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

Monique G. De Sain-Van Der Velden, George A. Kaysen, Hugh A. Barrett, Frans Stellaard, Mireille M. Gadellaa, Hieronymus A. Voorbij, Dirk Jan Reijngoud, Ton J. Rabelink

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemia is a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart disease as well as a loss of renal function in these patients. The hyperlipidemia usually is characterized by increased cholesterol levels, although hypertriglyceridemia may be present as well. The factors that determine the phenotype of nephrotic dyslipidemia are not understood, nor has the primary stimulus for nephrotic hyperlipidemia been identified. One hypothesis is that nephrotic hyperlipidemia is the result of a coordinate increase in synthesis of proteins by the liver. To address these issues we simultaneously measured the in vivo rate of VLDL apolipoprotein B100 (apo B100) secretion, LDL apo B100 synthesis and albumin synthesis in patients with a nephrotic syndrome (N = 8) and compared them with a control group (N = 7) using a primed/continuous infusion of the stable isotope L-[1-13C] valine for six hours. Kinetic data were analyzed by multicompartmental analysis. Patients studied had combined hyperlipidemia as reflected by an significant increase in both VLDL and LDL apo B100 pool sizes. In contrast, the albumin pool size was significantly decreased. VLDL apo B100 levels were primarily increased as a consequence of a decrease in fractional catabolic rate (FCR) rather than from an increase in the absolute synthesis rate (ASR). Both VLDL apo B100 and triglycerides were inversely related to the fractional catabolism (FCR) of VLDL apo B100 (r2 = 0.708; P = 0.0088) while neither had any relationship to the ASR of VLDL apo B100. In contrast to VLDL, increased LDL apo B100 was not a consequence of decreased catabolism. The LDL apo B100 ASR was significantly increased (P = 0.001) in the nephrotic patients compared to controls. Low density lipoprotein apo B100 ASR was greater than that of VLDL apo B100 in some patients, suggesting that LDL in these patients was not only derived from VLDL delipidation, but also by an alternative secretory pathway. There was no clear relationship between the ASR of VLDL apo B100 and the ASR of albumin within the current study population. Our data indicate that increased VLDL in nephrotic patients results from a decreased catabolism, while increased LDL results from increased synthesis.

Original languageEnglish (US)
Pages (from-to)994-1001
Number of pages8
JournalKidney International
Volume53
Issue number4
DOIs
StatePublished - 1998

Fingerprint

VLDL Lipoproteins
Apolipoproteins
LDL Lipoproteins
Hyperlipidemias
Albumins
Nephrotic Syndrome
Hypertriglyceridemia
Secretory Pathway
Valine
Dyslipidemias
Isotopes
Myocardial Ischemia
Triglycerides
Cholesterol

Keywords

  • Albumin
  • Apo B100
  • Lipoproteins and nephrotic syndrome
  • Nephrotic syndrome
  • Stable isotopes

ASJC Scopus subject areas

  • Nephrology

Cite this

De Sain-Van Der Velden, M. G., Kaysen, G. A., Barrett, H. A., Stellaard, F., Gadellaa, M. M., Voorbij, H. A., ... Rabelink, T. J. (1998). Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis. Kidney International, 53(4), 994-1001. https://doi.org/10.1111/j.1523-1755.1998.00831.x

Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis. / De Sain-Van Der Velden, Monique G.; Kaysen, George A.; Barrett, Hugh A.; Stellaard, Frans; Gadellaa, Mireille M.; Voorbij, Hieronymus A.; Reijngoud, Dirk Jan; Rabelink, Ton J.

In: Kidney International, Vol. 53, No. 4, 1998, p. 994-1001.

Research output: Contribution to journalArticle

De Sain-Van Der Velden, MG, Kaysen, GA, Barrett, HA, Stellaard, F, Gadellaa, MM, Voorbij, HA, Reijngoud, DJ & Rabelink, TJ 1998, 'Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis', Kidney International, vol. 53, no. 4, pp. 994-1001. https://doi.org/10.1111/j.1523-1755.1998.00831.x
De Sain-Van Der Velden, Monique G. ; Kaysen, George A. ; Barrett, Hugh A. ; Stellaard, Frans ; Gadellaa, Mireille M. ; Voorbij, Hieronymus A. ; Reijngoud, Dirk Jan ; Rabelink, Ton J. / Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis. In: Kidney International. 1998 ; Vol. 53, No. 4. pp. 994-1001.
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