Longitudinal Kidney Function Trajectories and Their Association With Hemoglobin and Transfusion Phenotype in Adults With β‐Thalassemia

ABSTRACT Renal functional trajectories and their associations with hemoglobin exposure remain incompletely characterized in adults with β‐thalassemia. We analyzed 994 adults (806 transfusion‐dependent thalassemia [TDT], 188 non‐transfusion‐dependent thalassemia [NTDT]) followed in the Italian Webthal network for up to 16 years. eGFR was estimated using CKD‐EPI 2021 and analyzed using mixed‐effects models. Baseline hyperfiltration was present in 22%, but was not associated with significantly faster subsequent eGFR decline. Overall eGFR declined by −1.13 mL/min/1.73 m 2 /year (95% CI, −1.20 to −1.07), with a steeper trajectory in TDT than NTDT. In 877 patients (5529 observations), models incorporating one‐year‐lagged, time‐varying hemoglobin and baseline eGFR showed that hemoglobin–eGFR associations differed across transfusion phenotypes. Among phenoconverted patients, higher lagged hemoglobin was associated with a more negative age‐related eGFR slope, persisting in sensitivity analyses accounting for baseline eGFR. Adjustment for hemoglobin did not eliminate phenotype‐related differences in slopes. Chelation regimen was not associated with slope differences in the selected long‐term monotherapy subgroup. Thus, renal trajectories vary by transfusion phenotype, and their associations with hemoglobin exposure are heterogeneous. Whether declining eGFR reflects attenuation of hyperfiltration or progressive renal injury cannot be established from these observational data.