From the Guidelines
Triglycerides are elevated in nephrotic syndrome primarily due to impaired clearance of lipoproteins from the bloodstream, increased hepatic synthesis of lipoproteins, and decreased catabolism of triglycerides. In nephrotic syndrome, the kidneys leak large amounts of protein, particularly albumin, into the urine, leading to hypoalbuminemia, which triggers the liver to increase production of lipoproteins, including very low-density lipoproteins (VLDL) rich in triglycerides 1. Additionally, there is decreased activity of lipoprotein lipase, the enzyme responsible for breaking down triglycerides in the bloodstream. The combination of increased hepatic synthesis of lipoproteins and decreased catabolism results in elevated triglyceride levels. Urinary loss of regulatory proteins that normally inhibit hepatic lipoprotein synthesis may also contribute to this process.
Some key points to consider in the management of hypertriglyceridemia in nephrotic syndrome include:
- Addressing and treating lifestyle factors, such as obesity and metabolic syndrome, as well as secondary factors, including diabetes, chronic liver or kidney disease, and hypothyroidism 1
- Considering medical therapy to reduce the risk of pancreatitis in patients with fasting triglyceride levels ≥500 mg/dL 1
- Focusing on treating the underlying cause of nephrotic syndrome, as lipid abnormalities typically improve when proteinuria decreases and serum albumin levels normalize.
It is essential to note that the severity of hypertriglyceridemia often correlates with the degree of proteinuria and hypoalbuminemia, highlighting the importance of managing the underlying condition to improve lipid profiles 1.
From the Research
Mechanisms of Elevated Triglycerides in Nephrotic Syndrome
- The nephrotic syndrome results in hyperlipidemia and alterations in lipid and lipoprotein metabolism, including increased serum triglycerides 2.
- The pathophysiology of nephrotic hyperlipidemia is complex, involving both increased hepatic synthesis of lipids and apolipoproteins, and reduced clearance of chylomicrons and very low-density lipoproteins 3.
- The increased hepatic synthesis of lipids may be due to changes in plasma albumin concentration, plasma oncotic pressure, or a local effect of viscosity at the hepatic sinusoidal level 4.
Lipoprotein Abnormalities in Nephrotic Syndrome
- Characteristically, total plasma cholesterol and triglyceride levels are elevated, as are very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) cholesterol 5.
- High-density lipoprotein (HDL) concentrations may be normal, but HDL subtypes are abnormally distributed, with a reduction of HDL2 and an increase in HDL3 5.
- Lipoprotein (a) [Lp (a)] levels may also be elevated, contributing to the increased risk of cardiovascular disease 5.
Clinical Significance of Elevated Triglycerides in Nephrotic Syndrome
- The lipoprotein profile in nephrotic syndrome is characterized by elevations of total plasma cholesterol and often triglycerides, which may contribute to the development of atherosclerosis and progression of chronic renal failure 6.
- Although the benefits of treatment with lipid-lowering drugs have not been proven, short-term studies in adults with nephrotic syndrome have documented safety and efficacy of these medications, including hydroxymethylglutaryl-CoA reductase inhibitors ("statins") 6.