Role of hyperlipidemia in progressive renal disease: focus on diabetic nephropathy.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicine, University of Melbourne, Austin, Victoria, Australia.
K
K
Jandeleit-Dahm
Z
Z
Cao
A J
AJ
Cox
D J
DJ
Kelly
R E
RE
Gilbert
M E
ME
Cooper
D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D000069059:Atorvastatin; D002986:Clinical Trials as Topic; D003928:Diabetic Nephropathies / Q000188:drug therapy; D018450:Disease Progression; D015870:Gene Expression / Q000187:drug effects; D006538:Heptanoic Acids / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000503:physiopathology*; D017403:In Situ Hybridization; D007674:Kidney Diseases / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008148:Lovastatin / Q000627:therapeutic use; D008297:Male; D009392:Nephrectomy; D017035:Pravastatin / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000627:therapeutic use; D016212:Transforming Growth Factor beta / Q000235:genetics
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D008148:Lovastatin; D000069059:Atorvastatin; D019821:Simvastatin; D017035:Pravastatin