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R Vanholder

Publications and source records attributed to R Vanholder.

At least 19 recordsLinked to original sources
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

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↗
PubMed1992

Polymorphonuclear cell function and infection in dialysis.

End-stage renal disease is characterized by enhanced susceptibility for infectious diseases, carrying an important risk of morbidity and mortality. In the host's defense against bacterial infection, a central role is played by phagocytic ingestion of bacteria, followed by their destruction after metabolic production of oxygen free radical species. Our studies have concentrated on the energy delivery by the hexose monophosphate shunt (HMS) to NAD(P)H-oxidase, the enzyme responsible for free radical production. This evaluation was realized by measuring, in whole blood, the CO2 produced from standard quantities of radiolabeled glucose, with data normalized for the number of polymorphs in each sample. Our studies indicate that: (1) glycolysis is disturbed in uremic outpatients from a SCrea of 6 mg/dl and a CCr of 15 ml/min; (2) similar functional disturbances are found in pre-dialysis blood samples of hemodialyzed patients; (3) this functional disturbance is further intensified during dialysis with cuprophan, which is not the case for non-complement activating dialyzers; (4) the response is especially suppressed towards Staphylococcus Aureus, the bacterial species responsible for the majority of infections in uremia; (5) that functional disturbances are mainly related to uremic toxicity, dialyzer membrane bio(in)compatibility, and uremic anemia. Biochemical disturbances in PMNL, induced by a multifactorial patho-physiologic process, may therefore be related to the enhanced incidence of infection in uremic patients.

Glycolysis↗
PubMed1992

The effect of adding Br or Zn supplements to the dialysate on the concentrations of Br and Zn in the blood of hemodialysed patients.

The effect of adding Br or Zn supplementation to the dialysate on the concentrations of Br and Zn in the blood of hemodialysed patients, is investigated. Patients with end-stage renal failure on hemodialysis show an abnormal trace element pattern. Our patients showed lowered serum Br and Zn concentrations. Four patients were subjected to dialysates with varying Br content. The impact on their serum and packed cells concentrations was evaluated. The supplementation resulted in an increase in the concentrations in serum and in packed cells. The Br concentration in serum and packed cells closely followed the dialysate content. In order to restore the Zn concentration to the normal level a ZnCl2 solution was added to the dialysate of 4 other patients. Zn accumulated in the patient as a consequence of its diffusion against the concentration gradient.

Bromine↗
PubMed1992

Behaviour of 12 trace elements in serum of uremic patients on hemodiafiltration.

The concentrations of the trace elements As, Au, Cd, Cs, Cu, Fe, Hg, Mo, Rb, Se and Zn were studied in the serum of 5 patients with end-stage renal failure who were undergoing treatment with hemodiafiltration. The concentrations of the following elements differ significantly from the reference values: As, Cd, Cu, Hg and Mo are higher, while Rb, Se, Zn and some of the Cs values are lower. The observed concentration deviations may be due to the uremic state and/or the dialysis process. To asses the contribution of the latter, the elements were determined in the substitution fluid and in the dialysate before and after blood contact and passage through the artificial kidney. Our findings suggest that the concentration abnormalities could be related to the substitution fluid for Cs, Rb, Se and Zn and to the dialysate for Mo and Rb.

Aged↗
PubMed1992

Pseudomonas septicemia due to deficient disinfectant mixing during reuse.

We describe a cluster of four septicemias with pseudomonas, that occurred in a unit performing formaldehyde reuse of capillary dialyzers. Samples of blood, heparin solutions, dialysate and effluent of reused dialyzers, were evaluated bacteriologically and upon the adequacy of the reuse procedure. Pseudomonas aeruginosa, vesicularis and/or xanthomonas maltophilia were found on the blood cultures obtained during the septicemic reactions, and in the effluent of two reprocessed dialyzers not yet used (greater than 10(4) CFU/ml). These two dialyzers had also extremely low formaldehyde concentrations (0.0014 and 0.005% versus the expected 4%). Membrane and antibiogram characteristics of a Pseudomonas aeruginosa strain, recovered from the blood cultures in one patient, and of a strain found in the effluent of one of the two contaminated reprocessed dialyzers, were the same. The problem was attributed to the inadequate mixing of the disinfectant with the tap water used in the automated reprocessing device, in the absence of an alarm disclosing this failure.

Aged↗
PubMed1992

Phagocyte metabolic activity during hemodialysis with different dialyzers not affecting the number of circulating phagocytes.

Overall leukocyte counts decrease during certain forms of hemodialysis, but little information is available on the intradialytic evolution of phagocytic metabolic function, especially during dialysis with dialyzers not affecting the number of circulating phagocytes. This study evaluated the phagocytic capacity of granulocytes and monocytes to generate CO2 out of glucose under basic unchallenged conditions and after stimulation with latex or zymosan, before and after 15, 60 and 240 minutes of dialysis with reused cuprophan, AN69S, polysulphone, polymethylmethacrylate and hemophan hemodialyzers. Phagocytic metabolic function was assessed in whole blood on the basis of 14CO2-production from labelled glucose during the phagocytic process. There were no changes in basic unchallenged CO2-production with any of the dialyzers. Reactivity to latex and zymosan, expressed per number of phagocytes, showed no decrease, irrespective of the membrane type. For polymethylmethacrylate and reused cuprophan, a slight but significant increase in metabolic reactivity was observed in response to latex and zymosan. The test employed may give a screening picture of the phagocytic reaction to contact with dialyzers and membranes and thus of their degree of biocompatibility towards the phagocyte system.

Biocompatible Materials↗
PubMed1991

Subfractions in uremic plasma ultrafiltrate inhibit calcitriol metabolism.

Previous study from our laboratory has demonstrated that uremic plasma ultrafiltrate suppresses both the production rate (PR) and metabolic clearance rate (MCR) of calcitriol in normal rats. To characterize the the substances responsible for the suppression of the synthesis and degradation of calcitriol, we fractionated 20 ml uremic plasma ultrafiltrates into 13 fractions using high-performance liquid chromatography (HPLC) and studied the effect of each fraction on calcitriol metabolism. We measured the MCR and PR of calcitriol in normal rats after they were infused for 20 hours with each fraction dissolved in 20 ml normal saline. Using a UV absorption and fluorescence emission technique, several known uremic compounds were identified as individual peaks corresponding to the fractions. We found that fractions 4, and 6 to 13 markedly reduced the MCR of calcitriol. The patterns of the MCR suppression by the HPLC fractions suggest that there were at least two groups of chemically distinguishable compounds. Infusion of a solution containing all 13 fractions of the uremic ultrafiltrate also inhibited the calcitriol synthesis. One of the 13 fractions (fraction 4, containing uric acid, xanthine, and hypoxanthine) was further fractionated into eight subfractions. Infusion of subfractions 4 to 7 markedly reduced both the PR and MCR of calcitriol. We conclude that uremic plasma ultrafiltrate contains factors that inhibit calcitriol synthesis and degradation. These substances have molecular weight less than 2,000 Daltons.

Animals↗
PubMed1991

Phagocytosis in uremic and hemodialysis patients: a prospective and cross sectional study.

Leukocyte response to phagocytic challenge was assessed in uremic and hemodialysis patients in a prospective and cross sectional study. Using latex, zymosan and staphylococcus as phagocytic challenge, the utilization of glucose-I-C14 and the generation of reactive oxygen species was measured in these patients. In uremic, non-dialysis dependent patients, the response to phagocytosis was significantly reduced when creatinine exceeded 6 mg/dl and prior to initiation of dialysis (mean serum creatinine 9.3 +/- 0.3 mg/dl) was less than half that of patients with normal renal function (P less than 0.01). In a prospective study of 15 patients initiated on dialysis, the metabolic response of their leukocytes was assessed sequentially. In eight patients, initiation of dialysis with cuprophane (Cu) membrane lead to a further decline (60%) in their metabolic response to phagocytosis at the end of four weeks of dialysis compared to pre-initiation of dialysis (P less than 0.01), whereas in seven other patients, dialysis with non-complement activating membranes did not result in a significant decline. Prospective cross-over studies of chronic hemodialysis patients corroborated these findings; eight patients dialyzed with new CU membranes had a significant decline of their metabolic response to phagocytic challenge acutely at the end of each dialysis and in pre-dialysis samples after two weeks of Cu dialysis, whereas their response returned back to baseline after two weeks of dialysis with non-complement activating membrane. In prospective and cross sectional studies, a decreased response to phagocytic stimulus was a predictor of hospitalization, primarily for infectious reasons.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellulose↗
PubMed1991

Effects of purine derivatives on calcitriol metabolism in rats.

The effects of theophylline and sodium urate on metabolic production (PR) and clearance rate (MCR) of calcitriol were determined by the constant isotope infusion method in normal rats. Calcitriol PR was significantly reduced after infusion for 20 h of either theophylline (1 mg/h, PR = 22.3 +/- 1.6 ng.kg-1.day-1, P less than 0.001, n = 5) or sodium urate (0.5 mg/h, PR = 18.6 +/- 1.2 ng.kg-1.day-1, P less than 0.001, n = 5) compared with control rats infused with saline (PR = 32.0 +/- 1.5 ng.kg-1.day-1, n = 5). Renal 1 alpha-hydroxylase activity of kidney homogenate was significantly inhibited in rats infused with theophylline or urate. Suppression of 1 alpha-hydroxylase activity was also observed when the kidney homogenate was preincubated for 3 h with various concentrations of xanthine (0.11-3.0 mg/dl). In addition, the MCR of calcitriol was decreased in rats infused with either theophylline (MCR = 21.0 +/- 0.88 microliter.min-1.100 g-1, P less than 0.005) or urate (MCR = 22.9 +/- 0.91 microliter.min-1.100 g-1, P less than 0.05) compared with saline-infused control rats (MCR = 25.2 +/- 0.41 microliter.min-1.100 g-1). Because calcitriol degradation is a receptor-mediated process that requires binding of the receptor-hormone complex to chromatin, we studied the binding affinity of labeled calcitriol receptor for DNA-cellulose in the presence of theophylline or urate. Both theophylline and urate inhibited receptor binding affinity for DNA-cellulose. We conclude that these purine derivatives suppress calcitriol synthesis and inhibit receptor binding affinity for DNA. The altered receptor binding affinity could explain the decreased MCR of calcitriol.

Animals↗