Clinical samples from non-dialysis chronic kidney disease (ND-CKD) patients showed that declined renal function was associated with a significant increase in OPG and sclerostin.244 Among them, serum OPG levels are tightly associated with the severity of kidney damage,245 diabetic nephropathy,246 cardiovascular mortality risk in patients with chronic kidney disease,247 and 5-year all-cause mortality in patients with chronic kidney disease.248 However, in vivo studies to illustrate the detailed regulation of OPG in renal functions are required. This evidence concerns the gene TNFRSF11B and Nephropathy.