Nephrol Dial Transplant (2003) 18: 1234
© 2003 European Renal Association-European Dialysis and Transplant Association
Letters
About the pleiotropic effects of statins in human
Servizio Diabetologia Dipartimento Struttura Clinica Medica e Patologia Medica University of SassariItaly Email: giantono2001{at}yahoo.it
Sir,
We read with interest the recent report by Usui et al. [1] in NDT regarding the pleiotropic effects of the HMG-CoA reductase inhibitor cerivastatin on glomerular injury and blood pressure in rats with streptozotocin-induced diabetes. Previously, we showed that simvastatin given in a random order blind fashion to normotensive type 2 diabetic patients (T2DM) with increased urinary albumin excretion (AER+) was able to significantly reduce AER as compared to placebo [2]. Later, we could show that simvastatin and cholestyramine were equally effective in reducing total and LDL cholesterol in borderline hypertensive AER+ T2DM, but only simvastatin significantly decreased AER, blood pressure and urinary glycosaminoglycan excretion [3]. These data clearly showed, for the first time in humans, that the effects of simvastatin are largely independent from the reduction of LDL cholesterol. Besides the proposed mechanisms [1,4], at the moment we are working on the hypothesis that statins might influence AER in T2DM subjects, affecting LDL oxidation status and autoantibodies against oxidized LDL. This hypothesis is in line with our previous demonstration that the LDL-C/triglyceride ratio in plasma (modified after statin therapy) correlates well with the oxidative status [5].
References
- Usui H, Shikata K, Matsuda M et al. HMG-CoA reductase inhibitor ameliorates diabetic nephropathy by its pleiotropic effect in rats. Nephrol Dial Transplant 2003; 18:265–272
[Abstract/Free Full Text] - Tonolo G, Ciccarese M, Brizzi P et al. Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long term simvastatin treatment. Diabetes Care 1997; 20:1891–1895[Abstract]
- Tonolo G, Melis MG, Formato M et al. Additive effects of simvastatin beyond its effects on LDL cholesterol in hypertensive type 2 diabetic patients. Eur J Clin Invest 2000; 30:980–987[CrossRef][Web of Science][Medline]
- Danesh FR, Sadeghi MM, Amro N et al. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors prevent high glucose-induced proliferation of mesangial cells via modulation of Rho GTPase/p21 signalling pathway: implications for diabetic nephropathy. Proc Natl Acad Sci USA 2002; 99:8301–8305
[Abstract/Free Full Text] - Brizzi P, Tonolo G, Carusillo F et al. Plasma lipid composition and LDL oxidation. Clin Chem Lab Med 2003; 41:56–60[Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||