Relation of serum lipids and lipoproteins with progression of CKD: The CRIC study

Abstract

Background and objectives: Hyperlipidemia is common in patients with CKD. The objective of this study was to evaluate whether measures of plasma lipids and lipoproteins predict progression of kidney disease in patients with CKD.

Design, setting, participants, & measurements: Prospective cohort study in adults (n=3939) with CKD aged 21-74 years recruited between 2003 and 2008 and followed for a median of 4.1 years. At baseline, total cholesterol, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), apoA-I , apoB, and lipoprotein(a) [Lp(a)] were measured. The outcomes were composite end point of ESRD or 50% decline in eGFR from baseline (rate of change of GFR).

Results: Mean age of the study population was 58.2 years, and the mean GFR was 44.9 ml/min per 1.73 m(2); 48% of patients had diabetes. None of the lipid or lipoprotein measures was independently associated with risk of the composite end point or rate of change in GFR. However, there were significant (P=0.01) interactions by level of proteinuria. In participants with proteinuria<0.2 g/d, 1-SD higher LDL-C was associated with a 26% lower risk of the renal end point (hazard ratio [HR], 0.74; 95% confidence interval [95% CI], 0.59 to 0.92; P=0.01), and 1-SD higher total cholesterol was associated with a 23% lower risk of the renal end point (HR, 0.77; 95% CI, 0.62 to 0.96; P=0.02). In participants with proteinuria>0.2 g/d, neither LDL-C (HR, 0.98; 95% CI, 0.98 to 1.05) nor total cholesterol levels were associated with renal outcomes. Treatment with statins was reported in 55% of patients and was differential across lipid categories.

Conclusions: In this large cohort of patients with CKD, total cholesterol, triglycerides, VLDL-C, LDL-C, HDL-C, apoA-I, apoB, and Lp(a) were not independently associated with progression of kidney disease. There was an inverse relationship between LDL-C and total cholesterol levels and kidney disease outcomes in patients with low levels of proteinuria.

Keywords: chronic kidney disease; lipids; progression of chronic renal failure.

Figure 1.

Crude event rates for ESRD or 50% decline in GFR stratified by quartiles of total cholesterol (mg/dl) at baseline. The error bars delineate the 95% confidence interval.

Figure 2.

Hazards ratios for renal outcome (ESRD or 50% decline in GFR) per 1-SD increase in total cholesterol (TC) in subgroups of inflammation/malnutrition, proteinuria, eGFR, statin use, and diabetes. Model adjusted for age, race, sex, diabetes, BP, statin use at baseline, smoking, 24-hour urine protein (UPr) excretion, body mass index, clinical center, alcohol use, and baseline eGFR. The error bars delineate the 95% confidence interval.

Figure 3.

Hazard ratios for renal outcome (ESRD or 50% decline in GFR) per 1-SD increase in LDL cholesterol in subgroups of inflammation/malnutrition, proteinuria, eGFR, statin use, and diabetes. Model adjusted for age, race, sex, diabetes, BP, statin use at baseline, smoking, 24-hour urine protein (UPr) excretion, body mass index, clinical center, alcohol use, baseline eGFR. The error bars delineate the 95% confidence interval.