Renal disease statins

Fibric adds Clofibrate Gemfibrozil Fenofibrate Increase VLtt-catabolism PPAR , agonist LDLi 5-20% HDL t 10%-20% TG i 20%-S0% Gl upset, dyspepsia, gallstones, T LFTs, myopathy Nonmetabolism Warfarin Cyclosporine Statins Liver or severe renal disease primary biliary cirrhosis preexisting gallbladder disease... 

The susceptibility factors for rhabdo-myolysis have been examined from data held by the Swedish Adverse Drug Reactions Advisory Committee [21 ]. There were 338 cases of serious muscle toxicity, of whom 190 were classified as having had rhabdomyolysis on the basis of highly raised creatine kinase activities. Renal disease, unusually strenuous muscular activity, and high dosage statins were clear susceptibility factors. The likelihood of myopathy is increased in subjects with a genetic variant... 

Dyslipidemia is common in patients with renal disease. Lipid-lowering medical treatment is commonly prescribed in adults with CKD based on the evident benefit of this approach for primary and secondary prevention of cardiovascular disease in the general adult population. Statin therapy is effective in reducing cardiovascular morbidity and mortality in adults with moderate to severe CKD although not in patients with ESRD. With respect to renoprotection, experimental evidence suggests that statins may retard renal disease progression not only by their lipid-lowering but also by lipid-independent pleiotropic effects [7]. 

Controlling blood triglyceride and cholesterol levels helps prevent heart disease and possibly strokes, and may slow the progression of diabetic kidney disease. The current data point towards a target total cholesterol of <3.5 mmol/L if the patient has microalbuminuria, and statins are very widely prescribed in diabetic patients with renal impairment. 

The hydrophilic statins (pravastatin, rosuvastatin) are only partly metabolised by the liver [1, 17, 19]. Pravastatin is also metabolised in the stomach [26]. The pharmacokinetics of pravastatin have been shown to change in liver disease, despite its dual route (renal and hepatic) of elimination [27]. Nonetheless, it has been used in liver disease and has been suggested as the statin of choice [26]. Liver metabolism is of minor importance in the clearance of rosuvastatin and its pharmacokinetics are not altered by mild to moderate liver impairment. However, the area under the curve (AUC) is increased in severe liver impairment [1]. Clinical experience with rosuvastatin in liver disease is lacking, and it therefore cannot be recommended. 

PUFAs suppress HMG-CoA reductase and ACE activities, inhibit platelet aggregation, enhance parasympathetic activity and, thus, enhance heart rate variabihty (and thus, have actions similar to that of fS-blockers), and possess diuretic properties either by themselves and/or by increasing the formation of PGAs and PGEs that have been shown to increase renal blood flow and augment diuresis. These actions of PUFAs are similar to that of the polypill that is a combination of aspirin, fS-blockers, statins, and ACE inhibitors, which is expected to reduce cardiovascular diseases by over 70-80% (92). This suggests that PUFAs could function as an endogenous polypill the evidence for this is detailed below. 

Rosuvastatin (crestor) is available in doses ranging between 5 and 40 mg. It has a t of 20—30 hours and may be taken at any time of day. Since experience with rosuvastatin is more limited, treatment should be initiated with 5-10 mg daily, increasing stepwise if needed. If the combination of gemfibrozil with rosuvastatin is used, the dose of rosuvastatin should not exceed 10 mg. Rosuvastatin at a dose of 80 mg (dose not approved by the FDA) was noted to cause proteinuria and hematuria and isolated cases of renal failure. Other statins have also been observed to cause proteinuria, apparently by inhibiting tubular protein reabsorption. Whether statin-induced proteinuria is harmful or beneficial, especially in patients with chronic kidney disease, remains to be determined. 

All fibrates increase the lithogenicity of bile. Clofibrate has been associated with increased risk of gallstone formation gemfibrozil and fenofibrate reportedly do not increase biliary tract disease. Renal failure and hepatic dysfunction are relative contraindications to fibrate therapy. Combined statin-fibrate therapy should be avoided in patients with impaired renal function. Gemfibrozil should be used with caution and at a reduced dosage to treat the hyperlipidemia of renal failure. Fibrates should not be used by children or pregnant women. 

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