Dyslipidemia and lipid-lowering therapy in patients on renal replacement therapy: a literature review

Chronic kidney disease (CKD) is associated with high risk for cardiovascular disease (CVD). This association is multifactorial, but CKD is often associated with dyslipidemia, which likely contributes. Patients with CKD have dyslipidemia even at early stages of renal dysfunction and dyslipidemia tends to progress with deterioration of kidney function. The dyslipidemia in CKD is largely due to increased triglyceride levels, decreased HDL-C and varying levels of LDL-C. Current management of CKD may also affect lipid levels. Robust clinical trials demonstrate that statins are safe and efficacious in both lipid lowering and prevention of CVD events in pre-end stage CKD and post-transplant. However, there is no evidence of improved CVD outcomes with statin use in dialysis patients. This review will focus on mechanisms underlying dyslipidemia in CKD and clinical trial evidence for lipid lowering therapy in patients with CKD.

Moderate chronic kidney disease (CKD) (defined by an estimated glomerular filtration rate of 30-60 ml/min) is associated with mild hypertriglyceridemia related to delayed catabolism of triglyceride-rich lipoprotein particles. Altered apolipoprotein C-III (apoC-III) metabolism may contribute to dyslipidemia in CKD. To further characterize the dyslipidemia of CKD, we investigated the kinetics of plasma apoC-III in 7 nonobese, nondiabetic, non-nephrotic CKD subjects and 7 age- and sex-matched healthy controls, using deuterated leucine ([5, 5, 5, ²H₃]leucine), gas chromatography-mass spectrometry, and multicompartmental modeling. Compared with controls, CKD subjects had higher concentrations of plasma and VLDL triglycerides and plasma and VLDL apoC-III (P < 0.05). The increased plasma apoC-III concentration was associated with a decreased apoC-III fractional catabolic rate (FCR) (1.21 ± 0.15 vs. 0.74 ± 0.12 pools/day, P = 0.03). There were no differences between apoC-III production rates of controls and those of CKD subjects. In CKD subjects, plasma apoC-III concentration was significantly and negatively correlated with apoC-III FCR (r = -0.749, P = 0.05) but not with apoC-III production rate. Plasma apoC-III concentration was positively correlated with plasma and VLDL triglycerides and VLDL apoB concentrations and negatively correlated with VLDL apoB FCR (P < 0.05 for all). ApoC-III FCR was negatively correlated with plasma and VLDL triglycerides and VLDL apoB concentration and positively correlated with VLDL apoB FCR (P < 0.05 for all). Altered plasma apoC-III metabolism is a feature of dyslipidemia in moderate CKD. Modification of apoC-III catabolism may be an important therapeutic target for reducing cardiovascular disease risk in moderate CKD.

Introduction Dyslipidemia is a major problem in chronic kidney disease (CKD) and haemodialysis patients. Although there has been much progress and reduction in the prevalence of dyslipidemia after the Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel), there were few specific recommendations for the evaluation and treatment of dyslipidemias in CKD patients in these reports. Besides, the NCEP guidelines are applicable to patients with stages 1–4 CKD and not specifically concerned with stage 5 CKD and kidney transplant recipients. It is also evident that when these guidelines were published, there were no large randomized controlled trials evaluating the effects of lipid-lowering therapy in this patient group. Given the fact that patients with CKD should be considered in the highest risk group for cardiovascular disease, it was decided that specific recommendations regarding dyslipidemia should be applied to patients with CKD. Thus from the outset of Kidney Disease Outcomes Quality Initiative (K/DOQI), it was strongly agreed that the management of dyslipidemias in patients with kidney disease would be one of the most important issues. However, recent randomized controlled trials showed that dyslipidemia treatment in these patients had shown modest benefit at best with regard to cardiovascular mortality. The specific recommendations about dyslipidemias in CKD patients are reviewed along with the new studies and future perspectives. Conclusion While preparing the dyslipidemia guidelines for CKD patients, the K/ DOQI working group anticipated from the beginning that all the guidelines should be updated whenever new information becomes available. We do not know whether trial results from the general population are applicable to all patients with CKD. A new guideline incorporating the data of a recent research is necessary. Introduction The number of patients with chronic kidney disease (CKD) is increasing. Unfortunately, the survival of CKD patients remains poor. Among other factors, cardiovascular disease (CVD) is the leading cause of death in CKD patients. Both traditional and non-traditional factors play a role for increased cardiovascular mortality. Among traditional risk factors, diabetes, hypertension and dyslipidemia are the leading causes. Anaemia, inflammation, oxidative stress, disorders of calcium phosphorus metabolism, arterial stiffness and malnutrition can be stated as non-traditional risk factors1–3. Thus, it is of no question that CKD patients can be considered as high-risk patients. In previous reports such as Adult Treatment Panel (ATP) III, there was no specific interest regarding the dyslipidemia in CKD patients. Thus in response to the recommendations of the National Kidney Foundation (NKF) Task Force on CVD, the NKF Kidney Disease Outcomes Quality Initiative (K/DOQI) convened a work group to develop guidelines for the management of dyslipidemias, one of the risk factors for CVD in CKD. This critical review gives brief information about these guidelines first and the interpretation of these guidelines based on the recently conducted randomized prospective studies thereafter.

Who Impels Nephrology: Women

Managing Dyslipidemia in Chronic Kidney Disease

Perceived knowledge among patients cared for by nephrologists about chronic kidney disease and end-stage renal disease therapies

Correlations of serum magnesium with dyslipidemia in patients on maintenance hemodialysis

Liver is the primary organ for clearance of triglyceride-rich remnant lipoproteins (TRL) via LDL receptor (LDLR), ), LDLR-related protein-1 (LRP1) and syndecan-1. Elevated plasma TRL due to reduced liver clearance is a major cause of dyslipidemia, cardiovascular disease and mortality in chronic kidney disease (CKD). Although substantial effort has been put into understanding the molecular mechanisms underlying dyslipidemia in CKD and development of novel therapies, dyslipidemia related to CKD still remains a huge challenge. Recently, heparan sulfate proteoglycans (HSPG) has been reported to facilitate LDLR degradation by proprotein convertase subtilisin kexin type-9 (PCSK9). In this thesis, we have investigated i) the effects of CKD on primary hepatic lipoprotein receptors (LDLR, LRP1 and syndecan-1); ii) the interaction of PCSK9 and hepatic HSPGs in connection to plasma lipids and iii) whether lipid lowering therapies are associated with reductions in plasma PCSK9 and syndecan-1 and clinical outcomes. The studies reported in this thesis provide novel insights into the mechanisms underlying dyslipidemia in renal diseases that involve increased hepatic HSPG interaction with PCSK9 leading to reduced clearance of TRL. At present, where current cholesterol-lowering strategies to treat dyslipidemia in CKD are still insufficient, studies present in this thesis suggest that PCSK9 inhibition can be beneficial in improving lipid levels in CKD. Further, our study opens new venues for future development of cost-effective heparin mimetics as PCSK9 inhibitors.

Chronic kidney disease (CKD) increases the risk of cardiovascular disease (CVD), with dyslipidemia being a contributing risk factor. In patients with CKD, diminished antioxidant, anti-inflammatory, and cholesterol transport capacities of high-density lipoprotein cholesterol (HDL-C) may contribute to atherosclerosis and poor CVD outcomes. Different lipid-lowering therapies (LLTs) have demonstrated efficacy in correcting dyslipidemia in patients without kidney disease, including substantial elevations in HDL-C levels with triglyceride-lowering therapies, such as fibrates and niacin, as well as novel HDL-targeted therapies, including cholesterol-ester transfer protein inhibitors. However, the effects of HDL-elevating therapies in populations without kidney disease may not readily be extrapolated to patients with CKD, given the distinct dyslipidemia patterns and the lack of high-quality clinical trials in this population. Despite plausible mechanisms of HDL-elevation to improve clinical outcomes, current clinical guidelines only recommend statin use for the treatment of hyperlipidemia in patients with non-dialysis-dependent CKD. In this narrative review, we discuss how HDL-C functionality is affected in patients with CKD and explore evidence investigating different LLTs for HDL elevation and improved clinical outcomes in this population. In patients with CKD, we recommend further investigation of HDL-targeted therapies, comparative effectiveness evaluation of HDL-elevating LLTs versus statins across various clinical endpoints, and whether HDL-C elevation mediates these outcomes.

Chronic kidney disease (CKD) represents a major public health issue worldwide and entails a high burden of cardiovascular events and mortality. Dyslipidaemia is common in patients with CKD and it is characterized by a highly atherogenic profile with relatively low levels of HDL-cholesterol and high levels of triglyceride and oxidized LDL-cholesterol. Overall, current literature indicates that lowering LDL-cholesterol is beneficial for preventing major atherosclerotic events in patients with CKD and in kidney transplant recipients while the evidence is less clear in patients on dialysis. Lipid lowering treatment is recommended in all patients with stage 3 CKD or worse, independently of baseline LDL-cholesterol levels. Statin and ezetimibe are the cornerstones in the management of dyslipidaemia in patients with CKD, however alternative and emerging lipid-lowering therapies may acquire a central role in near future. This position paper endorsed by the Italian Society of Nephrology aims at providing useful information on the topic of dyslipidaemia in CKD and at assisting decision making in the management of these patients.

Lipid Management in Chronic Kidney Disease, Hemodialysis, and Transplantation

KDOQI US Commentary on the 2013 KDIGO Clinical Practice Guideline for Lipid Management in CKD

Clinical practice guidelines for managing dyslipidemias in kidney transplant patients: a report from the Managing Dyslipidemias in Chronic Kidney Disease Work Group of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative

COVID and Kidney: The Struggle So Far.

Background and Aims Patients with chronic kidney disease (CKD) carry an extremely high burden for atherosclerotic cardiovascular disease (ASCVD), which worsens as CKD progresses. Several international guidelines, including the 2013 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines, have recommended the use of lipid-lowering therapy (LLT) in this high-risk population. To evaluate the implementation of these recommendations in real-world practice, we assessed patterns of dyslipidemia management among patients with CKD. Specific objectives include describing the prevalence and intensity of LLT prescription [stratified by estimated glomerular filtration rate (GFR) and whether requiring renal replacement therapy or not] as well as adherence to guideline recommendations on LLT use. Method We conducted a single-center, cross-sectional study covering the period of January 2019 to December 2023. A review of inpatient and outpatient medical records of the Department of Medicine, University of the Philippine—Philippine General Hospital was done. Eligible patients were at least 18 years of age, and diagnosed with CKD. Exclusion criteria included having a concomitant diagnosis of Acute Kidney Injury, and being pregnant or breastfeeding at any point in the study period. Sociodemographic, clinical, and laboratory data were based off the latest entry in each patient's medical record. No clinical data were collected beyond those that were available on the records. Classification of statin intensity was based on the 2019 American Heart Association/American College of Cardiology Guidelines on the Management of Blood Cholesterol as well as the 2020 Philippine Clinical Practice Guidelines on the Management of Dyslipidemia. All analyses were descriptive and done using STATA 18. Categorical variables were summarized as frequencies and percentages. Continuous variables were reported as measures of central tendency [i.e. mean (SD) or median (IQR), as appropriate]. Results Of the 3845 patients included in the study, 2922 (76%) were prescribed LLT. The most common LLT were statins (92%), followed by statin/ezetimibe combinations (6%), then statin/fibrate combinations (2%). None were prescribed PCKS9 inhibitors, niacin, omega-3 fatty acids, or bile acid sequestrants. Among non-dialytic patients, the distribution of LLT use was as follows: a) eGFR ≥ 60 ml/min/1.73 m2: 40% (173/431) b) eGFR 30-60 ml/min/1.73 m2: 76% (1198/1576) c) eGFR &amp;lt;30 ml/min/1.73 m2: 84% (1551/1838). Among dialytic patients, 68% (601/884) were already on LLT prior to initiation of dialysis while 35% (283/884) were started on LLT after dialysis initiation. Notably, 89% (786/884) of these dialytic patients were still on moderate-to-high-intensity statin doses. Based on recommendations from the 2013 KDIGO guidelines, only 78% (2610/3334) of eligible patients were prescribed on LLT, while 61% (312/511) of ineligible patients were prescribed on LLT. Similar rates of adherence were seen to other international guideline recommendations on the management of dyslipidemia in CKD (e.g. 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol, 2019 European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidaemias, 2020 Clinical Practice Guidelines for the management of dyslipidemia in the Philippines). Conclusion Real-world LLT use among CKD patients remains high, even at lower eGFRs. More importantly, a large proportion of patients remain under- and over-treated, highlighting significant gaps between guideline recommendations and real-world clinical practice. Further investigation regarding the underlying reasons for these practice variations is necessary to improve quality of care, and safely reduce the burden of dyslipidemia and ASCVD among CKD patients.