Dyslipidemia often is a concern in patients with chronic kidney disease (CKD) because mortality in this population typically is the result of cardiovascular complications.
Pharmaceutical and lifestyle modifications including diet and exercise are used to manage dyslipidemia. For CKD patients, it is important to understand which lipid profiles are most commonly associated with CKD to help understand the relationship between dyslipidemia and the progression of renal disease.
Lipid profiles and CKD
Investigators analyzed 2007-2008 data from the Korean National Health and Nutrition Examination Survey (KNHANES) to assess associations between lipid profiles and CKD (J Korean Med Sci 2012;27:1524-1529. The population excluded individuals younger than 19 years on lipid-lowering medications and with histories of malignancy, absence of laboratory data, or who had not fasted 12 hours prior to blood draw.
The researchers defined CKD stage 3 as an estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2. The investigators assessed total cholesterol (TC), high-density lipoprotein (HDL), non-HDL cholesterol (nHDL), calculated LDL (cLDL), and triglycerides (TG), as well as four primary lipid ratios: TC/HDL, TG/HDL, cLDL/HDL, and nHDL/HDL. The results were separated into quartiles and separated by gender.
The overall CKD prevalence in this population was 6.4%. In women, the researchers found significant positive associations between all four aforementioned ratios and CKD. The strongest association was found between TG/HDL and CKD, which also was the only ratio found to be significant in men. In addition, cLDL/HDL and CKD may have been trending in the male population.
The investigators adjusted odds ratios for CKD prevalence stratified by lipid ratios for age, systolic blood pressure, fasting plasma glucose, waist circumference, BMI, and smoking, alcohol drinking, and exercise status. The highest TG/HDL quartile in men was associated with a 1.82 times increased risk of CKD stage 3 compared with the lowest quartile, but the overall trend was borderline significant. In women, the highest quartiles of TC/HDL, TG/HDL, and nHDL/HDL were associated with a 1.75, 2.45, and 1.75 times increased risk of CKD stage 3, respectively. In women, all four ratios had a significant positive trend in relation to CKD stage 3 prevalence.
These results primarily indicate that the TG/HDL ratio is independently associated with CKD status and is a stronger predictor than other lipid ratios. An increased TG/HDL ratio is used as an indicator of insulin resistance. For this study, investigators used fasting blood glucose as a control, but a diagnosis of diabetes mellitus was not mentioned. Because this is a cross-sectional, observational study, causality cannot be proved.
Additional studies may elucidate whether the high TG/HDL ratio itself induces nephrotoxicity or if these are simply correlative to other factors. The stronger associations found in females in this study may be due to the use of the Modification of Diet in Renal Disease (MDRD) study equation in estimated eGFR.
A recent meta-analysis of lipid-lowering medications in CKD and dialysis populations found that these therapies were effective in reducing likelihood of cardiac death and atherosclerosis-mediated cardiovascular events (Ann Intern Med 2012;157:251-262).
However, lipid-lowering therapies had no effect on preventing kidney failure, kidney graft failure, or decline in kidney function. This analysis focused on 18 randomized controlled trials looking at statins alone or used with ezetimibe. Fibrates are primarily used to manage elevated triglyceride levels, and a separate meta-analysis of data from CKD populations found that fibrates significantly reduced the risk of cardiovascular events in CKD populations, acutely reduced eGFR, and reduced albuminuria (J Am Coll Cardiol 2012;60:2061-2071).
The reduction in eGFR was attributed to a rise in creatinine and appears to be temporary and reversed when fibrate therapy is stopped. The rise in creatinine has caused concern, but studies have found that inulin clearance is not altered during fibrate use, which suggests that although eGFR declines, actual GFR may remain unchanged.
Serum triglycerides and CKD progression
Data suggest that elevated serum triglycerides influence CKD progression with some relationship to proteinuria. Further studies will be needed to assess if this relationship is strictly correlative or if any causal relationship exists. Dietary interventions to improve TG/HDL ratio are similar to those used for diabetes and insulin resistance, namely carbohydrate portion control, increases in the ratio of unsaturated fats to saturated fat intake, and loss of excess adipose tissue through caloric restriction and increased physical activity.
Dietitians may find this information beneficial when assessing lipid laboratory results and determining pertinent nutrition interventions in patients with progressive kidney decline. At this time, management of dyslipidemia is important for reduction of cardiovascular events, but the addition of lipid monitoring specifically for reduction of progressive renal impairment would offer another outcome variable and room for improved outcomes.