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Lipoprotein metabolism in chronic renal insufficiency

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Abstract

Chronic renal insufficiency (CRI) is associated with a characteristic dyslipidemia. Findings in children with CRI largely parallel those in adults. Moderate hypertriglyceridemia, increased triglyceride-rich lipoproteins (TRL) and reduced high-density lipoproteins (HDL) are the most usual findings, whereas total and low-density lipoprotein cholesterol (LDL-C) remain normal or modestly increased. Qualitative abnormalities in lipoproteins are common, including small dense LDL, oxidized LDL, and cholesterol-enriched TRL. Measures of lipoprotein lipase and hepatic lipase activity are reduced, and concentrations of apolipoprotein C-III are markedly elevated. Still an active area of research, major pathophysiological mechanisms leading to the dyslipidemia of CRI include insulin resistance and nonnephrotic proteinuria. Sources of variability in the severity of this dyslipidemia include the degree of renal impairment and the modality of dialysis. The benefits of maintaining normal body weight and physical activity extend to those with CRI. In addition to multiple hypolipidemic pharmaceuticals, fish oils are also effective as a triglyceride-lowering agent, and the phosphorous binding agent sevelamer also lowers LDL-C. Emerging classes of hypolipidemic agents and drugs affecting sensitivity to insulin may impact future treatment. Unfortunately, cardiovascular benefit has not been convincingly demonstrated by any trial designed to study adults or children with renal disease. Therefore, it is not possible at this time to endorse general recommendations for the use of any agent to treat dyslipidemia in children with chronic kidney disease.

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Abbreviations

AAP:

American Academy of Pediatrics

ADPKD:

Autosomal dominant polycystic kidney disease

AHA:

American Heart Association

Apo:

apoproteins (apolipoproteins)

ASCVD:

atherosclerotic cardiovascular disease

ATGL:

adipose triglyceride lipase

CE:

esterified cholesterol (cholesteryl esters)

CETP:

cholesteryl ester transfer protein

CKD:

chronic kidney disease

CRI:

chronic renal insufficiency

DHA:

docosahexaenoic acid

EPA:

eicosapentaenoic acid

ESRD:

end-stage renal disease

FFA:

free fatty acids (nonesterified fatty acids)

FSGS:

focal and segmental glomerulosclerosis

GFR:

glomerular filtration rate

HDL:

high-density lipoproteins

HDL-C:

HDL cholesterol (cholesterol content of HDL)

HL:

hepatic lipase

HSL:

hormone-sensitive lipase

HSPG:

heparan sulfate proteoglycans

IgAN:

immunoglobulin A nephropathy

IDL:

intermediate-density lipoproteins

IR:

insulin resistance

KDOQI:

National Kidney Foundation Kidney Disease Outcomes Quality Initiative

LCAT:

lecithin-cholesterol acyltransferase

LDL:

low-density lipoproteins

LDL-R:

LDL receptor

LPL:

lipoprotein lipase

LRP:

LDL-receptor-related protein

NKF:

National Kidney Foundation

PL:

phospholipids

PLTP:

phospholipid transfer protein

PON:

paraoxonase

PPAR:

peroxisome-proliferator-activated nuclear receptors

SNP:

single nucleotide polymorphisms

Statin:

3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitor

TG:

triglyceride

TRL:

triglyceride-rich lipoproteins [chylomicrons, very-low-density lipoproteins (VLDL) and their remnants]

VLDL:

very-low-density lipoproteins

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Acknowledgements

Dr. Saland is supported by NIH/NIDDK grant #K23DK071871. Dr. Ginsberg is supported by NIH grants R01 HL55638 and R01 HL73030. The authors thank Dr. Lisa Satlin for her suggestions in preparing this review.

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  1. Department of Pediatrics, The Mount Sinai School of Medicine, One Gustave L. Levy Place, P.O. Box 1664, New York, NY, 10029, USA

    Jeffrey M. Saland

  2. Department of Medicine, Columbia University School of Medicine, New York, NY, USA

    Henry N. Ginsberg

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  1. Jeffrey M. Saland
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Correspondence to Jeffrey M. Saland.

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Saland, J.M., Ginsberg, H.N. Lipoprotein metabolism in chronic renal insufficiency. Pediatr Nephrol 22, 1095–1112 (2007). https://doi.org/10.1007/s00467-007-0467-5

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