HMGCR and chronic kidney disease: The change of decreased HDL in CKD is primarily attributable to hypoalbuminemia and decreased expression of essential HDL constituents including apolipoprotein A. CKD induces hepatic HMG-CoA reductase upregulation and LDL receptor dysfunction through lysosomal impairment, creating a ‘double-hit’ mechanism that elevates LDL-C and TC [18,19].