Cold atmospheric plasma ameliorating skin barrier in chronic kidney disease

Chronic kidney disease (CKD)-associated skin complications, including pruritus and xerosis, remain clinically challenging due to poorly understood pathological mechanisms. We utilized human skin tissues, adenine-induced CKD mice, and HaCaT cells to evaluate CAP interventions, including direct irradiation and topical application of CAP-activated hydrogel, on epidermal barrier function. Both CKD patients and mice exhibited significant barrier impairment, characterized by suppressed markers of proliferation (PCNA), differentiation (CK1), cornified envelope (filaggrin, loricrin), and tight junctions (claudin-1). CAP treatment effectively reversed these abnormalities, restoring the keratinocyte proliferation/differentiation balance, promoting terminal differentiation, and reducing transepidermal water loss. Mechanistically, CAP coordinated epidermal homeostasis by activating the β-catenin/YAP1 pathway (promoting regeneration) while concurrently inhibiting PI3K/AKT signaling (facilitating differentiation). CAP effectively restores the molecular machinery required for skin barrier integrity in CKD, alleviating associated dermatopathology. These findings establish a scientific basis for CAP as a non-invasive therapy for CKD-related skin complications.