Managing Lipid Therapy in CKD Patients

JUNE 15, 2016
Chronic kidney disease (CKD), defined by at least 3 months of impaired kidney function or albuminuria, is a well-established risk factor for cardiovascular disease (CVD).1  
In a large meta-analysis, a linear increase in cardiovascular mortality was seen with decreasing estimated glomerular filtration rate (eGFR) below a threshold eGFR of 75 mL/min/1.73 m2, with mortality rates twice as high in stage 3 CKD (eGFR 30-59 mL/min/1.73 m2) and 3 times as high in stage 4 CKD (eGFR 15-29 mL/min/1.73 m2).

Patients with CKD have also been shown to have similar rates of myocardial infarction (MI) or coronary heart disease (CHD) compared to those with diabetes, which is why I consider CKD a CHD equivalent risk factor.

Dyslipidemia is common in CKD. Because of chronic inflammation and malnutrition, many patients with advanced CKD may even have low levels of serum lipoproteins in the absence of lipid-lowering drug therapy. As a result, even though patients with CKD should be considered part of the highest risk group for CVD, they’re often underdiagnosed and undertreated with cholesterol-lowering agents.

To address this key deficiency in the care of these patients, the Kidney Disease: Improving Global Outcomes (KDIGO) organization updated their clinical practice guidelines in 2013 to summarize evidence and recommend lipid management for all forms of CKD. This set of 13 recommendations spearheaded by prominent nephrologists, lipid specialists, and epidemiologists abandons lipid targets and focuses more on risk assessment driven mainly by age and eGFR.1

Pharmacotherapy in CKD Patients Not on Hemodialysis
The KDIGO committee doesn’t use specific low-density lipoprotein cholesterol (LDL-C) targets; instead, it focuses on statin therapy for managing dyslipidemia. It recommends statin therapy in all adults 50 years or older with CKD who aren’t on chronic dialysis. In this same age group with more advanced stages of CKD (Stage 3-5, eGFR <60 mL/min/1.73 m2), combination statin and ezetimibe treatment is recommended. 1-3

The recommendation for this combination comes from the SHARP trial, which randomized 9270 patients older than 40 years with CKD to simvastatin 20 mg plus ezetimibe 10 mg daily regardless of baseline LDL-C levels. The primary outcome of combined MI, coronary death, stroke, or arterial revascularization was reduced by 17% in the treatment group, with a 32% mean reduction seen in LDL-C levels. This came at the expense of a minor excess risk of myopathy without any increased risk of hepatitis, gallstones, or excess death from nonvascular causes.4

In younger adults (18-49 years) with CKD who aren’t on chronic dialysis, the KDIGO group recommends statin treatment only for those with 1 of the following: 1) known coronary disease (MI or coronary revascularization), 2) diabetes, 3) prior ischemic stroke, or 4) estimated 10-year incidence of coronary death or nonfatal MI of ≥10% based on the Framingham risk score used in the Adult Treatment Panel III Guidelines. However, using risk estimators to predict individual risk in this age group is difficult because they’re generally not validated in adults younger than 40 years and often underestimate risk in CKD patients.

Pharmacists caring for patients with CKD need to be aware that this population is at higher risk for side effects from lipid medications because of reduced renal excretion, polypharmacy, and multiple comorbidities. Given the risk of toxicity with high-dose statins, KDIGO recommends statin dosing based on regimens that have been studied and shown to be beneficial in randomized trials performed specifically in patients with eGFR <60 mL/min/1.73 m2. This includes moderate-intensity statins, such as daily atorvastatin 20 mg, rosuvastatin 10 mg, simvastatin 40 mg, pravastatin 40 mg, or fluvastatin 80 mg.

Similar to patients without CKD, fibrates should be avoided in combination with statins, and ezetimibe monotherapy isn’t recommended. Baseline transaminase levels should be measured in all CKD patients prior to starting statin therapy, although routine transaminase for CK levels isn’t recommended in the absence of clinical evidence for hepatotoxicity or myopathy.

Other lipid guidelines have some similarities to KDIGO but differ on their approach to treating CKD patients. The National Lipid Association (NLA) 2015 guidelines recommend a step-wise approach to risk management, first identifying the highest ASCVD risk category, and then treating to specific non-HDL-C and LDL-C goals based on the risk category. 2,5 Per the NLA approach, all patients with stage 3B (eGFR 30-44 mL/min/1.73 m2) or stage 4 CKD are considered high risk and would be treated to a goal non-HDL-C <130 mg/dL and LDL-C <100 mg/dL.

Although the NLA guidelines include those with CKD as high risk for ASCVD, the highly controversial ACC/AHA 2013 guidelines don’t specifically address CKD. These guidelines use a risk-based approach for individuals without clinical ASCVD, LDL ≥190 mg/dL, or diabetes. Moderate- or high-intensity statin treatment should be considered if 10-year risk is ≥7.5% in those 40 to 75 years with LDL-C 70 mg/dL to 189 mg/dL.6

Douglas Jennings, PharmD, FCCP, FAHA
Douglas Jennings, PharmD, FCCP, FAHA
Douglas Jennings, PharmD, FCCP, FAHA, FACC, currently practices as the clinical pharmacy manager in heart transplant and mechanical circulatory support at New York Presbyterian Columbia University Medical Center. He is a past chair of the American College of Clinical Pharmacy (ACCP) Cardiology PRN, and he is a fellow of ACCP, the American Heart Association, and the American College of Cardiology.