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Biomedical subjects

Raymond Vanholder

Publications and source records attributed to Raymond Vanholder.

At least 19 recordsLinked to original sources
PubMed2007

The glomerular filtration rate in an apparently healthy population and its relation with cardiovascular mortality during 10 years.

AIMS: Moderate-to-severe chronic renal failure is an established risk factor for cardiovascular disease and mortality. However, most studies have been performed in selected populations and the impact of very small decrements of renal function on long-term cardiac morbidity and mortality has not yet been established. Also, the cut-off level of glomerular filtration rate (GFR) from which cardiovascular risk increases has not exactly been established. This study wants to address these questions. METHODS AND RESULTS: Ten year follow-up of a representative population-based cohort comprised 8913 randomly selected, apparently healthy participants. Participants were randomly drawn from Belgian voting lists. Cardiovascular risk factors were noted. Serum creatinine values were corrected to isotope dilution mass spectrometry standard, and GFR was calculated using the recently modified 'modification of diet in renal disease' equation. Participants were followed for 10 years, and cause-specific death was registered by analysis of death certificates. The probability to die from all causes or from cardiovascular causes during the 10 year follow-up period increased in each quartile of GFR, even after correction for different other comorbid conditions. CONCLUSION: Even mild renal failure is an independent risk factor for cardiovascular mortality within 10 years in an apparently healthy unselected population. This detrimental effect starts already at a relatively high GFR of 90 mL/min/1.73 m2 and remains present after correction for other established cardiovascular risk factors.

Cardiovascular Diseases↗
PubMed2006

Mass-spectrometric identification of a novel angiotensin peptide in human plasma.

OBJECTIVE: Angiotensin peptides play a central role in cardiovascular physiology and pathology. Among these peptides, angiotensin II (Ang II) has been investigated most intensively. However, further angiotensin peptides such as Ang 1-7, Ang III, and Ang IV also contribute to vascular regulation, and may elicit additional, different, or even opposite effects to Ang II. Here, we describe a novel Ang II-related, strong vasoconstrictive substance in plasma from healthy humans and end-stage renal failure patients. METHODS AND RESULTS: Chromatographic purification and structural analysis by matrix-assisted laser desorption/ionisation time-of-flight/time-of-flight (MALDI-TOF/TOF) revealed an angiotensin octapeptide with the sequence Ala-Arg-Val-Tyr-Ile-His-Pro-Phe, which differs from Ang II in Ala1 instead of Asp1. Des[Asp1]-[Ala1]-Ang II, in the following named Angiotensin A (Ang A), is most likely generated enzymatically. In the presence of mononuclear leukocytes, Ang II is converted to Ang A by decarboxylation of Asp1. Ang A has the same affinity to the AT1 receptor as Ang II, but a higher affinity to the AT2 receptor. In the isolated perfused rat kidney, Ang A revealed a smaller vasoconstrictive effect than Ang II, which was not modified in the presence of the AT2 receptor antagonist PD 123319, suggesting a lower intrinsic activity at the AT1 receptor. Ang II and Ang A concentrations in plasma of healthy subjects and end-stage renal failure patients were determined by matrix-assisted laser desorption/ionisation mass-analysis, because conventional enzyme immunoassay for Ang II quantification did not distinguish between Ang II and Ang A. In healthy subjects, Ang A concentrations were less than 20% of the Ang II concentrations, but the ratio Ang A/Ang II was higher in end-stage renal failure patients. CONCLUSIONS: Ang A is a novel human strong vasoconstrictive angiotensin-derived peptide, most likely generated by enzymatic transformation through mononuclear leukocyte-derived aspartate decarboxylase. Plasma Ang A concentration is increased in end-stage renal failure. Because of its stronger agonism at the AT2 receptor, Ang A may modulate the harmful effects of Ang II.

Aged↗
PubMed2006

P-cresylsulphate, the main in vivo metabolite of p-cresol, activates leucocyte free radical production.

BACKGROUND: Chronic renal insufficiency is associated with the retention of solutes normally excreted by healthy kidneys. P-cresol, a prototype protein-bound uraemic retention solute, has been shown to exert toxic effects in vitro. Recently, however, it has been demonstrated that p-cresol in the human body is conjugated, with p-cresylsulphate as the main metabolite. METHODS: The present study evaluates the effect of p-cresylsulphate on the respiratory burst activity of leucocytes. RESULTS: P-cresylsulphate significantly increased the percentage of leucocytes displaying oxidative burst activity at baseline. Oxidative burst activity of stimulated leucocytes was however not affected. In contrast, p-cresol had no effect on the leucocytes at baseline, but inhibited leucocytes burst activity after stimulation. CONCLUSION: The present study demonstrates, for the first time, that p-cresylsulphate, the main in vivo metabolite of p-cresol, has a pro-inflammatory effect on unstimulated leucocytes. This effect could contribute to the propensity to vascular disease in the uraemic population.

Biomarkers↗
PubMed2006

Clamping of the dialysate outlet line in the Genius dialysis system does not alter dialysate flow or clearances.

BACKGROUND: The Genius dialysis system is advocated as a tool to perform slow extended daily dialysis (SLEDD) in patients with acute renal failure at the intensive care unit. At low blood flows however, it is sometimes problematic to maintain sufficient systemic pressure in the dialysate circuit, a problem that can be overcome by clamping the dialysate outflow line. This intervention can however decrease the flow in the dialysate circuit, and can thus potentially decrease the clearance. This article analyses the impact of this intervention on the blood and dialysate flows and on the removal of retention products. METHODS: The study was done in 20 stable chronic dialysis patients to avoid additional bias caused by changing comorbidities in ICU patients. Patients were treated by Genius, once with clamping and once without clamping, cross-over in a randomized fashion, and with 1 week interval. Flows in the dialysate and blood circuit were measured with a transsonic flow probe. Urea, creatinine, Beta 2 microglobulin and phosphate were measured in the dialysate, and in the serum before and after dialysis. RESULTS: There was no clinically significant difference in blood or dialysate flows, nor in clearance or removal of retention products during the sessions with or without clamping. CONCLUSIONS: The technique of using clamping of the dialysate outflow line in the Genius system to increase systemic pressure, when the system is used in SLEDD, is a safe technique which does not alter the clearances.

Aged↗
PubMed2006

The changing epidemiology of acute renal failure.

Different definitions of acute renal failure (ARF) abound. The existence of multiple definitions makes it difficult to determine the true epidemiological characteristics of this condition. Despite this difficulty, it has been possible to detect notable variations in the epidemiology of ARF during the past few decades. The absolute incidence of ARF has increased, while associated mortality rate has remained relatively static. Several factors have contributed to this altered epidemiology. Here, we discuss the relative contribution of these factors, which include site of disease onset (developed or developing countries, community or hospital or intensive care unit), patient age, infections (HIV, malaria, leptospirosis and hantavirus), concomitant illnesses (cardiopulmonary failure, hemato-oncological disease), and interventions (hematopoietic progenitor cell and solid organ transplantation).

Acute Kidney Injury↗
PubMed2006

Epidemiologic aspects of the Bam earthquake in Iran: the nephrologic perspective.

BACKGROUND: Acute renal failure is a serious, preventable, and potentially reversible midterm complication after mass disasters. In 2003, an earthquake struck Bam, Iran. This article studies the epidemiologic aspects of the earthquake from a nephrologic perspective. METHODS: A questionnaire was sent to the reference hospitals. The resulting database of 2,086 traumatized patients hospitalized in the first 10 days was analyzed. RESULTS: Mean age was 29.0 +/- 15.6 years. Compared with the resident population, the percentage of patients was lower among children and teenagers younger than 15 years and higher among young and middle-aged adults (P < 0.001). There was no significant difference between mean ages of patients with acute renal failure and other patients. Time under the rubble was longer for patients with acute renal failure (6.2 +/- 4.1 versus 2.1 +/- 3.9 hours; P < 0.001). These patients were hospitalized later (3.1 +/- 2.8 versus 1.5 +/- 1.7 days after the disaster; P < 0.001) and longer (16.7 +/- 12.8 versus 12.5 +/- 11.3 days; P < 0.001). Sepsis (11.6% versus 0.5%), disseminated intravascular coagulation (7.3% versus 0.3%), adult respiratory distress syndrome (9.1% versus 1.4%), fasciotomy (38.9% versus 1.9%), amputation (6.1% versus 0.5%), and death (12.7% versus 1.9%) were markedly more frequent among patients with acute renal failure (P < 0.001 for all). CONCLUSION: Hospitalized patients were mostly young and middle-aged adults. Patients with acute renal failure were entrapped longer and hospitalized later and for longer periods. Medical complications, surgical procedures, and mortality were greater in the latter group. Early extrication and quick hospitalization with appropriate multidisciplinary care are cornerstones to prevent acute renal failure and its subsequent mortality in earthquake conditions.

Acute Kidney Injury↗
PubMed2006

Online hemodiafiltration.

Online hemodiafiltration (HDF) is an extracorporeal technique for solute removal in renal failure, which takes advantage of an enhancement of convective treatment by the large amount of ultrapure nonpyrogen dialysate being used for substitution of the ultrafiltered volume. It offers many advantages aside from its safe inflammatory profile, which is attributable to the use of ultrapure dialysate and highly biocompatible dialysis membranes. Due to an improved convective clearance, significantly increased removal of large or protein-bound uremic retention solutes can be achieved, with a potential benefit on cardiovascular morbidity and mortality. Recent observational data indicate that online HDF offers a survival advantage even after adjustment for comorbidity and dialysis efficiency. Research has been ongoing to maximize further the effectiveness of the technique by new technical innovations such as transmembrane-pressure feedback control or mid-dilution online HDF.

Hemodiafiltration↗
PubMed2006

Peritoneal dialysis in Europe: an analysis of its rise and fall.

There is a wide variability in the utilization of peritoneal dialysis throughout Europe that cannot be explained by differences in medical factors alone. Over the last years, the utilization of peritoneal dialysis has even changed in individual countries. The main factors of this variation are not medical, but rather changes in reimbursement and other financial considerations. The overall structure of the health care in an individual country is to a large extent determining the use of a renal replacement therapy modality.

Costs and Cost Analysis↗
PubMed2005

Sevelamer prevents uremia-enhanced atherosclerosis progression in apolipoprotein E-deficient mice.

BACKGROUND: The novel phosphate binder sevelamer has been shown to prevent the progression of aortic and coronary calcification in uremic patients. Whether it also decreases the progression of atheromatous plaques is unknown. The aim of our study was to examine the effect of sevelamer administration on the development of atherosclerosis and aortic calcification in the uremic apolipoprotein E-deficient mouse as an established model of accelerated atherosclerosis. METHODS AND RESULTS: Female mice were randomly assigned to 4 groups: 2 groups of nonuremic mice (sevelamer versus control) and 2 groups of uremic mice (sevelamer versus control). Sevelamer was given at 3% with chow. The increases in serum phosphorus concentration and calcium-phosphorus product observed in uremic control mice were prevented by sevelamer. Serum total cholesterol was increased in the 2 uremic mouse groups and remained unchanged in response to sevelamer. After 8 weeks of sevelamer treatment, uremic mice exhibited a significantly lower degree of atherosclerosis (P<0.001) and vascular calcification than uremic control mice. Of interest, sevelamer exerted an effect on both intima and media calcification (P=0.005) in uremic mice. Among possible mechanisms involved, we found no evidence for the modulation by sevelamer of inflammation or selected uremic toxins. In contrast, nitrotyrosine staining as a measure of oxidative damage was significantly decreased in response to sevelamer treatment in control and uremic mice (P<0.005). CONCLUSIONS: Sevelamer delays not only vascular calcification but also atherosclerotic lesion progression in uremic apolipoprotein E-deficient mice. It opens the possibility of a cholesterol-independent action of sevelamer on atheroma formation via effects on mineral metabolism, oxidative stress, or both.

Animals↗
PubMed2005

The importance of standardization of creatinine in the implementation of guidelines and recommendations for CKD: implications for CKD management programmes.

BACKGROUND: In an attempt to reduce late referral and to improve the care of patients with chronic kidney disease (CKD), different organizations have issued guidelines on when to refer patients to the nephrologist. Most suggest referral of patients with a GFR below 60 ml/min/1.73 m2, and demand referral if the GFR is below 30 ml/min/1.73 m2. It is recommended to use the abbreviated MDRD equation to estimate GFR. This formula is, however, sensitive to the creatinine assay methodology. In addition, the impact of the implementation of such guidelines on the nephrology practice has never been evaluated. This study (i) identifies the true burden of CKD in a population and simulates the effects of a 100% implementation of the guidelines on the nephrology work load, and (ii) evaluates the validity of the estimated GFR using the abbreviated MDRD formula when routinely provided. METHODS: Different laboratories (both hospital and private) in our region were asked to report on all the serum creatinine values performed during the first week of December 2004. If patients had more than one determination, only the lowest serum creatinine value was retained. Patients already known to a nephrology unit were not included. GFR was calculated using the abbreviated MDRD, using the serum creatinine as reported by these laboratories, or after correction to the MDRD-standard using different published equations. RESULTS: 20,108 patients, with a mean age of 53.4+/-16.2 years, 48% females, had at least one serum creatinine determination in the observation period. According to the K/DOQI CKD classification, 20.2, 1.6 and 0.8% of females and 13.3, 1.6 and 0.6% of males were in stage 3, 4 and 5, respectively, when the abbreviated MDRD formula was used with the serum creatinine value as reported by the laboratories. Important differences in classifications were obtained when the different correction formulae for creatinine were applied. According to the current recommendations, this would lead to a mandatory referral of 1650-2400 CKD stage 4 patients per 100 000 inhabitants and a suggested referral of another 4100-15 360 CKD stage 3 patients per 100,000 inhabitants to a nephrology unit. CONCLUSION: Implementation of the current guidelines for referral of CKD patients to nephrologists would lead to an overload of the nephrology care capacities. Large differences in estimated GFRs with different corrections for serum creatinine are observed, resulting in important CKD classification differences. Standardization of serum creatinine assays is mandatory before guidelines, and especially the routine provision of the estimated GFR by the abbreviated MDRD formula, can be implemented in clinical practice.

Adult↗
PubMed2005

Detection of angiotensin II in supernatants of stimulated mononuclear leukocytes by matrix-assisted laser desorption ionization time-of-flight/time-of-flight mass analysis.

Angiotensin II (Ang II) is the major vasoactive component of the renin-angiotensin system. Several components of the renin-angiotensin system have been demonstrated in different tissues. Whereas the roles of tissue and renal renin-angiotensin system have been studied in detail, much less is known on whether the corpuscular elements of circulating blood contribute to Ang II production. Here we examined whether, in addition to vasculature, blood cells also contribute to the circulating Ang II levels. Mononuclear leukocytes were obtained from healthy subjects and were incubated. The resulting supernatant was chromatographed using different chromatographic methods. The vasoconstrictive effects of aliquots of the resulting fractions were tested. Each fraction with a vasoconstrictive effect was analyzed by mass spectrometry. In one fraction with a strong vasoconstrictive effect, Ang II was identified. Mononuclear lymphocytes produced Ang II in amounts sufficient to stimulate Ang II type 1 receptors. Moreover, in mononuclear leukocytes, renin as well as angiotensin-converting enzyme mRNA expression was detectable by RT-PCR. These findings demonstrate that mononuclear leukocytes are a source of Ang II. Ang II secretion by these cells may play a significant role in humoral vascular regulation. In conclusion, the isolation of Ang II in supernatants of mononuclear leukocytes adds a further physiological source of Ang II to the current view of angiotensin metabolism. The quantitative role of lymphocyte-derived Ang II secretion compared with the other sources of Ang II should be defined further, but the release found under the present conditions is at least sufficient to elicit vasoconstrictive effects.

Angiotensin II↗
PubMed2005

Noninvasive assessment of local pulse pressure: importance of brachial-to-radial pressure amplification.

The advocated SphygmoCor procedure uses a radial-to-aorta transfer function with calibration on brachial instead of radial artery pressure to assess the central pulse pressure. We compared these values with carotid artery pulse pressures obtained from a validated calibration method, assuming mean minus diastolic blood pressure constant throughout the large artery tree. From 44 healthy subjects (21 males; 22 to 68 years) pressure waves were obtained at the radial, brachial, and carotid artery with applanation tonometry. Using the calibration method, radial and carotid artery pressures were assessed from brachial artery waves and pressures. The effect of brachial-to-radial pulse pressure amplification, brachial pulse pressure, mean pressure, age, gender, height, body mass index, and smoking on differences between the 2 methods was assessed. Brachial artery pressure was 118+/-12/72+/-10 mm Hg. SphygmoCor central pulse pressure was 9.7+/-4.6 mm Hg lower (P<0.001) than the carotid artery pulse pressure (33.0+/-6.8 versus 42.7+/-8.9 mm Hg). The difference between the 2 methods strongly depended (P<0.001) on brachial-to-radial artery pulse pressure amplification (5.8+/-5.1 mm Hg; 12+/-11%) and less on brachial artery pulse pressure (P=0.005). After calibration of the radial pressure wave with radial instead of brachial artery pressures, the difference between SphygmoCor central pulse pressure and carotid pulse pressure decreased with 4 mm Hg. The advocated SphygmoCor procedure systematically underestimates the central pulse pressure with brachial-to-radial pulse pressure amplification as important determinant. Therefore, calibration of radial artery pressure waves on brachial artery pressures should be avoided. The underestimation of central aortic pulse pressure caused by the radial-to-aorta transfer function itself is much less than previously reported.

Adult↗