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Title: | Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy. | Austin Authors: | Jandeleit-Dahm, K;Cao, Zemin;Cox, Allison J;Kelly, D J;Gilbert, Richard E;Cooper, Mark E | Affiliation: | Department of Medicine, University of Melbourne, Austin, Victoria, Australia | Issue Date: | 1-Jul-1999 | Publication information: | Kidney International. Supplement; 71(): S31-6 | Abstract: | It has been suggested that lipids promote renal injury and that 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors confer renoprotection in certain renal diseases, including diabetic nephropathy.Sprague-Dawley rats were randomized to sham, subtotal nephrectomy (STNx) or STNx + atorvastatin groups. After 12 weeks, proteinuria, renal function, glomerular injury, renal transforming growth factor-beta (TGF-beta) gene expression and macrophage (ED1-positive cells) accumulation were assessed. In addition, the effects of HMG CoA reductase in human diabetic nephropathy were reviewed.Atorvastatin therapy was associated with a modest reduction in proteinuria and glomerulosclerosis without influencing lipid levels or renal function in STNx rats. These effects were associated with decreased renal TGF-beta 1 gene expression and less glomerular and tubulointerstitial macrophage accumulation. The renoprotective effects of HMG CoA reductase inhibitors in both insulin- and non-insulin-dependent diabetic subjects with either incipient or overt nephropathy appear to be highly variable.HMG CoA reductase inhibition appears to confer renoprotection via effects on prosclerotic cytokines such as TGF-beta and macrophage accumulation, independent of their lipid-lowering properties. The role of lipid-lowering agents in early or overt diabetic nephropathy remains to be fully ascertained. | Gov't Doc #: | 10412733 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/9169 | Journal: | Kidney International. Supplement | URL: | https://pubmed.ncbi.nlm.nih.gov/10412733 | Type: | Journal Article | Subjects: | Animals Anticholesteremic Agents.therapeutic use Clinical Trials as Topic Diabetic Nephropathies.drug therapy Disease Progression Gene Expression.drug effects Heptanoic Acids.therapeutic use Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors.therapeutic use Hyperlipidemias.physiopathology In Situ Hybridization Kidney Diseases.drug therapy.pathology.physiopathology Kidney Glomerulus.drug effects.metabolism.pathology Lovastatin.therapeutic use Male Nephrectomy Pravastatin.therapeutic use Pyrroles.therapeutic use Rats Rats, Sprague-Dawley Simvastatin.therapeutic use Transforming Growth Factor beta.genetics |
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