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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 127 records · Page 7Linked to original sources
PubMed1997

Uremic toxins.

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Cardiovascular System↗
PubMed1997

Pharmacokinetics of recombinant hirudin in hemodialyzed end-stage renal failure patients.

Recently, hirudin was used for the first time as an anticoagulant during hemodialysis in men. Pharmacokinetic data of this compound in end-stage renal failure are however not available. In this study, the pharmacokinetics of recombinant hirudin (HBW 023) was evaluated in hemodialysis-treated end-stage renal failure patients. HBW 023 was administered as a bolus at the start of a single dialysis (0.02 to 0.08 mg/kg) in 20 patients, and plasma hirudin levels were followed during this and the 5 following dialyses, without additional hirudin administration. The initial dialysis (HD1) was performed with a low flux polysulfone dialyzer, the following dialyses (up to HD6) with a high flux polysulfone dialyzer and regular heparin. Hirudin levels averaged 504.0 +/- 214.0 and 527.7 +/- 217.1 ng/ml in the middle and at the end of HD1, and then gradually decreased to 15.2 +/- 15.2 ng/ml at the end of HD6. Pharmacokinetic data were compared to those obtained in healthy controls (n = 5), receiving the same dose, and reaching the same peak hirudin level. Hirudin half-life was > 30 times longer in hemodialysis patients (51.8 +/- 15.6 vs. 1.7 +/- 1.5 h, p < 0.001), whereas area under the curve was > 60 times higher (34,669 +/- 14,898 vs. 545 +/- 205 ng/ml x h, p < 0.001). Distribution volume was lower in hemodialysis patients (11.0 +/- 3.1 vs. 14.1 +/- 2.01, p < 0.05). Hirudin disappearance rate was the same during high flux polysulfone dialysis as during interdialytic periods. Hirudin removal was markedly higher in those patients still maintaining some residual renal function and parameters of hirudin removal were significantly correlated to residual creatinine clearance. It is concluded that hirudin removal from the body is markedly depressed in hemodialyzed end-stage renal failure patients and that even minor residual renal function may increase this removal rate.

Adolescent↗
PubMed1996

Basal metabolism of intraperitoneally injected carrier-free 74As-labeled arsenate in rabbits.

The time-dependent occurrence of [74As]arsenate metabolites in Flemish Giant rabbits was investigated. As absorbed rapidly, reaching maximal concentrations in plasma and packed cells after 30 min and 2 hr, respectively. The [74As]arsenate in plasma and packed cells was reduced to [74As]arsenite, to 35 and 50% of the total 74As, respectively. The concentration of methylated As species in plasma and packed cells increased rapidly after 30 min. About 18% of total plasma 74As maximally bound to transferrin. Two-thirds of total 74As in packed cells bound to hemoglobin. Whereas little or no [74As]monomethylarsonic acid, one of the main As metabolites in humans, could be found in other animals, it is present in measurable amounts in the Flemish Giant. Furthermore, the plasma clearance rate of 74As species is lower than that in other rabbits and more similar to that of humans. The tissue 74As distribution varied widely with the highest concentrations in kidneys, liver, and lungs. 74As accumulated in bone whereas other tissues and blood showed rapid clearance rates. In muscle and heart an important part of arsenic was associated with components insoluble in phosphate-buffered isotonic saline. Binding of arsenic to soluble tissue proteins was most important in the kidneys, liver, and spleen. [74As]Arsenate metabolites were detected in all tissues. The relative amounts of [74As]arsenite or [74As]monomethylarsonic acid seldom exceeded 15% of total tissue 74As. The proportion of [74As]dimethylarsenic acid in the low molecular 74As fraction increased steadily. Substantial amounts of [74As]monomethylarsonic acid were found in the tissues..

Animals↗
PubMed1996

Disturbed host defense in peritoneal cavity during CAPD: characterization of responsible factors in dwell fluid.

In this study, the factors in overnight dwell fluid (8 to 10 hr dwell) depressing granulocyte (GC) NAD(P)H-oxidase dependent radical species production are characterized. At present, most studies have essentially focused on fresh, unspent dialysate and on peritoneal macrophages. The response to Staphylococcus aureus (Staph A) was dose-dependently depressed for both GC CO2 production (from 91.3 +/- 8.4 to 9.0 +/- 1.5 dpm/10(3) GC, P < 0.01) and chemiluminescence (CL) (peak from 7.3 +/- 0.8 to 1.6 +/- 0.8 cps x 10(3)/GC, P < 0.01). Stimulation with formyl-methionine-leucine-phenylalanine (f-MLP), phorbol myristic acid (PMA), Staphylococcus epidermidis (Staph Epi), E. coli, latex and zymosan revealed a parallel depression, pointing to an intrinsic metabolic defect, rather than failure of particle ingestion. The addition of glucose to the normal cell medium to obtain the same concentration as in the CAPD effluent (2.9 +/- 0.3 mg/dl) depressed function but not to the same extent as the genuine PD effluent. Opsonization of Staph A and E. coli induced a partial correction. No effect of pH or osmolality was observed. HPLC fractionation of CAPD effluent on a polarity based gradient revealed an elution of depressive factors in hydrophobic fractions with a nadir in F7 and F12. Analysis of the elution pattern of various uremic solutes revealed elution in F12 of p-cresol, a solute with known inhibitory effect on GC function. These events may be related to recent peritonitis (CL in response to Staph A 0.3 +/- 0.1 in effluent of 6 patients with recent peritonitis versus 2.6 +/- 0.8 cps x 10(3)/GC in 12 patients without recent peritonitis (P < 0.01). We conclude that the GC response is depressed in the presence of CAPD effluent due to excess glucose, lack of opsonization, and uremic solutes of which p-cresol is one of the responsible compounds.

Ascitic Fluid↗
PubMed1996

Recombinant human erythropoietin corrects anaemia during the first weeks after renal transplantation: a randomized prospective study.

BACKGROUND: Studies on the effect of recombinant human erythropoietin (rHuEpo) on haematopoiesis in patients with kidney transplants, have been limited to progressive chronic graft failure, late after transplantation. In the present prospective randomized study, the efficacy of rHuEpo in the correction of anaemia during the first weeks after renal transplantation (RTP) was evaluated. METHODS: Patients were allocated to either an Epo- (n = 14) or a non-Epo-treated group (n = 15). Epo (150 U/kg.week s.c.) was started at a haematocrit (Hct) < 30% and was increased at weekly intervals by 30 U/kg.week, as long as Hct remained < 25%. RESULTS: In the Epo group, Hct increased from a nadir of 22 +/- 4% 2 weeks after RTP to 30 +/- 4% at week 4 and to 36 +/- 4% at week 6 (P < 0.001 and P < 0.0001 respectively vs week 2). Corresponding values in the non-Epo group were 25 +/- 6%, 28 +/- 6% (P = NS) and 32 +/- 6% (P < 0.05 vs week 2) (overall evolution Epo vs non-Epo: P = 0.038 by variance analysis). The differences in Hct between the Epo and non Epo group were even more marked in patients without major complications (variance analysis P = 0.009). The Epo-treated patients required fewer post-surgical blood transfusions (0.005 vs 0.014/days follow-up, P < 0.05), in spite of greater post-surgical blood losses, especially at day 1 (P < 0.05) and the presence of more major complications (7 vs 4) and a higher number of ganciclovir-treated patients (4 vs 0; P < 0.05). The maximum Epo dose after RTP was > 2x higher than the one required before RTP (197.1 +/- 45.1 vs 85.0 +/- 76.0 U/kg.week; P < 0.05). CONCLUSIONS: It is concluded that rHuEpo during the first weeks after RTP is of benefit in the correction of the Hct in the early post-surgical period, in spite of relative Epo resistance.

Adult↗
PubMed1996

Novel frameshift mutation in a heterozygous woman with Fabry disease and end-stage renal failure.

UNLABELLED: It is generally accepted that Fabry disease (angiokeratoma corporis diffusum) is an X-linked disorder resulting from the deficient activity of the lysosomal enzyme alpha-galactosidase. In males, the enzymatic defect leads to accumulation of glycosphingolipids, particularly in the kidney which causes end-stage renal disease. We report here a woman who presented in 1987 with focal and segmental glomerulosclerosis and required hemodialysis 4 years later when her son was evaluated for proteinuria. In these patients morphologic, biochemical, and genetic investigations were performed to explore the possibility of a hereditary renal disorder. Ultrastructural examination of the son's renal biopsy specimen revealed lamellated osmiophilic inclusions in the glomeruli, typical of Fabry disease. Four months after kidney transplantation in the mother, a graft biopsy specimen also revealed dense lamellated inclusions on electron microscopy. The leukocyte alpha-galactosidase activity was 0.008 mumol/min.10(9) cells in the son and 0.070 in the mother (range 0.100-0.500 mumol/min.10(9) cells). The diagnosis of Fabry disease was confirmed in both patients by the identification by DNA sequencing of a novel mutation in the alpha-galactosidase gene: one single base pair deletion in exon 3 (7317delA). IN CONCLUSION: (1) end-stage renal disease may occur in heterozygous women with Fabry disease; (2) morphologic lesions due to glycosphingolipid accumulation may be observed in the renal allograft after transplantation, and (3) DNA analysis confirmed the diagnosis by demonstrating a frameshift mutation, which has as yet not been reported.

Adult↗
PubMed1996

Two-pool versus single-pool models in the determination of urea kinetic parameters.

The mathematics used for urea kinetic modeling are currently based on a single-pool distribution of urea throughout the body. In this study, we evaluated which one of a single- or a two-pool model would be more appropriate for the prediction of directly measured urea decay during hemodialysis. A numerical method was used which minimizes the relative root mean square (RMS) error between a calculated single- or two-pool urea decay curve and the measured intradialysis decay in 13 equilibrated dialysis patients. Using a two-pool model, the RMS error was markedly lower (1.27 +/- 0.72%) than the values obtained with a single-pool model, either based on multiple urea concentrations (RMS error 3.14 +/- 1.36%; p < 0.01 vs. two-pool model) or only on pre- and postdialysis urea (RMS error 5.00 +/- 2.38%; p < 0.001). This resulted for the single-pool model in an overall underestimation of urea generation, distribution volume (V) and protein catabolic rate and in an overestimation of Kt/V versus the two-pool model. In individual cases, the difference reached up to 18.7%. Comparison of V calculated from the two-pool model versus V values determined from anthropometric formulae (Watson) resulted in similar mean values (34.05 +/- 4.87 vs. 33.09 +/- 4.19 liters; p = NS), with a weak correlation (n = 13, r = 0.75, p = 0.003). Individual values, however, again differed by up to more than 20%. In conclusion, the use of single-pool kinetic models, as well as of anthropometric estimations of V, should be regarded with care, especially when individual patients are considered instead of groups. The two-pool model follows the directly measured urea decay more exactly which results in substantial differences in calculated kinetic parameters.

Aged↗
PubMed1996

The utility of single-strand conformation polymorphism (SSCP) analysis: results obtained in families with Fabry's disease.

Single-strand conformation polymorphism (SSCP) analysis is a widely used and relatively simple method for detection of sequence polymorphisms in DNA fragments. We have used this technique to screen the alpha-galactosidase gene, with the aim of identifying the disease causing mutations in families with Fabry's disease. Five single-base shift mutations were found, but a single base-pair deletion could not be recognized by SSCP. The risk of mistaking a neutral polymorphism for a mutation is illustrated, and the utility as well as the limitations of SSCP in screening and diagnostic use are discussed.

Fabry Disease↗
PubMed1996

Accumulation of arsenic species in serum of patients with chronic renal disease.

Speciation of arsenic was determined in serum of 19 non-hemodialysis (non-HD) and 18 HD patients. The respective mean values of serum creatinine in these groups were 410 +/- 250 and 914 +/- 173 mumol/L (reference range for healthy subjects: females 50-80; males 57-93 mumol/L). The mean total arsenic concentrations were 5.12 +/-5.58 and 6.47 +/- 4.28 micrograms/L, respectively (reference value: 0.958 +/-1.52 micrograms/L). Dimethylarsinic acid (DMA) and arsenobetaine (AsB) were the major As species in serum of the non-HD and HD patients, with mean values of 0.82 +/- 1.05 and 1.93 +/- 1.51 micrograms/L for DMA and 3.55 +/- 4.58 and 3.47 +/- 2.89 micrograms/L for AsB, respectively. Serum concentrations of inorganic As and monomethylarsonic acid in both groups were below the detection limits for these compounds. Measurement of As concentration before vs after 4 h of HD treatment indicated that 68% of total As in serum was removed, as was 16% of the total As in packed cells. The efficiency of DMA and AsB removal during dialysis corresponded to that of total As.

Adult↗
PubMed1995

Determination of total arsenic in serum and packed cellsof patients with renal insufficiency.

In order to investigate the arsenic level in serum and packed cells of patients with renal insufficiency, total arsenic (As) concentrations were determined with hydride generation atomic absorption spectrometry (HGAAS) in serum (S) and packed cells (PC) of 31 non-dialyzed patients. The accuracy of the method was tested by the analysis of arsenic in 3 certified reference materials. Patients showed a three-fold increase of arsenic concentrations in serum and a two-fold increase of arsenic in packed cells compared with controls. Patients (n=10) with higher serum creatinine (>2.0 mg/dL), urea (>0.70 g/L) and urinary protein (mean+/-SD: 1.12+/-0.82 g/L) showed higher arsenic concentrations (5.8+/-3.3 microg/L in serum and 18.0+/-16.7 microg/kg in packed cells) compared with those with lower creatinine (<1.6 mg/dL), urea (<0.6 g/L) and urinary protein (mean+/-SD: 0.27+/-0.82 g/L) (n=16, serum arsenic 1.2+/-1.2 microg/L, packed cells arsenic 2.6+/-1.9 microg/kg). The significant differences (both p < 0.001) in S and PC-arsenic levels of patients in group I and II implies a relationship between the arsenic level and the degree of chronic renal insufficiency.

Journal Article↗