Statins and small GTPases: Koch's postulates and chronic kidney disease.

Clarke WR et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Identification of patients with autosomal dominant polycystic kidney disease at highest risk for end-stage renal disease. Volume progression in autoso-mal dominant polycystic kidney disease: the major factor determining clinical outcomes. Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease. Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. Effect of antihyper-tensive therapy on renal function and urinary albumin excretion in hypertensive patients with autosomal dominant polycystic kidney disease. Fick-Brosnahan GM et al. Diuretics versus angiotensin-converting enzyme inhibitors in autosomal dominant polycystic kidney disease. Effect of inhibition of converting enzyme on renal hemodynamics and sodium management in polycystic kidney disease. et al. Differences in hormonal and renal vascular responses between normotensive patients with autosomal dominant polycystic kidney disease and unaffected family members. The pathogenesis of hypertension in auto-somal dominant polycystic kidney disease. The renin-angiotensin-aldosterone system and autosomal dominant polycystic kidney disease. Torres V et al. HALT PKD Study: efficacy of renin-angiotensin-aldosterone system (RAAS) blockade in prevent-ing/slowing renal function decline in autosomal dominant polycystic kidney disease (ADPKD) NIH/NIDDK for the HALT PKD Study. Introduction Statins (3-hydroxy-3-methylglutaryl-CoA reductase in-hibitors) are attracting more and more attention as car-diovascular and renal protective agents. Evidence from in vitro and rodent experiments indicates that this is not mediated via cholesterol-lowering effects, simply because culture dishes and rodents do not respond to statins with a decrease in plasma cholesterol. However, these so-called pleiotropic effects of statins are much harder to prove in humans, where in secondary prevention trials even 434 Nephrol Dial Transplant (2008) 23: Editorial Comments normo-cholesterolemic subjects exhibit a decrease in LDL cholesterol [1]. Pleiotropic effects of statins appear to depend partly, but not wholly, on the activation of small guano-sine triphosphate (GTP)-binding proteins such as Ras, Rho and Rac. The activation depends on a post-translational modification termed isoprenylation. Isoprenoid interme-diates of the cholesterol biosynthetic pathway, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) must be attached to these small GTP-binding proteins to achieve activation (Figure 1) [2]. Small GTP-binding proteins display a host of deleterious effects that all impact on the cardiovascular system and the kidney, including downregulation of eNOS, upregulation of NADPH oxidase and activation of the AT1 receptor, to mention just a few. Other pleiotropic actions of statins include enhancement of eNOS phosphorylation …