Increase in hematocrit with SGLT-2 inhibitors - Hemoconcentration from diuresis or increased erythropoiesis after amelioration of hypoxia?

Abstract

Background and aims: The SGLT2-inhibitors significantly reduce heart failure hospitalization and progression to end-stage kidney disease. An increase in hemoglobin/hematocrit is seen with SGLT2i-inhibitor treatment. This increase has been attributed to hemoconcentration resulting from a diuretic effect. In this review, we present evidence suggesting that the hematocrit increase is not due to hemoconcentration, but to an increase in erythropoiesis due to amelioration of hypoxia and more efficient erythropoietin production with SGLT2-inhibitor treatment.

Methods: We performed a detailed review of the literature in PubMed for articles describing various mechanisms linking hematocrit increase with SGLT2-inhibitor use to their cardio-renal benefits.

Results: The best predictor of cardio-renal benefits with SGLT2-inhibitors is an increase in hematocrit and hemoglobin. If this hemoconcentration is a results of diuresis, this would be associated with volume contraction and a deterioration in renal function, as seen with long-term diuretic use. This is the opposite of what is seen with the use of SGLT2-inhibitors, which are associated with long-term preservation of renal function. There is now growing evidence that the increase in hematocrit can be attributed to an increase in erythropoiesis due to amelioration of renal hypoxia and more efficient erythropoietin production with SGLT2-inhibitor treatment. Increased erythropoiesis leads to an increase in RBC count which improves myocardial/renal tissue oxygenation and function.

Conclusion: The increase in hematocrit with SGLT2i treatment is not due to hemoconcentration, but to an increase in erythropoiesis due to amelioration of hypoxia and more efficient erythropoietin production with SGLT2i treatment.