INTRODUCTION — Lipoprotein abnormalities are common in patients with all stages of chronic kidney disease (CKD) [1-7]. Hypertriglyceridemia is the primary lipid abnormality among CKD patients, although abnormalities in cholesterol and apolipoproteins also occur [8].
This topic reviews the pathogenesis, epidemiology, and treatment of lipid and lipoprotein abnormalities in nondialysis CKD patients. The pathogenesis and significance of lipid abnormalities in nephrotic syndrome and following kidney transplantation, the association between CKD and coronary heart disease (CHD), and the management of lipids in patients with CKD who require dialysis are discussed separately:
●(See "Lipid abnormalities in nephrotic syndrome".)
●(See "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation".)
●(See "Chronic kidney disease and coronary heart disease".)
COMMON LIPID ABNORMALITIES — As in non-CKD patients, lipoprotein abnormalities may involve triglycerides, cholesterol, high-density lipoprotein (HDL), and lipoprotein(a) (Lp(a)).
Triglycerides — Hypertriglyceridemia is the primary lipid abnormality among CKD patients. Approximately 40 to 50 percent of CKD patients have fasting triglyceride levels >200 mg/dL (2.26 mmol/L). In the absence of other comorbid conditions, hypertriglyceridemia is seldom profound; the plasma levels are usually below 500 mg/dL.
Hypertriglyceridemia among CKD patients is caused by an increased production rate and by a lower catabolic rate. Impaired carbohydrate tolerance and enhanced hepatic very-low-density lipoprotein (VLDL) synthesis might contribute to the increased production of triglyceride-rich lipoproteins [2]. The reduced catabolic rate is likely caused by a decreased activity of the two enzymes lipoprotein lipase and hepatic triglyceride lipase, which cleave triglycerides into free fatty acids for energy production or storage [3,4,9]. This impaired clearance results from alterations in the composition of circulating triglycerides, which become enriched with apolipoprotein C-III. This increases the ratio of the inhibitory apolipoprotein C-III to the activating apolipoprotein C-II, resulting in a net decrease plasma lipase activity, hence lower clearance rate of triglyceride-rich lipoproteins and accumulation of lipoprotein remnants in the plasma [3,4,9,10]. (See "Lipoprotein classification, metabolism, and role in atherosclerosis", section on 'Apolipoproteins' and "Hypertriglyceridemia in adults: Approach to evaluation", section on 'Atherosclerotic cardiovascular disease'.)
Other potential contributors to decreased triglyceride clearance include secondary hyperparathyroidism causing a decreased synthesis of lipoprotein lipase [11-13] and the retention of other circulating inhibitors of lipoprotein lipase, such as pre-beta-HDL [14]. Pre-beta-HDL is the HDL moiety that interacts with the ABCA1 transporter, which is critical for macrophage cholesterol efflux.
Cholesterol — Approximately 20 to 30 percent of CKD patients have total serum cholesterol levels >240 mg/dL (6.2 mmol/L) [1-7]. It should be emphasized that various CKD subpopulations have markedly different plasma cholesterol concentrations, with very high concentrations in patients with nephrotic syndrome or patients treated by maintenance peritoneal dialysis, in contrast to the normal or low concentrations in maintenance hemodialysis patients [8].
An increased low-density lipoprotein/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio is commonly observed [15]. The increased ratio is due to both a modest decrease in HDL-C [16] and increased LDL-C [15]. Approximately 10 to 45 percent of CKD patients have LDL-C levels >130 mg/dL (3.4 mmol/L) [1-7].
Although low plasma HDL-C concentration has been a well-established predictor of cardiovascular events in the general population, interventional trials that examine strategies to raise HDL-C concentrations failed to demonstrate the expected positive effect on clinical outcomes. The association between HDL-C concentration and cardiovascular outcomes in the general population may, in fact, be U-shaped [17]; a similar U-shaped relationship may also exist with the risk of infectious diseases [18]. Hence, plasma cholesterol levels may be more than a biomarker for cardiovascular diseases but may also be a marker of other comorbidities that affect patient outcomes. (See "HDL cholesterol: Clinical aspects of abnormal values".)
Consistent with the aforementioned studies in the general population, a large study of more than 33,000 hemodialysis patients revealed a U-shaped association with an increased risk for total and cardiovascular mortality in patients with plasma HDL-C concentrations below 30 mg/dL and above 60 mg/dL [19]. A second, large study of 38,377 patients with estimated glomerular filtration rate (eGFR) 15 to 59 mL/min/1.73 m² found that HDL-C ≤40 mg/dL was associated with a higher risk of all-cause, cardiovascular, and cancer-related mortality in men and women, and HDL-C >60 mg/dL was associated with a lower risk of mortality in women but not in men [20].
Another study in almost two million men with a median follow-up of nine years reported that individuals with HDL-C concentrations <30 mg/dL had a 10 to 20 percent higher risk for CKD and/or progression of CKD compared with individuals with concentration ≥40 mg/dL [21]. Genetic studies provide no or only weak support for a causal association of HDL-C with CKD [22,23].
The changes in functional properties of the HDL particle in chronic dialysis patients result in impaired cholesterol efflux capacity and impaired reverse cholesterol transport from peripheral cells such as cholesterol-laden macrophages to the liver, resulting in an increased risk for atherosclerotic cardiovascular diseases [24]. There are, however, few studies on changes in reverse cholesterol transport in nondialyzed CKD patients [25].
The composition of HDL particles and their atheroprotective properties may be different among CKD patients. As an example, there is downregulation of lecithin-cholesterol acyltransferase, which results in reduced esterification of cholesterol and therefore contributes to the reduced reverse cholesterol transport [26]. Other components of the HDL particle with major changes in CKD patients are serum amyloid A, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), advanced oxidation protein products (AOPP), apolipoprotein A-IV, and various microRNAs. In the 4D trial, serum amyloid A-HDL was predictive of a higher risk of a cardiac event rate and all-cause mortality [27]. These data support the concept of dysfunctional HDL in the pathogenesis of atherosclerotic cardiovascular disease in CKD [28,29]. On the other hand, data from the CARE FOR HOMe study suggest that neither HDL quantity nor HDL composition or function independently predict cardiovascular outcome among nondialysis CKD patients [30].
Our understanding of the roles of many of these HDL components in the pathogenesis of kidney and cardiovascular disease is still rather rudimentary [25]. Furthermore, there may also be a decrease in the antioxidant properties of HDL particles and an increase in the oxidative modification of LDL particles in CKD, potentially predisposing these patients to cardiovascular diseases [29,31].
The clinical significance of elevated cholesterol concentrations among CKD patients is not clear and appears to be somewhat different from non-CKD patients. Whereas, in non-CKD patients, a higher serum total cholesterol progressively increases the risk of coronary disease and cardiovascular death, among CKD patients, the association between LDL-C and coronary risk tends to diminish as the estimated glomerular filtration rate (eGFR) decreases [32], and some studies have found no association between lipid levels and mortality among CKD patients [33-35]. There are studies suggesting that the association between serum total cholesterol concentration and cardiovascular disease is modified by the presence of inflammation and malnutrition, conditions that become more common with decreasing kidney function [36,37]. (See "Overview of established risk factors for cardiovascular disease", section on 'Lipids and lipoproteins'.)
Lipoprotein(a) — Plasma Lp(a) concentrations increase with decreasing GFR, but they are highest in patients with nephrotic syndrome and in peritoneal dialysis patients [38-41]. High Lp(a) concentrations are among the strongest genetically determined risk factors for cardiovascular disease in the general population [42-44] (see "Lipoprotein(a)", section on 'Disease associations'). Similar observations have been made in patients of various CKD stages [45-47].
The role of the kidney in the metabolism of Lp(a) is not fully understood. Lower Lp(a) concentrations in the renal vein compared with the renal artery [48] and fragments of apolipoprotein(a), the major apolipoprotein of Lp(a), in urine [49,50] suggest an important function of the normal kidney in its metabolism. Turnover studies using stable isotope technology revealed an impaired catabolism of Lp(a) in hemodialysis patients [38] but an increased production rate in patients with nephrotic syndrome [51]. (See "Chronic kidney disease and coronary heart disease", section on 'Chronic kidney disease as an independent risk factor for CHD'.)
Additional studies are required to determine the relationship between lipids/lipoproteins and clinical outcomes, and these studies should account for changes in composition and functional activities of the lipoproteins. Randomized trials are required to establish causal relationships and provide definitive guides for the management of Lp(a).
SCREENING AND MONITORING — We screen all CKD patients with a lipid panel that includes total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. This is consistent with the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [52]. Many guidelines recommend the measurement of lipoprotein (a) (Lp(a)) for cardiovascular risk stratification [53], and that measurement of Lp(a) should be performed at least once in each person's lifetime [54].
Among most patients, regardless if they are treated with statins or not, we recheck lipids annually, with the exception of Lp(a), which is checked only once or when changes in the CKD stage occur. Annual measurements allow assessment of compliance, optimal dosing of medications, and consideration of additional cholesterol-lowering drugs such as ezetimibe as well as further diet or lifestyle changes. Among patients with markedly abnormal values who may require titration of medications, we check lipids more frequently (ie, every three to six months). The KDIGO guidelines take a somewhat different approach and state that routine follow-up monitoring of lipids in patients taking medication is not necessary but may be useful for detection of nonadherence [14].
TREATMENT
Management of LDL-C to reduce cardiovascular risk — In general, management of low-density lipoprotein cholesterol (LDL-C) to reduce cardiovascular risk is similar in patients with nondialysis CKD and in patients without CKD [55]. Our approach depends in part upon whether the patient already has established atherosclerotic cardiovascular disease (secondary prevention) or does not already have established atherosclerotic cardiovascular disease (primary prevention) (table 1). (See 'Secondary prevention: CKD patients with established atherosclerotic cardiovascular disease' below and 'Primary prevention: CKD patients without established atherosclerotic cardiovascular disease' below.)
The use of lipid-lowering therapy in patients treated with dialysis, issues related to muscle toxicity, the general safety of statins in CKD patients, and the effects of statins on cardiovascular and noncardiovascular outcomes are discussed separately. (See "Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis)", section on 'Lipid modification' and "Statin muscle-related adverse events".)
The use of lipid-lowering therapy for transplant recipients is discussed elsewhere. (See "Kidney transplantation in adults: Lipid abnormalities after kidney transplantation", section on 'Treatment'.)
Secondary prevention: CKD patients with established atherosclerotic cardiovascular disease — Patients with nondialysis CKD who have established atherosclerotic cardiovascular disease (prior history of coronary, cerebrovascular, or peripheral arterial disease) should receive maximally tolerated statin therapy, similar to patients with established atherosclerotic cardiovascular disease who do not have CKD (table 1). In various trials of patients with established cardiovascular disease, the subgroups of patients with CKD derived similar relative benefits from statins on major outcomes as the subgroups without CKD [56].
The treatment of such patients, including goal LDL-C and monitoring, is presented separately. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Our approach' and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Chronic kidney disease patients'.)
Typically, atorvastatin is used in patients with CKD because renal dosing is not required, although other statins have been examined and shown to be beneficial in CKD populations [52]. (See "Statins: Actions, side effects, and administration", section on 'Chronic kidney disease'.)
Primary prevention: CKD patients without established atherosclerotic cardiovascular disease
Our approach — We recommend statin therapy for primary prevention (ie, in the absence of established atherosclerotic cardiovascular disease) in most patients with nondialysis CKD, although the practice differs somewhat among the UpToDate authors and editors (table 1):
●Some UpToDate authors and editors recommend statin therapy in all patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and suggest (a weaker recommendation) statin therapy for patients with CKD and eGFR ≥60 mL/min/1.73 m2 if they are 50 years of age or older or have other cardiovascular risk factors (eg, diabetes, hypertension, smoking, low levels of high-density lipoprotein cholesterol [HDL-C], high levels of lipoprotein(a) [Lp(a)]).
●Other UpToDate contributors recommend statins for primary prevention in nondialysis CKD patients if the predicted 10-year absolute risk of having a major cardiovascular event is 7.5 to 10 percent or greater but not if the predicted 10-year risk is less than 5 percent. Patients with a predicted 10-year risk of 5 to 7.5 percent are frequently offered treatment. This approach is similar to the management of LDL-C for primary prevention in patients without CKD. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)
In practice, this discrepant approach applies only to a small fraction of patients with nondialysis CKD because, as noted elsewhere, patients with CKD have a high prevalence of traditional cardiovascular risk factors (eg, hypertension, diabetes, older age) and because the number of traditional cardiovascular risk factors correlates with the severity of CKD. Thus, most patients with CKD (particularly those with eGFR <60 mL/min/1.73 m2) have a high predicted 10-year cardiovascular risk by virtue of their traditional risk factors. (See "Chronic kidney disease and coronary heart disease", section on 'Association between CKD and CHD in community-based populations' and "Chronic kidney disease and coronary heart disease", section on 'Traditional risk factors'.)
In general, we prescribe moderate-intensity statin therapy for primary prevention of cardiovascular disease (including in patients with CKD) and do not target a specific LDL-C goal (see "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease"). The exceptions are patients with suspected heterozygous or homozygous familial hypercholesterolemia (who typically have an LCL-C ≥190 mg/dL [4.9 mmol/L]). The evaluation and treatment of such patients are discussed elsewhere. (See "Familial hypercholesterolemia in adults: Overview".)
Moderate-intensity statin doses that have shown benefit in CKD patients include atorvastatin 20 mg daily, fluvastatin 80 mg daily, pravastatin 40 mg daily, rosuvastatin 10 mg daily, and simvastatin 20 to 40 mg daily (table 2). Atorvastatin is frequently chosen for patients with CKD because it undergoes hepatic clearance and does not require renal dose adjustments. In addition, atorvastatin may have beneficial effects on proteinuria and preservation of kidney function [52,57].
As noted above, we monitor lipids annually and encourage treatment adherence as necessary based upon total cholesterol and LDL-C levels. (See 'Screening and monitoring' above.)
Baseline transaminases should be checked among CKD patients who are initiating statins, but subsequent monitoring of transaminases is probably not necessary, due to the low incidence of abnormalities among patients with normal baseline transaminases [52]. We do not routinely monitor creatine kinase (CK) levels in the absence of symptoms of myopathy (see "Statin muscle-related adverse events"). An exception is in patients on statins in addition to other medications that also increase the risk of rhabdomyolysis (eg, fibric acid derivatives, calcineurin inhibitors).
Adherent patients who do not respond to statin therapy by decreasing LDL-C concentrations may have a high plasma Lp(a) concentration, since Lp(a) consists of 30 to 45 percent cholesterol, which is also measured as part of the total cholesterol or LDL-C fraction [58]. If a patient has an Lp(a) concentration of 200 mg/dL, roughly 60 to 90 mg/dL of the measured LDL-C is derived from the Lp(a). Since Lp(a) levels are not influenced by statins [59], the truly statin-accessible cholesterol (ie, Lp(a)-corrected LDL-C) is actually markedly lower. As an example, an uncorrected LDL-C value of 100 mg/dL may truly reflect an accessible LDL-C value of only 10 to 40 mg/dL if the Lp(a) concentration is 200 mg/dL. No major change of LDL-C levels can be expected with statins in such a setting.
Rationale for our approach — The best data supporting the use of statins for primary prevention of cardiovascular events in patients with nondialysis CKD come from the Study of Heart and Renal Protection (SHARP) trial and from meta-analyses of statin trials that included subgroups of patients with CKD. These data demonstrate a reduction in cardiovascular risk with statin therapy in patients with nondialysis CKD.
The SHARP trial randomly assigned 9270 patients with CKD (including 6247 nondialysis patients) who had a serum creatinine of at least 1.7 mg/dL (150 microm/L), if male, or 1.5 mg/dL (130 microm/L), if female, to placebo or to the combination of simvastatin 20 mg daily plus ezetimibe (an inhibitor of intestinal cholesterol absorption) 10 mg daily [60]. Nearly all patients had an eGFR <60 mL/min/1.73 m2; patients were not enrolled if they had a prior history of coronary heart disease (CHD). In the subgroup who were not treated with maintenance dialysis, simvastatin/ezetimibe lowered the incidence of the primary composite outcome of coronary death, myocardial infarction, ischemic stroke, or any revascularization procedure (9.5 versus 11.9 percent) after 4.9 years of follow-up. Discontinuation of the study medication due to myalgia was significantly more common with simvastatin/ezetimibe therapy compared with placebo (1.1 versus 0.6 percent), but the rates of other adverse effects were similar between treatment groups. Despite the benefit on the combined endpoint, there was no difference between groups on all-cause mortality.
These results are supported by meta-analyses of CKD subgroups from large statin trials for cardiovascular prevention [56,61-63]; some of these meta-analyses also included the SHARP trial. Each of these studies found that statin therapy reduced the rates of cardiovascular events, cardiovascular mortality, and all-cause mortality. Most analyses reported outcomes among the combined group of dialysis patients, kidney transplant recipients, as well as nondialysis CKD patients; however, post-hoc subgroup analyses suggest that the beneficial effects are limited to patients not receiving dialysis [61,62]. In one meta-analysis, among CKD patients not receiving dialysis, statins were associated with a relative reduction in all-cause mortality (11 studies or subgroups; relative risk [RR] 0.81, 95% CI 0.74-0.88), cardiovascular mortality (8 studies or subgroups; RR 0.78 95% CI 0.68-0.89), and cardiovascular events (14 studies or subgroups; RR 0.76, 95% CI 0.73-0.80) [56].
The rationale to prescribe statins for all nondialysis CKD patients with an eGFR <60 mL/min/1.73 m2, and in many CKD patients with higher eGFR values, is based upon the fact that even mild-to-moderate CKD (including albuminuria with a normal eGFR) is associated with an increased relative risk for cardiovascular disease [64,65] and upon the data showing that cardiovascular risks can be reduced by statin treatment. (See "Chronic kidney disease and coronary heart disease".)
The rationale to use predicted 10-year absolute cardiovascular risk to guide statin therapy is based upon the notion that, in general, therapeutic decisions are made based upon the absolute benefits and harms of a particular treatment and not the relative benefits and harms. As a hypothetical example, a 40-year-old, nondiabetic, non-smoking, White man with total cholesterol of 140 mg/dL (3.6 mmol/L), HDL-C of 60 mg/dL (1.6 mmol/L), and systolic pressure of 135 mmHg has a predicted 10-year risk of 0.5 percent for atherosclerotic events. If this patient had an eGFR of 55 mL/min/1.73 m2, the relative risk would be approximately 30 percent higher, corresponding to an absolute 10-year risk of only 0.65 percent. Thus, even in a patient with reduced eGFR and therefore a higher relative risk, the absolute benefit from long-term statin therapy would be small if the patient lacked other cardiovascular risk factors. Although the traditionally used calculators to predict 10-year risk (eg, the American College of Cardiology/American Heart Association and Framingham calculators) are less accurate in patients with CKD [66-70], the addition of eGFR and albuminuria does not meaningfully improve the ability to predict cardiovascular outcomes [65].
Management of other lipid disorders
Lipid disorders in nephrotic syndrome — Recommendations for hyperlipidemic patients with nephrotic syndrome and eGFR ≥60 mL/min/1.73 m2 are discussed elsewhere.
Hypertriglyceridemia — The nonpharmacologic management of hypertriglyceridemia among CKD patients (eg, dietary modification) is similar to that in the general population. Therapeutic lifestyle changes include dietary modification, weight reduction if overweight, increased physical activity, and reduced alcohol intake [52,66]. Dietary modifications could be a low-fat diet (less than 15 percent of total calories), reduction of monosaccharides and disaccharides, reduction of dietary carbohydrates, and use of fish oils. Cautions should be taken in instituting dietary restriction in order to avoid malnutrition. (See "Hypertriglyceridemia in adults: Management", section on 'General measures'.)
We typically do not use fibrates, as they are more likely to produce side effects, particularly when given concurrently with statins [52,66]. However, rare CKD patients who have serum total triglycerides >10 mmol/L (886 mg/dL) despite nonpharmacologic interventions may require specific treatment of triglycerides in order to prevent pancreatitis and possibly reduce cardiovascular risk. For these patients, fibrates are most effective in lowering serum triglyceride levels [71]. Such patients should only be treated by clinicians with expertise in lipid disorders, and the dose needs to be adjusted for decreased kidney function. (See "Hypertriglyceridemia in adults: Management" and "Statin muscle-related adverse events", section on 'Concurrent drug therapy'.)
Niacin also lowers serum triglyceride levels and increases serum HDL-C levels, although we seldom prescribe it in CKD patients. The addition of niacin to statin did not reduce cardiovascular events in a trial of CKD patients [72]. Niacin also has side effects such as flushing and gastrointestinal distress. In addition, niacin is no longer available in many countries.
The Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) evaluated the effect of gemfibrozil in patients with established CHD and an HDL-C <40 mg/dL (1.03 mmol/L). Within this cohort of 2531 people, there were 1044 men with impaired creatinine clearance including 638 and 406 patients with creatinine clearances of 60 to 75 and 30 to 59.9 mL/min, respectively [73]. Among these patients with impaired creatinine clearance, gemfibrozil therapy lowered the risk of the primary endpoint of coronary death and nonfatal myocardial infarction (18.2 versus 24.3 percent, hazard ratio [HR] 0.73, 95% CI 0.56-0.96). However, gemfibrozil therapy had no effect on total mortality (HR 1.03) and caused a significant decline in kidney function; 5.9 and 2.8 percent of gemfibrozil and placebo-treated patients, respectively, experienced a sustained increase in creatinine values that remained 0.5 mg/dL higher than baseline for the remainder of follow-up (p = 0.02).
Lipoprotein(a) — There are no drugs that produce an isolated lowering of Lp(a). However, post hoc analyses from the PCSK9 trials FOURIER and ODYSSEY [74] found that these agents reduce Lp(a) by 25 to 30 percent, which may contribute to the beneficial effects on the cardiovascular outcomes.
Other treatments that can reduce Lp(a) include novel antisense oligonucleotides against apolipoprotein(a), the main protein of the Lp(a) particle, and lipoprotein apheresis. In preclinical studies, these antisense oligonucleotides lowered Lp(a) concentrations up to 90 percent [75]. Whether this intervention also decreases cardiovascular events is unknown. In some countries, lipoprotein apheresis is used to treat patients with high Lp(a) concentrations and progressive cardiovascular disease despite optimal lipid-lowering medication. This intervention results in a dramatic lowering of cardiovascular events [76], although sham apheresis was not performed as a control.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Chronic kidney disease in adults".)
SUMMARY AND RECOMMENDATIONS
●Lipid abnormalities are common in patients with all stages of chronic kidney disease (CKD). Mild-to-moderate hypertriglyceridemia is the primary lipid abnormality among CKD patients, although abnormalities in low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp(a)) also occur. (See 'Introduction' above and 'Common lipid abnormalities' above.)
●We screen all CKD patients with a lipid panel that includes total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides. We obtain at least one measure of Lp(a) for cardiovascular risk stratification. We recheck lipids annually, with the exception of Lp(a), which is checked only once or when changes in the CKD stage occur. (See 'Screening and monitoring' above.)
●In general, management of LDL-C to reduce cardiovascular risk is similar in patients with nondialysis CKD and in patients without CKD. Our approach depends in part upon whether the patient already has established atherosclerotic cardiovascular disease (secondary prevention) or does not already have established atherosclerotic cardiovascular disease (primary prevention) (table 1) (see 'Management of LDL-C to reduce cardiovascular risk' above):
•Secondary prevention – Patients with nondialysis CKD who have established atherosclerotic cardiovascular disease (prior history of coronary, cerebrovascular, or peripheral arterial disease) should receive maximally tolerated statin therapy, similar to patients with established atherosclerotic cardiovascular disease who do not have CKD. Typically, atorvastatin is used in patients with CKD because renal dosing is not required, although other statins have been examined and shown to be beneficial in CKD populations. (See 'Secondary prevention: CKD patients with established atherosclerotic cardiovascular disease' above.)
Statin dosing, LDL-C goal, and monitoring of such patients are presented separately. (See "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Our approach' and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease", section on 'Chronic kidney disease patients' and "Statins: Actions, side effects, and administration", section on 'Chronic kidney disease'.)
•Primary prevention – We recommend statin therapy for primary prevention (ie, in the absence of established atherosclerotic cardiovascular disease) in most patients with nondialysis CKD, although the practice differs slightly among the UpToDate authors and editors (table 1):
-Some UpToDate authors and editors recommend statin therapy in all patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 and suggest statin therapy for patients with CKD and eGFR ≥60 mL/min/1.73 m2 if they are 50 years of age or older or have other cardiovascular risk factors (eg, diabetes, hypertension, smoking, low levels of HDL-C, high levels of Lp(a)).
-Other UpToDate contributors recommend statins for primary prevention in nondialysis CKD patients if the predicted 10-year absolute risk of having a major cardiovascular event is 7.5 to 10 percent or greater but not if the predicted 10-year risk is less than 5 percent. Patients with a predicted 10-year risk of 5 to 7.5 percent are frequently offered treatment. This approach is similar to the management of LDL-C for primary prevention in patients without CKD. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease".)
●Recommendations for hyperlipidemic patients with nephrotic syndrome and eGFR ≥60 mL/min/1.73 m2 are discussed elsewhere.
●The nonpharmacologic management of hypertriglyceridemia among CKD patients (eg, dietary modification, alcohol restriction, weight reduction, increase in physical activity) is similar to that in the general population. We typically do not use fibrates, as they are more likely to produce side effects, particularly when given concurrently with statins. However, rare CKD patients who have serum total triglycerides >10 mmol/L (886 mg/dL) despite nonpharmacologic interventions may require specific treatment of triglycerides in order to prevent pancreatitis and possibly reduce cardiovascular risk. (See "Hypertriglyceridemia in adults: Management" and "Statin muscle-related adverse events", section on 'Concurrent drug therapy'.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Gerald B Appel, MD, who contributed to earlier versions of this topic review.
