The Efficacy and Safety of the 3-Hydroxy-3-methylglutaryl-CoA Reductase Inhibitors in Chronic Kidney Disease, Dialysis, and Transplant Patients

Abstract

SummaryCoronary heart disease (CHD) is the leading cause of death in Western civilizations, in particular in chronic kidney disease (CKD) patients. Serum total cholesterol and LDL have been linked to the development of atherosclerosis and progression to CHD in the general population. However, the reductions of total and LDL cholesterol in the dialysis population have not demonstrated the ability to reduce the morbidity, mortality, and cost burden associated with CHD. The patients at greatest risk include those with pre-existing CHD, a CHD-risk equivalent, or multiple risk factors. However, data in the dialysis population are much less impressive, and the relationship between plasma cholesterol, cholesterol reduction, use of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, and reduction in incidence of CHD or effect on progression of renal disease have not been proven. Adverse event information from published trials indicates that agents within this class share similar tolerability and adverse event profiles. Hepatic transaminase elevations may occur in 1 to 2% of patients and is dose related. Myalgia, myopathy, and rhabodmyolysis occur infrequently and are more common in kidney transplant patients and patients with CKD. This effect appears to be dose related and may be precipitated by administration with agents that inhibit cytochrome P-450 isoenzymes. Caution should be exercised when coadministering any statin with drugs that metabolize through cytochrome P-450 IIIA-4 in particular fibrates, cyclosporine, and azole antifungals. Elderly patients with CKD are at greater risk of adverse drug reactions, and therefore the lowest possible dose of statins should be used for the treatment of hyperlipidemia.

Effects of vitamin E-coated dialysis membranes on anemia, nutrition and dyslipidemia status in hemodialysis patients: a meta-analysis

“…This result suggested that vitamin E-bonded dialyzer therapy might not be efficacious for controlling the HD-induced atherosclerosis and dyslipidemia, particularly when compared with other approved lipid-lowering drugs. 42 Several important potential study limitations to this systematic review should be acknowledged. Firstly, mostly included studies were of low quality and small-size, only two studies explained the randomization method, and most of studies were not blinded designed.…”

Eicosapentaenoic Acid (EPA) Decreases the All-Cause Mortality in Hemodialysis Patients

“…Statins have been shown to decrease the mortality and CVD events in people with early stages of CKD, but have little or no effect on the HD population, and have uncertain effects in kidney transplant recipients (23). The detailed relationships among the plasma cholesterol level, cholesterol reduction, the use of statins, and the reduction of CVD have not been proven in the HD population (24). Thus, although fibrates and statins are not indicated for HD patients without hyperlipidemia, EPA or DHA supplementation may be suitable for treating milder disorders of lipid metabolism because of their rare induction of adverse reactions.…”

Contrasting Cholesterol Management Guidelines for Adults with CKD

“…10 Older individuals with CKD have a reduced life expectancy, high competing risk for other CKD-related outcomes, and a higher risk for statin-related adverse events and drug-drug interactions. [23][24][25] These factors can reduce the potential benefit of statin initiation among the very old with CKD. Given the high prevalence of CKD among individuals $80 years of age, 26 studies are needed to identify the benefits of statins for this high-risk group.…”