Secretory Leukocyte Protease Inhibitor: A Pleiotropic Molecule in Potential Diagnosis and Therapy of Acute Kidney Injury

Acute kidney injury (AKI) remains a common clinical syndrome associated with high morbidity and mortality. Yet, effective diagnostic biomarkers and specific therapeutic interventions are still lacking. Secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor with pleiotropic functions, has emerged an early diagnostic biomarker for AKI. Clinical studies reveal significant elevation of serum SLPI in AKI patients compared to non-AKI patients at the acute phase following post cardiovascular surgery, supporting its diagnostic potential. Beyond, current evidence highlights the biological functions of SLPI in inhibiting NF-κB activities, suppressing neutrophil extracellular trap formation, modulating phagocytosis, regulating cell apoptosis, proliferation, differentiation, and potentially fibrosis, across various disease contexts. Preclinical studies demonstrate that administration of recombinant SLPI ameliorates renal dysfunction in multiple AKI models, including ischemia-reperfusion injury and nephrotoxic models induced by gentamicin or cisplatin. Furthermore, the antifibrotic properties of SLPI underscore its therapeutic potential in halting AKI progression to chronic kidney disease. By integrating available evidence, this review aims to elucidate the diagnostic and therapeutic values of SLPI in AKI and propose promising SLPI-based strategies for managing the challenging condition of AKI.