Evaluation of Anemia Management in a Contemporary Population of Patients With Chronic Kidney Disease in Canada Since the Publication of Target Hemoglobin Trials: A Retrospective Observational Cohort Study.

Background: Guidelines for anemia management in chronic kidney disease (CKD) adopted a conservative approach in response to landmark clinical trials demonstrating lack of benefit and potential harm associated with higher hemoglobin targets. Although the findings have been applied to all CKD populations, the concordance between trial populations and those being treated in clinical practice has not been well described. Objective: We sought to evaluate trends in hemoglobin distribution and erythropoiesis stimulating agent (ESA) use among adult patients with CKD, and compare their characteristics to those of participants from landmark hemoglobin target trials. Design: Retrospective observational cohort study. Setting: A provincial clinical information system was used to identify patients with CKD under the care of a nephrologist in British Columbia between April 1, 2007 and March 31, 2018. Patients: Adult patients (over 18 years) with estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73m Measurements: Hemoglobin was measured in grams per litre (g/L) and treated as both a continuous and categorical variable. ESA use was defined as the proportion of patients who received at least one prescription for ESA therapy. The dose of ESA was quantified as an average monthly dose of epoetin alfa or darbepoetin alfa. Methods: Descriptive statistics were used to compare characteristics of patients in the study population to those of trial participants including Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), Correction of Hemoglobin and Outcomes in Renal Insufficiency (CHOIR), and Cardiovascular Risk Reduction by Early Anemia Treatment with Epoetin Beta trial (CREATE). Polytomous logistic regression was used to estimate odds ratios (OR) of different hemoglobin levels across cohort years. The model was adjusted for age, sex, race, comorbid conditions, eGFR, proteinuria, etiology of CKD and iron parameters. Results: A total of 29,033 patients were included in the analysis (mean age 71 years, 45% female, median eGFR 29 mL/min/1.73m Limitations: Measurement of hemoglobin may have been subject to confounding by indication, for example due to a bleeding episode. Physicians may have elected not to treat certain patients with ESA therapy, introducing selection bias. Data regarding blood transfusions were not available. Conclusions: Despite a minority of patients meeting criteria for prior hemoglobin target trials, the universal adoption of guidelines favoring a conservative approach to anemia has culminated in a higher likelihood of patients experiencing severe anemia. The implications of this, particularly patient-reported outcomes, warrant further investigation.