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Biomedical subjects

R Vanholder

Publications and source records attributed to R Vanholder.

At least 37 records · Page 2Linked to original sources
PubMed2003

Serum potassium in the crush syndrome victims of the Marmara disaster.

BACKGROUND: Hyperkalemia is a major cause of mortality in the patients who suffer from crush syndrome in the aftermath of major earthquakes. The aim of this study is to investigate the frequency and effects of hyperkalemia in the 639 victims of catastrophic Marmara earthquake that struck northwestern Turkey, in August 1999. PATIENTS AND METHODS: Within the first week of disaster, questionnaires were sent to 35 reference hospitals that treated the victims. Information on serum potassium which was provided in 595 out of 639 questionnaires was submitted to analysis. RESULTS: In the patients who were admitted within the first 3 days of the disaster (n = 401) serum potassium was 5.4 +/- 1.3 mEq/l, which was higher than in those admitted thereafter (n = 171) (4.5 +/- 1.1 mEq/l) (p = 0.02). Considering the whole series, males (p = 0.01), patients needing dialysis support (p < 0.001) and non-survivors (p = 0.001) were characterized by higher serum potassium at admission. Seventy patients' serum potassium was above 7 mEq/l, while 22 patients were hypokalemic (< 3.5 mEq/l). Admission potassium correlated with many clinical and laboratory variables indicating the severity of the trauma, and a logistic regression model with clinical and laboratory parameters upon admission, revealed potassium as the most significant predictor of dialysis needs in the victims admitted within the first 3 days (p = 0.008, OR = 3.33). Among the victims who were admitted to hospitals 1 week after the disaster, 8 had serum potassium levels above 6.5 mEq/l; among 4 of them were complicated by hyperkalemia even higher than 7.5 mEq/l. These findings undeline the importance of hyperkalemia during clinical course. CONCLUSION: The most important and fatal medical complication in crush syndrome patients is hyperkalemia. Risk of fatal hyperkalemia continues even after hospitalization. Empirical therapy at the scene is indicated especially in male victims with severe soft tissue traumas. Early detection and treatment of hyperkalemia may improve the final outcome of renal disaster victims.

Adolescent↗
PubMed2003

[Uremic toxins].

Uremic toxins are compounds which exert biological action and which are retained in the body of patients with renal failure, whereas they normally should be excreted by the healthy kidneys into the urine. Only few retention solutes conform with the strict definition of uremic toxins. Uremic solutes can be subdivided into small water soluble compounds, small protein bound compounds and middle molecules. Most small water soluble compounds are not very toxic and the toxic ones often show a kinetic behavior that is different from that of urea. The uremic solutes that play a role in inflammation and cardio-vascular complications most often are middle molecules and/or protein bound. Hence, once more, the current marker urea is not representative for their mechanistic behavior.

Cardiovascular Diseases↗
PubMed2002

The 13C-octanoic acid breath test: validation of a new noninvasive method of measuring gastric emptying in rats.

Currently available rat models for measuring gastric emptying are hampered by the necessity to kill the animals at the end of each experiment, which makes repetitive testing impossible. We have developed and validated a noninvasive test model, adapted from the 13C-octanoic breath test in humans, for repetitive measurements of gastric emptying in rats. Male Wistar rats were trained on a fixed protocol to eat a piece of pancake doped with 1 microg 13C-octanoic acid after 12 h fasting, and to stay thereafter in cylindrical glass cages. Breath tests were performed by a fully automated system of computer-guided switching valves, which collected consecutive breath samples. All breath samples were analysed by gas chromatography and isotope mass spectrometry. The area under the curve (AUC) from the cumulative 13CO2 excretion from 0 to 6 h was determined by the trapezium method to calculate the gastric half-emptying times (t(1/2)). Inter-day variability was determined. The effect of subcutaneous or intraperitoneal injection of saline was studied. The test was further validated for pharmacological interventions by oral administration of cisapride and parenteral administration of atropine, to induce, respectively. acceleration and delay of gastric emptying. Mean gastric emptying times +/- SD of 24 rats were 119.3 +/- 28.2 min, 138.7 +/- 26.0 min, and 124.5 +/- 30.9 min on three different test days. The mean coefficient of variation of three repeated measurements in the same 24 rats was 17.5%. No significant differences were observed after subcutaneous or intraperitoneal injection of saline. In a second test series of eight rats, cisapride significantly accelerated gastric emptying (mean t(1/2) 112.7 +/- 33.1 min, P < 0.05), while atropine caused a significant delay (mean t(1/2) 205.9 +/- 24.9 min, P < 0.05) when compared to control test results (mean t(1/2) 140.7 +/- 16.7 min) in the same rats. We validated the 13C-octanoic breath test to study gastric emptying in rats. This test method obviates the necessity to kill laboratory animals and allows repetitive measurements of gastric emptying to study its physiology or pathophysiology as well as the effect of pharmacological agents.

Animals↗
PubMed2002

Alternative timeframes for hemodialysis.

Routinely, maintenance hemodialysis is applied according to an alternate day time schedule with dialysis sessions lasting 3 to 5 h. In analogy with continuous ambulatory peritoneal dialysis, a more gradual and more consistent removal pattern could be achieved by modifying this timeframe, e.g., by applying daily hemodialysis and/or by prolonging hemodialysis sessions to 8 h or more. Recently, a number of dialysis units implemented such alternative timeframes. Both the clinical and metabolic status showed dramatic improvements with beneficial effects on blood pressure, anemia, and potassium and phosphate levels. These changes occurred despite decreases in the dosage of the drugs administered to cope with these problems. However, controlled studies comparing morbidity and mortality of these alternative timeframes to the more traditional approaches are lacking at this moment.

Humans↗
PubMed2002

Gastric emptying of solids in cirrhotic and peritoneal dialysis patients: influence of peritoneal volume load.

INTRODUCTION: A delay in gastric emptying rate has been reported in peritoneal dialysis patients, often normalizing after evacuation of the dialysate. To evaluate the effect of the intraperitoneal volume, we compared this finding with a cirrhotic model in which gastric emptying was studied before and after a large-volume paracentesis. METHODS AND DESIGN: We used the 13C-octanoic acid breath test to measure gastric half-emptying time (T1/2) for solids in patients with alcoholic cirrhosis, non-diabetic peritoneal dialysis patients, and a control population (asymptomatic volunteers). Cirrhotic patients underwent the test on two consecutive mornings before and after an evacuating paracentesis. Peritoneal dialysis patients were studied twice on consecutive days: once with the dialysate present intra-abdominally ("full"), and once with an emptied abdomen ("empty"). Biochemical analysis was carried out on blood samples before the first test. All cirrhotics underwent a 13C-aminopyrine breath test to assess residual liver function. RESULTS: Gastric emptying in cirrhotics showed no difference before or after paracentesis (median T1/2 108.0 min v. 117.9 min), but it was delayed significantly versus normal in both tests. There was no correlation with biochemical parameters, Child-Pugh score, or 13C-aminopyrine breath test results. Gastric half-emptying times of "full" peritoneal dialysis patients (median T1/2 103.1 min) were significantly higher than those of "empty" peritoneal dialysis patients (median T1/2 68.9 min) and asymptomatic volunteers (median T1/2 60.1 min). "Empty" peritoneal dialysis patients showed no gastroparesis. CONCLUSION: In alcoholic cirrhotic patients with ascites, gastric emptying of solids is delayed, independently of the volume of ascites. In peritoneal dialysis patients, gastric emptying was delayed when "full" and normalized after drainage of the dialysate.

Adult↗
PubMed2002

Incidence of infectious morbidity and mortality in dialysis patients.

Infections remain among the major causes of disease, hospitalization and death in uremic patients, especially in those treated by dialysis. Several pathophysiologic factors enhance this infectious risk: (1) breakdown of protective barriers; (2) affinity of bacteria for foreign materials; (3) bioincompatibility; (4) uremic toxin retention; (5) deficiency and resistance to vitamin D; (6) carriership of germs, and (7) malnutrition. Twenty to 30% of dialysis patients develop infection, and 20-30% of these die from their infection. Sepsis is significantly more frequent, and mortality secondary to sepsis is 50 times higher than in the normal population. Bacteremia (prevalence 1 episode/100 patient-months) is mainly caused by Gram-positive species, especially in vascular access-related infection and infection of unknown origin. Among these Gram-positive germs, staphylococci play a predominant role. The most frequent and most morbid viral infections are associated with hepatitis. Whereas the incidence of hepatitis B decreases, hepatitis C has become the major variant. The incidence of tuberculosis has increased up to 15 times, and in the Western world it mainly affects patients who immigrated from endemic areas. Fungal infections are also frequent, especially in the setting of peritoneal dialysis. In conclusion, infections remain a frequent and morbid problem in dialysis patients. Preventive measures should be applied more vigorously.

Dialysis↗
PubMed2002

Vascular access.

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Antibiotic Prophylaxis↗
PubMed2002

Dyspepsia and gastroparesis in chronic renal failure: the role of Helicobacter pylori.

AIMS: Many patients with chronic renal failure have dyspeptic symptoms. In the present study, we assessed the Helicobacter pylori (Hp) status, dyspeptic symptoms and gastric emptying rates in uremic patients. The present study was undertaken to compare chronic renal failure patients not under dialysis therapy (predialysis), hemodialysis (HD) patients and peritoneal dialysis (PD) patients for these variables and to search for a possible causative role of Hp. METHODS: We used a standardized questionnaire to assess dyspeptic symptoms. Gastric emptying rates were determined by the 13C-octanoic acid breath test. HD patients were examined outside a dialysis session, PD patients were examined with a "full" abdomen. Specific Helicobacter pylori IgG was measured by a second-generation enzyme-linked immunosorbent assay. RESULTS: Sixty-six HD patients. 58 predialytic patients and 28 PD patients were included. Prevalences of Hp infection were highest in HD patients (46.2%) and predialysis patients (42.3%) compared to PD patients (28.6%) (p < 0.02). On the contrary, the prevalence of dysmotility-like dyspepsia was higher in PD patients (67.9%) when compared to HD patients (33.3%) (p < 0.01) and predialytic patients (53.6%) (difference not significant). Neither dyspepsia nor delayed gastric emptying were related to the presence of Helicobacter pylori IgG antibodies. CONCLUSION: A positive Helicobacter status based on serology was not related to the presence of dyspepsia or gastroparesis in uremic patients, whether on dialysis therapy or not. Dyspeptic complaints as well as gastroparesis are most prevalent in patients on peritoneal dialysis. The physiopathological mechanisms and clinical impact of these findings merit further investigation.

Adult↗
PubMed2001

Kinetics of the protein-bound, lipophilic, uremic toxin p-cresol in healthy rats.

P-Cresol, a partially lipophilic and protein-bound compound is related to several biochemical alterations in uremia. Because p-cresol kinetics have never been studied, we investigated its kinetic behavior in rats. Results were compared with those obtained with creatinine, a water soluble, non-protein-bound uremic retention solute, which is currently used as a marker of uremic retention. Healthy rats were divided into 3 groups with comparable body weight: (1) a control group (n=6); (2) a group (n=7) which received an intravenous bolus of 3 mg p-cresol; and (3) a group (n=5) which received an intravenous bolus of 18 mg creatinine. Blood samples were collected at 0, 5, 30, 60, 120, 180 and 240 minutes after administration for the determination of p-cresol and creatinine. Urine was collected at 1-hour intervals. p-Cresol concentrations were assessed by HPLC. Pharmacokinetic parameters of p-cresol and creatinine were calculated from the serum concentration-time curves using non-compartmental analysis. Each compound showed a concentration at time point 5 min (p-cresol: 6.7 +/- 1.4 mg/L and creatinine: 141 +/- 12 mg/L) which was comparable with values observed in uremic patients; these concentrations decreased gradually towards min 240 (p-cresol: 0.6 +/- 0.3 mg/L and creatinine: 4 +/- 2 mg/L, p<0.05 vs. 5 min in both cases). No p-cresol was found in the serum of control rats and these rats showed no changes in serum concentration of creatinine. Urinary excretions were strikingly different (p-cresol: 23 +/- 10% and creatinine: 95 +/- 25% of the administered dose, p<0.05). The half-life of p-cresol was twice as long as that of creatinine (1.5 +/- 0.8 vs. 0.8 +/- 0.1 h, p<0.05). Total clearance (CLt) was much higher for p-cresol than for creatinine (23.2 +/- 4.5 vs. 8.1 +/- 0.4 mL/min/kg, p<0.01); renal clearance (CLr), however, was substantially lower for p-cresol (4.8 +/- 2.0 vs. 8.2 +/- 1.9 mL/min/kg, p<0.05). Whereas CLt and CLr were similar for creatinine, CLt of p-cresol largely exceeded its CLr (p<0.05). The volume of distribution (Vd) was also much larger for p-cresol than for creatinine (2.9 +/- 1.4 vs. 0.6 +/- 0.1 L/kg, p<0.01). After injection of p-cresol, an additional chromatographic peak appeared in serum and in urine samples. Although at min 240 serum concentration of p-cresol had decreased to 10% of the peak value, only 23% of the administered amount was excreted in the urine and the CLr was +/- 50% lower compared to that of creatinine. Non-renal clearance and Vd of p-cresol were, however, substantially larger. These data may be of value to explain the different behavior of p-cresol in renal failure and dialysis, compared to creatinine.

Animals↗
PubMed2001

Non-ideal behaviour of free vanadate on a Superose 12 size-exclusion column. Application to in vivo 48V-labelled rat spleen homogenate.

Seven chromatographic columns were evaluated for the recovery of 48V-radiolabelled vanadate. Further, the behaviour of vanadate (H2VO4-) was studied on a size-exclusion column Superose 12 as a function of (a) buffer salt molarity, (b) different buffer salts, (c) different buffers and (d) organic solvents added to the buffer. As opposed to the unsatisfactory recovery of V-compounds on other columns, we recovered the vanadium quantitatively. We observed that in most cases vanadate eluted after the total volume of the Superose 12 column. This indicates a non-ideal behaviour of vanadate. However, through this non-ideal behaviour it was possible to separate low-molecular-mass bound (Mr<5000) and unbound vanadium which would not be possible under normal behaviour. A possible explanation for this non-ideal behaviour of vanadium is put forward. The method has been successfully applied for the fractionation of different vanadium species in rat spleen homogenate.

Animals↗
PubMed2001

Life-threatening hyperkalemia during combined therapy with angiotensin-converting enzyme inhibitors and spironolactone: an analysis of 25 cases.

PURPOSE: The beneficial effects of spironolactone are additive to those of ACE inhibitors among patients with heart failure and/or hypertension; however, it is essential to identify patients prone to develop serious hyperkalemia during combined treatment and to evaluate the associated morbidity and mortality. SUBJECTS AND METHODS: We studied 25 patients treated with ACE inhibitors and spironolactone who were admitted to the emergency room with a serum potassium level > 6 mmol/L. Patients were followed up for at least one month after admission. RESULTS: The mean age of the patients (11 males, 14 females) was 74 +/- 13 years. Five patients were diabetics. On admission, the serum potassium was 7.7 +/- 0.7 mmol/L and the serum creatinine was 3.8 +/- 1.8 mg/dL; these values were significantly higher than the most recent follow-up laboratory measurements (4.6 +/- 0.5 mmol/L and 1.9 +/- 1.2 mg/dL, respectively) obtained at 13 +/- 5 weeks before admission. The arterial pH on admission was 7.3 +/- 0.1 and the plasma bicarbonate was 18 +/- 5 mmol/L. The main causes for acute renal failure were dehydration (n = 12) and worsening heart failure (n = 9). The mean daily dose of spironolactone was 57 +/- 32 mg and 12 patients were concomitantly treated with other drugs that may cause hyperkalemia. Two patients died, and 2 patients were resuscitated but survived. Hemodialysis was necessary in 17 patients; 12 patients were admitted to the intensive care unit. The mean duration of hospitalization was 12 +/- 6 days. Two patients needed to be started on maintenance hemodialysis therapy. CONCLUSION: A combination of ACE inhibitors and spironolactone should be considered with caution and monitored closely in patients with renal insufficiency, diabetes, older age, worsening heart failure, a risk for dehydration, and in combination with other medications that may cause hyperkalemia. A daily spironolactone dose of 25 mg should not be exceeded.

Aged↗
PubMed2001

Diabetes-induced microvascular dysfunction in the hydronephrotic kidney: role of nitric oxide.

BACKGROUND: Renal hemodynamics in early diabetes are characterized by preglomerular and postglomerular vasodilation and increased glomerular capillary pressure, leading to hyperfiltration. Despite intensive research, the etiology of the renal vasodilation in diabetes remains a matter of debate. The present study investigated the controversial role of nitric oxide (NO) in the renal vasodilation in streptozotocin-induced diabetic rats. METHODS: In the renal microcirculation, basal tone and response to NO synthase blockade were studied using the in vivo hydronephrotic kidney technique. L-arginine analog N-nitro-L-arginine methyl ester (L-NAME) was administered locally to avoid confounding by systemic blood pressure effects. The expression of endothelial NO synthase (eNOS) was investigated in total kidney by immunocytochemistry and in isolated renal vascular trees by Western blotting. Urinary excretion of nitrites/nitrates was measured. RESULTS: Diabetic rats demonstrated a significant basal vasodilation of all preglomerular and postglomerular vessels versus control rats. Vasoconstriction to L-NAME was significantly increased in diabetic vessels. After high-dose L-NAME, there was no difference in diameter between diabetic and control vessels, suggesting that the basal vasodilation is mediated by NO. Immunocytochemically, the expression of eNOS was mainly localized in the endothelium of preglomerular and postglomerular vessels and glomerular capillaries, and was increased in the diabetic kidneys. Immunoblots on isolated renal vascular trees revealed an up-regulation of eNOS protein expression in diabetic animals. The urinary excretion of nitrites/nitrates was elevated in diabetic rats. CONCLUSION: The present study suggests that an up-regulation of eNOS in the renal microvasculature, resulting in an increased basal generation of NO, is responsible for the intrarenal vasodilation characteristic of early diabetes.

Animals↗
PubMed2001

Intervention of the Renal Disaster Relief Task Force in the 1999 Marmara, Turkey earthquake.

BACKGROUND: Major earthquakes are followed by a substantial number of crush syndromes and pigment-induced acute renal failures (ARFs). The natural evolution of this problem rapidly leads to death. Today's possibilities of dialysis therapy enable saving numerous lives that otherwise would be lost. Currently, the primary problem is organizational, if huge catastrophes occur and complex therapeutic options need to be offered to a large number of victims. METHODS: Following the 1988 Spitak earthquake in Armenia, the International Society of Nephrology (ISN) established the Renal Disaster Relief Task Force (RDRTF) in order to anticipate organizational problems related to renal care in the aftermath of large natural and human-made catastrophes. The proposed concept was one of a dialysis advance team, which would assess the needs and possibilities of dialysis treatment, to be followed by supportive manpower and supplies. This article describes the organizational aspects of a rescue action that was undertaken following the Marmara earthquake, which occurred on August 17th, 1999, in northwestern Turkey. In conjunction with Médecins Sans Frontières, a team landed at Istanbul Airport less than 22 hours after the disaster, and logistic and material support as well as manpower were provided over a period of approximately one month. Specific attention was paid to the choice of the renal replacement therapy, the transport of victims and materials, the implementation of preventive rehydration, and the problem of chronic renal failure patients dialyzed in the damaged area. CONCLUSIONS: We demonstrate how previously anticipated international support may offer moral, financial, as well as logistical help to local nephrological communities confronted with serious disasters.

Acute Kidney Injury↗
PubMed2001

The Marmara earthquake: epidemiological analysis of the victims with nephrological problems.

BACKGROUND: Crush syndrome resulting from earthquakes is a major cause of morbidity and mortality, as seen during the catastrophic Marmara earthquake that struck Northwestern Turkey in August 1999. This report analyzes the epidemiological characteristics of the crush syndrome victims of this disaster. METHODS: In order to analyze the nephrological problems caused by this earthquake, questionnaires were prepared within the first week of the disaster and sent to 35 reference hospitals that treated the victims. Data obtained by these questionnaires are the subject of this report. RESULTS: Of the 5302 hospitalized patients in reference hospitals, 639 (12.0%) suffered from nephrological problems, and 477 (9.0%) needed dialysis support. Considering the patients with renal problems, there was not any significant difference in gender; however, the incidence of children younger than 10 years and the older population (older than 60 years of age) was significantly lower as compared with the resident population of the affected area (P < 0.001). Nonsurvivors were older (34.5 +/- 16.1 years) than survivors (31.2 +/- 14.4 years, P = 0.048), while no deaths were recorded under the age of 10. Most patients (70.1%) were admitted within the first three days after the earthquake, and the mortality rate among these victims was higher (17.7%) as compared with victims admitted thereafter (10.0%, P = 0.016). The average time period under the rubble was 11.7 +/- 14.3 hours, which was not significantly different between survivors and nonsurvivors, while the victims who required dialysis support spent shorter durations under the rubble, as compared with the ones who were not dialyzed at all (10.3 +/- 9.5 vs. 15.9 +/- 23.1 hours, P < 0.001). CONCLUSION: Victims of catastrophic earthquakes are characterized by a high incidence of renal problems and the need for dialysis support. The incidence of nephrological problems is lower in children, while the period of time under the rubble is not a prognostic indicator of survival.

Adolescent↗
PubMed2001

Blunted response to vitamin D in uremia.

It has been demonstrated that many chains in the vitamin D pathway are affected by uremia. Uremic solute retention is responsible for changes in calcitriol production, resulting in a net decrease of blood calcitriol levels. This effect contributes to the calcitriol deficiency currently observed in renal failure. Next to the altered production and metabolization of calcitriol, altered expression of the vitamin D receptor (VDR) and altered binding properties of the hormone receptor complex to the DNA could also contribute to the relative status of calcitriol resistance in renal failure. These alterations could finally result in an impairment of the end biological action of calcitriol.

Animals↗
PubMed2001

Protein-bound uremic solutes: the forgotten toxins.

The present concept of dialysis focuses mainly on the removal of small water-soluble compounds, and also, the currently applied kinetic parameters of dialysis adequacy are based on the behavior of water-soluble compounds. Nevertheless, many of the currently known biological effects in uremia are attributable to compounds with different physicochemical characteristics, and among these, protein-bound solutes play an important role. In this article, we review the characteristics and consequences of changes in protein binding in uremia, as well as the toxicity of the protein-bound uremic solutes 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF), indoxyl sulfate, hippuric acid, homocysteine, and p-cresol. Starting from the example of p-cresol, we then summarize the impact of protein-binding on dialytic removal, whereby it is concluded that this removal is largely hampered by this protein-binding compared with that of classic markers such as urea and creatinine. Alternative removal strategies, such as strategies to modify intestinal generation or absorption, are considered.

Animals↗