CRRT 2023 Meeting: Targeting Amino Acid Transport to Improve Acute Kidney Injury Outcome.

BACKGROUND:In acute kidney injury (AKI), proximal tubules are a primary site of injury, resulting in significant alterations in amino acid transport and metabolism. However, little is known about the therapeutic potential of targeting amino acid transporters. Here, we briefly review the first experimental evidence that targeting the sodium-coupled amino acid transporter SLC6A19 (B0AT1) can improve AKI outcome. SUMMARY:SLC6A19 is expressed in the small intestine and early proximal tubules, where it absorbs and reabsorbs most of the ingested and filtered neutral amino acids, respectively. Systemic SLC6A19 deficiency alleviates renal cellular senescence and suppresses subsequent inflammation and fibrosis in a murine model of aristolochic acid-induced nephropathy, which targets the proximal tubule. The underlying mechanisms remain to be determined, but potentially may include reduced tubular workload, an inhibitory effect on SGLT2, downstream shift in transport and preconditioning of late proximal tubules, and induction of a fasting-like phenotype and lowering tubular accumulation of branched-chain amino acids, which all can promote tubular health.