Search PubMed⌕ Search

Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 163 records · Page 9Linked to original sources
PubMed1993

Contributing factors to the inhibition of phagocytosis in hemodialyzed patients.

Although polymorphonuclear (PMNL) glucose consumption as an index of metabolic response to phagocytosis in the production of free radical species is depressed in hemodialyzed patients, substantial interindividual differences are registered. Studies evaluating to what variables these differences are related are, however, lacking. In the present study, the relation of several factors to PMNL functional capacity in the breakdown of glucose to CO2 by the hexose monophosphate shunt (HMS) is considered in an individual and multifactorial regression analysis. Starting from a database, collected in 126 stabilized hemodialysis patients, PMNL HMS-response to standard quantities of latex and zymosan was correlated to 14 numerical parameters: time since the start of dialysis, hematocrit, serum creatinine, phosphorus, ferritin, albumin, parathormone, albumin before and after administration of desferrioxamine, residual creatinine clearance, PCR, TACurea, Kt/V and age. In addition, the non-numeric parameters of sex, biocompatibility of dialyzers, and primary diagnosis were also considered. A significant correlation was found for time on dialysis (P < 0.001), hematocrit (P < 0.001), ferritin (P < 0.05), PTH (P < 0.001) and aluminum (P < 0.05). The highest correlation coefficients were found for time on dialysis (latex: N = 126, r = 0.50, P < 0.001; zymosan: N = 126, r = 0.58, P < 0.001). Multivariate correlation analysis of one clinical parameter together with time on dialysis to PMNL response showed that the correlation was strongly weakened or disappeared for ferritin, aluminum and PTH, but not for hematocrit. Our data indicate that time since the start of dialysis is an important, but not unique factor, influencing polymorphonuclear functional capacity in a hemodialysis population.

Bacterial Infections↗
PubMed1993

Urea kinetic modeling: comparing the options.

In this study 6 commercially produced kinetic modeling packages utilizing a variable volume, single pool urea model, as well as formulae to determine the delivery of therapy, have been compared by applying to each the same set of rigorously collected data for a group of 12 patients. Comparison of the kinetically derived parameters (urea generation rate [G], urea distribution volume [V], delivery of therapy [Kt/V], and normalized protein catabolic rate [nPCR]) showed that the values obtained for both G and V differed between packages owing to the numerical methods and the clearance used in the solution of the differential equations. Although a broad agreement between the values established for Kt/V and nPCR was noted, the 95% limits of agreement indicated that it would be prudent to exercise caution when comparing results established by different modeling packages.

Adult↗
PubMed1993

Mechanism of decreased intestinal calcitriol receptor concentration in renal failure.

The biological actions of calcitriol and its receptor synthesis are believed to be mediated through the calcitriol-receptor complex interacting with nuclear chromatin of target cells. Thus inhibition of the receptor interaction with DNA could diminish the biological actions of calcitriol and upregulation of its receptor. We found that uremic ultrafiltrate reduced the receptor interaction with DNA in vitro. DNA-cellulose chromatography showed that the receptor from normal rats and rats infused with normal ultrafiltrate eluted as a single peak at 0.22 M KCl, whereas chronic renal failure rats and rats infused with uremic ultrafiltrate had two receptor peaks, i.e., one of normal activity at 0.22 M KCl and the other of weak activity at 0.12 M KCl. Furthermore, infusion of uremic ultrafiltrate to normal rats reduced the intestinal calcitriol receptor concentration (397 +/- 15.8 vs. 307 +/- 15.4 fmol/mg protein, both n = 4, P < 0.005). Uremic ultrafiltrate also suppressed the calcitriol-induced upregulation of the receptor (816 +/- 34.6 vs. 606 +/- 35.3 fmol/mg protein, P < 0.005). It appears that uremic toxins may reduce the biological action of calcitriol in renal failure by inhibiting receptor synthesis and the interaction of the hormone-receptor complex with nuclear chromatin.

Animals↗
PubMed1993

More than tenfold increase of arsenic in serum and packed cells of chronic hemodialysis patients.

Arsenic concentrations were determined in serum and packed cells of 7 chronic hemodialysis patients, in fresh dialysate and in a heparin solution. The analytical technique was radiochemical neutron activation analysis. The accuracy of the method was tested by the analysis of As in certified reference materials. Patients showed elevated serum and packed cell arsenic concentrations compared with controls (serum, range: 2.3-79.8 ng As/ml, median: 11.5 ng As/ml; versus range: 0.132-4.783 ng As/ml, median: 0.38 ng As/ml; packed cells, range: 2.1-68.4 ng As/g, median: 9.5 ng As/g; versus range: 0.51-14.44 ng As/g, median: 3.17 ng As/g). Arsenic concentrations remained unaltered, before versus after a single hemodialysis treatment. The arsenic contents of serum and packed cells were significantly correlated (n = 7, r = 0.96, p < 0.05). No arsenic could be detected in the heparin solution or in the dialysate.

Aged↗
PubMed1993

Antibiotics and energy delivery to the phagocytosis-associated respiratory burst in chronic hemodialysis patients: a comparison of cefodizime and cotrimoxazole.

Twenty-three stabilized chronic uremic patients with no active or recent infection were treated for 10 days with either cefodizime (5 x 2 g intravenously, n = 10) or cotrimoxazole (960 mg orally b.i.d., n = 8) in order to evaluate the effects on the depressed polymorphonuclear metabolic response to phagocytic challenge; a separate group of 5 patients received placebo. Ex vivo evaluation in whole blood of energy delivery to the phagocytosis-associated respiratory burst activity in response to latex and zymosan challenge was determined by measuring hexose-monophosphate shunt NAD(P)H-oxidase-related glycolytic activity. Cefodizime induced a statistically significant increase in the baseline-depressed glycolytic response for both latex and zymosan challenge, in contrast to cotrimoxazole and placebo. Depressed phagocytosis-related metabolic function in hemodialyzed patients was stimulated by cefodizime in recommended therapeutic doses but not by cotrimoxazole, the effect persisting for at least 2 weeks after the end of treatment.

Adult↗
PubMed1993

Depressed phagocytosis in hemodialyzed patients: in vivo and in vitro mechanisms.

Infection is a frequent complication and the major cause of death among end-stage renal patients. Polymorphonuclear phagocytes (PMNL) are important in host defense mainly because of bacterial destruction by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-related free radical production following phagocytosis. In this study, hexose monophosphate pathway glycolytic activity, delivering energy to NADPH oxidase, is evaluated in vivo and in vitro, in healthy controls and in dialyzed renal failure patients. Our results show a marked parallel and correlated inhibition in the response to three stimuli for phagocytic activity (Staphylococcus aureus, formyl-methionine-leucine-phenylalanine, phorbol myristic acid) in predialysis samples. These data point to a main suppression of metabolic pathways, possibly beyond protein kinase C. This response is further suppressed at the 15th minute of cuprophane dialysis, for all stimuli studied (-40 to -94%; p < 0.001) except PMA. PMNL response remains intact during dialysis with non-complement-activating dialyzers. In vitro experiments confirm decreased PMNL glycolytic activity after the suspension of cuprophane fragments in normal whole blood. We conclude that polymorphonuclear cell energy delivery to NADPH oxidase is impaired in patients with end-stage renal failure. The impaired response against various stimuli is different in predialysis blood samples compared to samples collected during cuprophane dialysis, and may be related to two different conditions. These events probably contribute to the acquired immune suppression of uremia and the high incidence of infection among dialysis patients.

Cellulose↗
PubMed1993

Infectious morbidity and defects of phagocytic function in end-stage renal disease: a review.

Infectious diseases remain among the most morbid events and are an important cause of death in ESRD. These events are related to an acquired immunodeficiency that progresses during the development of uremic retention, as part of the broader spectrum, displayed by the "uremic syndrome". A central role in the hose defense against bacterial infection is played by the phagocytic polymorphonuclear white blood cells, which are characterized by the capacity to ingest bacteria (phagocytosis), which is followed by the destruction of those bacteria (killing capacity). This article reviews the mechanisms of development and the potential causes that have been held responsible for this aspect of the defective immune function. The observed changes are attributed to alterations in receptor expression, although more convincing evidence points in the direction of metabolic functional disturbances, especially in the NAD(P)H-oxidase-dependent production of oxygen free radicals. The most important causative factors are: uremic toxicity, iron overload, renal anemia, dialyzer bioincompatibility, and the type of renal replacement therapy. It is concluded that the phagocytic defect in ESRD is multifactorial and that each factor should be managed by specific therapeutic approaches.

Humans↗
PubMed1993

Effect of uric acid on plasma levels of 1,25(OH)2D in renal failure.

Previous studies from these laboratories have demonstrated that uremic biologic fluids contain substances that suppress 1,25(OH)2D metabolism. Among these substances, it was found that uric acid suppresses 1 alpha-hydroxylase activity and synthesis of 1,25(OH)2D in rats. In this study, the effect of uric acid on plasma concentrations of 1,25(OH)2D in patients with renal failure was examined. Nine patients with stable chronic renal failure (serum creatinine, 1.9 to 6.4 mg/dL) were studied. None of the patients received vitamin D supplementation. Plasma concentrations of Ca, P, parathyroid hormone, creatinine, uric acid, 1,25(OH)2D, and 25(OH)D were measured before and 1 wk after the patients received allopurinol, 300 mg daily. Plasma creatinine, Ca, P, parathyroid hormone, and 25(OH)D did not change before or after allopurinol treatment. However, plasma uric acid decreased significantly from 7.3 +/- 0.4 to 4.0 +/- 0.4 mg/dL (P < 0.01) and plasma concentration of 1,25(OH)2D rose from 30.8 +/- 2.7 to 38.2 +/- 4.8 pg/mL (P < 0.01) after the ingestion of allopurinol. Allopurinol itself did not appear to directly enhance 1 alpha-hydroxylase activity in rats. It was concluded that a short-term administration of allopurinol suppresses plasmic uric acid and increases plasma 1,25(OH)2D in patients with chronic mild to moderate renal failure.

Adult↗
PubMed1993

A technique for the laboratory determination of recirculation in single needle dialysis.

Recirculation is an important factor in single needle dialysis and, if high, can compromise treatment efficiency. To provide information regarding recirculation characteristics of access devices used in single needle dialysis, we have developed a new technique to characterise recirculation and have used this to measure the recirculation of a Terumo 15G fistula needle and a VasCath SC2300 single lumen catheter. The experimentally obtained results agreed well with those established clinically (8.5 +/- 2.4% and 18.4 +/- 3.4%). The experimental results have also demonstrated a dependence on access type, pump speeds and fistula flow rate. A comparison of experimental data with theoretical predictions showed that the latter exceeded those measured with the largest contribution being due to the experimental fistula.

Arteriovenous Shunt, Surgical↗
PubMed1992

Cefodizime: enhancement of depressed phagocytosis-associated respiratory burst activity in chronic uremic patients.

Patients with renal failure are highly susceptible to infection, in part because uremia decreases the killing capacity of phagocytic leucocytes. Phagocytosis-associated respiratory burst activity was investigated at different stages of renal impairment by measuring the 14CO2 production during metabolism of labeled glucose by phagocytic cells. Non-dialyzed end-stage renal failure and haemodialysis patients showed a decrease in phagocytosis to about 50% of normal (p less than 0.05). In a second phase of the study, six haemodialysis patients received 2 g cefodizime (CDZ) i.v. after dialysis for ten days (five doses). Phagocytosis was determined at baseline and was followed until day 29. A clear, long-lasting stimulatory effect of CDZ on phagocytosis after both latex and zymosan challenge was found. It is concluded that a usual CDZ dosage regimen stimulates depressed phagocytosis in haemodialysis patients, and that this stimulatory effect persists for at least two weeks after the end of treatment. Uremic patients with infection may benefit from this additional property of CDZ.

Cefotaxime↗
PubMed1992

Biocompatibility issues in hemodialysis.

Hemodialysis, as a life-saving treatment modality for uremic patients, implies a repeated and compulsory contact of blood with foreign materials. As a consequence, biocompatibility problems are unavoidable. The same applies for the material used for the creation of vascular access, and for the alternative dialysis method, CAPD (continuous ambulatory peritoneal dialysis), although each system might cause its own and specific problems. Although in early dialysis the focus has been on maintenance of life and elimination of toxins, later on the important morbid implications of this lack of biocompatibility have been recognized. Eight major problems will be discussed, especially in the perspective of recent new findings in this field: (1) coagulation and clotting; (2) complement and leukocyte activation; (3) susceptibility to infection; (4) leaching or spallation; (5) surface alterations of solid materials; (6) allergic reactions; (7) shear; (8) transfer of compounds from contaminated dialysate. After description of the major biochemical and clinical implications of these problems, ways to prevent morbid events and future perspectives will be described.

Biocompatible Materials↗
PubMed1992

Correction of deficient phagocytosis during erythropoietin treatment in maintenance hemodialysis patients.

Studies on the influence of erythropoietin (EPO) on granulocyte or monocyte function are scant. In this study, the effect of EPO on polymorphonuclear cell (PMN) respiratory burst activity was evaluated in a double-blind, placebo-controlled study in 22 patients on maintenance hemodialysis. As an index of phagocyte respiratory burst activity, the increase in 14CO2 production from labeled glucose-1-C, after challenge with latex and zymosan, was measured on predialysis whole blood samples, before and after EPO-treatment. As controls, 56 nonuremics and 49 non-EPO-treated hemodialysis patients were evaluated. Before EPO treatment 14CO2 production was depressed to 75.7% (latex) and 54.6% (zymosan) of healthy controls (P less than 0.01). A marked improvement was observed after a mean treatment period of 4 months (latex, 115 +/- 12 to 172 +/- 14; zymosan, 178 +/- 19 to 412 +/- 36 dpm/10(3) PMN, P less than 0.01). Placebo treatment induced no changes. The improvement became more pronounced with prolongation of treatment. A significant correlation between hematocrit and 14CO2 production was observed in the EPO treatment group (latex: n = 44, r = 0.47, P less than 0.05; zymosan: n = 44, r = 0.57, P less than 0.001). No correlation was found with serum ferritin. We conclude that the depressed phagocyte glycolytic activity of hemodialyzed uremics is normalized during correction of anemia by EPO. This may be attributed to factors other than a reduction in the body iron stores.

Adult↗
PubMed1992

A longitudinal, five year survey of urea kinetic parameters in CAPD patients.

This study reports on the five years' evolution of the KT/V urea index and protein catabolic rate (PCR) in 16 CAPD patients who were treated with a constant daily dialysis dose. Total KT/V urea index decreased with time from a value of 0.96 +/- 0.06 at the start to 0.55 +/- 0.05 at five years of treatment. This decline was due to the opposite changes of two important parameters affecting the index. First, the contribution of the residual urinary KT/V gradually decreased from 28.6% at the start to 8 to 9% after four years. Second, the distribution volume of urea calculated as a constant fraction of body weight gradually increased. The body weight increased from 58.2 +/- 2.79 kg at start to 70.6 +/- 3.33 kg at five years. Peritoneal urea clearances and ultrafiltration rates remained stable. In 12 patients with stable body weight between 24 and 48 months, PCR decreased from 0.98 +/- 0.05 to 0.87 +/- 0.05 g/kg/day. A positive correlation between KT/V urea and PCR and a negative correlation between KT/V urea and number of hospitalization days, peritonitis rates and peripheral nerve conductivity was found. The same negative correlation was found when only the KT/V urea index obtained during the first year of treatment was considered. In conclusion, the KT/V urea index decreases in CAPD patients primarily because residual renal function decreases and body weight increases, while the peritoneal clearing for urea is maintained. The index correlates with some clinical parameters, and may have some prognostic value.

Adult↗
PubMed1992

Endotoxin transfer through dialysis membranes: small- versus large-pore membranes.

In this in-vivo study, dialysate and serum endotoxin was evaluated before and after haemodialysis with small-pore (PS400) and large-pore (PS600) polysulphone dialysers, and before and after haemodiafiltration with the PS600 filter. The source of the endotoxin was the presence in dialysate of Pseudomonads at a concentration of 10(3)-10(4) CFU/ml. Endotoxin was measured by a modified chromogenic limulus amoebocyte lysate (LAL) assay. In spite of dialysate endotoxin concentrations greater than 100 pg/ml, no changes in pre- versus posttreatment LAL reactivity were observed in PS400 dialysis and PS600 haemodiafiltration. In contrast, PS600 haemodialysis was related to an increase in serum LAL reactivity from 1.3 +/- 1.5 to 3.8 +/- 2.0 pg/ml (n = 15, P less than 0.01), and five patients (33.3%) showed a post-dialysis value in excess of 5 pg/ml. Our data are consistent with the absence of in-vivo endotoxin transfer during haemodialysis with small-pore dialyser membranes, and during haemodiafiltration with membranes with larger pores. An increase in LAL reactivity during haemodialysis with membranes with larger pores is, however, present, presumably due to the occurrence of backdiffusion/filtration with that specific strategy.

Diffusion↗
PubMed1992

Pain at the injection site of subcutaneously administered erythropoietin in maintenance hemodialysis patients: a comparison of two brands of erythropoietin.

Local pain due to subcutaneous erythropoietin (EPO) injection into the thigh was studied using a verbal score ranging from 0 to 4. Equivoluminous doses of epoetin-alpha (Cilag) and epoetin-beta (Boehringer) were compared in 2 controlled single-blind experiments: 10 dialysis patients were treated at random for 4 weeks at consecutive sessions with both brands of EPO, and 40 patients were treated in 1 session only with the 2 brands simultaneously. Pain scores were 1.12 +/- 0.28 versus 0.15 +/- 0.06 (p less than 0.05) and 1.75 +/- 0.19 versus 0.08 +/- 0.04 for epoetin-alpha and epoetin-beta, respectively (p less than 0.001). Treatment acceptance was 48% for epoetin-alpha versus 83% for epoetin-beta (p less than 0.05).

Aged↗