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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 73 records · Page 4Linked to original sources
PubMed2000

The removal of uremic toxins.

Three major groups of uremic solutes can be characterized: the small water-soluble compounds, the middle molecules, and the protein-bound compounds. Whereas small water-soluble compounds are quite easily removed by conventional hemodialysis, this is not the case for many other molecules with different physicochemical characteristics. Continuous ambulatory peritoneal dialysis (CAPD) is often characterized by better removal of those compounds. Urea and creatinine are small water-soluble compounds and the most current markers of retention and removal, but they do not exert much toxicity. This is also the case for many other small water-soluble compounds. Removal pattern by dialysis of urea and creatinine is markedly different from that of many other uremic solutes with proven toxicity. Whereas middle molecules are removed better by dialyzers containing membranes with a larger pore size, it is not clear whether this removal is sufficient to prevent the related complications. Larger pore size has virtually no effect on the removal of protein-bound toxins. Therefore, at present, the current dialytic methods do not offer many possibilities to remove protein-bound compounds. Nutritional and environmental factors as well as the residual renal function may influence the concentration of uremic toxins in the body fluids.

Creatinine↗
PubMed2000

Delayed gastric emptying in dyspeptic chronic hemodialysis patients.

Hemodialysis patients frequently experience such dyspeptic symptoms as nausea, vomiting, abdominal distension, early satiety, and anorexia. Gastroparesis might be a cause of malnutrition, and parameters of gastric emptying are inversely correlated with serum albumin levels. The aim of the present study is to determine whether delayed gastric emptying is related to dyspeptic symptoms. In 54 hemodialysis patients, a standardized history for dyspeptic symptoms was taken. In addition, gastric emptying for solids was measured in 26 patients, using the (13)C-octanoic acid breath test. There was a high prevalence of dysmotility-like dyspepsia in the hemodialyzed population. A significant difference in gastric emptying between dyspeptic hemodialysis patients and healthy volunteers and between dyspeptic and nondyspeptic hemodialysis patients was shown. There was a significant correlation between gastric emptying and dysmotility-like dyspepsia. Serum albumin level inversely correlated with gastric emptying. In conclusion, there is a high prevalence of dysmotility-like dyspepsia in hemodialysis patients. Dyspeptic patients have significantly delayed gastric emptying compared with both healthy volunteers and nondyspeptic patients.

Adult↗
PubMed2000

Vitamin E-bonded cellulose membrane and hemodialysis bioincompatibility: absence of an acute benefit on expression of leukocyte surface molecules.

Dialysis with unmodified cellulose membranes is associated with such bioincompatibility phenomena as leukopenia, increased expression of adhesion molecules on leukocytes, and release of reactive oxygen species. Dialysis biocompatibility can be improved by modifications in the structure of the cellulose membrane to diminish leukocyte activation and/or protect against the released free oxygen radicals. Excebrane (Terumo Corp, Tokyo, Japan) is a vitamin E-modified cellulose membrane. In the present study, the effect of dialysis with Excebrane membranes on granulocyte and monocyte counts; CD11b, CD11c, and CD45 expression on the surface of granulocytes; and CD14 expression on monocytes was evaluated and compared with low-flux polysulfone membranes. Fifteen minutes after the start of dialysis, granulocytopenia and monocytopenia were more pronounced with the Excebrane membrane compared with polysulfone. The increase in basal expression of CD11b and CD45 on circulating granulocytes was more pronounced during dialysis with Excebrane than polysulfone membranes. Regarding the increased expression on in vitro stimulation with phorbol myristate acetate, blunted upregulation was obtained during dialysis using Excebrane membranes for CD11c and CD45 expression on granulocytes and CD14 expression on monocytes. In conclusion, such indices of membrane bioincompatibility as leukocyte counts and expression of leukocyte surface molecules show more profound alterations with Excebrane than the standard low-flux polysulfone membrane in both basal and in vitro activated states.

Biocompatible Materials↗
PubMed2000

Intradialytic removal of protein-bound uraemic toxins: role of solute characteristics and of dialyser membrane.

BACKGROUND: The efficiency of dialysis membranes is generally evaluated by assessing their capacity to remove small, water-soluble and non-protein-bound reference markers such as urea or creatinine. However, recent data suggest that protein-bound and/or lipophilic substances might be responsible for biochemical alterations characterizing the uraemic syndrome. METHODS: In the present study, the total concentrations of four uraemic retention compounds (indoxyl sulphate, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) and p-cresol) and of tryptophan, the only protein-bound amino acid and a precursor of indoxyl sulphate, were compared with those of urea and creatinine in pre- and post-dialysis serum and in dialysate of 10 patients; two high-flux (HF) membranes (cellulose triacetate (CTA) and polysulphone (PS)) and a low-flux polysulphone (LFPS) membrane were compared in a crossover design, using HPLC. RESULTS: Except for hippuric acid (67.3+/-17.5% decrease), major differences were found in the percentage removal of the classical uraemic markers on one hand (creatinine 66.6+/-7.0% and urea 75.5+/-5.8% decrease) and the studied protein-bound and/or lipophilic substances on the other (indoxyl sulphate, 35.4+/-15.3% and p-cresol 29.0+/-14.2% decrease; tryptophan, 27.5+/-40.3%, and CMPF, 22.4+/-17.5% increase; P<0.01 vs urea and creatinine in all cases). Hippuric acid removal was more pronounced than that of the remaining protein-bound compounds (P<0. 01). After correction for haemoconcentration, per cent increase of tryptophan and CMPF was less substantial, while per cent negative changes for the remaining compounds became more important. There was a correlation between creatinine and urea per cent removal at min 240 (r=0.51, P<0.01), but all the other compounds showed no significant correlation with either of these two. The three membranes were similar regarding the changes of total solute concentrations from the start to the end of dialysis. CONCLUSIONS: Urea and creatinine are far more efficiently removed than the other compounds under study, except for hippuric acid. There are no striking differences between the HF membranes. Moreover, compared with the LF membrane these HF membranes do not appear to be superior in removing the studied compounds.

Aged↗
PubMed2000

New perspectives for prevention/treatment of acute renal failure.

Acute renal failure continues to be a difficult clinical problem in critically ill patients, despite advances in critical care and dialysis. This review focuses on some of the current issues in the nondialytic and dialytic management of these patients. Critical analysis of some still frequently used drugs in these patients such as diuretics and dopamine in so-called 'renal doses' has revealed little beneficial effect. Recent data are in conflict with previous suggestions that biocompatible membranes have a positive effect on the recovery of renal function and on patient mortality. The choice between intermittent haemodialysis and continuous renal replacement therapy should be made on an individual basis and not on the basis of 'dogmatic' opinion.

Journal Article↗
PubMed2000

Effect of regional citrate anticoagulation on leukopenia, complement activation, and expression of leukocyte surface molecules during hemodialysis with unmodified cellulose membranes.

BACKGROUND: Dialysis with complement-activating membranes is associated with leukopenia, which is related to an increased expression of adhesion molecules on leukocytes. Citrate chelates calcium and has been claimed to attenuate leukopenia. METHODS: In this study, the effects of citrate anticoagulation on leukocyte and granulocyte counts, complement activation, and the expression of CD11b, CD11c, and CD45 on the surface of granulocytes were evaluated during hemodialysis with unmodified cellulose membranes. Standard heparin was compared to citrate in three different schedules: citrate was infused to obtain a concentration of either 7 or 10 mmol/l blood. CaCl(2) was administered into the dialyzer outlet at 8. 25 mmol Ca(2+)/h (citrate 10 mmol/l) or at 11 mmol Ca(2+)/h (citrate 7 and 10 mmol/l) to reconstitute the calcium levels in the blood returning to the patient. RESULTS: The use of citrate at a high concentration (10 mmol/l) was associated with a blunted upregulation of CD11b, both at the inlet and at the outlet bloodline; for CD11c a reduced upregulation was observed on granulocytes harvested from the inlet bloodline. No effects of citrate were observed on leukopenia, granulocytopenia, or complement activation. A positive correlation between the decrease in systemic ionized Ca(2+) concentration and the increase in CD11b and CD11c expression was found. CONCLUSION: Citrate/CaCl(2) administration affects leukocyte adhesion molecule expression in a dose-dependent way; however, no significant effect could be demonstrated on leukopenia and complement activation.

Adult↗
PubMed2000

Subclinical hepatic encephalopathy: role of tryptophan binding to albumin and the competition with indole-3-acetic acid.

BACKGROUND: The role of tryptophan (TRY) and its metabolites in the pathogenesis of hepatic encephalopathy is conflicting. The aim of the present study is to investigate in posthepatitis cirrhotic patients with encephalopathy the serum levels of TRY and those of its metabolite indole-3-acetic acid, as well as TRY binding curve to serum albumin and the competition with indole-3-acetic acid. The presence of a relationship between encephalopathy severity and circulating free TRY was also investigated. METHODS: Serum TRY and indole-3-acetic acid were analyzed by HPLC; binding of TRY to serum albumin and the competition with indole-3-acetic acid was studied by equilibrium dialysis. RESULTS: Serum-free TRY was significantly higher in cirrhotic patients (43.33 +/- 14.70 vs 28.87 +/- 8.77 mumol/L, P = 0.02). The binding capacity of albumin was reduced in cirrhotics and further decreased by the addition of indole-3-acetic (K = 6.63 +/- 0.97 x 10(3) mol/L-1, gamma = 1.16 +/- 0.45 x 10(2) mol/L-1 in normal sera vs K = 1.04 +/- 0.20 x 10(3) mol/L-1, gamma = 1.91 +/- 0.92 10(2) mol/L-1 in cirrhotic sera). A multivariate analysis showed that among the psychometric tests the only independent predictor of serum levels of free TRY was the Block Design (R2 = 0.94, B = 0.16 +/- 0.01, beta = 0.97; P < 0.0001). CONCLUSIONS: A high percent ratio of free/total TRY and indoleacetic acid (IAA) was found in cirrhotic patients with hepatic encephalopathy. The concentrations of serum-free IAA and TRY correlated with the degree of subclinical encephalopathy, suggesting a role of these compounds in the development of mental derangement in liver cirrhosis.

Adult↗
PubMed2000

Progression of renal failure in patients with compromised renal function is not always present: evaluation of underlying disease.

BACKGROUND: It has been proposed that, once renal function has been restricted in chronic kidney disease, compensatory hyperfiltration results in a compulsory deterioration of renal function. PATIENTS AND METHODS: In this study, 83 patients originally starting from a serum creatinine (S(crea)) between 2.0 and 5.0 mg/dl were followed for the evolution of renal function. This overall population, with a follow-up (FU) of(M +/- SD) 67 +/- 50 months, was stratified into two groups based upon their slope of 1/S(crea), whereby the median of this slope (-0.0019) was taken as the cut-off value. RESULTS: There was an expected decline of renal function in the group with the lowest slope (group A = progression) whereas renal function remained stable in the group with the highest slope (group B = no progression). This evolution occurred in spite of a similar S(crea) in both groups at the start of the study (group A: 2.45 +/- 0.71 mg/100 ml (n = 41) vs. group B: 2.94 +/- 0.88 mg/100 ml (n = 42); p = ns) and an even higher creatinine clearance in group A (group A: 46.43 +/- 18.65 mg/100 ml(n = 41)vs. group B: 34.03 +/- 20.11 mg/100 ml (n = 42); p = 0.0049). Group B contained a higher number of patients with interstitial nephritis (34/42 = 81% vs. 6/41 = 15%; p < 0.00001) while patients with chronic glomerulopathy could be found especially in group A (23/41 = 56% vs. 8/42 = 19%; p < 0.00001). Proteinuria was continuously higher in group A (start FU: p = 0.0097; FU 72 months: p = 0.0155) and tended to decrease in group B (start FU, 0.89 +/- 1.42 g/l (n = 42) vs. FU 72 months, 0.41 +/- 0.78 g/l (n = 26); p = 0.0474) whereas no significant decrease was observed in group A (start FU, 2.16 +/- 2.83 g/l (n = 41) vs. FU 72 months, 1.77 +/- 0.72 g/l (n = 6); p = ns). CONCLUSION: Within the time limit and patient inclusion criteria of this FU, a compromised renal function does not necessarily result in a further decline. This study points more towards a major role for the underlying nature of renal disease.

Creatinine↗
PubMed2000

Problems and solutions for artificial kidney.

The uremic syndrome is the prototype of a slowly progressive endogenous intoxication, when a detoxifying organ (in this case the kidney) fails. It is characterized by the gradual retention of a host of metabolites, which is in part corrected by dialysis, allowing survival with an acceptable quality of life. This paper reviews the main problems of hemodialysis today, and possible solutions. Adequacy of dialysis is estimated currently from the concentration of urea, which is used as a marker molecule. The problem is that urea is not really toxic by itself. Other markers with known toxicity, such as middle molecules (300-12,000 D) and protein bound compounds should be considered. The question then arises whether the classical dialytic concept based on diffusion should be modified. Adsorptive systems may be strong binders of protein bound solutes. Other concepts that are now arising, and that may add to toxin removal, are slow and daily dialysis. Another question that could be raised is whether it would not be possible to support toxin removal, by administering peroral sorbants. Dialysis patients are prone to vascular disease and die early from cardio-vascular complications. One of the solutions for this problem could be to bring the blood of dialyzed patients into contact with antioxidants (e.g. vitamin C or E). The risk for perdialytic hemodynamic instability is increased in many dialysis patients. The ideal solution would be to develop an "intelligent" dialysis system, whereby blood volume and plasma osmolality are sensed continuously, and ultrafiltration and dialysate sodium concentration are adapted in function of this evolution. An adequate vascular access is indispensable to perform adequate dialysis, but thrombotic/stenotic complications are frequent. This could be prevented by molecular biological modification of vascular grafts, whereby genetic information is entered into the cells, blocking the natural chain of events that otherwise unavoidably leads to neointimal hyperplasia and atherosclerosis. Another old dream is to develop a wearable artificial kidney, whereby patients can move around, and be treated 24 hours per 24 hours, in stead of being treated intermittently at a specific location by the dialysis machine. According to some authors, part of the natural renal function could be replaced by cultured renal tubular cells, which are brought in contact with the blood of the patients. It is concluded that thrilling improvements lie ahead in the future, but the following questions arise: 1) What is the cost of all these improvements? 2) Will it remain possible to reimburse all this? 3) What is going to happen in transplantation, mainly regarding improvements in immunosuppression and the development of xenotransplantation?

Forecasting↗
PubMed1999

Study by means of high-performance liquid chromatography of solutes that decrease theophylline/protein binding in the serum of uremic patients.

Substantial changes in protein binding of drugs occur during the progression of renal insufficiency. Protein-bound uremic solutes play a role in the inhibition of drug protein binding. We previously demonstrated that hippuric acid in uremic ultrafiltrate was an inhibitor of the theophylline protein binding. The present study was undertaken to extend the yield of protein-bound uremic solutes by displacing ligands in uremic serum from their binding sites by five deproteinization methods. The inhibitory effect on theophylline protein binding of the deproteinized uremic serum was higher than with ultrafiltrate (p < 0.05). The influence of 30 semi-preparative HPLC fractions from deproteinized uremic serum on the theophylline protein binding was evaluated to identify the responsible compounds and to compare their relative individual impact. The theophylline protein binding was calculated as a percentage (bound versus total). The most important decrease of the protein binding was observed in HPLC fractions 6, 10 to 13, 15 and 28 with protein binding of: 61.5 +/- 10.8, 64.5 +/- 7.6, 60.9 +/- 10.1, 47.5 +/- 3.3, 60.0 +/- 6.7, 60.7 +/- 6.3 and 61.3 +/- 6.9%, respectively versus 69.1 +/- 2.4% for control serum (p < 0.05). The responsible compounds were characterized in the fractions by co-elution: 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF), indole-3-acetic acid, indoxyl sulfate, hippuric acid, p-hydroxyhippuric acid and tryptophan. Their concentration was determined by analytical HPLC and a solution containing these compounds at the same concentration as in deproteinized uremic serum was composed. This solution was added to control serum and decreased the theophylline protein binding from 69.0 +/- 4.4% to 61.3 +/- 1.3%, which was less important than in genuine uremic serum (44.4 +/- 3.8%, p < 0.05). Dose-response curves with the characterized compounds revealed that the most important role in binding inhibition could be attributed to hippuric acid and CMPF. Our data suggests that the yield of protein binding inhibiting compounds is more important with deproteinized uremic serum than with uremic ultrafiltrate. The identified uremic compounds are not entirely representative for the decreased protein binding of theophylline, indicating that additional factors than those identified in this study affect the protein binding as well.

Blood Proteins↗
PubMed1999

Reduced incidence of acute renal graft failure in patients treated with peritoneal dialysis compared with hemodialysis.

In a case-control study performed in two centers, the incidence of delayed graft function (DGF), defined as the necessity to perform dialysis after transplantation, was analyzed according to prior treatment with continuous ambulatory peritoneal dialysis (CAPD; n = 117) or hemodialysis (HD; n = 117). The patients were matched for age, sex, HLA compatibility, and cold ischemia time. The patients were followed up for 6 months to monitor renal graft function (serum creatinine [Screa] level immediately after transplantation, at 6 weeks, at 6 months) and postoperative complications. No significant differences were found in the warm ischemia time of the graft or previous time on dialysis. DGF occurred in 27 CAPD patients (23.1%) and 59 HD patients (50.4%; P < 0.0001). The decline in Screa level after transplantation was faster in CAPD patients: the time for Screa level to decrease 50% after transplantation (T1/2Screa) was reached after 5.0 +/- 6.6 days in the CAPD group compared with 9.8 +/- 11.5 days in the HD group (P < 0.0001). A greater number of patients developed acute rejection episodes in the CAPD group (P < 0. 05), but Screa level was not different in the two groups 6 weeks and 6 months after transplantation. No differences were observed in infectious or surgical complications. This study shows that immediate renal function after transplantation is better in CAPD patients and that peritoneal dialysis should be considered as a first choice for pretransplantation therapeutic modality.

Adult↗