HMG-CoA Reductase Inhibitors and Renal Function

[摘要] The presence of lipids in renal cells upregulates intracellular signaling pathways involved in inflammatory and fibrogenic responses, both of which are components of progressive renal injury. Lipids activate various growth factors that cause mesangial cell proliferation. Mesangial cells bind both LDL and oxidized LDL (ox-LDL), leading to yet more cell proliferation via multiple downstream effects. LDL stimulates the expression of monocyte chemoattractant protein-1 (MCP-1) mRNA, which increases monocyte chemotactic activity (1). LDL also stimulates the expression of fibronectin mRNA, which induces proliferation of mesangial matrix cells. In the extracellular matrix, ox-LDL induces podocyte apoptosis, decreases Akt activity, depletes nephrin (an adhesion molecule specific to the glomerular slit membrane), and induces the retraction of cultured podocytes, which leads to alterations in the glomerular barrier and increased albumin diffusion (2). Both LDL and ox-LDL induce the expression of NF-κB, which has been associated with inflammation in glomerulonephritis and the progression of chronic kidney disease (CKD) (3). It has also been found to induce the expression of genes that encode other cytokines, chemokines, interferons, growth factors, cell adhesion molecules, and MHC proteins involved in inflammation and proliferation (4).

[学科分类] 泌尿医学

[关键词] Bone marrow necrosis;Sickle cell disease;Hyperhemolysis syndrome