Review

Dyslipidaemia in nephrotic syndrome: mechanisms and treatment

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Abstract

Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B-containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome-associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently-developed anti-PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome.

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Acknowledgements

The authors acknowledge the expert assistance of L. Feurer (Center for Clinical and Translational Research, The Research Institute at Nationwide Childrens Hospital, Columbus, Ohio,USA) in creating initial drafts of the figures in this manuscript.

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  1. Center for Clinical and Translational Research, The Research Institute at Nationwide Children's Hospital, 700 Children's Drive, W303, Columbus, Ohio 43205, USA.

    • Shipra Agrawal
    • , Joshua J. Zaritsky
    • , Alessia Fornoni
    •  & William E. Smoyer

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The authors declare no competing financial interests.

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Correspondence to William E. Smoyer.

Glossary

Sialylation

Addition of sialic acid groups onto molecules such as oligosaccharides and carbohydrates.

Glycocalyx

Layer of glycoproteins and sugar moieties surrounding the outer surface of the cell membrane of some bacteria, epithelia and other cells.

Tangier disease

A rare inherited disorder characterized by significantly reduced levels of HDL in the blood.

Lipid raft

A subdomain of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids.

Lipid apheresis

A non-surgical therapy and a form of apheresis that removes LDL from a patient's blood.