 6 months before and after the index creatinine value. RESULTS: Absolute rates of coronary death or nonfatal myocardial infarction were consistently greater than 10 per 1,000 person-years for people with CKD and 50 years or older, regardless of CKD stage. However, absolute rates of the composite outcome were consistently less than 10 per 1,000 person-years for those younger than 50 years. LIMITATIONS: Single Canadian province, median follow-up only 4.0 years. CONCLUSIONS: People with CKD who are 50 years or older should be considered at the highest risk of coronary events. In contrast, consideration of other risk factors will be required when assessing future risk among people with CKD who are younger than 50 years.

Using linked administrative data to study periprocedural mortality in obesity and chronic kidney disease (CKD).

Both obesity and chronic kidney disease (CKD) are associated with adverse periprocedural outcomes, but it is unknown how these two common conditions interact to influence risk. We examined the feasibility of combining a new procedure-related, obesity-specific flag with administrative and laboratory data and assessed the joint association between obesity and CKD with mortality. Since 2007, Alberta physicians may claim a fee supplement for performing eligible surgical and non-surgical procedures on patients with documented BMI ≥ 35 kg/m(2). We linked this information to the Alberta Kidney Disease Network registry. Participants were classified into four mutually exclusive groups based on the presence/absence of both obesity (BMI ≥ 35 kg/m(2)) and CKD (eGFR < 60 mL/min/1.73 m(2)). Mortality was assessed at 30 days following the index procedure. Of 393 659 participants, 9% were obese. Overall, 8% had obesity only, 78% neither obesity nor CKD, 13% CKD only and 1% both obesity and CKD. Unadjusted risks of mortality at 30 days were 0.3, 0.4, 2.0 and 2.1%, respectively--but decreased to 0.1, 0.2, 0.3 and 0.3%, respectively, after adjustment for age, sex, socioeconomic status, procedure type and other comorbidities. Administrative data can be feasibly combined with disease registries to study obesity-related outcomes. Results from the linked dataset demonstrated face validity--subjects with both obesity and CKD were at increased risk of periprocedural mortality, and this was driven in part by differences in age and comorbidity.

Association between LDL-C and risk of myocardial infarction in CKD.

LDL cholesterol (LDL-C) is an important marker of coronary risk in the general population, but its utility in people with CKD is unclear. We studied 836,060 adults from the Alberta Kidney Disease Network with at least one measurement of fasting LDL-C, estimated GFR (eGFR), and proteinuria between 2002 and 2009. All participants were free of stage 5 CKD at cohort entry. We followed participants from first eGFR measurement to March 31, 2009; we used validated algorithms applied to administrative data to ascertain primary outcome (hospitalization for myocardial infarction) and Cox regression to calculate adjusted hazard ratios (HRs) for myocardial infarction by LDL-C categories within eGFR strata. During median follow-up of 48 months, 7762 patients were hospitalized for myocardial infarction, with incidence highest among participants with the lowest eGFR. Compared with 2.6-3.39 mmol/L (referent), the risk associated with having LDL-C above 4.9 mmol/L seemed greatest for GFR≥90 ml/min per 1.73 m(2) and least for eGFR=15-59.9 ml/min per 1.73 m(2). Specifically, the adjusted HRs (95% confidence intervals) of myocardial infarction associated with LDL-C of ≥4.9 compared with 2.6-3.39 mmol/L in participants with eGFR=15-59.9, 60-89.9, and ≥90 ml/min per 1.73 m(2) were 2.06 (1.59, 2.67), 2.30 (2.00, 2.65), and 3.01 (2.46, 3.69). In conclusion, the association between higher LDL-C and risk of myocardial infarction is weaker for people with lower baseline eGFR, despite higher absolute risk of myocardial infarction. Increased LDL-C may be less useful as a marker of coronary risk among people with CKD than the general population.