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Norbert Lameire

Publications and source records attributed to Norbert Lameire.

At least 19 recordsLinked to original sources
PubMed2003

Comparative kinetics of the uremic toxin p-cresol versus creatinine in rats with and without renal failure.

BACKGROUND: p-cresol, which is extensively metabolized into p-cresylglucuronide in the rat, is related to several biochemical and physiologic alterations in uremia and is not removed adequately by current hemodialysis strategies. The knowledge of its in vivo kinetic behavior could be helpful to improve the current removal strategies. METHODS: We investigated the kinetic behavior of intravenously injected p-cresol (10 mg/kg) in rats with normal and decreased renal function, and compared the results with those obtained for creatinine (60 mg/kg) under similar conditions. Renal failure was obtained by 5/6 nephrectomy. Both p-cresol and p-cresylglucuronide were analyzed using reversed-phase high-performance liquid chromatography (RP-HPLC). The relation between the p-cresylglucuronide peak height and the underlying amount of p-cresol was determined after hydrolysis of the glucuronide with beta-glucuronidase. We calculated urinary excretion of p-cresol with and without taking p-cresylglucuronide into account. In addition, total, renal, and non-renal clearance, half-life, and volume of distribution were calculated for p-cresol. RESULTS: Over a 4-hour period, p-cresol serum concentration showed only a minimal decline in rats with decreased renal function (t1/2 = 11.7 +/- 0.4 hours), compared to rats with normal renal function (t1/2 = 1.4 +/- 0.7 hours). A similar observation was made for p-cresylglucuronide. In rats with normal renal function, 21.0 +/- 10.0% of the injected p-cresol was excreted in urine as p-cresol and 60.7 +/- 25.0% as p-cresylglucuronide; in rats with renal failure, the respective amounts were 6.7 +/- 7.5% and 32.0 +/- 25.3% (P < 0.05 vs. normal renal function) (total recovery 81.81 +/- 31.07% vs. 38.50 +/- 32.09%, P < 0.05). The volume of distribution of p-cresol was approximately 4 times larger than that of creatinine, but was not significantly affected by renal failure. Not only renal, but also non-renal and total clearance, were much lower in rats with decreased renal function. CONCLUSION: The present data sheds a light on the kinetic behavior of p-cresol in uremic patients; the large volume of distribution, especially, might explain the inadequate dialytic removal of p-cresol. In addition, a substantial amount of p-cresol is removed by metabolism, and both renal and non-renal clearance are disturbed in uremia.

Animals↗
PubMed2003

New insights in uremic toxins.

The retention in the body of compounds, which normally are secreted into the urine results in a clinical picture, called the uremic syndrome. The retention compounds responsible for the uremic syndrome are called uremic toxins. Only a few of the uremic retention solutes fully conform to a true definition of uremic toxins. Uremic patients develop atheromatotic vascular disease more frequently and earlier than the general population. The classical risk factors seem to be less important. Other factors have been suggested to be at play, and among those uremic toxins are mentioned as potential culprits. The identification, classification and characterization of the solutes responsible for vascular problems seems of utmost importance but is far from complete due to a lack of standardization and organization. The European Uremic Toxin Work Group (EUTox) has as a primary aim to discuss, analyze and offer guidelines in matters related to the identification, characterization, analytical determination and evaluation of biological activity of uremic retention solutes. The final aim remains the development of new strategies to reduce the concentration of the most active uremic solutes. These activities will at first be concentrated on reducing factors influencing cardiovascular morbidity and mortality.

Humans↗
PubMed2003

The organization and interventions of the ISN Renal Disaster Relief Task Force.

This article describes first the organization of the ISN Renal Disaster Relief Task Force-European branch founded by the ISN Commission on ARF. The task force aims at rapid dialysis intervention in case of acute disasters associated with a high number of ARF cases caused by crush syndrome. The organization involves European volunteers consisting of nephrologists, dialysis nurses, and technicians willing to go to disaster areas as far as India, the Middle East, and North Africa to assist the local nephrologic communities. In addition, an important role in the organization is played by Médecins sans Frontiières, the industry, and several nurses' and technicians' associations. The major intervention of the task force was at the occasion of the Marmara earthquake in Turkey in 1999. Additional more recent and minor interventions occurred in India and Algeria.

Advisory Committees↗
PubMed2003

Outcome in a post-cardiac surgery population with acute renal failure requiring dialysis: does age make a difference?

BACKGROUND: Acute renal failure (ARF), requiring dialysis (ARF-d), develops in 1-5% of patients undergoing cardiac surgery and is associated with higher in-hospital mortality. Age is one of the known risk factors for the development of ARF. As the ageing population is increasing, the nephrologist will be faced with a large population of elderly patients requiring dialysis following cardiac surgery. The aim of our study was to evaluate the influence of age on and the risk factors for in-hospital mortality. METHODS: Eighty-two patients with ARF following cardiac surgery and requiring dialysis between January 1997 and October 2001 were included. Two groups of patients were studied: the younger population (<70 years, 42 patients, mean age 59+/-10) and an elderly population (>/=70 years, 40 patients, mean age 76+/-4). Severity of disease was evaluated using the SAPS (Simplified Acute Physiology Score), the Liano score and the SHARF (Stuivenberg Hospital Acute Renal Failure) score. RESULTS: Overall mortality in the population with ARF-d was 56.1%. No difference in mortality rate was found between the younger (61.9%) and elderly patient group (50.0%). The two groups were very similar in baseline and procedural characteristics with exception of body weight (P=0.02) and preoperative glomerular filtration rate (P=0.0001). No significant difference was found in the scoring systems between the old and the young (SAPS P=0.52; Liano P=0.96; SHARF T0 P=0.06; SHARF T48 P=0.15). Mortality in the elderly was significantly correlated with hypotension before starting renal replacement therapy (RRT) (P=0.002), mechanical ventilation (P=0.002), presence of multiorgan failure (MOF) (P=0.0001) and higher scores in the severity models (SAPS: P=0.01; Liano: P<0.0001 and SHARF: P<0.0001). CONCLUSION: The outcome in the elderly requiring dialysis due to ARF post-cardiac surgery is comparable with the outcome in a younger population. No significant difference was found in severity of disease between the elderly and the younger. Variables predicting mortality in the elderly are the presence of MOF, mechanical ventilation and hypotension 24 h before starting RRT. These findings indicate that at the time the nephrologist is called for an elderly patient requiring dialysis due to ARF following cardiac surgery, age per se is not a reason to withhold RRT.

Acute Kidney Injury↗
PubMed2003

Urinary excretion of the uraemic toxin p-cresol in the rat: contribution of glucuronidation to its metabolization.

BACKGROUND: Increasing evidence indicates that lipophilic and/or protein-bound substances such as p-cresol are responsible for adverse physiological alterations in uraemic patients. To better understand the evolution of p-cresol disposition in renal failure and dialysis patients, it is necessary to determine its kinetic characteristics and biotransformation pathways. METHODS: We studied the biotransformation of p-cresol after intravenous injection of the compound in eight rats with normal renal function. Urine was collected in four 1 h intervals. To evaluate the presence of p-cresol metabolites, beta-glucuronidase was added to urine samples and the isolated unidentified chromatographic peak observed in previous experiments was submitted to tandem mass spectrometry (MS/MS) analysis. RESULTS: Administration of p-cresol produced a p-cresol peak and an unknown peak, suggesting biotransformation of the compound. Addition of beta-glucuronidase to urine samples and incubation at 37 degrees C resulted in a marked decrease in the unidentified peak height (P<0.001) together with an increase in p-cresol peak height (P<0.001), suggesting that the unidentified peak was composed, at least in part, of p-cresylglucuronide. Mass spectrometry (MS) and MS/MS analysis of the isolated unidentified peak confirmed the presence of p-cresylglucuronide. Linear regression between the peak height of p-cresylglucuronide before enzyme treatment and the increase in p-cresol peak height after enzyme treatment in samples incubated with beta-glucuronidase allowed us to calculate the amount of p-cresylglucuronide as its p-cresol equivalents. This revealed that 64% of the injected p-cresol was excreted as glucuronide. There was no change in peak heights when sulphatase was added to the urine. When p-cresol and p-cresylglucuronide levels were combined, approximately 85% of all administered p-cresol was recovered in the urine. In addition, the combined urinary excretion of p-cresol and p-cresylglucuronide was more than four times greater than excretion of p-cresol by itself (P<0.01). CONCLUSIONS: In rats with normal renal function, intravenous administration of p-cresol results in immediate and extensive metabolization of the compound into p-cresylglucuronide. The elimination of p-cresol from the body depends largely on the urinary excretion of this metabolite.

Animals↗
PubMed2003

Specific characteristics of peritoneal leucocyte populations during sterile peritonitis associated with icodextrin CAPD fluids.

BACKGROUND: Icodextrin dialysate used for peritoneal dialysis contains an iso-molar glucose polymer solution, which provides sustained ultrafiltration over long dwell times and is considered a valuable approach to reduce intraperitoneal glucose exposure. However, several side effects have been described, including abdominal pain and allergic and hypersensitivity reactions. Also, reactions compatible with chemical peritonitis have been reported. Over the period of a few months (January 2002-May 2002), a remarkable increase in the number of continuous ambulatory peritoneal dialysis (CAPD) patients using icodextrin dialysate diagnosed with sterile peritonitis was observed in our unit. METHODS: Five of the CAPD patients using icodextrin dialysate in our unit and diagnosed with sterile peritonitis were screened for leucocyte count and leucocyte differentiation during a follow-up period of 77 +/- 23 days. In addition, expression of CD14, a receptor for lipopolysaccharide (LPS), on the peripheral and peritoneal monocyte population was analysed. These results were compared to CAPD patients suffering from bacterial peritonitis. RESULTS: The peritoneal leucocyte count of CAPD patients using icodextrin dialysate and diagnosed with sterile peritonitis did not decrease significantly before treatment with icodextrin dialysate was interrupted, whereas it currently disappeared within 2-4 days in proven bacterial peritonitis. The sterile, cloudy icodextrin effluent contained an excess of macrophages on the day of diagnosis, whereas in bacterial peritonitis essentially an increase in the granulocyte population was observed. No elevation in the eosinophil population was observed. In contrast to bacterial peritonitis, we observed no increase in CD14 expression on the peripheral and peritoneal macrophages on the day of presentation and during the follow-up period. CONCLUSIONS: Specific batches of the icodextrin CAPD fluids contain a macrophage chemotactic agent, which causes a sustained inflammatory state in the peritoneal cavity. Because no increase in the expression of the LPS receptor CD14 could be observed, the increased peritoneal leucocyte count is probably not caused by LPS or LPS-like (possibly peptidoglycan-like) contamination.

Glucans↗
PubMed2003

Corticosteroids induce expression of aquaporin-1 and increase transcellular water transport in rat peritoneum.

The water channel aquaporin-1 (AQP1) is the molecular counterpart of the ultrasmall pore responsible for transcellular water permeability during peritoneal dialysis (PD). This water permeability accounts for up to 50% of ultrafiltration (UF) during a hypertonic dwell, and its loss can be a major clinical problem for PD patients. By analogy with the lung, the hypothesis was tested that corticosteroids may increase AQP1 expression in the peritoneal membrane (PM) and improve water permeability and UF in rats. First, the expression and distribution of the glucocorticoid receptor (GR) in the PM and capillary endothelium was documented. Time-course and dose-response analyses showed that a daily IM injection of dexamethasone (1 or 4 mg/kg) for 5 d induced an approximately twofold increase in the expression of AQP1 at the mRNA and protein levels. The GR antagonist RU-486 completely inhibited the dexamethasone effect. The functional counterpart of the increased AQP1 expression was a significant increase in sodium sieving and net UF across the PM, contrasting with a lack of effect on the osmotic gradient and permeability for small solutes. The latter observation reflected the lack of effect of corticosteroids on nitric oxide synthase (NOS) activity and endothelial NOS isoform expression in the PM. In conclusion, corticosteroids induce AQP1 expression in the capillary endothelium of the PM, which is reflected by increased transcellular water permeability and UF. These data emphasize the critical role of AQP1 during PD and suggest that pharmacologic regulation of AQP1 may provide a target for manipulating water permeability across the PM.

Animals↗
PubMed2003

Recent concepts in the molecular biology of the peritoneal membrane - implications for more biocompatible dialysis solutions.

This paper reviews some important recent findings on the molecular biology of the peritoneal membrane. It attempts to correlate in vitro and in vivo experimental results with the possible clinical consequences. The most common functional alteration during long-term CAPD is increased peritoneal small-solute transport rate, resulting in impaired ultrafiltration and decreased dialysis efficiency. This contribution first discusses the most relevant advances in the biochemistry and molecular biology of the peritoneal membrane following peritonitis and as consequence of the continuous exposure to unphysiological dialysis fluids. In a second part the preliminary experimental and clinical experience with more biocompatible fluids is summarized. The most relevant structural and functional alterations of the membrane following repeated peritonitis is the consequence of the response of the peritoneum to infective organisms involving the inflammatory cytokines and the interaction between membrane resident cell populations: macrophages, mesothelial cells and fibroblasts. In this setting, human biopsy studies and animal experiments have identified an increase in the peritoneal-associated vasculature, which seems to be the primary cause of increased solute transport. The structural and functional alterations in the membrane in long-term peritoneal dialysis are thought to be the consequence of the toxicity of glucose, either directly or indirectly through the generation of glucose degradation products or the formation of advanced glycation end-products. In particular, an important role for vascular endothelial growth factor and nitric oxide as downstream mediators of the alterations has been suggested. Finally, the last part of this paper reviews the actual and future research aimed at an amelioration of the biocompatibility of the dialysis fluids. Replacing glucose by other osmotic agents, changing the sterilization process, replacing the lactate buffer by bicarbonate, blocking the formation of reactive carbonyl products and of the neoangiogenesis are the most promising changes to enhance the biocompatibility. Finally, gene therapy may in the future have an important contribution. Ex vivo gene therapy involves harvesting peritoneum samples to isolate mesothelial cells that will be genetically modified before re-implantation into the peritoneal cavity.

Animals↗
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

Experimental diabetes induces functional and structural changes in the peritoneum.

BACKGROUND: Peritoneal dialysis (PD) is an established renal replacement therapy in diabetic patients, but the influence of diabetes on the peritoneal membrane (PM) remains debated. We have used functional, biochemical and molecular studies in vivo and in vitro to substantiate the changes induced by diabetes and hyperglycemia in the PM. METHODS: Peritoneal equilibration tests were performed 2, 4, and 6 weeks after induction of diabetes with streptozotocin (STZ) in rats. Morphological analyses, determination of nitric oxide synthase (NOS) activities, and expression studies for NOS isoforms and advanced glycation end products (AGE) were performed in parallel. Additional studies were conducted in diabetic rats treated with insulin, non-diabetic rats fed with urea, and cultured bovine aortic endothelial cells (BAEC). RESULTS: In comparison with controls, diabetic rats were characterized by: increased permeability for small solutes and decreased sodium sieving; capillary proliferation; increased endothelial NOS (eNOS) and AGE immunoreactivity; up-regulation of eNOS and down-regulation of neuronal NOS; and increased NOS activity in the PM. The changes, which culminated at week 6, were prevented by chronic insulin treatment in diabetic rats. In contrast to hyperglycemia, hyperosmolality alone did not induce functional or structural changes in the PM. Studies in BAEC showed that high glucose incubation led to increased activity and expression of eNOS, a prerequisite for vascular proliferation. CONCLUSIONS: These data demonstrate that chronic hyperglycemia is associated with functional and structural changes in the peritoneum that parallel with selective regulation of NOS isoforms and AGE deposits. The alterations are prevented by insulin treatment, which suggests that adequate control of diabetes can preserve PM integrity in diabetic patients prior to PD.

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↗