Child Kidney Dis.  2022 Jun;26(1):25-30. 10.3339/ckd.22.020.

Mechanism, clinical consequences, and management of dyslipidemia in children with nephrotic syndrome

• Baek HS

• KMID: 2531931
• DOI: http://doi.org/10.3339/ckd.22.020

Abstract

Dyslipidemia in nephrotic syndrome (NS) is often characterized by marked increases in the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and other lipoproteins, such as very low-density lipoprotein, intermediate-density lipoprotein, and lipoprotein(a). It has been suggested that impaired catabolism of lipoproteins and cholesterol is mainly due to decreased lipoprotein lipase and hepatic lipase activity, and increased biosynthesis of lipoproteins in the liver. The management strategies for dyslipidemia in patients with NS consist of lifestyle modification, lipid-lowering agents represented by statins, second-line agents such as fibrates and bile acid sequestrants, and lipid apheresis. Compared with dyslipidemia in adult NS patients, whose risks of atherosclerotic disease and progressive renal injury are considered high, clinical data on dyslipidemia in pediatric NS patients are limited. Therefore, it is necessary to pay more attention to the evaluation and management of dyslipidemia in pediatric patients with NS in clinical practice.

Keyword

Dyslipidemia; Nephrotic syndrome; Child

Figure

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  Fig. 1. The pathophysiology and clinical consequences of dyslipidemia in nephrotic syndrome. In nephrotic syndrome, decreased hepatic lipase and lipoprotein lipase (LPL) activity in the extrahepatic tissues such as endothelium, muscle, and adipose tissue leads to impaired lipoprotein clearance, and thus increasing plasma levels of intermediate-density lipoproteins (IDL), very low-density lipoproteins (VLDL), triglycerides (TG). In addition, due to proteinuria and reduced free fatty acids (FFA) catabolism, as the ratio of FFA to albumin increases, levels of angiopoietin-like 4 (ANGPTL4) which inhibits lipase activity increase. Meanwhile, as the intrahepatic expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) increases, low-density lipoproteins receptor (LDLR) degradation increases, resulting in reduced uptake of low-density lipoproteins (LDL) into hepatocytes. Furthermore, increased expression and activity of acetyl CoA acetyltransferase 2 (ACAT2) and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase lead to elevation of plasma levels of LDL and cholesterol via increased synthesis and esterification of free cholesterol within the liver. Consequently, accumulation of oxidized LDL and IDL may cause glomerulosclerosis and other adverse effects on kidney by mesangial cell proliferation, podocyte injury, and tubular cell injury. Also, increased lipoproteins and cholesterol promote atherosclerosis represented by cerebrovascular disease.

Reference

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