Dynamic Hemoglobin Trajectories in Renal Anemia and Their Association with Frailty Progression and Cardiovascular...

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 trajectory patterns are associated with frailty worsening and CV events.

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 the 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.

Follow-up at 12 months was available for 182 of 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 participants who declined, 45% of participants who fluctuated, and 25% of participants who remained stable. 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.

A declining 12-month hemoglobin trajectory was associated with increased risk of frailty worsening and cardiovascular events compared with a stable profile.