Q:  I am confused about cholesterol levels in patients with CKD. How often should they be monitored and what type of treatment is recommended?

Cardiovascular Disease
A: The National Kidney Foundation (NKF) Task Force on Cardiovascular Disease (CVD) and the KDOQI Work Group on Chronic Kidney Disease (CKD) concluded that individuals with CKD should be placed in the highest risk category for CVD. Interventional guidelines for the assessment and management of dyslipidemias in persons with CKD were developed and published in 2003.

The prevalence of coronary heart disease (CHD) is declining in the general population, yet 50% of deaths in individuals with Stage 5 CKD are due to cardiovascular disease. There are numerous risk factors at work in this population, including anemia, increased plasma homocysteine levels, increased calcium intake, disorders of mineral metabolism, and abnormal nitric oxide metabolism, which may cause vasoconstriction and hypertension. Additionally, CKD alone is considered an independent risk factor for development of CHD, and renal replacement therapies increase oxidant stress and produce cytokines, pro-inflammatory fragments, and adhesion molecules in endothelial cells (Henrich, 2005).

Assessment of Dyslipidemia
All adults and adolescents with CKD should be evaluated for dyslipidemias. This assessment should include a complete fasting lipid profile with total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides. Patients with CKD should be evaluated at presentation, after a status change, and annually. Additionally, adults and adolescents in Stage 5 CKD should be evaluated on presentation, after a change of treatment or other conditions arise that cause dyslipidemias, and at least annually. The lipid profile should be drawn after an overnight fast, and patients with Stage 5 CKD on hemodialysis should have the profile drawn before dialysis or on nondialysis days (NKF, 2003).

The patient should be evaluated for major cardiovascular risk factors such as cigarette smoking, hypertension, family history of premature coronary heart disease, and low HDL (less than 40 mg/dl), and age. Assessment of risk factors specific to CKD such as anemia, hyperhomocysteinemia, bone metabolism disorders, and volume overload should also be considered (Burrows-Hudson & Prowant, 2005).

Patients should be evaluated for remedial, secondary causes of dyslipidemias. Medical conditions include nephrotic syndrome, hypothyroidism, diabetes, excessive alcohol consumption, and liver disease. Certain medications can also cause lipid alteration, including anticonvulsants, active anti-retroviral therapies, diuretics, beta-blockers, androgens, oral contraceptives, corticosteriods, cyclosporine, and sirolimus (NKF, 2003).

Treatment of Dyslipidemias
Recommendations of the NKFK/DOQI Clinical Practice Guidelines for Managing Dyslipidemias in CKD differ somewhat from the National Cholesterol Education Program Adult Treatment Panel (ATPIII). Drug therapy should be used for LDL greater than 100 mg/dl or after 3 months of therapeutic lifestyle changes to reduce the LDL to less than 100 mg/dl. The initial drug therapy suggested to reduce a high LDL is an HMG CoA reductase inhibitor or statin (NKF, 2003).

Fibrate or niacin therapy should be considered in individuals in Stage 5 CKD and with fasting triglyceride levels greater than 500 mg/dl. Gemfibrozil is the drug of choice because drug levels are not altered by decreased kidney function (NKF, 2003).

In individuals with Stage 5 CKD with fasting triglycerides greater than 200 mg/dl and non-HDL cholesterol greater than 130 mg/dl, treatment with therapeutic lifestyle changes and a statin should be considered to reduce HDL to less than 130 mg/dl. For those individuals who do not tolerate statins, fibrate therapy may be considered (NKF, 2003).

Therapeutic Life Style Changes
A lipid-lowering diet can reduce LDL with saturated fat less than 7% of total calories and should contain fiber and complex carbohydrates and a total fat content of 25%-30% of total calories. Care should be exercised when there is evidence of protein energy malnutrition.

Exercise can produce a small but beneficial improvement in dyslipidemia and has the added benefit of weight reduction. Use of a pedometer to attain 10,000 steps each day and emphasis on a type of daily motion and distance within ability is recommended.

Smoking cessation and alcohol in moderation are other therapeutic lifestyle changes that can improve dyslipidemia in the general population as well as those individuals with CKD (NKF, 2003).

Statin Use in CKD
Since therapeutic lifestyle changes can achieve only a modest reduction in LDL, the use of a statin should be considered. Elevations in hepatic transaminases can occur with treatment so it is recommended that baseline alanine and aspartate should be drawn and monitored during therapy. Myopathy can also occur and a baseline creatinine phosphokinase (CK) level should be obtained at the start of statin therapy and monitored on a regular basis. If the patient complains of muscle pain or tenderness, it is prudent to discontinue therapy and check a CK level. If the CK elevation is mild a reduction of dose and continued monitoring of symptoms and CK levels is indicated (NKF, 2003).

There is some evidence in the general population that statins play an important antiinflammatory role. Small studies in patients with kidney failure indicate some added benefit in reduction of C-reactive protein, reduced total cholesterol levels and increased serum albumin levels with the use of a statin (NKF, 2003).

Special Populations
CKD stages 1-4. In the Physicians’ Health trial, over 4,000 males were monitored over 14 years to evaluate the association between cholesterol and a decline in renal function. The results indicated that elevated total cholesterol, high non-HDL cholesterol and an elevated ratio of total cholesterol/HDL and low HDL were significantly associated with an increased risk of developing renal dysfunction in men with an initial creatinine less than1.5 mg/dl (Schaeffner et al., 2003).

A sub-analysis of the CARE (Cholesterol And Recurrent Events) study examined 690 patients with MDRD GFR less than 60 ml/min per 1.73 m2 randomized to pravastatin or placebo. The results indicate that GFR was not significantly different between the pravistatin and the placebo group. However, slower rate of decline in GFR was seen in the pravistatin group, especially in those individuals with proteinuria and a lower baseline GFR less than 50 ml/min (Tonelli, Moye, Sacks, Kiberd, & Curhan, 2003). Ongoing studies are testing the efficacy of lipid-lowering agents in decreasing cardiovascular disease in individuals with CKD and may well influence future recommendations regarding antilipemic therapy.

Nephrotic syndrome. Hypercholesterolemia and hypertriglyceridemia are common finding in patients with nephrotic syndrome. This response is partially due to the reduction in plasma onconic pressure that occurs in this condition. Drug therapy with statins and bile acid sequestrants can be helpful. Adjunctive therapy with angiotensin converting enzyme (ACE) or an angiotensin II recptor blocker to lower protein excretion has been recommended (Rose & Appel, 2005).

Renal transplant. Despite normal or nearly normal kidney function, hyperlipidemia is a common finding in renal transplant recipients. Some immunosuppresive agents such as calcinerin inhibitors and corticosteriods have dose-related effects on serum lipid levels. Clinical evidence indicates that replacing or discontinuing prednisone, cyclosporine or sirolimus may reduce the severity of dyslipidemia in the transplant recipient. The decision to change immunosuppression must be weighed against the risk of rejection versus development of CHD. Consideration must be given to the effects on blood pressure and posttransplant diabetes on overall development of CHD (NKF, 2003).
Care must be exercised when dosing statins and other lipid-lowering agents in transplant recipients since significant drug interactions and adverse effects can occur in combination with immunosuppresive agents (NKF, 2003).

Nursing Implications
Control of lipids with drug therapy is just one aspect of treatment for CHD in the individual with kidney failure. Blood pressure control, optimization of glucose levels, and therapeutic lifestyle changes can play a large part in decreasing the morbidity and mortality associated with CHD. Nephrology nurses are perfectly positioned to help improve patient outcomes with regard to CHD in all patients with any degree of kidney dysfunction.