#2175 Sodium-glucose cotransporter 2 (SGLT2) inhibitors-induced erythropoiesis and cardiovascular events in chronic kidney patients

Abstract

Abstract Background and Aims Prior research has established that in chronic kidney disease (CKD), elevating hemoglobin (Hb) levels above 11.5 g/dl correlates with heightened thromboembolic event risks and increased mortality. Similar findings are seen in heart failure patients with Hb levels exceeding 13 g/dl, following treatment with erythropoiesis-stimulating agents. Sodium-glucose cotransporter 2 (SGLT2) inhibitors consistently raise Hb levels in CKD patients, both anemic and non-anemic. This study aims to evaluate the consequences of Hb level elevation due to SGLT2 inhibitors beyond the safe threshold in CKD patients and to investigate its association with cardiovascular (CV) events. Method A retrospective observational study was conducted from January 2016 to December 2021, focusing on CKD patients treated with SGLT2 inhibitors. Patients receiving erythropoiesis-stimulating agents or undergoing renal replacement therapy were excluded. We assessed the impact of Hb level changes on atheroembolic events, blood pressure variations, and mortality, while considering demographic data, red blood cell parameters, and renal function indicators. Patients receiving iron treatment were excluded to ensure accurate ferrokinetic parameter assessment. Results The study included 79 CKD patients, predominantly male (76%) and primarily with type 2 diabetes mellitus (T2DM) as the CKD cause (67%). Average follow-up post-SGLT2 inhibitor initiation was 3.5 years (SD 1.4, 0.7-6.7 years). Hb levels increased mainly in the first six months of treatment, with an average increase of 0.7 g/dl/year from baseline (p < 0.01). Ferritin levels slightly decreased (p 0.002), while the transferrin saturation index remained stable. Baseline estimated glomerular filtration rate (eGFR) did not influence Hb increase. Various responses to SGLT2 inhibitors were noted based on baseline Hb levels. No significant association was found between elevated Hb levels (>16.0 g/dl) and increased atheroembolic events, mortality, or blood pressure changes. However, patients with Hb levels >13.0 g/dl experienced more CV events compared to those maintaining Hb ≤13.0 g/dl, though not statistically significant (0% vs 17.5%: p 0.30). Conclusion SGLT2 inhibitor treatment led to a significant Hb increase unless baseline levels were above 16.0 g/dl. Importantly, elevating Hb levels above 13.0 g/dl appears to be linked with a higher incidence of cardiovascular (CV) events, suggesting a potential risk associated with such an increase in Hb levels in this patient population. This finding underscores the necessity for further research to confirm this correlation and to delineate the safe therapeutic window for Hb levels in CKD patients treated with SGLT2 inhibitors.