Chronic kidney disease (CKD) is the 10th leading cause of death in the United States because of the increased risk for cardiovascular mortality. The major functional cell type of the kidney, tubular epithelial cells (TECs), possess a limited ability to regenerate tissues. Infections can cause proximal G2/M cell cycle arrest, senescence and paracrine secretion of the profibrotic cytokines transforming growth factor-β1 (TGF-β1) and connective tissue growth factor (CTGF), which stimulate extracellular matrix production ultimately leading to loss of the epithelial phenotype in TECs. Identification of targets controlling the G2/M cell cycle arrest in TECs may enable the development of therapeutics that can prevent CKD progression.