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N Lameire

Publications and source records attributed to N Lameire.

At least 19 recordsLinked to original sources

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↗

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↗

In vivo distribution and speciation of [114mIn]InCl3 in the Wistar rat.

Five Wistar rats were given an intraperitoneal injection of [114mIn]InCl3 during four consecutive days. One hour after the last injection the rats were sacrificed. The in vivo distribution of 114mIn was studied in the blood and in different organs. Differential centrifugation was used to study the distribution in liver, kidney and spleen homogenate. Rat serum, packed cell lysate, urine and the cytosol of liver, kidney and spleen homogenate were examined by size exclusion fast protein liquid chromatography. The results showed that serum accounts for 90% of the indium activity in whole blood. Indium is preferentially accumulated within the liver, spleen and kidney, the highest amount of 114mIn being localised in the cytosolic fraction followed by the mitochondria. Size exclusion experiments showed that, in rat serum, indium is exclusively bound to transferrin. These results differed from earlier in vitro incubation experiments of human serum with 114mIn. It was not possible, from the experiments described herein, to conclude unequivocally whether indium is bound to haemoglobin of packed cell lysate or to another high molecular mass compound. Indium is associated with the high molecular mass fraction in liver, kidney and spleen cytosol; only in kidney are small amounts of 114mIn found in the low molecular mass fraction. The in vivo inhibitory effect of indium on the delta-aminolaevulinic acid dehydratase (ALAD) enzymatic activity in red blood cells and kidney tissue, well documented by other researchers, could not be attributed to direct binding of indium with this enzyme.

Animals↗

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↗

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↗

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↗

Uremic toxins and peritoneal dialysis.

Uremic toxicity is related in part to the accumulation of toxic substances, the nature of which has only partly been characterized. Because of the use of a highly permeable membrane and better preservation of the residual renal function, it could be anticipated that some of these uremic toxins are more efficiently cleared across the peritoneal membrane, and that the plasma and tissue levels of these compounds are lower than in hemodialysis patients. This article analyzes the generation and removal of several uremic toxins in peritoneal dialysis patients. The following uremic toxins are discussed: beta2-microglobulin, advanced glycation end products, advanced oxidation protein products, granulocyte inhibitory proteins, p-Cresol, and hyperhomocysteinemia. Some recent studies are reviewed suggesting that uremic toxins are involved in the progression of renal failure and are at least partially removed by peritoneal dialysis. We conclude that, although the plasma levels of some of these compounds are lower in peritoneal dialysis versus hemodialysis patients, it does not mean that the peritoneal dialysis patient is "better" protected against the numerous disturbances caused by these toxins.

Animals↗

The anti-proliferative effect of calcitriol on HL-60 cells is neutralized by uraemic biological fluids.

BACKGROUND: It has been demonstrated that uraemic serum/ultrafiltrate inhibits cell-mediated immune response in vitro, and that it suppresses calcitriol synthesis and its biological actions. METHODS: In the present in vitro study, the effect of calcitriol, uraemic ultrafiltrate (UUF) and a combination of both on the human promyelocytic leukaemia cell line, HL-60, was studied by evaluating bromodeoxyuridine (BrdU) incorporation into the DNA, luminol-amplified chemiluminescence (CL) production, expression of CD14, and levels of vitamin D receptor mRNA (VDR mRNA) and CD14 mRNA. RESULTS: The ability of calcitriol to block cell proliferation (37.4+/-5.4 to 30.5+/-5.6% cells incorporating BrdU, P:<0.01) was neutralized when UUF was applied together with calcitriol (53.4+/-21.3% cells incorporating BrdU, P:<0.01 vs calcitriol alone). Similarly to what was observed for BrdU incorporation, the CL production of HL-60 cells was enhanced in the presence of calcitriol (20126+/-10154 to 61528+/-24021 cpm, P:<0.01), and was suppressed again in the presence of calcitriol and UUF (20916+/-12075 cpm, P:<0.01 vs calcitriol alone); finally UUF also inhibited the calcitriol-induced CD14 expression (71.1+/-11.2 to 54.9+/-17.7% CD14 positive cells, P:<0.05). On the other hand, the calcitriol-induced CD14 mRNA levels were not significantly different in the presence of calcitriol and UUF compared to calcitriol alone. This points to an inhibition by UUF at a post-transcriptional level. Similar data were found for VDR mRNA levels. UUF was fractionated by HPLC in four fractions, hydrophilic uraemic solutes being eluted first (F1) and hydrophobic solutes being eluted last (F4); fractions 1, 2 and 3 simultaneously affected both BrdU incorporation and CL production in a significant way. CONCLUSIONS: It is concluded that UUF contains factors that impair calcitriol-activated function of HL-60 cells. Hence, the differentiation and immune response of these promyelocytic leukaemia cells, as induced by the supplementation of calcitriol, is neutralized in the presence of uraemic biological fluids. This may be of relevance for the propensity to infection and malignancy of the uraemic patient.

Biological Factors↗

Relationship between gastric emptying and clinical and biochemical factors in chronic haemodialysis patients.

BACKGROUND: Gastroparesis is an important side-effect of end-stage renal disease because of its influence on nutritional status. METHODS: In this study, 56 equilibrated haemodialysis patients were evaluated by radioisotopic examination for gastric emptying time. These data were correlated to anthropometrical as well as biochemical parameters. RESULTS: The half-life time for gastric emptying was 83+/-34 min in the overall population, compared to 50+/-15 min in a normal reference population. Prealbumin, mean fibular nerve-conduction velocity and intra- as well as extracorpuscular folic acid were significantly different between patients with the lowest and highest gastric emptying times. Linear correlation analysis between the half-life for residual radioactivity and the remaining parameters yielded a significant correlation for blood urea nitrogen, serum folic acid, intracorpuscular folic acid, serum vitamin B(12), serum C-reactive protein, serum prealbumin and mean fibular nerve-conduction velocity. CONCLUSIONS: This study demonstrates that gastric emptying is significantly delayed in end-stage renal disease patients. The delay is associated with changes in biochemical indicators of nutritional status such as serum albumin and prealbumin.

Aged↗

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Journal Article↗

Pathophysiologic features and prevention of human and experimental acute tubular necrosis.

Acute renal failure (ARF) remains a common and potentially devastating disorder that affects as many as 5% of all hospitalized patients, with a higher prevalence in patients in critical care units. The focus of this article is on categorizing recent pathophysiologic and clinically relevant developments in the field. The vascular and tubular factors in the pathogenesis of ARF, together with the potential mechanisms of recovery and repair of the injured kidney, are discussed. A number of experimental and clinical interventions to prevent. ARF are summarized. Although the clinical treatment of these patients is still largely supportive and many recent clinical trials showed rather negative results, it is hoped that basic research will provide therapeutic tools to improve the grim prognosis of this disease in the future.

Animals↗

What is the renal replacement method of first choice for intensive care patients?

Renal replacement therapy for the patient with acute renal failure on the intensive care unit can be offered in several different formats: intermittent hemodialysis (IHD), continuous renal replacement therapy (CRRT), and slow low-efficient daily dialysis (SLEDD). It is frequently claimed that CRRT offers several advantages over IHD, but most of these, such as correction of metabolic acidosis, better recovery of renal function, better clinical outcome due to application of biocompatible dialysis membranes, correction of malnutrition, and better removal of cytokines, are not corroborated by the results of controlled prospective studies. There is also no evidence that CRRT results in a better survival, compared with IHD. The only potential advantages of CRRT that stood the test of clinical evaluation (hemodynamic stability, correction of hypervolemia, better solute removal) can be offered as well by SLEDD. In addition, the latter strategy is less expensive because the same infrastructure is used as for IHD, while the patient is not immobilized continuously, which leaves time free for other activities such as nursing care and technical investigations. SLEDD is a relatively young technique, so thorough clinical studies are lacking. Nevertheless, the hypothesis is proposed that SLEDD offers a valuable alternative to the classical dialysis strategies, applied in the intensive care patient.

Acute Kidney Injury↗

Mimicry of surreptitious diuretic ingestion and the ability to make a genetic diagnosis.

Gitelman's syndrome, also known as "hypocalciuric variant of Bartter's syndrome", is a cause of chronic hypokalemia and hypomagnesemia in adults. A specific gene has been found responsible for this disorder, encoding the thiazide-sensitive NaCl coporter (TSC) in the distal convoluted tubule. We describe a psychiatric patient with chronic symptomatic hypokalemia and hypomagnesemia whose electrolyte disturbances were subsequently misdiagnosed as an acute alcohol and benzodiazepine withdrawal syndrome, as chronic diuretic abuse and as a classical Bartter's syndrome. Finally, genetic investigation revealed the presence of mutations in the SLC12A3 gene leading to the proper diagnosis of Gitelman's syndrome. We emphasize that Gitelman's syndrome should be suspected in every hypokalemic patient with biochemical resemblance of diuretic ingestion, especially when repeated toxic screens for diuretics are negative. The ability to make a molecular-genetic diagnosis can be of practical benefit in confusing clinical settings.

Adult↗

Heparin-induced release of protein-bound solutes during hemodialysis is an in vitro artifact.

BACKGROUND: Several studies have pointed to a release of drugs or protein-bound solutes from their binding sites during heparinization. The effect is attributed to the metabolism of triglycerides to free fatty acids (FFAs), which compete with drugs for protein binding sites. This study evaluated the impact of intradialytic heparin on the free concentration of the uremic toxin p-cresol and on FFAS: METHODS: Blood samples from hemodialysis (HD) patients, before and during HD, were collected with selected anticoagulation strategies. We assessed the effects of standing time, temperature, pH, and the addition of a lipase inhibitor, tetrahydrolipstatin (THL) to blood samples on the free p-cresol concentration. p-Cresol was analyzed by HPLC with fluorescence detection. We measured FFAs by gas chromatography, and the free fractions of added valproic acid and phenytoin were evaluated by fluorescence polarization immunoassay. RESULTS: In blood samples (n = 22) not submitted to a specific treatment, free p-cresol increased from 9.9 +/- 5.1 to 31.9 +/- 22.3 micromol/L after 30 min of heparin HD (P < 0.001) and correlated significantly with FFAs (r = 0.80; P = 0.002; n = 12). There was no increase in free p-cresol during heparin-free HD (n = 6) and trisodium citrate HD (n = 9). In addition, p-cresol in ultrafiltrates (n = 3) did not correspond to the free p-cresol in heparinized blood, suggesting that the increase in free p-cresol was artifactual. The release of p-cresol in the test tube was enhanced by standing time (n = 6), sample temperature (n = 6), and alkaline pH (n = 6). Inhibition of lipase activity with THL prevented the increase of FFAs (n = 6) and the release of free p-cresol during HD (n = 22). These results were corroborated by the study of the free fraction of valproic acid (n = 6) and phenytoin (n = 6). CONCLUSIONS: The free concentrations of protein-bound solutes in plasma of heparinized patients are influenced by external factors that alter the lipase activity in the test tube. The free fraction does not increase during HD when lipase activity is neutralized at the time of blood sampling, so that previously reported increases are probably artifacts.

Aged↗

Advanced glycation end products: specific fluorescence changes of pentosidine-like compounds during short daily hemodialysis.

BACKGROUND: Advanced glycation end products (AGE) accumulate in uremia and represent an important etiopathogenetic cause of morbidity in dialyzed patients. Conventional hemodialysis treatment seems to be ineffective in lowering AGE levels. We wished to investigate whether daily hemodialysis (DHD), a treatment that seems to result in better clinical condition in end-stage renal disease patients, is effective in the reduction of these compounds. METHODS: We evaluated 10 non-diabetic patients on standard hemodialysis (SHD = 3 x 4 h/week) for more than 6 months by a crossover study. These patients were assigned randomly to 6 months of DHD (6 x 2 h/week) or 6 months of SHD. Then, they were switched to 6 months of the alternative treatment. At the end of these two periods, we studied pentosidine-like AGE compounds by measuring the total fluorescence at a wavelength characteristic for these substances: Ex: 335nm/Em:385nm; we also measured protein-linked pentosidine at the same time points. Finally, we determined the AGE-related total fluorescence in the deproteinized serum of 13 uremic patients on peritoneal dialysis (CAPD) and of 10 healthy controls. RESULTS: Pre-HD AGE-related total fluorescence obtained after 6 months of DHD was significantly lower than that obtained with standard HD (DHD = 201.3 +/- 36.4 AU/ml vs. SHD = 267.5 +/- 141.4 AU/ml, p = 0.03). The extraction rate per minute of dialysis was slightly, but not significantly higher during DHD than SHD (0.29 +/- 0.11% vs. 0.23 +/- 0.04, p = 0.07). AGE-related total fluorescence pre-HD values in patients treated by SHD and DHD were about 20-fold higher than in control subjects. They did not differ from CAPD patients. The pre-dialysis level of protein-linked pentosidine was significantly lower in DHD than in SHD (DHD = 16.12 +/- 4.71 pmol/mg protein, SHD = 22.64 +/- 6.86 pmol/mg protein, p < 0.01). CONCLUSIONS: DHD showed a reduction in AGE-related total fluorescence, although the mean value remained higher than in control subjects. DHD is also accompanied by a decrease in protein-linked pentosidine.

Arginine↗

Peritoneal dialysis favorably influences early graft function after renal transplantation compared to hemodialysis.

BACKGROUND: Delayed graft function (DGF) and acute renal failure (ARF) after renal transplantation negatively influence short- and long-term graft outcome. Peritoneal dialysis as pretransplantation dialysis modality was reported to influence favorably the recovery of renal function immediately after kidney transplantation. It has been hypothesized that fluid status was the factor explaining this better outcome. This hypothesis was tested in this study by multivariate analysis, also including other factors related to DGF and ARF. METHODS: The records of peritoneal dialysis (PD; n=40) and hemodialysis (HD; n=79) patients receiving a first cadaveric kidney transplantation at the University Hospital Gent were analyzed. RESULTS: DGF and ARF were observed in 33 (27 HD and 6 PD, P=0.03) and 14 (14 HD and 0 PD, P=0.01) patients, respectively. The number of days needed to reach a serum creatinine 50% below that before transplantation (T1/2(SCr)), was correlated with cold ischemia time (CIT) (P<0.001) and body weight gain (BWG) (P<0.01) and was inversely correlated with urinary output in the first 24 hr (P<0.001), fluid load (P<0.001), and central venous pressure (P<0.001). A multivariate model with CIT (P<0.001), PD as pretransplantation dialysis mode (P=0.01), urinary output in the first 24 hr (P=0.001), BWG (P=0.05), and fluid load (P=0.01) resulted in an R2 of 0.32 (P<0.001). Using Cox regression analysis, the relative risk for a prolonged T1/2(SCr) increased with 4%/hr CIT (P=0.01) and with 1%/kg BWG (P=0.02). Fluid load decreased the relative risk with 5%/liter (P<0.001) and PD as pretransplantation modality favorably modified the relative risk by a factor of 1.6 (P=0.01). CONCLUSION: PD as pretransplantation dialysis modality can reduce the incidence and the severity of delayed recovery of renal function after renal transplantation. This protective effect was independent from CIT, and fluid status, two other major influencing factors.

Acute Kidney Injury↗