Distinct Hemoglobin Trajectories and Their Prognostic Implications in Chronic Kidney Disease: Findings From the KNOW-CKD Cohort

Rationale & Objective Anemia is a common comorbidity in patients with chronic kidney disease (CKD) and has been associated with adverse kidney and cardiovascular outcomes. However, longitudinal patterns of hemoglobin (Hb) change and their prognostic implications remain unclear. We aimed to identify distinct Hb trajectories and evaluate their associations with clinical outcomes in CKD Study Design This was a prospective observational cohort study using data from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were followed longitudinally with repeated hemoglobin measurements for up to 10 years. Setting & Participants Adults with CKD stages 1–5 (non–dialysis dependent) and baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m 2 were eligible. Participants were required to have at least 12 months of follow-up. Exposure Group-based trajectory modeling (GBTM) was applied to repeated Hb measurements at baseline, 6 months, and annually to identify subgroups with similar longitudinal Hb patterns. Outcome The primary endpoint was a composite kidney outcome (≥50% decline in eGFR, doubling of serum creatinine, initiation of dialysis, or kidney transplantation). Secondary endpoints were cardiovascular events and all-cause mortality. Analytic Approach Hb trajectories were modeled using GBTM, specifying Hb as a continuous outcome and time as the independent variable. Candidate models with two to seven groups were compared, and the final model was chosen based on statistical fit and clinical interpretability. Results GBTM identified four distinct Hb trajectories: high, moderately high, intermediate, and low. Compared with the intermediate trajectory, the high group showed substantially lower risk of the composite kidney outcome (hazard ratio [HR], 0.151; 95% confidence interval [CI], 0.083–0.276), the moderately high group showed comparable risk (HR, 0.686; 95% CI, 0.480–0.980), and the low group had higher risk (HR, 1.300; 95% CI, 0.901–1.877). No significant associations were observed with cardiovascular events or all-cause mortality after full adjustment. Conclusions Distinct Hb trajectories were strongly associated with kidney outcomes in CKD. Sustained higher Hb trajectories conferred favorable renal prognosis, whereas persistently low trajectories predicted adverse outcomes. Beyond static Hb values, trajectory-based assessment may provide a novel framework for individualized risk stratification and anemia management in CKD.