Mechanisms of dyslipidemia in chronic kidney disease

Abstract

LETTERS TO THE EDITORMechanisms of dyslipidemia in chronic kidney diseaseMichal Chmielewski and Boleslaw RutkowskiMichal Chmielewski and Boleslaw RutkowskiPublished Online:01 Sep 2009https://doi.org/10.1152/ajprenal.00269.2009MoreSectionsPDF (27 KB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInEmailWeChat to the editor: We have read with interest the article by Kim et al. (3) published in the American Journal of Physiology-Renal Physiology. It extends our understanding of the mechanisms involved in the development of lipid disorders in the course of chronic kidney disease (CKD), an area that is still far from being fully elucidated. In their study on a nephrectomy model of CKD, the authors demonstrated decreased gene expression and protein abundance of the nuclear, i.e., active, fraction of sterol regulatory element-binding protein-2 (SREBP-2) in the remnant kidneys. This nuclear transcription factor is regarded as the major regulator of cholesterol synthesis. Moreover, both gene expression and protein abundance of renal SREBP-1, the transcription factor involved in lipogenesis, was also found to be reduced. We regard this as an important and a very intriguing finding. Previous studies have demonstrated increased SREBP expression in kidneys of animals with diabetic (5) and age-related nephropathy (2). Both in the course of diabetes and in an aging kidney, this increase leads to enhanced lipid synthesis and to renal lipid accumulation, phenomena that contribute to kidney injury and to CKD progression. In contrast, according to the study by Kim et al. (3), CKD caused by nephrectomy results in decreased SREBP expression and lipid synthesis, pointing to a hypothesis that patomechanisms of renal lipid accumulation differ depending on the origin of CKD.Another intriguing conclusion that could be derived from this study is that SREBP expression and lipid synthesis during experimental CKD are different in particular organs. Our studies on a similar model of CKD achieved by a nephrectomy showed enhanced gene expression and protein abundance of SREBP-1 in white adipose tissue (4) and of SREBP-2 in livers (1) of CKD rats. These alterations were followed by increased lipogenesis and cholesterol synthesis in these tissues, contributing to overt hypertriglyceridemia and hypercholesterolemia found in experimental CKD. Increased plasma lipid concentrations, in turn, could enable enhanced lipid influx to the kidneys, a finding demonstrated by Kim et al. (3) in their study. All of these studies complement each other, and still many more are needed to fully clarify the mechanisms that lead to lipid disorders in CKD, their significance in the progression of kidney injury and in patient outcome.REFERENCES1 Chmielewski M, Sucajtys-Szulc E, Kossowska E, Swierczynski J, Rutkowski B, Boguslawski W. Increased gene expression of liver SREBP-2 in experimental chronic renal failure. Atherosclerosis 191: 326–332, 2007.Crossref | PubMed | ISI | Google Scholar2 Jiang T, Liebman SE, Lucia MS, Li J, Levi M. Role of altered renal lipid metabolism and the sterol regulatory element binding proteins in the pathogenesis of age-related renal disease. Kidney Int 68: 2608–2620, 2005.Crossref | PubMed | ISI | Google Scholar3 Kim HJ, Moradi H, Yuan J, Norris K, Vaziri ND. Renal mass reduction results in accumulation of lipids and dysregulation of lipid regulatory proteins in the remnant kidney. Am J Physiol Renal Physiol 296: F1297–F1306, 2009.Link | ISI | Google Scholar4 Korczynska J, Stelmanska E, Nogalska A, Szolkiewicz M, Goyke E, Swierczynski J, Rutkowski B. Upregulation of lipogenic enzymes genes expression in white adipose tissue of rats with chronic renal failure is associated with higher level of sterol regulatory element binding protein-1. Metabolism 53: 1060–1065, 2004.Crossref | PubMed | ISI | Google Scholar5 Sun L, Halaihel N, Zhang W, Rogers T, Levi M. Role of sterol regulatory element-binding protein 1 in regulation of renal lipid metabolism and glomerulosclerosis in diabetes mellitus. J Biol Chem 277: 18919–18927, 2002.Crossref | PubMed | ISI | Google Scholar Download PDF Previous Back to Top FiguresReferencesRelatedInformationCited ByCardiovascular Risk Factors, Inflammation, and Corneal Arcus: The Singapore Malay Eye StudyAmerican Journal of Ophthalmology, Vol. 150, No. 4Reno-protective effects of atorvastatin independent of blood cholesterol loweringAcademic Journal of Second Military Medical University, Vol. 30, No. 7 More from this issue > Volume 297Issue 3September 2009Pages F835-F835 Copyright & PermissionsCopyright © 2009 the American Physiological Societyhttps://doi.org/10.1152/ajprenal.00269.2009PubMed19692497History Published online 1 September 2009 Published in print 1 September 2009 Metrics