Prolonged hyperlipidaemia in nephrotic syndrome is a major risk factor for multiple disease complications, including accelerated atherosclerosis, myocardial infarction, stroke, chronic kidney disease and thrombosis
Direct lipid-induced cellular injury to podocytes, mesangial cells and, potentially, renal tubular cells as a result of dyslipidaemia increasingly seems to have a role in the pathogenesis of nephrotic syndrome
Given the available evidence, we suggest that statins should be the first-line treatment for prolonged hyperlipidaemia in patients with nephrotic syndrome, given their efficacy in the treatment of other diseases and the fact that they are well tolerated
Alternative, less supported treatments include LDL apheresis, cholesterol absorption inhibitors, nicotinic acid and bile acid sequestrants; targeting proprotein convertase subtilisin/kexin type 9 is another potential treatment for hyperlipidaemia in patients with nephrotic syndrome
Treatment recommendations in children are limited by a lack of data for both the efficacy and the risk of pharmacological interventions
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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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.
The authors declare no competing financial interests.
Addition of sialic acid groups onto molecules such as oligosaccharides and carbohydrates.
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.
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Agrawal, S., Zaritsky, J., Fornoni, A. et al. Dyslipidaemia in nephrotic syndrome: mechanisms and treatment. Nat Rev Nephrol 14, 57–70 (2018). https://doi.org/10.1038/nrneph.2017.155
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