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

Kidney Int Suppl. 1999 Jul;71:S31-6. doi: 10.1046/j.1523-1755.1999.07109.x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticholesteremic Agents / therapeutic use
  • Atorvastatin
  • 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
  • Kidney Diseases / pathology
  • Kidney Diseases / physiopathology*
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / metabolism
  • Kidney Glomerulus / pathology
  • Lovastatin / therapeutic use
  • Male
  • Nephrectomy
  • Pravastatin / therapeutic use
  • Pyrroles / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Simvastatin / therapeutic use
  • Transforming Growth Factor beta / genetics

Substances

  • Anticholesteremic Agents
  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Transforming Growth Factor beta
  • Lovastatin
  • Atorvastatin
  • Simvastatin
  • Pravastatin