Anemia and Clinical Outcomes in Patients with Non-dialysis Dependent or Dialysis Dependent Severe Chronic Kidney Disease: a Danish Population-based Study

Background: Routine clinical evidence is limited on clinical outcomes associated with anemia in patients with severe chronic kidney disease (CKD).

Methods: We linked population-based medical databases to identify individuals with severe CKD (eGFR < 30 mL/min/1.73 m) 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.

Results: We 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.

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.