The role of TLR4 on diabetic nephropathy has been extensively explored in preclinical studies but, to our knowledge, our work is the first to describe the impact of TLR4 on CKD progression in a model that resembles nondiabetic human disease with characteristics that include progressive albuminuria, loss of kidney function, glomerulosclerosis, and interstitial fibrosis. Here, TLR4 is linked to chronic kidney disease.