Managing Dyslipidemia in Chronic Kidney Disease

Abstract

The incidence of chronic kidney disease (CKD) in the U.S. continues to increase, and now over 10% of the U.S. population has some form of CKD. Although some patients with CKD will ultimately develop renal failure, most patients with CKD will die of cardiovascular disease before dialysis becomes necessary. Patients with CKD have major proatherogenic lipid abnormalities that are treatable with readily available therapies. The severe derangements seen in lipoprotein metabolism in patients with CKD typically results in high triglycerides and low high-density lipoprotein (HDL) cholesterol. Because of the prevalence of triglyceride disorders in patients with CKD, after treating patients to a low-density lipoprotein goal, non-HDL should be calculated and used as the secondary goal of treatment. A review of the evidence from subgroup analysis of several landmark lipid-lowering trials supports treating dyslipidemia in mild to moderate CKD patients with HMG-CoA reductase inhibitors. The evidence to support treating dyslipidemia in hemodialysis patients, however, has been mixed, with several outcome trials pending. Patients with CKD frequently have mixed dyslipidemia and often require treatment with multiple lipid-lowering drugs. Although statins are the cornerstone of therapy for most patients with CKD, differences in their pharmacokinetic properties give some statins a safety advantage in patients with advanced CKD. Although most other lipid-lowering agents can be used safely with statins in combination therapy in patients with CKD, the fibrates are renally metabolized and require both adjustments in dose and very careful monitoring due to the increased risk of rhabdomyolysis. After reviewing the safety and dose alterations required in managing dyslipidemia in patients with CKD, a practical treatment algorithm is proposed.

Dyslipidemia in patients with chronic kidney disease: etiology and management

“…Compared with the control group, the event rate has been reduced in the group that was receiving simvastatin (control group 39.2% vs simvastatin group 28.2%) and has resulted in the 11% absolute risk reduction. 27 Similar results have been obtained in the Anglo-Scandinavian Cardiac Outcomes Trial in which a subgroup of 6,517 patients with kidney dysfunction have been analyzed after receiving 10 mg of atorvastatin per day during a median of 3.3 years follow-up. Atorvastatin has significantly reduced the risk for the primary composite end point of nonfatal myocardial infarction (MI) and fatal coronary heart disease by 39%.…”

“…In the subgroup of 1,700 patients with mild CKD (creatinine clearance <75 mL/min) receiving 40 mg pravastatin per day, there was a 28% (95% CI 0.55-0.95; p=0.02) RR reduction and a 4% absolute risk reduction in the primary end point that included death from coronary disease and symptomatic nonfatal MI. 23,27 Some studies have shown statins to be renoprotective not just because of their ability to reduce lipid levels, but because of their ability to reduce interstitial inflammation, improve renal hemodynamics and decrease glomerular proteinuria which could result in the reduction of renal function decline. This was confirmed by the analysis of a subgroup of patients in the TNT study.…”

“…However, not all combined cerebrovascular events and total mortality was significantly reduced. 6,12,13,[26][27][28] The A Study to Evaluate the Use of Rosuvastatin in Subjects on Regular Dialysis: An Assessment of Survival and Cardiovascular Events (AURORA) is an international prospective double-blind study that included 2,776 HD patients. They have been randomized to receive 10 mg of rosuvastatin per day or placebo.…”

A study of lipid profile in non-diabetic chronic kidney disease

“…Several multicentre international trials have been conducted but the results were inconclusive and further studies were recommended for answering the questions of the reasons for dyslipidemia and ideal lipid lowering strategy to be used in hemodialysis patients. 9 However, the relationship between dyslipidemia and CV risk in patients with renal disease is less clear than in those with normal renal function, as is the efficacy of statins for preventing CV risk. A lack of evidence exists since patients with CKD were excluded from the major trials that target dyslipidemia treatment in primary and secondary prevention of CV disease.…”

Lipid Abnormalities in Patients with Chronic Kidney Disease: Implications for the Pathophysiology of Atherosclerosis

“…Compared with ageand gender-matched controls, there are increased levels of inflammatory markers in the coronary vessels and blood of CKD patients [28][29][30] . Multiple putative risk factors for coronary artery disease (CAD) are present in CKD patients, including insulin resistance, increased oxidative stress, inflammation, anemia, excessive smoking, endothelial dysfunction, and reduced nitric oxide availability 31,32) . When present, proteinuria and the consequent hypoalbuminemia contribute to altered lipid abnormalities in CKD patients.…”