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1.
Kidney Int ; 65(3): 1064-75, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14871427

ABSTRACT

BACKGROUND: Dyslipidemia is often observed in patients with end-stage renal disease (ESRD) and is associated with cardiovascular diseases. Peritoneal dialysis treatment may further deteriorate the lipoprotein abnormalities, suggesting that peritoneal dialysis alters lipid metabolism. METHODS: To study the mechanisms involved in these abnormalities in peritoneal dialysis, we measured insulin sensitivity, free fatty acids release, de novo lipogenesis (DNL), very low-density lipoprotein (VLDL) apoB100 kinetics and cholesterol synthesis in vivo in ESRD (N= 6), peritoneal dialysis patients (N= 5), and controls (N= 7) using stable isotopes. RESULTS: Insulin sensitivity, as assessed by an euglycemic hyperinsulinemic clamp, tended to be lower in ESRD and peritoneal dialysis compared to controls [P= 0.08 by analysis of variance (ANOVA)]. Free fatty acid release during the euglycemic hyperinsulinemic clamp tended to be higher in ESRD and peritoneal dialysis compared to controls (P= 0.08 by ANOVA), while DNL and fractional cholesterol synthesis were normal. VLDL-1 apoB100 (P < 0.05) and VLDL-2 apoB100 pool sizes (P < 0.05) were significantly higher in peritoneal dialysis patients compared to controls. The increased VLDL-1 apoB100 pool size was explained by increased VLDL-1 apoB100 synthesis (P < 0.05) in combination with reduced VLDL-1 apoB100 catabolism (P < 0.01), while the increased VLDL-2 apoB100 pool was explained by reduced catabolism (P < 0.01). CONCLUSION: Both VLDL-1 apoB100 and VLDL-2 apoB100 pool sizes are increased in peritoneal dialysis patients, due to disturbances both in synthesis and catabolism. VLDL-1 apoB100 production is, at least partially, explained by increased free fatty acid availability secondary to peripheral insulin resistance, thus identifying insulin resistance as potential therapeutic target in peritoneal dialysis patients.


Subject(s)
Apolipoproteins B/metabolism , Cholesterol, VLDL/metabolism , Kidney Failure, Chronic/metabolism , Kidney Failure, Chronic/therapy , Peritoneal Dialysis , Acetates/pharmacokinetics , Adult , Apolipoprotein B-100 , Carbon Isotopes , Cholesterol, VLDL/biosynthesis , Deuterium , Fatty Acids, Nonesterified/metabolism , Female , Glucose Clamp Technique , Humans , Hyperinsulinism/metabolism , Insulin/blood , Lipolysis , Male , Middle Aged , Palmitates/pharmacokinetics , Valine/pharmacokinetics
2.
Kidney Int ; 64(4): 1495-504, 2003 Oct.
Article in English | MEDLINE | ID: mdl-12969171

ABSTRACT

BACKGROUND: Hypoalbuminemia and hyperfibrinogenemia are frequently observed in patients with chronic renal failure (CRF) and are both associated with cardiovascular diseases. The mechanisms responsible for hypoalbuminemia and hyperfibrinogenemia in CRF are unknown. METHODS: In the present study, both albumin and fibrinogen kinetics were measured in vivo in predialysis patients (N = 6), patients on peritoneal dialysis (N = 7) and control subjects (N = 8) using l-[1-13C]-valine. RESULTS: Plasma albumin concentration was significantly lower in patients on peritoneal dialysis compared to control subjects (P < 0.05). Plasma fibrinogen was significantly increased in both predialysis patients (P < 0.01) as well as patients on peritoneal dialysis (P < 0.001) in comparison to control subjects. In contrast to albumin, fibrinogen is only lost in peritoneal dialysate and not in urine. The absolute synthesis rates (ASR) of albumin and fibrinogen were increased in patients on peritoneal dialysis (ASR albumin, 125 +/- 9 mg/kg/day versus 93 +/- 9 mg/kg/day, P < 0.05; ASR fibrinogen, 45 +/- 4 mg/kg/day versus 29 +/- 3 mg/kg/day, P < 0.01) compared to control subjects. Albumin synthesis is strongly correlated with fibrinogen synthesis (r2 = 0.665, P < 0.0001, N = 21). In this study, the observed hypoalbuminemia in patients on peritoneal dialysis is likely not explained by malnutrition, inadequate dialysis, inflammation, metabolic acidosis, or insulin resistance. We speculate that peritoneal albumin loss is of relevance. CONCLUSION: Synthesis rate of albumin and fibrinogen are coordinately up-regulated. Both albumin and fibrinogen are lost in peritoneal dialysis fluid. To compensate protein loss, albumin synthesis is up-regulated, but the response, in contrast to predialysis patients, does not fully correct plasma albumin concentrations in peritoneal dialysis patients. The increase in fibrinogen synthesis introduces an independent risk factor for atherosclerosis, since plasma fibrinogen pool is enlarged.


Subject(s)
Fibrinogen/biosynthesis , Kidney Failure, Chronic/metabolism , Serum Albumin/biosynthesis , Adult , Albuminuria/complications , Case-Control Studies , Dialysis Solutions/chemistry , Female , Fibrinogen/metabolism , Humans , Hypoalbuminemia/etiology , Kidney Failure, Chronic/therapy , Liver/metabolism , Male , Middle Aged , Peritoneal Dialysis/adverse effects , Up-Regulation
3.
Clin Biochem ; 35(7): 545-53, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12493583

ABSTRACT

OBJECTIVE: To determine the contribution of albumin synthetic and catabolic rates to steady state levels in a patient with idiopathic hypoalbuminemia. METHODS: Using L-[1-(13)C] valine, both FSR (fractional synthesis rate) as well as FCR (fractional catabolic rate) were studied. Human albumin cDNA analysis and determination of the exact albumin mass by electrospray mass spectrometry were performed. RESULTS: Compared with controls, plasma albumin concentration in the patient was reduced (6.7 vs. 37.0 +/- 2.6 g/L). Albumin FSR (= FCR in steady state) was increased compared to controls. The ASR (absolute synthesis rate) of albumin was decreased based on the enrichment in plasma valine and KIV, but estimated to be normal based on VLDL apoB100 at plateau compared to controls. Direct estimation of albumin FCR rejected the latter. No mutation was found in the transcribed region of albumin gene. The exact mass of albumin (66.493 Da) was not different from controls. CONCLUSION: The hypoalbuminemia was a result of accelerated clearance of albumin from plasma in addition to defective albumin synthesis. This study also shows that the chosen method of the precursor pool could lead to misinterpretation of data in hepatic protein synthesis.


Subject(s)
Hypoalbuminemia/metabolism , Serum Albumin/metabolism , Adult , Amino Acids/isolation & purification , Amino Acids/metabolism , Apolipoproteins B/classification , Apolipoproteins B/isolation & purification , Apolipoproteins B/metabolism , Blood Protein Electrophoresis , Carbon Isotopes , Control Groups , DNA/analysis , DNA/genetics , DNA/metabolism , Humans , Kinetics , Male , Models, Biological , Pentanoic Acids/isolation & purification , Pentanoic Acids/metabolism , Serum Albumin/genetics , Spectrometry, Mass, Electrospray Ionization , Valine/metabolism , Valine/pharmacokinetics
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