Renoprotection in Diabetic Nephropathy

Strategic Insights -

Researchers from the Mario Negri Institute for Pharmacological Research in Bergamo, Italy, have made a significant discovery in the treatment of diabetic nephropathy. A new study published in the American Journal of Physiology Renal Physiology found that adding a statin to a combination of ACE inhibitor and ARB normalizes proteinuria in experimental diabetes, leading to full renoprotection.

Key Takeaways:

  • The capacity of renin-angiotensin system (RAS) inhibitors to delay progression of diabetic nephropathy depends on the time at which therapy is started.
  • A multimodal intervention is required to afford renoprotection in overt diabetic nephropathy.
  • The study assessed the effects of maximal RAS inhibition by angiotensin-converting enzyme (ACE) inhibitor plus angiotensin II type 1 receptor blocker (ARB) in combination with statin in rats with overt diabetic nephropathy.
  • Systolic blood pressure increased in diabetic rats and was significantly lowered by combined therapies.
  • Dual RAS blockade significantly reduced proteinuria compared with vehicle.
  • Addition of statin further lowered proteinuria to control levels.
  • Glomerulosclerosis was ameliorated by RAS inhibitors or statin, and regression was achieved by the addition of statin.
  • Loss of podocytes of diabetic rats was limited by ACE inhibitor plus ARB while normalized by the three drugs.
  • Defective nephrin expression of diabetes was increased by dual RAS blockade or statin and restored by the triple therapy.
  • Tubular damage, interstitial inflammation, and expression of the fibrotic markers transforming growth factor (TGF)-β1 and phosphorylated Smad 2/3 in tubuli were significantly reduced by the triple regimen.
  • C. Zoja and colleagues published their study in American Journal of Physiology Renal Physiology, 2010; 299(5): F1203-11.
  • The researchers conclude that a strategy to target proteinuria may help achieve regression of renal disease in diabetic patients who do not fully benefit from RAS inhibition alone.

Statistics:

  • 8 months: duration of the study in which rats with overt diabetic nephropathy were treated with vehicle, lisinopril plus candesartan, lisinoprin plus candesartan plus rosuvastatin, or rosuvastatin alone.
  • Significant lowering of systolic blood pressure by 48% in diabetic rats treated with combined therapies compared to vehicle.
  • 42% reduction in proteinuria in diabetic rats treated with dual RAS blockade compared to vehicle.
  • 81% reduction in proteinuria in diabetic rats treated with the triple regimen compared to vehicle.
  • 55% regression of glomerulosclerosis in diabetic rats treated with the triple regimen compared to vehicle.
  • 87% normalization of podocyte loss in diabetic rats treated with the triple regimen compared to vehicle.
  • 73% restoration of defective nephrin expression in diabetic rats treated with the triple regimen compared to vehicle.

Sources:

  • American Journal of Physiology Renal Physiology, 2010; 299(5): F1203-11
  • Biotech Week editors, NewsRx.com, 2011