Amino acid infusion and SGLT2 inhibitors for kidney protection: Plausible adverse impact of tubular transport load on renal tissue oxygenation

Amino acids and SGLT2 inhibitors (SGLT2i) have recently been reported to attenuate the risk of hypoxic acute kidney injury (AKI), determined by changes in estimated glomerular filtration rate (GFR) following cardiac surgery and interventions with radiocontrast media, respectively. Yet, strategies to prevent or treat hypoxic AKI by the intensification of GFR, such as the administration of amino acids, in fact may predispose to intensified renal hypoxia and potential injury through enhanced tubular transport activity. Likewise, SGLT2i may intensify medullary hypoxia by translocating oxygen consumption for tubular transport from proximal to distal nephron segments. The outer medulla is particularly susceptible to hypoxic AKI, since intense regional oxygen consumption is barely met by a limited local blood supply, as reflected by low ambient oxygenation under normal conditions. In fact, declining GFR during AKI to large extent attenuates medullary hypoxia by the reduction of solute delivery for reabsorption in the distal nephron. Therefore, as outlined in this review, despite encouraging clinical outcomes, the safety, regarding renal parenchymal integrity, of enhancing GFR with amino acid infusion or by translocation of tubular transport to distal nephron segments by SGLT2i, administered to prevent AKI, should be assured, possibly by the determination of biomarkers of renal injury. Changes in renal oxygen expenditure, particularly within the hypoxic medulla should be considered in designing therapeutic interventions, conceivably with efforts aimed at reducing, rather than enhancing medullary tubular transport. • Amino acid infusion attenuates the decline in kidney function after heart surgery. • SGLT2 inhibitors may decrease the risk of radiocontrast-associated AKI (RA-AKI). • Such interventions may enhance distal tubular transport and intensify medullary hypoxia. • The impact of such interventions on medullary integrity has not been evaluated so far. • Tubular oxygen consumption should be taken ito account in strategies of AKI prevention.