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Cholesterol Metabolism in Chronic Kidney Disease: Physiology, Pathologic Mechanisms, and Treatment

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Sphingolipid Metabolism and Metabolic Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1372))

Abstract

High plasma levels of lipids and/or lipoproteins are risk factors for atherosclerosis, nonalcoholic fatty liver disease (NAFLD), obesity, and diabetes. These four conditions have also been identified as risk factors leading to the development of chronic kidney disease (CKD). Although many pathways that generate high plasma levels of these factors have been identified, most clinical and physiologic dysfunction results from aberrant assembly and secretion of lipoproteins. The results of several published studies suggest that elevated levels of low-density lipoprotein (LDL)-cholesterol are a risk factor for atherosclerosis, myocardial infarction, coronary artery calcification associated with type 2 diabetes, and NAFLD. Cholesterol metabolism has also been identified as an important pathway contributing to the development of CKD; clinical treatments designed to alter various steps of the cholesterol synthesis and metabolism pathway are currently under study. Cholesterol synthesis and catabolism contribute to a multistep process with pathways that are regulated at the cellular level in renal tissue. Cholesterol metabolism may also be regulated by the balance between the influx and efflux of cholesterol molecules that are capable of crossing the membrane of renal proximal tubular epithelial cells and podocytes. Cellular accumulation of cholesterol can result in lipotoxicity and ultimately kidney dysfunction and failure. Thus, further research focused on cholesterol metabolism pathways will be necessary to improve our understanding of the impact of cholesterol restriction, which is currently a primary intervention recommended for patients with dyslipidemia.

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Abbreviations

ABCA1:

ATP-binding cassette transporter (ABC) A1

ABCG1:

ATP-binding cassette subfamily G member 1

ACAT1:

Acyl CoA: cholesterol acyltransferase 1 sterol-O-acyltransferase 1

Apo:

Apolipoprotein

ApoA1:

Apolipoprotein A1

ATP:

Adenosine triphosphate

Bmal1:

Aryl hydrocarbon receptor nuclear translocator-like protein 1

BMI:

Body mass index

Cd36:

Scavenger receptor class B

CKD:

Chronic kidney disease

Clk Δ19/Δ19 :

Clock mutant mice

CVD:

Cardiovascular disease

ESKD:

End-stage kidney disease

FASN:

Fatty acid synthase

FXRs:

Farnesoid X receptors

GFRs:

Glomerular filtration rates

HDAC1:

Histone deacetylase 1

HDL:

High-density lipoprotein

HK2 cells:

Human proximal tubule cells

HIF:

Hypoxia-inducible factor

HMGCR:

3-Hydroxy-3-methylglutaryl-CoA reductase

KO:

Knock out

LCAT:

Lecithin-cholesterol acyltransferase

LDL:

Low-density lipoprotein

LDLr:

Low-density lipoprotein receptor

IncRNAs:

Long noncoding RNAs

LPL:

Lipoprotein lipase

LOX-1:

Lectin-like oxLDL receptor-1

LXRs:

Liver X receptors

miRNAs:

MicroRNAs

MTP:

Microsomal triglyceride transfer protein

NAFLD:

Nonalcoholic fatty liver disease

NCEH1:

Neutral cholesterol ester hydrolase 1

NPC1:

Niemann-Pick C1

NPC1L1:

NPC1-like intracellular cholesterol transporter 1

NRs:

Nuclear receptors

Nrf2:

Nuclear factor-erythroid factor 2-related factor 2

NS:

Nephrotic syndrome

PCSK9:

Proprotein convertase subtilisin/kexin type 9

PHD2:

Hypoxia-inducible factor prolyl hydroxylase 2

PKD:

Polycystic kidney disease

PLTP:

Phospholipid transfer protein

PPARs:

Peroxisome proliferator-activated receptors

ROS:

Reactive oxygen species

RPTECs:

Renal proximal tubule epithelial cells

Shp:

Small heterodimer partner

SPRING:

SREBF pathway regulator in Golgi 1

SR-A1:

Scavenger receptor class A

SR-B1:

Scavenger receptor class B type 1

SREBPs:

Sterol regulatory element-binding proteins

USP20:

Ubiquitin C-terminal hydrolase 20

VLDLs:

Very light density lipoproteins

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Acknowledgement

This work was supported in part by NIH National Heart, Lung, and Blood Institute Grant R56 HL137912-01 and American Heart Association Grant-In-Aid 16GRNT30960027 to X. Pan.

The author declares no competing financial interests.

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  1. Xiaoyue Pan

    Present address: Department of Foundations of Medicine, New York University Long Island School of Medicine, Mineola, NY, USA

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      Xian-Cheng Jiang

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    Pan, X. (2022). Cholesterol Metabolism in Chronic Kidney Disease: Physiology, Pathologic Mechanisms, and Treatment. In: Jiang, XC. (eds) Sphingolipid Metabolism and Metabolic Disease. Advances in Experimental Medicine and Biology, vol 1372. Springer, Singapore. https://doi.org/10.1007/978-981-19-0394-6_9

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