Key result
High altitude exposure in CKD patients on SGLT2 inhibitors links to hemoglobin overshoot and thrombosis.
Why the study?
Does altitude affect the hemoglobin response and thrombotic risk in CKD patients treated with SGLT2 inhibitors?
Cohort (n=206)
Yes
Does altitude affect the hemoglobin response and thrombotic risk in CKD patients treated with SGLT2 inhibitors?
p-value: p=0.03
SGLT2 inhibitors increase hemoglobin levels in CKD patients across all altitudes, but living at high altitude (>2,000 m) may increase the risk of thrombotic events associated with hemoglobin overshoot.
Background: SGLT2 inhibitors increase hemoglobin levels and may cause erythrocytosis. Patients living at altitude might be more prone to this effect. This study examines altitude's impact on the hematological response to SGLT2 inhibition in patients with chronic kidney disease (CKD). Methods: This retrospective study compared patients at altitude (French Alps and Mexico) with sea-level controls in France. Inclusion required >3 months of SGLT2 inhibitor use. Linear mixed-effects model assessed hemoglobin trajectories over time, adjusting for altitude, age, sex, diabetes, baseline eGFR, diuretic use and comorbidities. Results: A total of 206 patients (70±12 years, 74.8% men) were included: 57 at sea level, 59 in the Alps (787±275 m), and 90 in Mexico (2,220±243 m). Dapagliflozin and empagliflozin were prescribed in 85% and 15% of cases, respectively. Baseline eGFR was 37 (30-48) mL/min/1.73 m 2 and hemoglobin 13.3±1.7 g/dL. Hemoglobin levels increased significantly from baseline to 3, 6, and 12 months ( P <0.001). Mean increases were 0.3, 0.7, and 1.4 g/dL at sea level; 0.4, 1.2, and 1.4 g/dL in the Alps; 0.6, 0.7, and 1.0 g/dL in Mexico at 3, 6, and 12 months, respectively. The linear mixed-effects model demonstrated significant effects of time (F=15.21 P <0.001), altitude (F=3.6, P =0.03), and sex (F=20.2, P <0.001) with no significant overall time-by-altitude interaction. However, significant time-by-altitude interactions were observed among patients with CKD stages 4-5 and women. Over 12 months, erythrocytosis occurred in 3.8% of women and 19.5% of men. Eight thrombotic events occurred in seven patients, all at >2,000 m: adjusted analyses showed independent associations with hemoglobin change at 6 and 12 months (OR 2.3 and 2.6 respectively). Conclusions: Patients with CKD on SGLT2 inhibitors showed a progressive increase in hemoglobin over 12 months, consistent across altitudes, although with a time-by-altitude interaction in advanced CKD and in women. Hemoglobin overshoot increased thrombotic risk at high altitude.
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Aoun et al. (2026) conducted a cohort in chronic kidney disease (CKD) (n=206). High altitude vs. Sea level was evaluated on hemoglobin trajectories over time (p=0.03). High altitude exposure in CKD patients on SGLT2 inhibitors was significantly associated with hemoglobin trajectories (P=0.03), and hemoglobin overshoot increased thrombotic risk at high altitude.
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