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Biomedical subjects

Raymond Vanholder

Publications and source records attributed to Raymond Vanholder.

At least 73 records · Page 4Linked to original sources
PubMed2003

Toxicity of free p-cresol: a prospective and cross-sectional analysis.

BACKGROUND: Uremic syndrome is the consequence of the retention of solutes usually cleared by the healthy kidneys. p-Cresol can be considered a prototypic protein-bound uremic toxin. It is conceivable, analogous with drugs, that the non-protein-bound fraction of p-cresol exerts toxicity. This aspect had never been evaluated, nor have the factors influencing the free fraction of p-cresol. METHODS: In a transsectional study we evaluated the relationship between prehemodialysis free p-cresol and the ratio of free to total p-cresol (F:T) to clinical and biological factors in 44 chronic renal failure patients. The evolution of free p-cresol was assessed prospectively in 12 patients showing a change in serum albumin of at least 5 g/L over time. Hospitalization days attributable to infection and the free p-cresol concentrations were noted over a 1-year period. The impact of free p-cresol in vitro on leukocyte functional capacity was evaluated by chemiluminescence. RESULTS: We observed a correlation between total and free p-cresol (r = 0.84; P <0.001). In the multivariate analyses, free p-cresol and F:T showed a negative correlation with albumin. A shift from normal serum albumin to hypoalbumininemia in 12 patients led to an increase in free p-cresol from 5.9 +/- 3.2 to 8.2 +/- 4.5 micro mol/L (P <0.05; 0.64 +/- 0.35 to 0.89 +/- 0.49 mg/L). Free p-cresol (P <0.05) was higher in the patients hospitalized for infectious disease. In vitro, free p-cresol was higher in a 25 g/L than in a 50 g/L albumin solution (P <0.05). Leukocyte chemiluminescence production was more inhibited in the low albumin (high free p-cresol) solution (28% +/- 6% vs 21% +/- 8%; P <0.05). CONCLUSIONS: Hypoalbuminemia and total p-cresol increase the free fraction of p-cresol. Patients hospitalized for infections have higher free p-cresol. In vitro, high free p-cresol has a negative impact on leukocyte chemiluminescence production. These data demonstrate the toxicity of free p-cresol.

Blood Proteins↗
PubMed2002

Behaviour of vanadate and vanadium-transferrin complex on different anion-exchange columns. Application to in vivo 48V-labelled rat serum.

The behaviour of free [48V]vanadate and [48V]vanadium-transferrin complex was investigated on five different anion-exchange columns (Mono Q 5/5 HR, Hitrap Q HP, Sepharose Q FF, Sepharose DEAE FF and Hitrap Q XL). The recovery of both V-compounds was quantitative. The peak shape and retention time of vanadate varied according to the type of column. The vanadium-transferrin complex also showed different elution patterns depending on the type of column. Especially in case of the Sepharose Q FF, Mono Q 5/5 HR and Hitrap Q XL columns the vanadium-transferrin binding was degraded during elution on the column. The results clearly prove that care should be taken as to the choice of column for speciation purposes of vanadium compounds in order to prevent various artefacts showing up in the chromatograms. A Hitrap Q HP column was used to fractionate different vanadium compounds in rat serum.

Animals↗
PubMed2002

Fractionation of vanadium complexes in serum, packed cells and tissues of Wistar rats by means of gel filtration and anion-exchange chromatography.

Male Wistar rats were intraperitoneally injected with [(48)V]vanadium tracer to (1) investigate the distribution of vanadium over different tissues and (2) study the distribution of vanadium over the proteins and peptides in serum, packed cells and homogenates of tissues by means of liquid chromatography experiments (size exclusion, ion exchange). Target organs were primarily kidney, bone, spleen and liver. In serum we found that vanadium was mainly bound to transferrin; however, a small amount was also bound to albumin. Besides these two complexes, a significant part of vanadium occurred as readily exchangeable ("free") vanadium. In packed cells, vanadium is mainly bound to hemoglobin and to two abundant low molecular mass complexes. The chromatograms of tissues (kidney, liver, testes, spleen and lung) show similar high molecular mass complexes (vanadium co-elutes with ferritin, transferrin and hemoglobin). Between the low molecular mass complexes there are similar peaks for spleen, testes and kidneys on the one hand, and liver and lung on the other hand, albeit the differences are small. In the case of lung, there is an additional low molecular mass peak.

Animals↗
PubMed2002

Fractionation of vanadium in urine of Wistar rats as a function of time after intraperitoneal injection.

[(48)V]Vanadium was intraperitoneally injected into Wistar rats. Urine and feces were collected at regular intervals (n=19) between 1 and 144 h after injection. In case of urine, maximal excretion (V activity/ml urine) of vanadium was seen 3 h after injection. In case of feces, a maximum appeared 32 h after injection. Urine samples were fractionated on two types of gel filtration column (Superose 12 HR 10/30 and Superdex Peptide 10/30). We found that vanadium in urine exists as both high (protein-bound) and low molecular mass species and that the partition about these forms depends on the time elapsed after injection. After 1 h, respectively, four (one high molecular and three low molecular mass species) and five (one high molecular and four low molecular mass species) vanadium peaks were present in the chromatograms of the Superose 12 and the Superdex Peptide columns. Then 3 h after injection, a different high molecular species showed up in the chromatograms, while the first high molecular and some low molecular mass species disappeared. Vanadium in urine after 8 h occurred as one high (slightly different from the high molecular complex after 3 h) and one low molecular mass complex. However, after 48 h the pattern changed again and vanadium in urine was excreted largely as one low molecular mass species, presumably one of the species that also occurred 1 h after injection but was not present in the period 6-24 h.

Animals↗
PubMed2002

Renal replacement therapies in the aftermath of the catastrophic Marmara earthquake.

BACKGROUND: Renal replacement therapy is of vital importance in the treatment of crush syndrome victims, who are frequently encountered after catastrophic earthquakes. The Marmara earthquake, which struck Northwestern Turkey in August 1999, was characterized by 477 victims who needed dialysis. METHOD: Within the first week of the disaster, questionnaires containing 63 clinical and laboratory variables were sent to 35 reference hospitals that treated the victims. Information considering the features of dialyses obtained through these questionnaires was submitted to analysis. RESULTS: Overall, 639 casualties with renal complications were registered, 477 of whom (mean age 32.3 +/- 13.7 years, 269 male) needed dialysis. Among these, 452 were treated by a single dialysis modality (437 intermittent hemodialysis, 11 continuous renal replacement therapy and 4 peritoneal dialysis), while 25 victims needed more than one type of dialysis. In total, 5137 hemodialysis sessions were performed (mean 11.1 +/- 8.0 sessions per patient) and mean duration of hemodialysis support was 13.4 +/- 9.0 days; this duration was shorter in the non-survivors (7.0 +/- 8.7 vs. 10.0 +/- 9.8 days, P = 0.005). Thirty-four victims who underwent continuous renal replacement therapy had higher mortality rates (41.2 vs. 13.7%, P < 0.0001). Only eight victims were treated by peritoneal dialysis, four of whom also required hemodialysis or continuous renal replacement therapy. The mortality rate in the dialyzed victims was 17.2%, a significantly higher figure compared to the mortality rate of the non-dialyzed patients with renal problems (9.3%; P = 0.015). CONCLUSION: Substantial amounts of dialysis support may be necessary for treating the victims of mass disasters complicated with crush syndrome. Dialyzed patients are characterized by higher rates of morbidity and mortality.

Acute Kidney Injury↗
PubMed2002

P-cresol, a uremic toxin, decreases endothelial cell response to inflammatory cytokines.

BACKGROUND: Infectious diseases are among the most morbid events in uremia. The uremic toxin p-cresol may play a role in the immunodeficiency of uremia by depressing phagocyte functional capacity. Leukocyte adhesion to endothelium, a key event in the immune response, is mediated by endothelial adhesion molecules. These include intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, which are induced by various inflammatory cytokines. We asked whether p-cresol alters endothelial adhesion molecule expression and modifies endothelial/leukocyte adhesion. METHODS: Human umbilical vein endothelial cells (HUVEC) were incubated with p-cresol in the presence or absence of tumor necrosis factor (TNF) or interleukin-1beta (IL-1beta). Thereafter, the endothelial molecules ICAM-1, VCAM-1, and E-selectin were quantitated and the monocyte (THP-1) adhesion to HUVEC measured. RESULTS: P-cresol decreased cytokine-induced protein and mRNA expression of ICAM-1 and VCAM-1. In addition, p-cresol significantly decreased the adhesion of THP-1 to cytokine-stimulated HUVEC. CONCLUSIONS: P-cresol may play a role in the immune defect of uremic patients by inhibiting cytokine-induced endothelial adhesion molecule expression and endothelium/monocyte adhesion.

Antineoplastic Agents↗
PubMed2002

An update on the referral pattern of patients with end-stage renal disease.

This article first describes the epidemiology and reasons of late referal to the nephrologist of patients suffering from end-stage renal disease (ESRD). Depending on the definition, between 25 and 50% of worldwide ESRD patients are referred very late. Second, the relation of late referral to the quality of pre-ESRD care, its impact on the selection of dialysis modality, on the time of start of dialysis and on the use of an adequate vascular access, are discussed. Finally, the economic aspects of late referral are described and ways to improve the referral pattern are proposed.

Costs and Cost Analysis↗
PubMed2002

Behavior of non-protein-bound and protein-bound uremic solutes during daily hemodialysis.

BACKGROUND: In the last few years, renewed interest in daily short hemodialysis (DHD; six 2-hour sessions per week) has become apparent as a consequence of the better clinical outcome of patients treated by this schedule. Uremic syndrome is characterized by the retention of a large number of toxins with different molecular masses and chemical properties. Some toxins are water soluble and non-protein bound, whereas others are partially lipophilic and protein bound. There is increased evidence that protein-bound toxins are responsible for the biochemical and functional alterations present in uremic syndrome, and the kinetics of urea is not applicable to these substances for their removal. The aim of this study is to investigate whether DHD is accompanied by increased removal of non-protein-bound and protein-bound toxins and a decrease in their prehemodialysis (pre-HD) serum levels. PATIENTS AND METHODS: We studied 14 patients with end-stage renal disease treated by standard HD (SHD; three 4-hour sessions per week) for at least 6 months and randomly assigned them to a two-period crossover study (SHD to DHD and DHD to SHD). Patients maintained the same dialyzer, dialysate, and Kt/V during the entire study. At the end of 6 months of SHD and 6 months of DHD, we evaluated hemoglobin levels, hematocrits, recombinant human erythropoietin doses, and pre-HD and post-HD concentrations of serum urea, creatinine, uric acid, and the following protein-bound toxins: 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, p-cresol, indole-3-acetic acid, indoxyl sulfate, and hippuric acid. RESULTS: Values for hemoglobin, hematocrit, and recombinant human erythropoietin dose did not change during the two study periods. Pre-HD concentrations of creatinine, urea, and uric acid decreased on DHD (creatinine, from 8.7 +/- 1.9 to 7.8 +/- 1.6 mg/dL; P < 0.05; urea, from 149.4 +/- 28.8 to 132.7 +/- 40 mg/dL; P = 0.05; uric acid, from 9.14 +/- 1.49 to 8.16 +/- 1.98 mg/dL; P = 0.06). Concerning protein-bound toxins, lower pre-HD levels during DHD were reported for indole-3-acetic acid (SHD, 0.16 +/- 0.04 mg/dL; DHD, 0.13 +/- 0.03 mg/dL; P = 0.01), indoxyl sulfate (SHD, 3.35 +/- 1.68 mg/dL; DHD, 2.85 +/- 1.08 mg/dL; P = 0.02), and p-cresol at the borderline of significance (SHD, 0.96 +/- 0.59 mg/dL; DHD, 0.78 +/- 0.33 mg/dL; P = 0.07). CONCLUSION: Such non-protein-bound compounds as uric acid, creatinine, and urea were removed significantly better by DHD, and pre-HD serum levels were reduced. Furthermore, pre-HD concentrations of some protein-bound solutes, such as indole-3-acetic acid, indoxyl sulfate, and p-cresol, also were lower during DHD.

Creatinine↗
PubMed2002

Acute renal failure due to crush syndrome during Marmara earthquake.

During the earthquake in Marmara, Turkey (August 17, 1999), 87 of 476 victims (18.3%) admitted to Marmara University Hospital (Istanbul, Turkey) experienced renal failure caused by crush injuries. Fifty-nine patients (68%; 40 men, 19 women) required renal replacement therapy (RRT), whereas 28 patients (32%; 20 men, 16 women) recovered renal function under conservative treatment. The aim of the present study is to compare clinical and laboratory data from patients with crush syndrome who needed RRT with those who could be maintained on conservative medical treatment. Data for demographic, clinical, and laboratory findings of patients who had renal problems were collected retrospectively and analyzed. The proportion of men was significantly greater (68% versus 42%; P < 0.05), and time spent under the rubble was significantly shorter (9.4 +/- 6.9 versus 19.1 +/- 22.5 hours; P < 0.05) among patients who required RRT compared with those who recovered under conservative treatment. Patients who required RRT had significantly less urine output in the first 24 hours, underwent more fasciotomies, and needed more blood and fresh frozen plasma transfusions (P < 0.05). Blood urea nitrogen, creatinine, potassium, creatine kinase, and aspartate aminotransferase levels were significantly greater compared with patients managed conservatively both on admission and for the mean of values obtained during the first 2 weeks (P < 0.05). Furthermore, fasciotomies were the most powerful predictors of a later need for RRT. In a similar disaster in the future, these factors should be taken into consideration for priority in referral to medical centers with dialysis facilities.

Acute Kidney Injury↗
PubMed2002

An overview of morbidity and mortality in patients with acute renal failure due to crush syndrome: the Marmara earthquake experience.

BACKGROUND: On August 17, 1999 a major earthquake hit the most densely populated area at the eastern end of the Marmara Sea in northwestern Turkey. The number of documented cases of acute renal failure (ARF) following this event exceeded all similar cases previously reported for any single earthquake. The aim of this report was to provide an overview of the morbidity and mortality of all documented patients with ARF, due to crush injury, that were treated in hospitals with dialysis units following the Marmara earthquake. METHODS: Special questionnaires were sent out to all hospitals with dialysis units known to have admitted earthquake victims with ARF and related crush injuries. Responses to questionnaires from the Turkish Society of Nephrology (TSN) Task Force were collected from 35 hospitals in October 1999. We retrospectively evaluated patients, clinic and laboratory findings, surgical interventions, and frequency and duration of dialysis. Patients who died before or on admission and those with prior chronic renal disease were excluded from the study. RESULTS: A total of 639 patients (291 female and 348 male) with ARF due to crush injury were hospitalized in 35 hospitals. The mean age was 31.6+/-14.7 years and 71.1% were young adults within the range of 16-45 years. 477 patients (74.6%) received one or more dialysis treatments, 162 patients were not dialysed, 15 patients died before dialysis could be instituted, and 147 patients recovered without dialysis treatment. 340 patients were oliguric on admission. The most important abnormalities related to ARF as a result of crush injury morbidity, were oliguria (53.2%), uraemia (94%), high creatinine levels (87%), hyperkalaemia (42%), hyperphosphataemia (63%), hypocalcaemia (83%), and high creatinine phosphokinase levels (73 %). 512 patients had a total of 790 extremity injuries. Eighty-three patients (12.9%) had fractures of the extremities and non-extremity fractures were observed in 59 (9.2%) patients. 323 fasciotomies were performed. Thoracic and abdominal trauma was observed in 110 patients (17.2%). Infection and sepsis were observed in 223 (34.9%) and 121 (18.9%) patients, respectively. Haematologic abnormalities were observed in 197 patients (33%) including 116 with Htc < or =30%. There were pulmonary problems in 96 patients (15%), cardiovascular problems in 198 patients (30.9%), gastrointestinal problems in 23 (3.16%), neurologic problems in 43 (6.7%), and psychiatric problems in 7 (1%) patients. Ninety-seven of the 639 patients with ARF as a result of crush injury died (15.2%), and mortality rates were 17.2 and 9.3% in dialysed and non-dialysed patients, respectively. Findings significantly associated with mortality were sepsis, thrombocytopenia, disseminated intravascular coagulation (DIC), acute respiratory distress syndrome (ARDS), and abdominal and thoracic traumas. CONCLUSIONS: We conclude that in cases of severe disasters such as major earthquakes, patients should be rapidly transferred to undamaged peripheral general hospitals. When proper dialysis and intensive care facilities together with around the clock dedicated human effort are available, crush injury-related ARF patients have a lower mortality. Mortality, when it occurs, is mainly associated with thoracic and abdominal trauma and medical problems such as DIC and/or ARDS/respiratory failure, often in conjunction with sepsis.

Acute Kidney Injury↗
PubMed2002

Clinical findings in the renal victims of a catastrophic disaster: the Marmara earthquake.

BACKGROUND: The clinical course of acute renal failure (ARF) related to crush syndrome is very complex, because of co-existing surgical and/or medical complications. After the devastating Marmara earthquake that struck Turkey in August 1999, 639 patients were identified with nephrological problems, whose clinical findings have been the subject of this analysis. METHODS: Specific questionnaires asking about 63 variables were sent to 35 reference hospitals that treated the victims. Clinical findings of the renal victims were analysed. RESULTS: At admission, high fever was noted in 31.8% of the patients; the temperature of non-survivors was higher (P=0.027). Mean blood pressure was higher in survivors (P=0.004) and dialysed victims (P <0.001). Most (61.4%) patients were oligo-anuric; oliguria lasted for 10.8+/-7.2 days. Thoracic and abdominal traumas were associated with a higher risk of mortality. 397 fasciotomies and 121 amputations were performed in 790 traumatized extremities. Fasciotomies were associated with sepsis (P<0.001) and dialysis needs (P<0.0001), while amputations were associated with mortality (P<0.0001). Medical complications, which were associated with dialysis needs (P<0.0001) and mortality (P<0.0001), were observed in 51.5% of patients. In a multivariate analysis model of medical complications, disseminated intravascular coagulation (DIC) (P<0.0001, OR=5.81), and adult respiratory distress syndrome (ARDS) (P=0.0001, OR=4.53) were predictors of mortality. CONCLUSIONS: In the aftermath of catastrophic earthquakes, clinical findings of the renal victims can predict the final outcome. While fasciotomies indicate dialysis needs, extremity amputations, abdominal and thoracic traumas are associated with higher rates of mortality in addition to DIC and ARDS.

Acute Kidney Injury↗
PubMed2002

The Marmara earthquake: admission laboratory features of patients with nephrological problems.

BACKGROUND: Earthquakes are major causes of morbidity and mortality. North-western Turkey was struck by a devastating earthquake in August 1999, which caused several thousand deaths. Among the most important morbid events in survivors were acute nephrological problems. METHODS: Within the first week of the disaster, specific questionnaires asking about 63 clinical and laboratory parameters were sent to 35 reference hospitals that were treating the victims. Of the registered 639 victims, 423 were admitted within the first 3 days of the disaster; the admission laboratory data of these 423 patients are the subject of this analysis. RESULTS: In the 423 patients (233 males, mean age 31.3+/-14.4 years), time under the rubble was 10.7+/-10.4 h. Mean values at admission were as follows: serum potassium 5.4+/-1.3 mEq/l, creatine phosphokinase 58205+/-77889 IU/l, albumin 2.6+/-0.7 g/dl, phosphorus 5.2+/-1.8 mg/dl, haematocrit 35.0+/-9.3%, leukocyte count 14945+/-6614/mm(3), platelet count 183975+/-134012/mm(3), blood urea nitrogen 55.1+/-28.9 mg/dl, and creatinine 3.9+/-2.3 mg/dl. Serum potassium above 6.5 mEq/l was noted in 91 patients (22.7%), an alarming finding for risk of fatal arrhythmias. Non-survivors were characterized by higher figures of serum potassium (P=0.001), as well as lower haematocrit (P=0.028), platelets (P<0.001), and serum albumin (P=0.003). In a multivariate analysis model of admission laboratory parameters, serum creatinine (P<0.001, o.r.=2.19), potassium (P=0.001, o.r.=3.64), and phosphorus (P=0.004, o.r.=1.78) predicted dialysis needs, whereas serum albumin (P=0.028, o.r.=0.23) and creatinine (P=0.039, o.r.=0.60) were related to mortality. CONCLUSIONS: Admission laboratory data may be useful for predicting dialysis needs and survival chance of disaster victims. High incidences of some life-threatening abnormalities dictate the need for empirical therapy even in the field.

Acute Kidney Injury↗
PubMed2002

In vitro evaluation of motilin agonism by macrolide immunosuppressive drugs.

BACKGROUND: The immunosuppressive drugs tacrolimus and sirolimus may have a stimulatory influence on gastric emptying, in view of their macrolide structure. The aim of this study was to investigate in vitro the possible interaction of tacrolimus and sirolimus with motilin receptors in the rabbit antrum and duodenum. METHODS: Rabbit duodenum strips were mounted under a load of 1 g in 10 ml organ baths containing Krebs solution. Erythromycin, tacrolimus, cyclosporin, and sirolimus were added to the bathing solution in a cumulative way; in a second series, after incubation with cyclosporin (10(-7) mol/l), tacrolimus (10(-8) mol/l), or sirolimus (3 x 10(-8) mol/l), a cumulative concentration-response curve to erythromycin was obtained. The effect of cumulatively added tacrolimus and nle(13)-porcine motilin on the contractile response to electrical field stimulation was tested in strips from the rabbit gastric antrum. Displacement by tacrolimus of (125)I-nle(13)-porcine motilin bound to its receptor was tested with crude homogenates of the smooth-muscle layer of the rabbit antrum. RESULTS: In rabbit duodenum strips, carbachol (10(-5) mol/l) induced a stable and reproducible contraction. Erythromycin induced concentration-dependent contractions. Expressed as a percentage of the response to carbachol, the maximal attained effect was 78%; the EC(50) was 4.8 x 10(-7) mol/l. Tacrolimus (10(-8) to 10(-5) mol/l), cyclosporin (10(-8) to 10(-5) mol/l), and sirolimus (10(-8) to 3 x 10(-5) mol/l) had no influence. The response to erythromycin (10(-8) to 3 x 10(-5) mol/l) in the presence of cyclosporin (10(-7) mol/l), tacrolimus (10(-8) mol/l), or sirolimus (3 x 10(-8) mol/l) did not differ from that obtained with erythromycin alone, except for a decrease of the EC(50) in the presence of tacrolimus (2.2 x 10(-7) mol/l) (P<0.05 vs erythromycin alone). Motilin enhanced the response to electrical field stimulation of rabbit antral strips, but tacrolimus had no stimulatory effect. Tacrolimus weakly displaced motilin bound to its receptor. The pIC(50) was 4.97. CONCLUSIONS: As opposed to erythromycin, neither tacrolimus nor sirolimus showed a contractile effect in the rabbit duodenum. Tacrolimus did not activate the neural motilin receptor of the rabbit gastric antrum and had low affinity for the smooth-muscle motilin receptor. It is thus unlikely that these macrolide immunosuppressive drugs possess gastroprokinetic effects via motilin agonism.

Animals↗