There is no specific cure for chronic kidney disease (CKD), which affects one in every ten adults. The unmet medical need has created significant interest in regenerative therapeutic approaches. Described herein is a radically new and innovative therapeutic approach identified by characterizing a novel mechanism of renal tissue repair and its role in glomerular injury. By targeting this mechanism in CKD, significant therapeutic benefit supported by rapid cellular remodeling of kidney tissues, coincident with structural and functional nephron regeneration. Methods and compositions for achieving the described therapeutic approach are fundamentally different from existing strategies.