Inverse Association Between Serum Non–High‐Density Lipoprotein Cholesterol Levels and Mortality in Patients Undergoing Incident Hemodialysis

Chang, Tae Ik; Streja, Elani; Ko, Gang Jee; Naderi, Nosratollah; Rhee, Connie M.; Kövesdy, Csaba P.; Kashyap, Moti L.; Vaziri, Nosratola D.; Kalantar‐Zadeh, Kamyar; Moradi, Hamid Reza

doi:10.1161/jaha.118.009096

Cited by 26 publications

(23 citation statements)

References 47 publications

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“…An association between conventional risk factors for mortality and better survival in patients with CKD, also termed “reverse epidemiology”, has been described in previous studies 23 , 24 . An inverse association between lipid levels and mortality in patients with CKD has also been reported in several studies 25 , 26 . On the other hand, a recent large randomized control trial showed that statin treatment lowered LDL cholesterol but had no substantial effect on the progression of kidney disease or overall and cause-specific mortality in patients with CKD 27 .…”

Section: Introductionsupporting

confidence: 69%

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3–5

Chiu

Huang

et al. 2020

Sci Rep

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Hsuan chiu 1 , pei-Yu Wu 2,3,4 , Jiun-chi Huang 2,3,4 , Hung-pin tu 5 , Ming-Yen Lin 2 , Szu-chia chen 2,3,4,6* & Jer-Ming chang 2,4 Dyslipidemia is common in patients with chronic kidney disease (cKD), however the relationship between dyslipidemia and mortality in patients with moderate to severe cKD remains controversial. non-high-density lipoprotein (HDL) cholesterol has been reported to be a more accurate predictor of clinical outcomes than conventional lipid measurements. Hence, the aim of this study was to investigate associations between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. We enrolled 429 pre-dialysis patients with stage 3 to 5 CKD from May 2006 to January 2010. The patients were divided into four groups according to quartiles of non-HDL cholesterol. The patients were followed until death or until January 2020. During a median 11.6 years of follow-up, there were 78 (18.2%) deaths overall and 32 (7.5%) cardiovascular deaths. In adjusted models, the patients in quartile 1 (hazard ratio [HR] 3.368; 95% confidence interval [CI] 1.388-8.176; p = 0.007), quartile 3 (HR 3.666; 95% CI 1.486-9.044; p = 0.005), and quartile 4 (HR 2.868; 95% CI 1.136-7.240; p = 0.026) of non-HDL cholesterol had a higher risk of overall mortality (vs. quartile 2). In addition, the patients in quartile 1 (HR 19.503; 95% CI 2.185-174.0925 p = 0.008), quartile 3 (HR 28.702; 95% CI 2.990-275.559; p = 0.004), and quartile 4 (HR 11.136; 95% CI 1.126-110.108; p = 0.039) had a higher risk of cardiovascular mortality (vs. quartile 2). Our study showed a U-shaped relationship between non-HDL cholesterol and the risk of overall and cardiovascular mortality in patients with CKD stage 3-5. Assessing non-HDL cholesterol may help to identify subjects at high-risk of adverse outcomes. Lipid disorders are a major public health issue worldwide, and many studies have reported the high rates of mortality, morbidity, and complications associated with dyslipidemia in the general population 1,2. Dyslipidemia is common in patients with chronic kidney disease (CKD) due to severe dysregulation of key metabolic pathways and enzymes, which can lead to a decrease in high-density lipoprotein (HDL) cholesterol and increase in triglyceride-rich lipoproteins 3. Lipid disorders in patients with CKD have been shown to both increase the risk of cardiovascular disease (CVD) and also to accelerate the progression to end-stage CKD 4-6. High levels of serum low-density lipoprotein (LDL) cholesterol have been clearly identified to be an important risk factor for increased CVD and mortality in the general population, however this cannot completely explain

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Section: Introductionsupporting

confidence: 69%

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3–5

Chiu

Huang

et al. 2020

Sci Rep

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“…Low levels of HDL-cholesterol are common among patients with CKD and ESRD 125-127 but they do not seem to be associated with increased cardiovascular risk after adjustment for traditional risk factors 128,129 . Some studies show a J-curve association with increased mortality among patients with ESRD who have very low or very high HDLcholesterol levels [130][131][132] . These data further support the importance of renal-function-induced changes in the composition and quality of lipoproteins.…”

Section: [H1] Lipids and Cardiovascular Diseasementioning

confidence: 99%

Lipid management in patients with chronic kidney disease

Ferro¹,

Mark²,

Kanbay³

et al. 2018

Nat Rev Nephrol

181

142

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Glomerular filtration rate is inversely associated with cardiovascular disease independent of conventional risk factors. An increased risk of cardiovascular disease is present even at minor levels of renal impairment and the risk is highest in patients with endstage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition, and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease or ESRD have a characteristic lipid pattern of hypertriglyceridemia and low HDL-cholesterol levels but normal LDL-cholesterol levels. In the general population, a clear relationship exists between LDL-cholesterol, coronary heart disease and ischaemic stroke. However, in patients with ESRD, LDL-cholesterol seems to show a negative association [Au: with these outcomes?] at below average LDL-cholesterol levels and a flat or weakly positive association with mortality at higher LDL-cholesterol levels. Overall, the available data suggest that lowering of LDL-cholesterol is beneficial for prevention of major atherosclerotic events in patients with chronic kidney disease and in kidney transplant recipient but is not beneficial in patients requiring dialysis. [Au: I've moved the description of the content of your Review to the end of the introduction as per our journal style. To fully reflect the content of your article, please finish off the abstrace with a couple of sentences relating to novel lipid-lowering therapies and the need for reconsideration of the KDIGO guidelines in the light of new data. We have a limit of 200 words for this section.] [Au: I have highlighted suggestions for glossary terms throughout your manuscript with a [G]. Please provide succinct, one-sentence definitions for these specialist terms.] [H1] Introduction Guidelines regarding the management of lipids in patients with chronic kidney disease (CKD) and especially in those with end-stage renal disease (ESRD) are inconsistent in part owing to important deficiencies in the available data. [Au: Edit OK?] In 2013 KDIGO produced a comprehensive clinical practice guideline for lipid management in CKD 1. [Au: I suggest that we cite your original Table 1 (now Table 3) in the discussion of KDIGO recommendations at the end of the review so that the table is included next to this discussion in the final layout rather than in the introduction to the Review.

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“…While traditional risk factors (diabetes, hypertension, and hypercholesterolemia) contribute to the elevated cardiovascular risk at early CKD stages, inflammation, malnutrition, loss of body weight, muscular mass, and cachexia become more dominant during advanced stages and predict the mortality rate. In this "reverse epidemiology" context, low cholesterol levels determine the highest rate of cardiovascular morbidity and mortality [4,5].…”

Section: Introductionmentioning

confidence: 99%

Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease

Baragetti

Ossoli

Strazzella

et al. 2020

JCM

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Low high-density lipoprotein-cholesterol (HDL-c) is the most remarkable lipid trait both in mild-to-moderate chronic kidney disease (CKD) patients as well as in advanced renal disease stages, and we have previously shown that reduced lecithin:cholesterol acyltransferase (LCAT) concentration is a major determinant of the low HDL phenotype. In the present study, we test the hypothesis that reduced LCAT concentration in CKD contributes to the progression of renal damage. The study includes two cohorts of subjects selected from the PLIC study: a cohort of 164 patients with CKD (NefroPLIC cohort) and a cohort of 164 subjects selected from the PLIC participants with a basal estimated glomerular filtration rate (eGFR) > 60 mL/min/1.73 m2 (PLIC cohort). When the NefroPLIC patients were categorized according to the LCAT concentration, patients in the 1st tertile showed the highest event rate at follow-up with an event hazard ratio significantly higher compared to the 3rd LCAT tertile. Moreover, in the PLIC cohort, subjects in the 1st LCAT tertile showed a significantly faster impairment of kidney function compared to subjects in the 3rd LCAT tertile. Serum from subjects in the 1st LCAT tertile promoted a higher reactive oxygen species (ROS) production in renal cells compared to serum from subjects in the third LCAT tertile, and this effect was contrasted by pre-incubation with recombinant human LCAT (rhLCAT). The present study shows that reduced plasma LCAT concentration predicts CKD progression over time in patients with renal dysfunction, and, even more striking, it predicts the impairment of kidney function in the general population.

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Inverse Association Between Serum Non–High‐Density Lipoprotein Cholesterol Levels and Mortality in Patients Undergoing Incident Hemodialysis

Cited by 26 publications

References 47 publications

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3–5

There is a U shaped association between non high density lipoprotein cholesterol with overall and cardiovascular mortality in chronic kidney disease stage 3–5

Lipid management in patients with chronic kidney disease

Low Plasma Lecithin: Cholesterol Acyltransferase (LCAT) Concentration Predicts Chronic Kidney Disease

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