1. The presence of cardiovascular disease is an important predictor of mortality in patients with end-stage renal disease, as it accounts for almost 50 percent of deaths

2. Compared with the general population, patients undergoing maintenance dialysis have a significantly increased incidence of CVD. This is due to both an increased prevalence of traditional risk factors for CVD and risk factors due to the severe loss of kidney function

3. renal dysfunction (even of a mild degree) is associated with an increase in CHD risk

4. it may be defined by a serum creatinine concentration that exceeds 1.5 mg/dL [133 micromol/L] or an estimated glomerular filtration rate that is less than 59 mL/min per 1.73 m2 or significant proteinuria. Data have also emphasized the importance of proteinuria as a risk factor, independent of glomerular filtration rate.

5. We recommend risk factor modification for all dialysis patients, given that CKD is a CHD risk equivalent.

6. Abnormalities in lipid metabolism occur in patients with all stages of chronic kidney disease The most common dyslipidemia in CKD and dialysis is hypertriglyceridemia, whereas the total cholesterol concentration can be normal or low, perhaps due in part to malnutrition

7. The pathogenesis of most lipid abnormalities in patients with CKD primary involves defective removal from the circulation. The diminished clearance of triglycerides, which can lead to hypertriglyceridemia, stems both from an alteration in the composition of circulating triglycerides (which become enriched with apolipoprotein C-III) and, perhaps later, from reductions in the activity of lipoprotein lipase and hepatic triglyceride lipase which are involved in triglyceride removal

8. Why lipoprotein lipase activity is reduced in CKD is not well understood but has been thought to reflect increased inhibitor activity [ 4 ]. The associated secondary hyperparathyroidism may play a contributory role, perhaps by increasing calcium accumulation within the cells in the liver and adipose tissue. Studies in humans and experimental animals with CKD suggest that parathyroidectomy can normalize serum triglyceride levels and hepatic lipase activity [ 10,11 ]. In experimental animals, benefit can also be achieved with verapamil by a similar mechanism [ 12 ], although this has not been confirmed in humans.4 10,11 verapamil 12

9. Another possible mechanism for hypertriglyceridemia in CKD is retention of a circulating inhibitor of lipoprotein lipase, such as pre-ß-HDL]. Pre-ß-HDL is a form of apolipoprotein A-I found in the non- lipoprotein fraction of normal plasma.

10. Other findings that are more common in CKD patients compared with the general population include the following: A lower serum concentration of HDL cholesterol, which is thought to be due to impaired maturation of these particles. A possible contributing mechanism is downregulation of lecithin- cholesterol acyltransferase leading to reduced esterification of cholesterol that is incorporated into HDL [ 14 ].14 Elevated serum concentrations of lipoprotein(a), apolipoprotein(a), and postprandial chylomicron remnants. Increased serum lipoprotein(a) levels are due in part to diminished renal clearance [ 15 ], while the reasons behind the reduction in hepatic clearance of chylomicron remnants are not known.15 Increased oxidation of LDL cholesterol.

11. Despite significant reductions in mean serum LDL levels, the 4-D, AURORA and SHARP trials found no definite clinical benefit with statin therapy in hemodialysis patients. However, SHARP showed a trend towards benefit specifically in atherosclerotic events, and post hoc analyses of AURORA and 4-D showed benefits among diabetic patients and among those with an LDL concentration greater than 145 mg/dL

12. Hypertriglyceridemia is the most common lipid disturbance in dialysis patients and is attributed to the retention of putatively atherogenic particles, such as lipoprotein remnants, in the plasma. Hypertriglyceridemia is not usually treated with pharmacological therapy in dialysis patients, although whether this practice is justified for secondary cardiovascular prevention is unclear. Drug therapy in patients without renal failure for cardiovascular protection may be beneficial in selected patients with isolated hypertriglyceridemia who have proven coronary disease, a strong family history of CHD, or multiple coexisting cardiac risk factors.

13. Whether this approach is beneficial in dialysis patients is not known, but it should be considered. For those with fasting triglycerides ≥500 mg/dL (≥5.65 mmol/L) that cannot be corrected by removing an underlying cause, treatment with lifestyle changes without causing malnutrition and a triglyceride-lowering agent should be considered. This indication is principally to prevent pancreatitis rather than any benefits in secondary prevention for cardiovascular events.

14. We recommend NOT initiating statin therapy in dialysis patients with no, mild or moderate increase in serum LDL-cholesterol levels, pending more definitive data ( Grade 1B ). We suggest continuing statin therapy in dialysis patients currently receiving these agents ( Grade 2C ). However, some clinicians would withdraw statin therapy in dialysis patients based upon the lack of benefit. In dialysis patients with very high LDL- cholesterol levels, the initiation of statins may be reasonableGrade 1B Grade 2C