Solute carrier inhibitors in kidney disease therapy: mechanisms and clinical implications

Recent single-cell sequencing analyses confirm that solute carriers (SLCs) are highly expressed in renal tubular epithelial cells, where they are critical for maintaining systemic metabolic homeostasis through solute reabsorption, secretion, and detoxification. SLC dysfunction underpins renal disorders, including chronic kidney disease, diabetic kidney disease, and acute kidney injury. Recent advances in SLC biology have enabled the development of selective inhibitors, offering precise pathway modulation with minimal off-target effects. Clinically, SLC inhibitors have demonstrated efficacy in nephrology, with five SLCs emerging as validated therapeutic targets: SLC5A2 (Na⁺-glucose co-transporter 2), SLC7A11 (xCT cystine/glutamate antiporter), SLC12A3 (Na⁺-Cl^- co-transporter), SLC22A12 (urate transporter 1), and SLC47A1 (multidrug and toxin extrusion protein 1). This article systematically reviews the pharmacological mechanisms of SLC inhibitors targeting these five transporters, analyzing their physiological and pathological roles in kidney diseases, and further discusses clinical applications and future prospects of SLC-targeted therapies in nephrology.