Abstract
BackgroundRoutine clinical evidence is limited on clinical outcomes associated with anemia in patients with severe chronic kidney disease (CKD).MethodsWe linked population-based medical databases to identify individuals with severe CKD (eGFR < 30 mL/min/1.73 m2) in Northern Denmark from 2000 to 2016, including prevalent patients as of 1 January 2009 or incident patients hereafter into the study. We classified patients as non-anemic (≥ 12/≥ 13 g/dl hemoglobin (Hgb) in women/men), anemia grade 1 (10–12/13 g/dl Hgb in women/men), 2 (8–10 g/dl Hgb), and 3+ (< 8 g/dl Hgb), allowing persons to contribute with patient profiles and risk time in consecutively more severe anemia grade cohorts. Patients were stratified by dialysis status and followed for clinical outcomes.ResultsWe identified 16,972 CKD patients contributing with a total of 28,510 anemia patient profiles, of which 3594 had dialysis dependent (DD) and 24,916 had non-dialysis dependent (NDD) severe CKD. Overall, 14% had no anemia, 35% grade 1 anemia, 44% grade 2 anemia and 17% grade 3+ anemia. Compared to patients with no anemia, adjusted hazard ratios (HRs) for NDD patients with grade 3+ anemia were elevated for incident dialysis (1.91, 95% CI 1.61–2.26), any acute hospitalization (1.74, 95% CI 1.57–1.93), all-cause death (1.82, 95% CI 1.70–1.94), and MACE (1.14, 95% CI 1.02–1.26). Similar HRs were observed among DD patients.ConclusionsAmong NDD or DD patients with severe CKD, presence and severity of anemia were associated with increased risks of incident dialysis for NDD patients and with acute hospitalizations, death and MACE for all patients.
Highlights
Anemia is common in patients with chronic kidney disease (CKD) and prevalence increases with CKD severity [1]
The duration of severe CKD, the number of acute hospitalizations, the proportion of patients on dialysis, with low estimated glomerular filtration rate (eGFR) (< 15 ml/min/1.73 m2) and with a high comorbidity score all increased with increasing anemia grade (Table 1)
The incidence rates of incident dialysis among non-dialysis dependent (NDD) patients and of acute hospitalization, all-cause deaths and major cardiovascular events (MACE) among all patients (Table 2) increased markedly with increasing anemia grades both when analyzing crude incidence rates per 100 person years (IR) and hazard ratios for clinical outcomes by anemia grade, and when these were adjusted for baseline differences in potential confounders (Table 2)
Summary
Anemia is common in patients with chronic kidney disease (CKD) and prevalence increases with CKD severity [1]. Treatment options for anemia include iron (oral and intravenous), erythropoietin stimulating agents (ESAs) and red blood cell transfusion to restore hemoglobin levels. Concerns have been raised regarding the cardiovascular safety of treating anemia to higher Hgb levels, in particular when using ESAs to target Hgb levels > 12 g/dl [14–16] This has resulted in a change of anemia management practices since 2011, with generally less intensive therapy and lower Hgb treatment targets [17, 18]. Following this change, high-quality longitudinal real-world data on the current impact of anemia on clinical outcomes are scarce. Routine clinical evidence is limited on clinical outcomes associated with anemia in patients with severe chronic kidney disease (CKD). Conclusions Among NDD or DD patients with severe CKD, presence and severity of anemia were associated with increased risks of incident dialysis for NDD patients and with acute hospitalizations, death and MACE for all patients
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