DYNAMIC HEMOGLOBIN TRAJECTORIES IN RENAL ANEMIA AND THEIR ASSOCIATION WITH FRAILTY PROGRESSION AND CARDIOVASCULAR EVENTS IN NON‑DIALYSIS CHRONIC KIDNEY DISEASE
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Background: In non-dialysis chronic kidney disease (ND-CKD), anemia, frailty, and cardiovascular (CV) complications intersect, yet the prognostic relevance of within-patient hemoglobin (Hb) change over time remains unclear. We tested whether distinct 12-month Hb trajectories patterns are associated with frailty worsening and CV events.
Methods: Adults with stage 3–5 ND-CKD and renal anemia (men <13 g/dL; women <12 g/dL) were enrolled at a single center (June–December 2023) and followed monthly for 12 months. Hb was measured monthly. Latent-class mixed models were used to derive stable, declining, and fluctuating Hb trajectories from all available Hb measurements during follow-up. Frailty was assessed at baseline, 6 months, and 12 months. Frailty worsening was prespecified as a ≥1-point increase in FRAIL score or new onset of weak grip or slow gait. Associations were evaluated using mixed-effects logistic regression (frailty worsening) and cause-specific Cox models (time-to-first composite CV event), adjusting for key clinical covariates.
Results: Follow-up at 12 months were available for 182/190 (95.8%) participants. Trajectory allocation was 39% stable, 41% declining (mean slope −0.18 g/dL/month), and 20% fluctuating (higher within-person variability). Frailty worsened in 57% of declining, 45% of fluctuating, and 25% of stable participants. Adjusted odds ratios versus Stable were 2.8 (95% CI 1.6–5.0) for Declining and 1.9 (0.9–4.0) for Fluctuating. Over 185 person-years, 46 composite CV events occurred (24.9/100 person-years), and adjusted hazard ratios were 2.6 (1.4–4.9) for Declining and 1.7 (0.8–3.6) for Fluctuating.
Conclusion: A 12-month Declining Hb trajectory was independently associated with substantially higher odds of frailty worsening and higher hazard of CV events compared with a Stable profile, whereas a Fluctuating pattern showed intermediate, non-significant associations. Longitudinal Hb trend monitoring may help identify ND-CKD patients who warrant closer anemia evaluation alongside frailty-focused interventions.
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