DOI: 10.34067/kid.0000001305 ISSN: 2641-7650

Impact of Altitude on Hemoglobin Response to Sodium-Glucose Cotransporter 2 Inhibitors in CKD

Mabel Aoun, Magdalena Madero, Ana Karen Fernández Yepez, Maize Ducret, William Hanf, Christopher Loens, Jean-Baptiste Philit, Michel Jadoul, Hans-Joachim Anders
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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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