SLCs in diabetic kidney disease: From pathogenic roles to therapeutic promises

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, with its burden rising alongside diabetes prevalence. Current treatments only slow disease progression, highlighting an urgent need for new therapeutic targets. Solute carrier (SLC) transporters, critical for nutrient transport and metabolic homeostasis, are emerging as key regulators in DKD pathogenesis. The efficacy of SGLT2 inhibitors further supports a significant role for SLCs in DKD. Through a comprehensive literature search (PubMed, Web of Science; September 2020-2025), this review synthesizes evidence on the regulatory roles and mechanisms of SLC family members in DKD progression. We summarize kidney-enriched SLC members and their distribution, focusing on SGLTs (SLC5), GLUTs (SLC2), SLC12A3, and SLC7A11 in DKD progression. These transporters mediate glucose, amino acids, and electrolyte flux, and are extensively involved in oxidative stress, ferroptosis, inflammation, and fibrosis. Finally, we discuss current status and future directions of SLC-based DKD therapies, aiming to overcome therapeutic bottlenecks and identify novel targets.