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Raymond Vanholder

Publications and source records attributed to Raymond Vanholder.

At least 37 records · Page 2Linked to original sources

In vivo distribution and fractionation of indium in rats after subcutaneous and oral administration of [(114m)In]InAs.

Two in vivo experiments were carried out in this study. In the first experiment five rats were given two subcutaneous injections of [(114m)In]InAs. Major sites of accumulation were spleen, liver and kidney. The intracellular distribution of indium was examined by differential centrifugation. The cytoplasmic fraction contained most of the indium activity followed by the mitochondrial fraction. Both outcomes are in close agreement with the results obtained in previous studies. Chromatographic separations on a preparative size exclusion column were carried out. It was shown that indium was mostly bound to high molecular mass compounds in serum and in the cytoplasmic fraction of spleen, liver and kidney. In a second experiment five rats were given four oral doses of [(114m)In]InAs over a short period. Prior to this experiment the in vitro solubility of cold InAs in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) was determined using graphite furnace atomic absorption spectroscopy. In the case of the SGF only 1.3% of an InAs suspension dissolved after 48 hours incubation at 37 degrees C. InAs was not soluble in SIF. Uptake of InAs after oral administration was minimal (<1%). Due to incomplete removal of traces of [(114m)In]InAs from the gastrointestinal tract, it was impossible to calculate accurately the in vivo distribution over the different organs. As the uptake and consequently the activity in the organs were very low, no further chromatographic separations could be carried out. Considering this very low uptake, it can be concluded that InAs will not accumulate in the body after oral exposure.

Administration, Cutaneous↗

Efficacy of erythropoietin administration in the treatment of anemia immediately after renal transplantation.

Anemia negatively impacts cardiovascular comorbidity and hospitalization. In animals, recombinant erythropoietin (RhuEPO) leads to faster recovery after acute tubular necrosis. This study evaluates the effect of RhuEPO (Recormon, Hoffman-La Roche, Basel, Switzerland) on the correction of anemia and kidney function after renal transplantation. Patients receiving a renal transplant were randomized to receive or not receive RhuEPO 100 U/kg three times per week if the hemoglobin (Hb) level was less than 12.5 g/dL. The time to reach an Hb level greater than 12.5 g/dL was 66.5+/-14.5 days versus 52.6+/-23.7 days in the non-EPO and EPO groups, respectively (P=0.05). After 3 months, Hb levels were not different between the non-EPO and EPO groups (12.6+/-1.5 g/dL vs. 12.0+/-1.5 g/dL, respectively), although there was a higher increase in the EPO group (4.1+/-1.1 g/dL vs. 3.2+/-1.1 g/dL, P=0.02). In a Cox regression analysis, EPO use (relative risk 7.2, P=0.004) and dose (relative risk=0.63, P=0.04) were retained as independent variables predicting the time to reach an Hb level greater than 12.5 g/dL. In the EPO group, 14 of 22 patients reached the target Hb level of more than 12.5 g/dL versus 12 of 18 patients in the non-EPO group (P=not significant). Serum creatinine levels were not different between groups. RhuEPO in the immediate posttransplantation period seems to have no relevant clinical impact on the correction of anemia. There was no difference in the evolution of serum creatinine levels. In view of the cost, the use of RhuEpo in the posttransplantation period should be limited to high-risk patients.

Anemia↗

Uridine adenosine tetraphosphate: a novel endothelium- derived vasoconstrictive factor.

Beyond serving as a mechanical barrier, the endothelium has important regulatory functions. The discovery of nitric oxide revolutionized our understanding of vasoregulation. In contrast, the identity of endothelium-derived vasoconstrictive factors (EDCFs) remains unclear. The supernatant obtained from mechanically stimulated human endothelial cells obtained from dermal vessels elicited a vasoconstrictive response in an isolated perfused rat kidney. A purinoceptor blocker had a greater effect than an endothelin receptor blocker in decreasing endothelially derived vasoconstriction in the isolated perfused rat kidney. The nucleotide uridine adenosine tetraphosphate (Up(4)A) was isolated from the supernatant of stimulated human endothelium and identified by mass spectrometry. Up(4)A is likely to exert vasoconstriction predominantly through P2X1 receptors, and probably also through P2Y2 and P2Y4 receptors. Plasma concentrations of Up(4)A that cause vasoconstriction are found in healthy subjects. Stimulation with adenosine 5'-triphosphate (ATP), uridine 5'-triphosphate (UTP), acetylcholine, endothelin, A23187 and mechanical stress releases Up(4)A from endothelium, suggesting that Up(4)A contributes to vascular autoregulation. To our knowledge, Up(4)A is the first dinucleotide isolated from living organisms that contains both purine and pyrimidine moieties. We conclude that Up(4)A is a novel potent nonpeptidic EDCF. Its vasoactive effects, plasma concentrations and its release upon endothelial stimulation strongly suggest that Up(4)A has a functional vasoregulatory role.

Adenine Nucleotides↗

Disseminated Mycobacterium avium complex infection in a renal transplant patient.

Organ transplant recipients are at an increased risk of developing opportunistic infections due to prolonged immunosuppression. We present the case of a renal transplant recipient with severe CD4 lymphopenia who developed disseminated Mycobacterium avium complex infection. Recovery from infection was paralleled by a progressive increase in CD4 lymphocytes. T lymphocyte subsets are not monitored routinely in organ transplants but may identify patients at risk of developing serious infectious complications.

Journal Article↗

Efficiency of the Genius batch hemodialysis system with low serum solute concentrations: the case of lithium intoxication therapy.

BACKGROUND: The Genius batch system consists of a 90-L closed reservoir, from which fresh dialysate is extracted at the top and to which spent dialysate is returned at the bottom. It was shown in long-term hemodialysis patients that almost the entire amount of unspent dialysate can be used before contamination of fresh with spent dialysate occurs. Separation is caused by differences in density, partly because of the presence of uremic solutes in spent dialysate. The question is raised whether this separation can be maintained during dialysis of patients who experience an intoxication without renal failure. METHODS: A patient intoxicated with lithium was dialyzed using the Genius system, prepared at 37 degrees C, during 300 minutes. With dialysate flow set at 300 mL/min (5 mL/s) and in the absence of mixing, urea is not expected at the inlet dialysate tubing before minute 300. RESULTS: In the dialysate inlet tubing, an abrupt increase in lithium and urea concentrations was observed 210 minutes after the start of the session, reflecting contamination of fresh with spent dialysate. At minute 210, only 60.9 L of 90 L of dialysate had crossed the dialyzer. In a control dialysis treatment in a patient with marked renal failure, this mixing occurred only at 300 minutes. CONCLUSION: In the present observation, it is shown that during Genius dialysis in a patient without renal failure, an earlier contamination of fresh with spent dialysate can occur, compared to conditions of renal failure.

Adult↗

Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.

BACKGROUND: Although patients with renal failure retain a large variety of solutes, urea is virtually the only currently applied marker for adequacy of dialysis. Only a limited number of other compounds have up until now been investigated regarding their intradialytic kinetics. Scant data suggest that large solutes show a kinetic behavior that is different from urea. The question investigated in this study was whether other small water-soluble solutes, such as some guanidino compounds, show a kinetic behavior comparable or dissimilar to that of urea. METHODS: This study included 7 stable conventional hemodialysis patients without native kidney function undergoing low flux polysulphone dialysis (F8 and F10HPS). Blood samples were collected from the inlet and outlet bloodlines immediately before the dialysis session, after 5, 15, 30, 120 minutes, and immediately after discontinuation of the session. Plasma concentrations of urea, creatinine (CTN), creatine (CT), guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), and methylguanidine (MG) were used to calculate corresponding dialyzer clearances. A two-pool kinetic model was fitted to the measured plasma concentration profiles, resulting in the calculation of the perfused volume (V(1)), the total distribution volume (V(tot)), and the intercompartmental clearance (K(12)); solute generation and overall ultrafiltration were determined independently. RESULTS: No significant differences were observed between V(1) and K(12) for urea (6.4 +/- 3.3 L and 822 +/- 345 mL/min, respectively) and for the guanidino compounds. However, with respect to V(tot), GSA was distributed in a smaller volume (30.6 +/- 4.2 L) compared to urea (42.7 +/- 6.0L) (P < 0.001), while CTN, CT, GAA, G, and MG showed significantly higher volumes (54.0 +/- 5.9 L, 98.0 +/- 52.3 L, 123.8 +/- 66.9 L, 89.7 +/- 21.4 L, 102.6 +/- 33.9 L, respectively; P= 0.004, = 0.033, = 0.003, < 0.001, = 0.001, respectively). These differences resulted in divergent effective solute removal: 67% (urea), 58% (CTN), 42% (CT), 76% (GSA), 37% (GAA), 43% (G), and 42% (MG). CONCLUSION: The kinetics of the guanidino compounds under study are different from that of urea; hence, urea kinetics are not representative for the removal of other uremic solutes, even if they are small and water-soluble like urea.

Aged↗

Dialysate partitioning in the Genius batch hemodialysis system: effect of temperature and solute concentration.

BACKGROUND: The Genius batch system contains a 75-L closed reservoir from which fresh dialysate is extracted at the top, and to which spent dialysate is returned at the bottom. In vivo studies have demonstrated that almost the entire amount of dialysate can be used before contamination of fresh with spent dialysate occurs. The question is raised whether density differences cause this separation, and what the relative contributions of temperature and solute content are. METHODS: As patient substitute, a container filled with dialysate was loaded with various amounts of urea. Temperature differences between spent and fresh dialysate were imposed by not heating the dialysate at the outlet line from the dialyzer (A), heating the outlet to obtain continuously equal temperatures at inlet and outlet (B), or to temperatures as in vivo (C). With a dialysate flow set at 300 mL/min, urea is not expected at the inlet before 250 minutes. RESULTS: With a urea concentration of 33 mg/dL, urea contamination at the dialysate inlet line occurred after 185 +/- 20 (A), 122 +/- 11 (B), and 175 +/- 12 minutes (C) of dialysis, whereas with 67 mg/dL, this happened at 219 +/- 5 (A), 162 +/- 11 (B), and 202 +/- 8 minutes (C). With 100 and 150 mg/dL, urea contamination appeared at 224 +/- 2 (A) and 204 +/- 14 minutes (B), and 227 +/- 5 (A) and 232 +/- 3 minutes (B), respectively. CONCLUSION: Both temperature differences between spent and fresh dialysate and solute content of spent dialysate contribute to dialysate partitioning in the Genius dialysis system.

Dialysis Solutions↗

Chronic kidney disease: a European perspective.

There is an exponential growth worldwide of patients with end-stage renal disease (ESRD). Prevalences, outcomes, and underlying causes of ESRD are relatively well documented through different organizations. It is, however, clear that a large part of the bad outcome of ESRD patients is due to deficient follow-up during the earlier chronic kidney disease (CKD) stages. Data on CKD, prevalence of the different stages, and the evolution to ESRD are rather scant, and available data are conflictive. This is at least partly due to the lack of an international standard for measurement of renal function. In addition, there is compiling evidence that presence of proteinuria, even with a normal renal function, predisposes to ESRD. Most authors now prefer the term "kidney injury" rather than "kidney failure" to indicate people at risk for evolution to ESRD or for complications of CKD. Detection of these patients at risk is important to implement measures to slow down progression of CKD and avoid secondary complications. As it is clear that most of these CKD patients die before they reach ESRD, it might be that by taking the necessary preventive measures, the number of ESRD patients might still further increase exponentially.

Adult↗

Survival and complications of indwelling venous catheters for permanent use in hemodialysis patients.

BACKGROUND: The risk factors influencing the survival of indwelling central vein catheters and their potential complications have not been assessed in depth and on a large scale. METHODS: We investigated the general characteristics of 245 single lumen cuffed tunneled catheters and analyzed their survival by Kaplan-Meier and Cox regression analysis. Risk factors for bacteremia and thrombosis were assessed by logistic regression analysis. RESULTS: The incidence of exit-site infection, tunnel infection, bacteremia and thrombotic events was 0.35, 0.25, 1.71, and 1.94/1000 catheter days, respectively. The mean survival time per catheter was 276 days. After censoring for non catheter-related events leading to the removal of the catheter (n = 245 with 120 catheters censored and 125 events), the mean survival time of the catheter appeared to be 615 +/- 67 days (95% CI of 483-747) and the median survival time 310 +/- 50 days (95% CI of 212-408). The localization of the catheter into the right internal jugular vein results in significantly better survival as compared with other insertion sites both in Kaplan-Meier (mean survival of 650 days compared to a mean survival of 519 days, P value < 0.009) and in Cox regression analysis (relative risk of 0.537, P value < 0.001). Localization of the catheter into the right internal jugular vein seemed to increase the risk for bacteremia (relative risk of 1.798, P value of 0.063). The use of anticoagulant agents was not protective for thrombosis, although this might be due to lack of power (relative risk of 0.626, P value of 0.141). CONCLUSION: We provide evidence of a mean survival in long-term hemodialysis catheter close to 2 years with an acceptable complication rate. If a long-term hemodialysis catheter is required, it is best placed in the right internal jugular vein.

Catheters, Indwelling↗

The European artificial organ scene: present status.

This article summarizes the current evolutions regarding artificial organs in Europe. The review emanates from the activities by four of the work groups of the European Society for Artificial Organs (ESAO) and is essentially based on the reports by these work groups at the latest ESAO meeting in Warsaw, Poland (2004). The topics are: apheresis, heart support, liver support, uremic toxins.

Artificial Organs↗

A new initiative in nephrology: 'Kidney disease: improving global outcomes'.

The burden of kidney disease: Improving global outcomes. Chronic kidney disease (CKD) is a worldwide public health problem with an increasing incidence and prevalence of patients requiring replacement therapy. There is an even higher prevalence of patients in earlier stages of CKD, with adverse outcomes such as kidney failure, cardiovascular disease, and premature death. Patients at earlier stages of CKD can be detected through laboratory testing and their treatment is effective in slowing the progression to kidney failure and reducing cardiovascular events. The evidence-based care of these patients are universal and independent of their geographic location. This paper describes the need to develop a uniform and global public health approach to the worldwide epidemic of CKD. It is to this end that a new initiative Kidney Disease: Improving Global Outcomes' has been established. Some current and future activities of this initiative are described. They include among others modification of the classification of CKD, the development of guidelines on hepatitis C, the organisation of consensus conferences like on Renal Osteodystrophy, and the creation of a website allowing the comparison of the five main English language clinical practice guidelines in kidney disease worldwide.

Chronic Disease↗

Improving salt balance in peritoneal dialysis patients.

Volume homeostasis is an important predictor of outcome in peritoneal dialysis. Because volume retention is driven by salt retention, maintenance of salt balance should be a concern to all nephrologists. An important factor in this is dietary salt restriction. This has long been neglected in peritoneal dialysis patients, where it was considered that the continuous nature of the therapy and residual renal function would be sufficient to remove any extra salt load. In patients with preserved renal function, diuresis and salt excretion can be enhanced by the application of high doses of loop diuretics. This practice seems not to have an impact on the further deterioration of renal function. Peritoneal salt removal can be enhanced using polyglucose. Also, the use of low sodium-containing dialysate can be efficient. These solutions are, however, not commercially available, and they need higher concentrations of glucose to obtain an efficient osmolarity. It should always be considered that, due to sodium sieving over the ultrasmall pores, fluid and salt removal are not always concordant.

Diet, Sodium-Restricted↗

Pathophysiology of ischaemic acute renal failure.

This chapter summarizes the pathophysiology of ischaemic acute renal failure from both the experimental and clinical points of view. Traditionally, the abrupt fall in glomerular filtration rate (GFR) is thought to be due to an interplay of haemodynamic and tubular abnormalities. The intrarenal haemodynamic alterations include renal vasoconstriction, leukocyte-endothelium interactions and loss of blood flow and GFR autoregulation. During recent years it has become evident that pronounced outer medulary ischaemia makes an important contribution. In severe and prolonged ischaemia, the tubular epithelial cells can undergo either sublethal or lethal cell damage. Cell death occurs by necrosis and apoptosis. The different mechanisms of post-ischaemic cell damage are discussed. The post-ischaemic kidney also shows a dramatic capacity for recovery. During this recovery phase some of the damaged cells undergo de-differentiation--which is an important step in regeneration of the tubular epithelium. Recent evidence points to the possibility that infiltration of the kidney with bone-marrow-derived stem cells contributes to the repair process. The molecular mechanisms and the effect of growth factors are summarized.

Acute Kidney Injury↗

Clinical characteristics of patients developing ARF due to sepsis/systemic inflammatory response syndrome: results of a prospective study.

BACKGROUND: Acute renal failure (ARF) in patients with sepsis provokes high mortality and financial cost. In this prospective study, we collected characteristics of patients in the intensive care unit (ICU) who developed sepsis/systemic inflammatory response syndrome (SIRS) to analyze differences between those who subsequently did or did not develop ARF. METHODS: All patients admitted to the ICU of the University Hospital Gent, Belgium, between January 1, 2001, and December 31, 2001, who developed sepsis/SIRS were included if they had a serum creatinine level less than 2 mg/dL (<177 micromol/L). RESULTS: Of 2,442 patients admitted to the ICU, 257 patients developed sepsis/SIRS. Of those, 29 patients (11%) developed ARF. In a univariate analysis, age, central venous pressure (CVP), and serum creatinine and blood urea nitrogen levels were greater (P = 0.003, P = 0.006, P < 0.001, and P < 0.001, respectively), whereas mean arterial and diastolic blood pressures, 24-hour urinary output, arterial pH, bicarbonate level, thrombocyte count, albumin level, and prothrombin time were lower (P = 0.05, P = 0.004, P = 0.005, P = 0.03, P = 0.009, P = 0.037, P = 0.05, and P = 0.006, respectively) in the ARF group. Prevalence of diabetes, sex, and need for ventilation were not different between the ARF and no-ARF groups, but in the ARF group, diuretic use, vasopressor use, and presence of primary hepatic failure were more prevalent (P = 0.001 for each). In a multivariate analysis, age, serum creatinine level, CVP, and presence of liver failure significantly contributed to a logistic regression model for ARF. CONCLUSION: Several parameters already were disturbed at the first day of SIRS/sepsis in patients who later developed ARF. Older age, elevated serum creatinine level despite elevated CVP, and presence of hepatic failure are predictive for ARF in septic patients.

Acute Kidney Injury↗

Interleukin/cytokine profiles in haemodialysis and in continuous peritoneal dialysis.

The uraemic syndrome is a complex condition that results from the retention of "waste" compounds that normally would be excreted into the urine or catabolized by the kidneys. In addition, inflammation has been implicated in symptoms associated with uraemia, including its role in the malnutrition-inflammation-atherosclerosis syndrome. Regarding vascular disease, traditional risk factors such as hypertension and gender do not seem to have the same significance in the uraemic population compared with patients without renal failure, and so the possibility has been raised that the uraemic toxins that result in the uraemic syndrome could play a role in this process. In this review, various questions are addressed regarding the involvement of cytokines in uraemia and the effects of dialysis membranes and fluids in patients receiving haemodialysis or peritoneal dialysis on cytokine levels. The effects of non-dialysis-related factors on levels of cytokines, mortality rates and other uraemic disorders are also discussed. It is concluded that cytokines are undoubtedly retained in uraemia, and that the loss of renal excretion almost certainly plays a key role in this process. Many cytokines have a pro-inflammatory role, probably resulting in a number of clinical events that are related to the increased morbidity and mortality of uraemic and haemodialysis patients. Any adjustment of the subtle balance between pro- and anti-inflammation by medical interventions should be conducted carefully because of an enhanced risk of serious infectious episodes. Bioincompatibility of dialysis techniques probably enhances the generation of cytokines as well as other uraemic toxins.

Cytokines↗

Features of chronic hemodialysis practice after the Marmara earthquake.

After disasters, treatment of chronic hemodialysis (HD) patients is problematic because of logistic and medical reasons. This study analyzes features of HD practice in the regions affected by the Marmara earthquake that struck northwestern Turkey in August 1999. Questionnaires asking about HD infrastructure, medical/social problems of chronic dialysis patients, and the fate of dialysis personnel after the disaster were sent to dialysis units located in the affected region. Data gathered from eight HD centers that responded to questionnaires were then analyzed. The number of HD centers and machines were 12 and 124, respectively, before the earthquake. The number of weekly HD sessions in the analyzed eight centers declined from 1093 before the disaster to 520, 616, and 729 1 wk, 1 mo, and 3 mo after the earthquake, respectively. In the effective seven centers, the number of HD personnel was 112 before the earthquake, which dropped to 86 and 94 1 and 3 mo after the disaster, respectively. Overall, there were 439 patients in the analyzed eight centers before the disaster, whereas data were provided on 356 (212 were male; mean age, 47.6 +/- 15.1 yr) dialysis patients. Six patients died, and seven were seriously and 28 mildly injured by the direct effects of trauma. The percentage of patients who received once-weekly dialysis increased from 2.3 to 7.2% within the first week, with a return to lower figures (4.1 and 2.8%) 1 and 3 mo afterward. Despite a decrease in the number of HD sessions, interdialytic weight gain decreased 1 wk after the disaster and BP measurements did not change significantly before and after the earthquake. A total of 301 and 31 patients left their dialysis centers, temporarily and permanently. After catastrophic earthquakes, despite a decrease in the number of HD sessions, patients comply with disaster conditions, likely by strictly following dietary and fluid restrictions.

Adolescent↗

Delayed graft function in renal transplantation.

PURPOSE OF REVIEW: Delayed graft function is an important determinant of patient and graft survival. A complex of pathologic mechanisms intervenes in the pathophysiology of this outcome. This paper reviews the main processes involved in delayed graft function as they relate to five chronologically related stages: donor tissue quality, brain death and related stress, preservation variables, immune factors, and recipient variables. RECENT FINDINGS: Dialyzed delayed graft function and nondialyzed slow graft function both have a negative impact on graft survival and on the incidence of acute rejection. Expanded-criteria donors, older donors, and non-heart-beating donors are more frequently used. The long-term results of the use of well-selected non-heart-beating donors are surprisingly good. The process of ischemia/reperfusion injury is already initiated in the brain-death donor and continues during preservation of the graft. Graft-infiltrating T cells, heat shock proteins, and heme oxygenase-1 are implicated in the process. Modifications in immunosuppressive therapy and pharmacologic modulations have an effect on delayed graft function. Delayed graft function plays a part in the incidence of acute rejection, impaired graft function, and survival of patients and grafts. SUMMARY: This review discusses the current literature on several recent findings of pathophysiologic mechanisms of, and possible therapeutic interventions in, delayed graft function.

Age Factors↗