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Lipid management in patients with nondialysis chronic kidney disease

Lipid management in patients with nondialysis chronic kidney disease
Literature review current through: Jan 2024.
This topic last updated: Jan 31, 2024.

INTRODUCTION — Lipoprotein abnormalities are common in patients with all stages of chronic kidney disease (CKD) [1-9]. Hypertriglyceridemia is the primary lipid abnormality among patients with CKD, although abnormalities in cholesterol and apolipoproteins also occur [10-12].

This topic reviews the pathogenesis, epidemiology, and treatment of lipid and lipoprotein abnormalities in patients with nondialysis CKD. 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 "Lipid abnormalities after kidney transplantation".)

(See "Chronic kidney disease and coronary heart disease".)

(See "Secondary prevention of cardiovascular disease in end-stage kidney disease (dialysis)", section on 'Lipid modification'.)

COMMON LIPID ABNORMALITIES — As in patients without CKD, plasma lipoprotein abnormalities may involve triglycerides, cholesterol, high-density lipoprotein (HDL), and lipoprotein(a) (Lp(a)).

Triglycerides — Hypertriglyceridemia is the primary lipid abnormality among patients with CKD. Approximately 40 to 50 percent of patients with CKD 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.

High serum triglyceride concentrations and a high triglyceride/HDL cholesterol (HDL-C) ratio are risk markers of CKD [13,14] and are associated with decline in eGFR and incidence of new-onset CKD [15-18]. However, in a Mendelian randomization study, genetic variants associated with higher, life-long triglyceride concentrations were not associated with kidney disease [19], suggesting that the relationship between serum triglycerides and kidney function decline is not causal. Higher triglycerides and a high triglyceride/HDL-C are also associated with atherosclerotic cardiovascular disease [20,21] and all-cause mortality [22,23], although not all studies support these observations [24].

Hypertriglyceridemia among patients with CKD 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 [3,4,25]. This impaired clearance results from alterations in the composition of circulating lipoproteins, which become enriched with apolipoprotein C-III, an inhibitor of lipoprotein lipase. 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 [3,4,25,26]. (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 in CKD include secondary hyperparathyroidism causing a decreased synthesis of lipoprotein lipase [27-29] and the retention of other circulating inhibitors of lipoprotein lipase, such as pre-beta-HDL [30]. Pre-beta-HDL is the HDL moiety that interacts with the ABCA1 transporter, which is critical for macrophage cholesterol efflux.

Total and LDL cholesterol — Approximately 20 to 30 percent of patients with CKD have total plasma 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 patients on maintenance hemodialysis [10].

The clinical significance of elevated serum cholesterol concentrations among patients with CKD is not clear and appears to be somewhat different from patients without CKD. In patients without CKD, a higher serum total cholesterol level is progressively associated with an increased risk of coronary disease and cardiovascular death. Among patients with CKD, however, the association between low-density lipoprotein cholesterol (LDL-C) and coronary risk tends to diminish as the estimated glomerular filtration rate (eGFR) decreases [31], and some studies have found no association between lipid levels and mortality among patients with CKD [24,32,33]. 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 [34,35]. (See "Overview of established risk factors for cardiovascular disease", section on 'Lipids and lipoproteins'.)

An increased LDL-C/HDL-C ratio is commonly observed [36]. The increased ratio is due to both a modest decrease in HDL-C [37] and increased LDL-C [36]. Approximately 10 to 45 percent of patients with CKD have LDL-C levels >130 mg/dL (3.4 mmol/L) [1-7].

HDL cholesterol — Although a low plasma HDL-C concentration is 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, in fact, appears to be U-shaped [38]; a similar U-shaped relationship exists between HDL-C concentration and the risk of infections [39]. These U-shaped relationships might be one of the reasons that explain the lack of clinical benefits with pharmacologic lowering of plasma HDL-C. (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 patients on hemodialysis 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 [40]. A second study of 38,377 patients with eGFR 15 to 59 mL/min/1.73 m² found a U-shaped relationship with mortality in females, with a nadir at HDL-C of 50 mg/dL, but not in males [41].

Individuals with HDL-C concentrations <30 mg/dL had a 10 to 20 percent higher risk for incident CKD and/or progression of CKD in one study compared with individuals whose HDL-C concentration was ≥40 mg/dL [42]. Genetic studies also provide some support for a causal association of HDL-C with CKD [19,43,44].

One of the possible explanations why the relationship between HDL-cholesterol and various outcomes is not straightforward is the fact that routine assays measure only one component of the HDL particles, namely HDL cholesterol. However, an HDL particle consists of more than 80 proteins and several hundred lipid species with various functions [9,45]. Changes in functional properties of the HDL particle 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 [46]. There are, however, few studies on changes in reverse cholesterol transport in patients with CKD [8,47].

The composition of HDL particles and their atheroprotective properties in patients with CKD may be different from those in patients without CKD. Our understanding of the roles of many of these HDL components in the pathogenesis of kidney and cardiovascular disease is still rather rudimentary [8]. As an example, there is downregulation of lecithin-cholesterol acyltransferase, which results in reduced esterification of cholesterol and therefore reduced reverse cholesterol transport [48]. Other components of the HDL particle with major changes in patients with CKD 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 that included patients on hemodialysis with diabetes mellitus, higher serum amyloid A in the HDL particle was predictive of a higher risk of a cardiac event rate [49]. In the same study, low serum apolipoprotein A-IV concentrations were associated with an increased risk for all-cause mortality and sudden cardiac arrest [50]. Along the same line, higher serum apolipoprotein A-IV was found to be an independent risk marker for reduced all-cause mortality, cardiovascular events, and heart failure in a cohort of more than 5000 patients with moderate CKD in the German Chronic Kidney Disease study [12]. These and several other studies support the concept of dysfunctional HDL in the pathogenesis of atherosclerotic cardiovascular disease in CKD [51,52], although not all studies reached similar conclusions [53].

Lipoprotein(a) — Plasma Lp(a) concentrations increase with decreasing GFR, but they are highest in patients with nephrotic syndrome and in patients on peritoneal dialysis [11,54-56].

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 [57] and fragments of apolipoprotein(a), the major apolipoprotein of Lp(a), in urine [58,59] suggest an important function of the kidney in its catabolism. Turnover studies using stable isotope technology revealed an impaired catabolism of Lp(a) in patients on hemodialysis [54] but an increased production rate in patients with nephrotic syndrome [60]. (See "Chronic kidney disease and coronary heart disease", section on 'Chronic kidney disease as an independent risk factor for CHD'.)

Two Mendelian randomization studies found that genetically increased serum Lp(a) concentrations were associated with an increased risk for CKD, suggesting that elevated Lp(a) concentrations in CKD are not only a consequence of CKD but may also contribute to the development of CKD [44,61].

In people without CKD, high Lp(a) concentrations are associated with a higher risk for cardiovascular disease, a finding bolstered by genetic studies [62-64]. Accordingly, various guideline and consensus statements recommend testing Lp(a) at least once in each adult person to characterize cardiovascular risks [45,65,66]. (See "Lipoprotein(a)", section on 'Disease associations'.)

Similar associations between higher Lp(a) concentrations, and also higher genetically determined Lp(a) concentrations, and cardiovascular disease risk have been described in patients with CKD [67-74].

SCREENING AND MONITORING — We screen all patients with CKD with a serum or plasma lipid panel that includes total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. This approach is similar to screening recommendations for the general population. (See "Screening for lipid disorders in adults".)

The sample should be obtained after at least nine hours of fasting. This is consistent with the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [75].

Many guidelines and consensus statements recommend the measurement of lipoprotein (a) (Lp(a)) for cardiovascular risk stratification in the general population, and that measurement of Lp(a) should be performed at least once in each person's lifetime [45,65,66,76]. We follow the same guidance in patients with CKD, and we repeat the Lp(a) measurement when the CKD stage worsens, if nephrotic syndrome develops, or if the patient is placed on peritoneal dialysis. However, if the initial Lp(a) concentration is below 10 mg/dL, repeated measurements can be omitted since expected increases are unlikely to result in a pronounced change of risk category. (See "Lipoprotein(a)".)

Among most patients, regardless of whether or not they are treated with statins, we recheck lipids annually (with the exception of Lp(a)). Annual measurements allow assessment of adherence, 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). Monitoring of and targeting serum lipid profiles are similar to those recommended for the general non-CKD population. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease" and "Management of low density lipoprotein cholesterol (LDL-C) in the secondary prevention of cardiovascular disease".)

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 [30].

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 [77]. 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: Patients with CKD and established atherosclerotic cardiovascular disease' below and 'Primary prevention: Patients with CKD 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 patients with CKD, 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 "Lipid abnormalities after kidney transplantation", section on 'Treatment'.)

Secondary prevention: Patients with CKD and established atherosclerotic cardiovascular disease — Patients with nondialysis CKD who have established atherosclerotic cardiovascular disease (prior history of coronary, cerebrovascular, peripheral arterial disease, or aortic aneurysm) 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 [78].

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".)

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 as well [75]. Ezetimibe can be added to a statin if necessary to achieve the LDL-C target in patients with CKD. A PCSK9 inhibitor can also be added to a statin with or without ezetimibe, but it requires parenteral injection. (See "Statins: Actions, side effects, and administration", section on 'Chronic kidney disease'.)

Primary prevention: Patients with CKD 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):

Since CKD per se is a cardiovascular risk factor, the authors of this topic and one of the section editors recommend statin therapy in all patients with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, regardless of other cardiovascular risk factors or calculated cardiovascular risk score.

These experts further 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 high-density lipoprotein cholesterol [HDL-C], high levels of lipoprotein(a) [Lp(a)]).

Other UpToDate contributors recommend statins for primary prevention in patients with nondialysis CKD 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.

In general, we prescribe moderate-intensity statin therapy for primary prevention of cardiovascular disease (including in patients with CKD). The authors target a serum LDL-C concentration of <70 mg/dL although other experts target a concentration <100 mg/dL (see "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease"). The exception to moderate-intensity (rather than high-intensity) statin therapy is 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.

Moderate-intensity statin doses that have shown benefit in patients with CKD 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 is metabolized by the liver and does not require renal dose adjustments. In addition, atorvastatin may have beneficial effects on proteinuria and preservation of kidney function [75,79].

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 patients with CKD 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 [75]. 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 plasma LDL-C concentrations may have a high plasma Lp(a) concentration, since Lp(a) consists of a certain, albeit variable, amount of cholesterol, which is also measured as part of the plasma total cholesterol or LDL-C fraction [80]. If a patient has an Lp(a) concentration of 200 mg/dL, roughly 40 to 60 mg/dL of the measured LDL-C would be derived from the Lp(a). Since Lp(a) levels are not influenced by statins [81], the truly statin-accessible cholesterol (ie, Lp(a)-corrected LDL-C) is actually lower.

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 patients not on dialysis) who had a serum creatinine of at least 1.7 mg/dL (150 microm/L) for males, or 1.5 mg/dL (130 microm/L) for females, to placebo or to the combination of simvastatin 20 mg daily plus ezetimibe (an inhibitor of intestinal cholesterol absorption) 10 mg daily [82]. 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 entire cohort and 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 (11.3 versus 13.4 percent in the entire cohort and 9.5 versus 11.9 percent in the CKD subgroup) 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 [78,83-85]; 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 patients on dialysis, kidney transplant recipients, as well as patients with nondialysis CKD; however, post-hoc subgroup analyses suggest that the beneficial effects are limited to patients not receiving dialysis [83,84]. In one meta-analysis, among patients with CKD 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) [78].

The rationale to prescribe statins for all patients with nondialysis CKD with an eGFR <60 mL/min/1.73 m2, and in many patients with CKD 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 [86,87] 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. This approach to deciding about statin therapy for primary prevention is discussed in detail elsewhere. (See "Low-density lipoprotein cholesterol-lowering therapy in the primary prevention of cardiovascular disease", section on 'Rationale for our approach and treatment goals'.)

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 patients with CKD (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 [75,88]. 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 [75,88]. However, rare patients with CKD who have serum total triglycerides >10 mmol/L (886 mg/dL) despite nonpharmacologic interventions may require specific pharmacologic 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 [89]. 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 patients with CKD. The addition of niacin to statin did not reduce cardiovascular events in a trial of patients with CKD [90]. 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 males with impaired creatinine clearance, including 638 and 406 patients with creatinine clearances of 60 to 75 and 30 to 59.9 mL/min, respectively [91]. 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 plasma Lp(a). However, post-hoc analyses from the PCSK9 trials FOURIER and ODYSSEY [92] found that these agents reduce Lp(a) by 25 to 30 percent, which may contribute to the beneficial effects on the cardiovascular outcomes. However, the relative Lp(a)-lowering effect was only 15 to 20 percent in cases of high pretreatment Lp(a) values.

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 [93-96]. 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 [97], although sham apheresis was not performed as a control due to ethical concerns.

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 patients with CKD, 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 patients with CKD with a plasma lipid panel that includes total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride concentrations. We obtain at least one measure of plasma Lp(a) concentration for cardiovascular risk stratification. We recheck lipids annually, with the exception of Lp(a). (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 as well. (See 'Secondary prevention: Patients with CKD and 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 "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):

-The authors of this topic and one of the 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 patients with nondialysis CKD 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 patients with CKD (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 in CKD, particularly when given concurrently with statins. However, rare patients with CKD who have serum total triglycerides >10 mmol/L (886 mg/dL) despite nonpharmacologic interventions may require specific pharmacologic 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.

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Topic 7204 Version 38.0

References

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