[Lipid metabolism disorders in chronic kidney failure].
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Apoproteins↗
Biomedical subjects
B Lacour
Publications and source records attributed to B Lacour.
Disorders of calcium and phosphorus metabolism after successful kidney transplantation.
Systematic study undertaken of 44 transplant patients with plasma creatinine below 0.11 mmol/L indicated renal phosphorus leak in approximately two-thirds of them and increased plasma PTH in all but one. Plasma 1,25(OH)2D was elevated in half the patients in whom it was measured. The lack of correlation found between plasma 1,25(OH)2D and plasma PTH or phosphorus probably indicates tubular lesions resulting in decreased production of 1,25(OH)2D. A phosphorus restriction test in 12 hypophosphatemic patients demonstrated that the reduced renal phosphorus reabsorption probably was due to both persisting hyperparathyroidism and a PTH-independent phosphorus leak.
Adolescent↗
Recent advances in factors that alter lipid metabolism in chronic renal failure.
The following conclusions and speculations can be tentatively drawn from the changes in lipoprotein composition and metabolism: (1) The presence of apo B-48 in serum VLDL and the high serum apo A-IV concentrations indicate a greater than normal contribution of alimentary remnant particles to the hypertriglyceridemia of uremic patients, (2) The presence of apo E and C in triglyceride-enriched serum LDL, together with the triglyceride enrichment of all lipoproteins, probably stems from a deficiency of lipoprotein lipase (LPL) and hepatic lipase (HL) activity, (3) The decreased ratio of serum apo C-II/C-III in VLDL is at least in part responsible for the depressed activity of LPL, (4) The accumulation of lipoprotein particles with distorted apoprotein and lipid patterns (particularly beta-VLDL with enrichment in cholesterol) could be associated with an increased atherogenesis because a recent study has demonstrated a strong association between raised serum IDL and VLDL concentrations and the degree of coronary atherosclerosis, (5) The increased apo E content of VLDL and HDL in uremic patients could particularly point to a disturbed cholesterol metabolism because such lipoproteins could interact with LDL at apo B, E receptors, (6) The decrease in serum HDL-cholesterol has been shown to be strongly associated with atheromatous vascular disease, and this could also hold for uremic patients; however, it is probable that low serum HDL-cholesterol together with a diminished capacity to form cholesterol-rich, apo E containing HDL represents a decrease in the antiatherogenic defense of the organism rather than an increased atherogenic potential [21].
Animals↗
[Problems of expressing lipase lipoprotein activity in adipose tissue in chronic kidney failure].
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Adipose Tissue↗
Aluminium-induced, reversible microcytic anemia in chronic renal failure: clinical and experimental studies.
Ten chronic hemodialysis patients with severe aluminium (Al) intoxication developed a microcytic anemia despite oral iron supplementation. Their microcytosis was reversible after deionization of the dialysis water. Ten age and sex matched hemodialysis patients who were not Al intoxicated but who had a comparable treatment schedule and time on dialysis had no such microcytosis. In order to investigate a possible direct role of Al we intoxicated uremic rats by daily (6/7 days a week) intraperitoneal injections of 30 nmoles/day of aluminium. After 3 months, the Al-intoxicated uremic rats had a significantly lower hematocrit (34.7%), hemoglobin (12.0 g/dl), and MCV (52.5 fl) than the control, vehicle-injected uremic animals (37.4%, 13.1 g/dl and 60.4 fl., respectively). The reticulocyte counts of the intoxicated rats were increased. Serum iron and transferrin iron binding capacity were unchanged. Thus aluminium intoxication of the uremic organism leads to a microcytic anemia possibly by interfering directly with normal hemoglobin synthesis.
Adult↗
[Isoelectrofocusing in the study of the heterogeneity of immunoglobulins G in man with or without proliferative symptomatology].
In the present investigation, the immunoglobulins G of human sera were studied after isoelectrofocusing using polyacrylamide flat bed gel. The heterogeneity of immunoglobulins was demonstrated in normal serum as well as in pathological situations. Isoelectrofocusing study was performed using the total serum or the immunoglobulin's preparations obtained after absorption and elution on staphylococcus protein A. These methods respect the integrity of immunoglobulins and allow the study of native immunoglobulins. Furthermore it was demonstrated the micro-heterogeneity of immunoglobulins (antibody) induced by antitetanic vaccination.
Dysgammaglobulinemia↗
[In vitro supplementation of pyridoxal phosphate for the optimisation of the determination of the catalytic activity of alanine aminotransferase and aspartate aminotransferase in kidney transplant patients (author's transl)].
Pyridoxal phosphate (PLP) is the coenzyme of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Thus, in vitro supplementation with PLP is important for the optimisation of the determination of catalytic activity of both enzymes. It patients with kidney transplants, stimulation by PLP is very important for ALT activity, which could be affected by plasma PLP deficiency. Furthermore, in this population catalytic activities are more frequently found increased using methods with PLP supplementation than without PLP supplementation (56% and 71% of patients for AST and ALT, respectively). These differences are not related to HBs antigen.
Adolescent↗
Effect of parathyroid hormone on rat enterocyte Na transport in vitro.
In the presence of b.PTH (1.2 I.U./ml) in the incubation medium, the Na efflux rate constant (degree KNa) of isolated rat enterocytes was significantly reduced when compared to control experiments. The mean depression of degree KNa induced by b.PTH was 26% as compared to control (100%). No depressant effect of b.PTH on degree KNa was observed when the isolated enterocytes were incubated with ouabain (4.0mM). Thus, b.PTH appeared to inhibit the ouabain-sensitive Na pump. When incubating the isolated epithelial cells in an EGTA-containing Ca free medium, b.PTH lost its capacity to inhibit degree KNa. Thus, the presence of extracellular Ca appeared necessary for the inhibitory effect of b.PTH. In contrast to its effect on degree KNa, b.PTH induced no change of net Na uptake by isolated enterocytes. Moreover, b.PTH did not induce significant changes in enterocyte cAMP or cGMP concentrations. It was concluded that b.PTH exerted a direct inhibitory effect on the ouabain-sensitive Na efflux rate constant of isolated rat enterocytes. The effect of b.PTH occurred without a measureable activation of the cyclic nucleotide system but needed the presence of Ca in the incubation medium to be operative.
Animals↗
Glaphenine-induced acute renal failure in the rat: a new experimental model.
Glaphenine, a nonsteroid analgesic compound, administered by gastric gavage in rats (800 mg/kg), induced nonoliguric reversible acute renal failure (ARF). Intratubular deposits were found in medullary collecting ducts. Intratubular hydrostatic pressure (Pt) increased from 11.7 +/- 0.7 to 30.0 +/- 0.9 mmHg. Renal failure was almost completely prevented by concomitant high water and solute diuresis, achieved by furosemide infusion in Wistar rats and by high salt intake in Brattleboro rats with diabetes insipidus. In the latter protected animals, Pt was only slightly elevated (17.0 +/- 0.5 mmHg). Urinary excretion of prostaglandin E2 (PGE2) dropped dramatically after glaphenine administration in Wistar rats; the fall was slight in Brattleboro rats in which PGE2 excretion was normally low. We conclude that tubular obstruction plays a prominent role in glaphenine-induced ARF in the rat. High water and solute diuresis prevented tubular obstruction. Reduced renal PGE2 synthesis is probably not involved in the pathophysiology of this ARF model, inasmuch as Brattleboro rats on a high salt intake were protected despite low basal urinary excretion of PGE2.
Acute Kidney Injury↗
Postheparin lipolytic activity in uremic patients treated by hemofiltration.
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Blood↗
Enzymic measurement of urinary pyrophosphate with a centrifugal analyzer.
We describe a simple, rapid, and fully automated technique for measuring urinary pyrophosphates with a centrifugal analyzer (the ENI GEMSAEC). This technique depends on the enzymic magnesium-dependent reaction with UDPG pyrophosphorylase (UTP: alpha-D-glucose-1-phosphate uridylyl transferase, EC 2.7.7.9) and spectrophotometry of the NADPH formed in a combined system of phosphorylation and reduction. Many samples of urine can be analyzed quickly without pretreatment, with high sensitivity (1.3 mA/mumol of substrate) and good reproducibility. The mean within-run coefficient of variation for a 50 mumol/L pyrophosphate solution was 1.4%. We determined the optimum enzyme and magnesium concentrations necessary for use in a 4-min reaction. Because there is no inhibitory effect of chloride and phosphate ions, pyrophosphate can be measured directly in urine, without prior extraction. With this technique, the mean value (and SD) for urinary pyrophosphate excretion by 30 healthy subjects was 39.3 (SD 17.2) mumol/24 h.
Autoanalysis↗
Early effects of 1 alpha,25-dihydroxy-vitamin D3 on phosphate absorption. A role for alkaline phosphatase?
Using ex vivo perfused intestinal loop from vitamin D-deficient rats, we studied the lumen-to-vein transport of 32Pi in intestines perfused intraluminally with [gamma-32P] ATP, [alpha-32P] ATP or 32Pi, and infused through their vascular connections with either 1,25(OH)2D3 (6nM) or ethanol vehicle. For intestines perfused with [gamma-32P] ATP in which the gamma-32P is easily liberated by alkaline phosphatase, 1,25(OH)2D3 infusion resulted in a significant and early (15 min) increase in net lumen-to-vein 32Pi transport. Pretreatment of rats with levamisole, an inhibitor of alkaline phosphatase, partially inhibited such 32Pi transport. For intestines infused with [alpha-32P] ATP, the lumen-to-vein transport of 32Pi did not differ in 1,25(OH)2D3-treated and in control intestines. For intestines perfused with 32Pi, 1,25(OH)2D3 infusion resulted in an early (15 min) increase in lumen-to-vein transport of 32Pi. It is concluded that 1,25(OH)2D3 rapidly stimulates intestinal Pi transport both directly and also by increasing inorganic phosphate content inside the intestinal lumen. The latter effect probably involves 1,25(OH)2D3-stimulated alkaline phosphatase activation.
Adenosine Triphosphate↗
[Study of the binding characteristics of chlorophenoxyisobutyric acid to serum proteins in chronically uremic patients : influence of dialysis and heparine (author's transl)].
The binding characteristics of chlorophenoxyisobutyric acid (CPIB) to serum proteins has been studied in 10 chronically uremic patients and 9 healthy subjects using the technique of equilibrium dialysis. Scatchard analysis of the results indicated a significant decrease in association constants for low as well as for high affinity sites. The number of binding sites however was not diminished thus suggesting the presence of competitive inhibitors. Such inhibitors were dializable, at least in part, as demonstrated by in vivo-hemodialysis and in vitro-dialysis experiments. The in vivo administration of 50 mg heparin intravenously led to a striking increase in the unbound fraction of serum CPIB whereas the addition of 10 IU/ml heparin in vitro induced no change of protein binding which is in favor of only an indirect effect of heparin. In conclusion, CPIB binding to serum proteins of chronically uremic patients as compared to normal volunteers was decreased leading to an increase of its unbound circulating fraction. The observed change of protein binding appeared to be due to the presence of competitive inhibitors in uremic serum.
Binding, Competitive↗
Parathyroid function and lipid metabolism in the rat.
The present investigation in experimental animals was designed to obtain further insight into the possible role of parathyroid hormone (PTH) in lipid metabolism. An endogenous hyperparathyroid state was induced in rats by a calcium-poor diet. This type of hyperparathyroidism was associated with a significant increase in serum cholesterol and triglyceride concentrations, a significant decrease in the serum clearance rate of intravenously infused Intralipid and a significant increase in hepatic tissue triglyceride content as compared to the values obtained in control animals. An exogenous type of hyperparathyroidism (parathyroid extract injections) was also accompanied by a slight increase in serum cholesterol and triglyceride concentrations as well as a decrease in plasma postheparin lipolytic activity (PHLA), but the changes did not reach the level of statistical significance. In the aparathyroid state, a significant decrease in serum cholesterol and triglyceride concentrations and a significant increase in plasma PHLA were observed as compared to control rats. In additional studies, it could be demonstrated that the endogenous hyperparathyroid state was not associated with increased intestinal absorption of [3H]triolein as compared to control animals. Furthermore, the hepatic triglyceride secretion rate in these hyperparathyroid rats was significantly lower than in normal rats. In conclusion, hyperparathyroidism induces an increase in serum cholesterol and triglyceride concentrations, the latter being due to decreased peripheral removal. The aparathyroid state induces opposite changes. Thus, normal parathyroid function is required for normal lipid metabolism in the rat.
Animals↗
Parathyroid function and erythrocyte production in the rat.
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2,3-Diphosphoglycerate↗
Rat enterocyte Na+ transport in vitro. Action of parathyroid hormone and calcitonin.
Parathyroid hormone (PTH) and calcitonin exert well known effects on the renal tubule which are thought to involve specific hormone receptors and adenyl cyclase. In the intestine, it is not clear whether the action of PTH and calcitonin is only indirect or also direct, and their mechanisms of action are much less well established. In the present study, possible direct effects of PTH and calcitonin on Na+ transport in isolated intestinal epithelial cells of rats were investigated. In the presence of bovine PTH (1.2 I.U/ml) in the incubation medium, the Na+ efflux rate constant (oKNa) of isolated enterocytes was significantly reduced when compared to that in control experiments with the hormone vehicle only. The mean depression of oKNa induced by bovine PTH was 26% as compared to the control (100%) and to that induced by ouabain (4.0 mM) which was 44%. No depressant effect of bovine PTH on oKNa was observed when the isolated enterocytes were incubated with ouabain (4.0 mM). Thus, bovine PTH appeared to inhibit the ouabain-sensitive Na+ pump. When incubating the isolated epithelial cells in an EGTA-containing CA2+-free medium, bovine PTH lost its capacity to inhibit oKNa. Thus, the presence of extracellular Ca2+ appeared necessary for the inhibitory effect of bovine PTH. In contrast to its effect on oKNa, bovine PTH induced no change in net Na+ uptake by isolated enterocytes. Moreover, no significant effect on enterocyte Na+ transport could be demonstrated for salmon or porcine calcitonin at two different concentrations in the incubation medium, Neither bovine PTH nor salmon calcitonin induced significant changes in enterocyte cyclic AMP or cycle GMP concentrations. It was concluded that bovine PTH, but not calcitonin, exerted a directed inhibitory effect on the ouabain-sensitive oKNa of isolated rat enterocytes. The effect of bovine PTH occurred without measurable activation of the cyclic nucleotide system but needed the presence of Ca2+ in the incubation medium to be operative.
Animals↗
Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in french haemodialysis units: II, Haemodialysis patients.
A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in 138 haemodialysis patients in a placebo-controlled randomised double-blind trial. In an interim analysis, hepatitis B infections were observed in 21% of the vaccine group and 45% of the placebo group (p less than 0.02). 2 of the infections in the vaccine group and 12 of the infections in the placebo group occurred after the third injection. 60% of the vaccine recipients had an immune response. 4 months after the first injection the mean titre of anti-HBs was 120 mlU/ml.
Adult↗
Randomised placebo-controlled trial of hepatitis B surface antigen vaccine in French haemodialysis units: I, Medical staff.
A vaccine against hepatitis B surface antigen (Institut Pasteur Production) was assessed in staff members from forty-eight French haemodialysis units where the risk of hepatitis B was high. Of 318 subjects who completed the protocol, 164 received three monthly injections of vaccine and 154 received corresponding injections of placebo. Hepatitis B infection was observed in 3.6% of the vaccine group and 12.3% of the placebo group (p less than 0.005). The 6 infections in the vaccine group all arose within 63 days from the first injections, whereas the 19 in the placebo group arose throughout the 12 months of follow-up. The rate of side-effects after injection did not differ in the two groups. 94% of the vaccine recipients had an immune response ( greater than 10 mIU/ml in at least 5 successive specimens). 4 months after the first injection the mean + or - 2 SE peak level of anti-HBs was 2433 + or - 1077 mIU/ml.
Clinical Trials as Topic↗