Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

Velden, Monique G. de Sain-van der; Kaysen, George A.; Barrett, Hugh A.; Stellaard, Frans; Gadellaa, Mireille M.; Voorbij, H. A. M.; Reijngoud, Dirk-Jan; Rabelink, Ton J.

doi:10.1111/j.1523-1755.1998.00831.x

Cited by 84 publications

(45 citation statements)

References 39 publications

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“…Specifically, patients with NS exhibit elevated levels of all Apo-B containing lipoproteins, due to reduced catabolism, including VLDL, IDL, LDL-C, and Lp(a); conversely, HDL-C levels are usually normal [53][54][55][56][57]. The pathogenesis includes increased production together with reduced clearance of lipoproteins [54,[58][59][60][61][62][63]. Specifically, elevation of plasma LDL in NS is thought to be due to increased LDL synthesis and depressed LDL catabolism [52].…”

Section: Nephrotic Syndromementioning

confidence: 99%

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Khurana

Silverstein

2015

Pediatr Nephrol

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Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Children with chronic kidney disease (CKD) and end-stage renal disease (ESRD) exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high, being present in 39-65 % of patients. Elevated lipid levels in children without renal disease are a risk factor for cardiovascular disease (CVD), while the risk for CVD in pediatric CKD/ESRD is unclear. The pathogenesis of dyslipidemia in CKD features various factors, including increased levels of triglycerides, triglyceride-rich lipoproteins, apolipoprotein C3 (ApoC-III), decreased levels of cholesterylester transfer protein and high-density lipoproteins, and aberrations in serum very low-density and intermediatedensity lipoproteins. If initial risk assessment indicates that a child with advanced CKD has 2 or more co-morbidities for CVD, first-line treatment should consist of nonpharmacologic management such as therapeutic lifestyle changes and dietary counseling. Pharmacologic treatment of dyslipidemia may reduce the incidence of CVD in children with CKD/ESRD, but randomized trials are lacking. Lipids are essential components of cell membranes, contributing to cell fuel, myelin formation, subcellular organelle function, and steroid hormone synthesis. Lipids are generally categorized by their density and other physical characteristics [1]. Since lipids such as cholesterol and triglycerides (TG) are insoluble in plasma, lipoproteins are required to transport all sources (e.g., diet) of lipids to areas in which the lipids can either be stored for future use or used immediately [2], although it should be noted that short-and medium-chain fatty acids also flow via the portal system as fatty acids. Specifically, low-density lipoproteins (LDL) carry the majority of cholesterol (forming LDL-C), while very low-density lipoproteins (VLDL) carry the majority of triglycerides.The broad categories of lipoproteins are chylomicrons, VLDL, LDL, and high-density lipoproteins (HDL Prevalence and sub-types of dyslipidemia in pediatric chronic kidney disease (CKD) and end-stage renal disease (ESRD)Children with CKD/ESRD exhibit various co-morbidities, including dyslipidemia. The prevalence of dyslipidemias in children with CKD and ESRD is high (39-65 %), but is significantly dependent on the cause and vintage of CKD (e.g., usually more common and severe with glomerular disease and proteinuria) and the stage of the disease [4,5]. The Chronic Kidney Disease in Children (CKiD) study included an assessment of the relationship between renal function and serum lipid levels. The most common type of dyslipidemia was hypertriglyceridemia. They found an inverse relationship between renal function (measured glomerular filtration rate, or GFR) and serum TG and total cholesterol (TC) levels; that is, as GFR declines, TG and TC levels generally increase. Conversely, there is a ...

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Section: Nephrotic Syndromementioning

confidence: 99%

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Khurana

Silverstein

2015

Pediatr Nephrol

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“…Palmitate synthesis rates were calculated by multiplying plasma triglyceridepalmitate concentration with the fraction of newly synthesized palmitate at the end of the 10-h label infusion period. Lipoprotein kinetics were determined using SAAM II modeling (16). The model used was described earlier (24) and is shown in Figure 1.…”

Section: Methodsmentioning

confidence: 99%

“…Cholesterol was extracted from total plasma and derivatized according to Neese et al (15). VLDL1, VLDL2, intermediate density lipoproteins (IDL) and LDL fractions were isolated from plasma by ultracentrifugation according to de Sain-van der Velden et al (16). Palmitate from VLDL fractions was methylated as described elsewhere (6).…”

Section: Methodsmentioning

confidence: 99%

Increased de novo Lipogenesis and Delayed Conversion of Large VLDL into Intermediate Density Lipoprotein Particles Contribute to Hyperlipidemia in Glycogen Storage Disease Type 1a

et al. 2008

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Glycogen storage disease type 1a (GSD-1a) is a metabolic disorder characterized by fasting-induced hypoglycemia, hepatic steatosis, and hyperlipidemia. The mechanisms underlying the lipid abnormalities are largely unknown. To investigate these mechanisms seven GSD-1a patients and four healthy control subjects received an infusion of [1-13 C]acetate to quantify cholesterogenesis and lipogenesis. In a subset of patients, [1-13 C]valine was given to assess lipoprotein metabolism and [2-13 C]glycerol to determine whole body lipolysis. Cholesterogenesis was 274 Ϯ 112 mg/d in controls and 641 Ϯ 201 mg/d in GSD-1a patients (p Ͻ 0.01). Plasma triglyceride-palmitate derived from de novo lipogenesis was 7.1 Ϯ 9.4 and 86.3 Ϯ 42.5 mol/h in controls and patients, respectively (p Ͻ 0.01). Production of VLDL did not show a consistent difference between the groups, but conversion of VLDL into intermediate density lipoproteins was relatively retarded in all patients (0.6 Ϯ 0.5 pools/d) compared with controls (4.3 Ϯ 1.8 pools/d). Fractional catabolic rate of intermediate density lipoproteins was lower in patients (0.8 Ϯ 0.6 pools/d) compared with controls (3.1 Ϯ 1.5 pools/d). Whole body lipolysis was similar, i.e., 4.5 Ϯ 1.9 mol/kg/ min in patients and 3.8 Ϯ 1.9 mol/kg/min in controls. Hyperlipidemia in GSD-1a is associated with strongly increased lipid production and a slower relative conversion of VLDL to LDL. (Pediatr Res 63: 702-707, 2008) G lycogen storage disease type 1a (GSD-1a, von Gierke Disease, OMIM#232200) is caused by deficiency of glucose-6-phosphatase ␣ (G6Pase-␣), which catalyzes the terminal steps in gluconeogenesis and glycogenolysis by converting glucose-6-phosphate to glucose and phosphate. G6Pase-␣ deficiency results in an inability to release glucose from liver, kidney, and possibly intestine. Phenotypical, G6Pase-␣ deficiency is characterized by growth retardation, hypoglycemia, hepatomegaly (massive hepatic steatosis) and lactic acidemia, as well as hypertriglyceridemia and hypercholesterolemia (1). Increased concentrations of cholesterol are found in both very LDL (VLDL) and LDL fractions whereas HDL cholesterol and apolipoprotein A-I concentrations are usually decreased (2,3). To control hypoglycemia in GSD-1a, patients often receive uncooked cornstarch which is accompanied by reductions in plasma lipid levels in GSD-1a (4,5). The underlying mechanisms responsible for disturbed lipid metabolism in GSD-1a are largely unknown. We have previously reported increased rates of hepatic de novo lipogenesis and cholesterogenesis in two patients with GSD-1a (6), which may drive VLDL production by the liver. Lipogenesis and cholesterogenesis have both been implicated in regulation of VLDL secretion (7-9). In addition, insulin is known to suppress hepatic VLDL production (10): prevailing low insulin concentrations in GSD-1a patients may contribute to increased VLDL production in these subjects, but quantitative data are not available. Furthermore, defective lipoprotein lipolysis might also contribute to hy...

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“…To show the mechanism of action in vivo in humans, apoB metabolism has been studied using stable isotopes. 13 C-Valine or another labelled amino acid was infused, and the incorporation of 13 C-valine into very low-density lipoprotein particles isolated from plasma samples was measured [25,27].…”

Section: Mechanism Of Actionmentioning

confidence: 99%

Applications of stable isotopes in clinical pharmacology

Schellekens

Stellaard

Woerdenbag

et al. 2011

Brit J Clinical Pharma

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101

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This review aims to present an overview of the application of stable isotope technology in clinical pharmacology. Three main categories of stable isotope technology can be distinguished in clinical pharmacology. Firstly, it is applied in the assessment of drug pharmacology to determine the pharmacokinetic profile or mode of action of a drug substance. Secondly, stable isotopes may be used for the assessment of drug products or drug delivery systems by determination of parameters such as the bioavailability or the release profile. Thirdly, patients may be assessed in relation to patient-specific drug treatment; this concept is often called personalized medicine. In this article, the application of stable isotope technology in the aforementioned three areas is reviewed, with emphasis on developments over the past 25 years. The applications are illustrated with examples from clinical studies in humans.

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Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

Cited by 84 publications

References 39 publications

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Etiology and management of dyslipidemia in children with chronic kidney disease and end-stage renal disease

Increased de novo Lipogenesis and Delayed Conversion of Large VLDL into Intermediate Density Lipoprotein Particles Contribute to Hyperlipidemia in Glycogen Storage Disease Type 1a

Applications of stable isotopes in clinical pharmacology

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