Abstract
<title>Abstract</title> <p>Chronic kidney disease (CKD) is driven by persistent inflammation, tubular injury, fibrosis, and metabolic failure, yet treatments that reverse these linked processes remain limited. Here we show that the pan-cyclin-dependent kinase (CDK) inhibitor CGP-60474 attenuates adenine-induced CKD in mice. Treatment improved kidney function and reduced tubular injury and fibrosis. Single-cell RNA sequencing revealed suppression of inflammatory programs in monocytes and neutrophils, alongside partial recovery of oxidative metabolism in tubular cells, particularly thick ascending limb and distal convoluted tubule populations. Computational analysis of cell–cell communication suggested weaker bidirectional signaling between myeloid and tubular cells, including SPP1, FN1, TNF, TGF-β, and complement signaling. Serum proteomics supported reduced systemic inflammation and lower kidney injury molecule-1 (KIM-1). Together, these findings indicate that CGP-60474 counteracts linked immune and metabolic dysfunction in CKD and support further evaluation of pan-CDK inhibition as a disease-modifying strategy.</p>