Abstract
Objective Chronic kidney disease (CKD), including nephrotic syndrome, is a major cause of cardiovascular morbidity and mortality. The literature indicates that CKD is associated with profound lipid disorders largely due to the dysregulation of lipoprotein metabolism which further aggravates the progression of kidney disease. The present study sought to determine the efficacy of atorvastatin treatment on hepatic lipid metabolism and renal tissue damage in CKD rats. Methods Serum, hepatic and faecal lipid contents and the expression and enzyme activity of molecules involved in cholesterol and triglyceride metabolism, along with kidney function, were determined in untreated adenine-induced CKD, atorvastatin-treated CKD (10 mg/kg/day oral for 24 days) and control rats. Key Findings CKD resulted in metabolic dyslipidaemia, renal insufficiency, hepatic lipid accumulation, upregulation of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, acyl-CoA cholesterol acyltransferase-2 (ACAT2) and the downregulation of LDL receptor protein, VLDL receptor, hepatic lipase, lipoprotein lipase (LPL), lecithin–cholesterol acyltransferase (LCAT) and scavenger receptor class B type 1 (SR-B1). CKD also resulted in increased enzymatic activity of HMG-CoA reductase and ACAT2 together with decreased enzyme activity of lipase and LCAT. Atorvastatin therapy attenuated dyslipidaemia, renal insufficiency, reduced hepatic lipids, HMG-CoA reductase and ACAT2 protein abundance and raised LDL receptor and lipase protein expression. Atorvastatin therapy decreased the enzymatic activity of HMG-CoA reductase and increased enzymatic activity of lipase and LCAT. Conclusions Atorvastatin improved hepatic tissue lipid metabolism and renal function in adenine-induced CKD rats.
Highlights
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiological processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate
CKD is consistently associated with reduced plasma high density lipoprotein (HDL) cholesterol concentration, impaired maturation of cholesterol ester-poor HDL-3 to cholesterol ester-rich HDL-2, increased HDL triglycerides and depressed plasma apoA-I [16]. ese abnormalities are primarily due to CKD-induced dysregulation of several important proteins such as lecithin-cholesterol acyltransferase (LCAT) [17, 18], scavenger receptor class B type 1 (SR-B1) [19,20,21] and ATP binding cassette A1 (ABCA1) [22]
The group treated with atorvastatin (10 mg/kg) did not show a significant improvement in body weight compared with CKD rats at the end of the 24-day treatment period
Summary
Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiological processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate. Cellular cholesterol homeostasis is regulated by the influx, biosynthesis, catabolism and efflux of cholesterol. An alteration in these processes can result in the conversion of BioMed Research International macrophages, mesangial cells and vascular smooth muscle cells into foam cells [9]. Cholesterol synthesis in the liver is mediated by several independent pathways including hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in cholesterol biosynthesis, whereas cholesterol catabolism is primarily mediated by the LDL receptor [10]. Lipase is an important enzyme expressed in a variety of tissues, including liver, skeletal muscle, heart and adipose tissue and catalyses the hydrolysis of triglycerides contained in the triglyceride-rich lipoproteins, such as VLDL and chylomicrons [13]. CKD is consistently associated with reduced plasma HDL cholesterol concentration, impaired maturation of cholesterol ester-poor HDL-3 (nascent HDL) to cholesterol ester-rich HDL-2 (mature HDL), increased HDL triglycerides and depressed plasma apoA-I [16]. ese abnormalities are primarily due to CKD-induced dysregulation of several important proteins such as lecithin-cholesterol acyltransferase (LCAT) [17, 18], scavenger receptor class B type 1 (SR-B1) [19,20,21] and ATP binding cassette A1 (ABCA1) [22]
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