The utility of non-HDL in managing dyslipidemia of stage 5 chronic kidney disease

P Pennell, B Leclercq, M I Delahunty, B A J Walters
Clinical Nephrology 2006, 66 (5): 336-47

BACKGROUND: The Kidney Disease Outcomes Quality Initiative (K/DOQI) treatment guidelines for managing dyslipidemia in patients with chronic kidney disease (CKD) designate CKD as a high-risk category for coronary heart disease and, in Stage 5 CKD patients, recommend maintaining low-density lipoprotein (LDL) < 100 mg/dl and, for patients with hypertriglyceridemia (> or = 200 mg/ dl), non-high-density lipoprotein (non-HDL) < 130 mg/dl, the latter to achieve very low-density lipoprotein (VLDL) < 30 mg/dl. More recently, the National Cholesterol Education Program has recommended an LDL target of < 70 mg/dl for high-risk patients.

AIMS: The purposes of this study were: to document the point prevalence of dyslipidemia in CKD patients at hemodialysis inception, prior to potential impact of dialysis treatments; to assess the hypothesis that non-HDL serves as a reliable surrogate marker for elevated VLDL; to examine the performance of K/DOQI guidelines in treating dyslipidemia; and to evaluate the utility of non-HDL as an alternative primary trigger/target of lipid-lowering therapy in Stage 5 CKD patients.

METHODS: Consistent with K/DOQI guidelines, lipid levels drawn immediately prior to hemodialysis sessions, thus possibly non-fasting, were analyzed in 21,893 incident dialysis patients by laboratory measurements of triglycerides, total cholesterol, and HDL and from calculated values of non-HDL, LDL, VLDL and intermediate-density lipoprotein.

RESULTS: Prevalence of dyslipidemia, by guideline definitions, was 82%, predominantly manifested by elevated triglycerides (52%) and VLDL (52%) and decreased HDL (51%), with less frequent elevations of LDL (40%) and total cholesterol (24%). Non-HDL > or = 130 mg/dl was neither a sensitive (61%) nor specific (75%) marker for elevated VLDL. There was a striking disparity between the high prevalence of dyslipidemia and the percentage of dyslipidemic patients qualified by K/DOQI guidelines for therapy. Non-HDL > or = 130 mg/dl was as effective in qualifying dyslipidemic patients for lipid-lowering therapy (54%) as the entire K/DOQI treatment algorithm (57%). Lowering the trigger of non-HDL to > or = 100 mg/dl would qualify 81% of dyslipidemic patients for treatment while offering the important advantage of being uninfluenced by the non-fasting state.

CONCLUSIONS: In Stage 5 CKD patients at hemodialysis inception, dyslipidemia is highly prevalent with predominance of the atherogenic triad (hypertriglyceridemia, elevated VLDL and reduced HDL). Non-HDL is a poor surrogate marker for VLDL. As a valid non-fasting lipid parameter, non-HDL alone at the level of > or = 130 mg/dl qualifies dyslipidemic Stage 5 CKD patients for therapy as effectively as the K/DOQI guidelines. Setting the non-HDL trigger/target cut-off at 100 mg/dl overcomes the insensitivity of non-HDL as a marker for atherogenic lipoproteins represented by the VLDL designation while ensuring more aggressive lipid-lowering therapy for Stage 5 CKD patients at high risk for cardiovascular events. Accordingly, non-HDL of 100 mg/dl is proposed as the all-encompassing primary trigger/target of lipid-lowering therapy in high-risk Stage 5 CKD patients, particularly those patients on dialysis in whom lipid samples obtained before dialysis cannot be guaranteed to be fasting.

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