Impact of hemoglobin levels on renal and non-renal clinical outcomes differs by chronic kidney disease stages: the Gonryo study

Background: Anemia greatly affects the development of renal and cardiovascular outcomes in chronic kidney disease (CKD) patients. However, the impact based on CKD stage remains unclear. Methods: We prospectively followed 2,602 Japanese CKD patients under the care of nephrologists. CKD was defined according to cause, estimated glomerular filtration rate <60 mL/min, and/or proteinuria. Patient outcomes [primary end-points: cardiovascular events (CVEs), all-cause mortality, and end-stage kidney disease (ESKD) requiring renal replacement therapy] were assessed in association with basal hemoglobin (Hb) levels (<10, 10–12 and ≥12 g/dL), stratified by CKD stages. Results: During follow-up, 123 patients developed CVEs, 41 died, and 220 progressed to ESKD. For stages G3, G4 and G5, ESKD frequencies were 2.8, 64.4, and 544.8 person-years, while CVEs and death were 25.6, 45.6, and 76.3 person-years, respectively. The combined endpoint rate was significantly higher in patients with Hb <10 versus Hb 10–12 g/dL, but a higher risk for CVEs and death with Hb <10 g/dL was found only in G3 [hazard ratio (HR) 4.49, (95 % confidence interval (95 % CI) 2.06–9.80)]. In contrast, risk for ESKD with Hb <10 g/dL was found only in G4 [HR 3.08 (95 % CI 1.40–6.79)] and G5 [HR 1.43 (95 % CI 1.01–2.05)]. No increased risks with higher Hb levels were found. Conclusion: The impact of renal anemia of Hb <10 g/dL on clinical outcomes differed by CKD stage, with a significantly high risk for CVEs and all-cause mortality in G3 and progression to ESKD in G4 and G5.