title: Systemic and renal lipids in kidney disease development and progression.
abstract: Altered lipid metabolism characterizes proteinuria and chronic kidney diseases. While it is thought that dyslipidemia is a consequence of kidney disease, a large body of clinical and experimental studies support that altered lipid metabolism may contribute to the pathogenesis and progression of kidney disease. In fact, accumulation of renal lipids has been observed in several conditions of genetic and nongenetic origins, linking local fat to the pathogenesis of kidney disease. Statins, which target cholesterol synthesis, have not been proven beneficial to slow the progression of chronic kidney disease. Therefore, other therapeutic strategies to reduce cholesterol accumulation in peripheral organs, such as the kidney, warrant further investigation. Recent advances in the understanding of the biology of high-density lipoprotein (HDL) have revealed that functional HDL, rather than total HDL per se, may protect from both cardiovascular and kidney diseases, strongly supporting a role for altered cholesterol efflux in the pathogenesis of kidney disease. Although the underlying pathophysiological mechanisms responsible for lipid-induced renal damage have yet to be uncovered, several studies suggest novel mechanisms by which cholesterol, free fatty acids, and sphingolipids may affect glomerular and tubular cell function. This review will focus on the clinical and experimental evidence supporting a causative role of lipids in the pathogenesis of proteinuria and kidney disease, with a primary focus on podocytes.
authors.affiliation: Peggy and Harold Katz Family Drug Discovery Center and Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Patricia
authors.initials: P
authors.lastname: Wahl
authors.affiliation: Peggy and Harold Katz Family Drug Discovery Center and Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Gloria Michelle
authors.initials: GM
authors.lastname: Ducasa
authors.affiliation: Peggy and Harold Katz Family Drug Discovery Center and Division of Nephrology and Hypertension, University of Miami Miller School of Medicine, Miami, Florida afornoni@med.miami.edu.
authors.forename: Alessia
authors.identifier: http://orcid.org/0000-0001-7902-2373
authors.initials: A
authors.lastname: Fornoni
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D018450:Disease Progression; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology*; D050356:Lipid Metabolism; D008074:Lipoproteins / Q000097:blood; D050199:Podocytes / Q000502:physiology*; D011507:Proteinuria / Q000209:etiology*
chemical_list: D008074:Lipoproteins; D002784:Cholesterol
keywords: cholesterol; dyslipidemia; kidney disease; lipids; podocytes