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Norbert Lameire

Publications and source records attributed to Norbert Lameire.

At least 37 records · Page 2Linked to original sources

Increased angiogenesis and permeability in the mesenteric microvasculature of rats with cirrhosis and portal hypertension: an in vivo study.

BACKGROUND: In vivo evidence for angiogenesis in the splanchnic vasodilation in portal hypertension (PHT) and cirrhosis is lacking. Vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS) are mediators of angiogenesis. The present study visualises in vivo structural changes (angiogenesis and vascular hyperpermeability) and examines the presence of VEGF and eNOS in the mesenteric microvasculature of animal models of PHT with and without cirrhosis. METHODS: Portal hypertension was induced by partial portal vein ligation (PPVL) and cirrhosis was induced by common bile duct ligation (CBDL) in rats. The mesenteric microcirculation was examined by intravital microscopy. Expression of VEGF, eNOS and CD31 in mesenteric tissue were studied by immunohistochemistry. RESULTS: An increased mesenteric angiogenesis was observed in PPVL and CBDL rats compared with Sham-operated and control rats, as shown by intravital microscopy and CD 31 staining. VEGF and eNOS expression was higher in CBDL and PPVL rats compared with control groups and correlated positively with vascular density. Macromolecular leakage was increased in cirrhotic rats compared with control and PPVL rats. CONCLUSION: Our study provides in vivo evidence of an increased angiogenesis in the mesenteric microvasculature of animal models of PHT and cirrhosis. Increased VEGF and eNOS expression in the mesentery of PPVL and CBDL rats may suggest their contribution. Microvascular permeability in the mesenteric vessels was only increased in cirrhotic rats.

Animals↗

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↗

What did we learn from animal models in peritoneal dialysis?

The development of animal models in peritoneal dialysis has led to some breakthroughs in the application of this dialysis modality in clinical practice. These breakthroughs are (1) a better understanding of the physiology and pathophysiology of solute transport and ultrafiltration mechanisms, (2) the observation and integration of the long-term structural and functional alterations of the membrane, (3) a better understanding of the biocompatibility issues involved in PD, leading to the clinical introduction of more biocompatible dialysis solutions and finally, (4) the development of colloid osmotic solutions containing polyglucose polymers for application in the long dwells. Intravital miscroscopy provides information in live animals about diverse functional parameters, such as blood flow rate, vessel diameter, permeability to macromolecules, leukocyte-endothelium interaction, capillary recruitment, and lymph vessel kinetics. Also evaluation of different parameters in a living experimental animal, allowing integration of function and structure is possible. A variety of chronic PD models have been developed, mainly to study effects of long-term peritoneal dialysate exposure on peritoneal membrane function and structure. The implementation of different blocking agents of biochemical substances in these models has elucidated many molecular biological mechanisms involved in these processes. The important roles of aquaporins, vascular endothelial growth factor, nitric oxide, advanced glycation end product formation and their receptor (RAGE) upregulation and the integrated roles of all these factors in the fibrotic alterations of the membrane as observed in patients on long-term PD have been investigated. More recently, genetically modified mice have been used as an important tool to investigate the molecular basis of peritoneal changes during dialysis and during acute peritonitis.

Animals↗

Contrast-Induced Nephropathy (CIN) Consensus Working Panel: executive summary.

With the advances made in radiology and cardiology, greater numbers of patients are expected to undergo exposure to iodinated contrast media in the years to come. Contrast-induced nephropathy (CIN) accounts for a significant number of cases of hospital-acquired renal failure, with adverse effects on prognosis and healthcare costs. The CIN Consensus Working Panel is an international multidisciplinary group convened to address the challenges of CIN. The group reviewed 865 published papers, chosen for potential relevance from a comprehensive literature search that identified over 4000 references. The results were used to compile reviews covering the epidemiology and pathogenesis of CIN, baseline renal function measurement, risk assessment, identification of high-risk patients, contrast medium use, and preventive strategies. In this executive summary, consensus statements and an algorithm for the risk stratification and management of CIN are presented.

Contrast Media↗

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↗

Effects of new peritoneal dialysis solutions on leukocyte recruitment in the rat peritoneal membrane.

OBJECTIVES: Peritonitis remains a principal cause of dropout in peritoneal dialysis (PD). The physiological host response to a peritoneal infection involves a rise in numbers of circulating leukocytes to the peritoneal cavity. We evaluated the effects of (1) conventional peritoneal dialysis fluid (PDF), (2) bicarbonate-based PDF, low in glucose degradation products, and (3) non-glucose PDF on peritoneal leukocyte recruitment in response to an inflammatory stimulus using intravital microscopy. METHODS: The visceral peritoneum was exposed to EBSS, conventional lactate-buffered and bicarbonate/lactate-buffered glucose-based PDF and three lactate-buffered non-glucose PDF-icodextrin, amino acid-based PDF and amino acid/glycerol-based PDF. The number of rolling, adhering and extravasated leukocytes and leukocyte rolling velocity was assessed at different time intervals after stimulation with lipopolysaccharide (LPS). RESULTS: Exposure to LPS dissolved in EBSS dramatically increased the number of rolling, adhering and extravasated leukocytes and decreased leukocyte rolling velocity. Conventional PDF completely abolished LPS-induced leukocyte recruitment. Bicarbonate/lactate-buffered PDF only minimally affected the process of leukocyte recruitment, whereas icodextrin PDF resulted in partial inhibition of the immune response. The amino acid-based and the amino acid/glycerol-based PDF inhibited leukocyte recruitment to a similar extent as conventional PDF. CONCLUSIONS: Bicarbonate/lactate-buffered PDF has superior biocompatibility towards peritoneal host defense, in spite of its high glucose concentrations. Lactate-buffered non-glucose containing PDF has substantial inhibitory effects on leukocyte recruitment, indicating that the bioincompatibility of high lactate concentrations and/or low pH may not be underestimated.

Amino Acids↗

Immunopathological changes in a uraemic rat model for peritoneal dialysis.

BACKGROUND: Peritoneal dialysis (PD) is a treatment modality for patients with renal failure. Both the uraemic state of these patients and chronic exposure to PD fluid are associated with the development of functional and structural alterations of the peritoneal membrane. In a well-established chronic PD rat model, we compared rats with normal renal function with subtotal nephrectomized rats that developed uraemia. METHODS: Uraemic and control rats received daily 10 ml conventional glucose containing PD fluid, via peritoneal catheters during a 6 week period. Uraemic and control rats receiving no PD fluid served as controls. Parameters relevant for peritoneal defence and serosal healing responses were analyzed. RESULTS: Uraemic animals were characterized by 2-3-fold increased serum urea and creatinine levels, accompanied by a significantly reduced haematocrit. Uraemia (without PD fluid exposure) induced new blood vessels in different peritoneal tissues, accompanied by increased accumulation of advanced glycation end products (AGEs) and elevated levels of angiogenic factors such as vascular endothelial growth factor and monocyte chemoattractant protein-1 (MCP-1) in peritoneal lavage fluid. A much stronger peritoneal response was observed upon PD fluid exposure in non-uraemic rats. This included the induction of angiogenesis and fibrosis in various peritoneal tissues, accumulation of AGEs, immunological activation of the omentum, damage to the mesothelial cell layer, focal formation of granulation tissues and increased MCP-1 and hyaluronan levels in peritoneal lavage fluid. Finally, chronic PD fluid instillation in uraemic rats did not induce an additional peritoneal response compared to PD fluid exposure in non-uraemic rats, except for the degree of AGE accumulation. CONCLUSIONS: Both uraemia and PD fluid exposure result in pathological alterations of the peritoneum. However, uraemia did not induce major additive effects to PD fluid-induced injury. These results substantially contribute to the understanding of the pathobiology of the peritoneum under PD conditions.

Animals↗

Efficacy of erythropoietin administration in the treatment of anemia immediately after renal transplantation.

Anemia negatively impacts cardiovascular comorbidity and hospitalization. In animals, recombinant erythropoietin (RhuEPO) leads to faster recovery after acute tubular necrosis. This study evaluates the effect of RhuEPO (Recormon, Hoffman-La Roche, Basel, Switzerland) on the correction of anemia and kidney function after renal transplantation. Patients receiving a renal transplant were randomized to receive or not receive RhuEPO 100 U/kg three times per week if the hemoglobin (Hb) level was less than 12.5 g/dL. The time to reach an Hb level greater than 12.5 g/dL was 66.5+/-14.5 days versus 52.6+/-23.7 days in the non-EPO and EPO groups, respectively (P=0.05). After 3 months, Hb levels were not different between the non-EPO and EPO groups (12.6+/-1.5 g/dL vs. 12.0+/-1.5 g/dL, respectively), although there was a higher increase in the EPO group (4.1+/-1.1 g/dL vs. 3.2+/-1.1 g/dL, P=0.02). In a Cox regression analysis, EPO use (relative risk 7.2, P=0.004) and dose (relative risk=0.63, P=0.04) were retained as independent variables predicting the time to reach an Hb level greater than 12.5 g/dL. In the EPO group, 14 of 22 patients reached the target Hb level of more than 12.5 g/dL versus 12 of 18 patients in the non-EPO group (P=not significant). Serum creatinine levels were not different between groups. RhuEPO in the immediate posttransplantation period seems to have no relevant clinical impact on the correction of anemia. There was no difference in the evolution of serum creatinine levels. In view of the cost, the use of RhuEpo in the posttransplantation period should be limited to high-risk patients.

Anemia↗

The pathophysiology of acute renal failure.

This article summarizes the pathophysiology of acute renal failure from both experimental and clinical points of view. Prerenal acute renal failure is an appropriate physiologic response to renal hypoperfusion and can complicate any disease characterized by either true hypovolemia or a reduction in the effective circulating volume. In acute tubular necrosis, the abrupt fall in glomerular filtration rate is thought to be caused by interplay of hemodynamic and tubular abnormalities. The postischemic kidney also shows a dramatic capacity for recovery. The molecular mechanisms and the effect of growth factors are also summarized.

Acute Kidney Injury↗

Disseminated Mycobacterium avium complex infection in a renal transplant patient.

Organ transplant recipients are at an increased risk of developing opportunistic infections due to prolonged immunosuppression. We present the case of a renal transplant recipient with severe CD4 lymphopenia who developed disseminated Mycobacterium avium complex infection. Recovery from infection was paralleled by a progressive increase in CD4 lymphocytes. T lymphocyte subsets are not monitored routinely in organ transplants but may identify patients at risk of developing serious infectious complications.

Journal Article↗

Phenytoin intoxication in critically ill patients.

Phenytoin intoxication can result in major and possibly life-threatening disorders. Furthermore, the hepatic clearance can become saturated, thus, shifting the elimination from first- to zero-order kinetics. This results in a slow elimination of the compound in case of intoxication. The treatment modalities for phenytoin overdose are limited. Taking into account the high level of protein binding, the molecule is not easily eliminated from the body by means of extracorporal epuration. Although reports exist on the use of MARS (molecular adsorbents recirculating system) dialysis, peritoneal dialysis, and standard dialysis for the elimination, in practice, hemoperfusion, is the most often applied technique. The authors report the case of a hypoalbuminemic patient with severe neurologic signs of phenytoin intoxication (total concentration moderately elevated, free fraction high). A combination of high-flux dialysis and hemoperfusion resulted in a considerable extraction of the drug, accelerating the natural clearance from the body and ameliorating clinical signs of intoxication. In selected patients (with a high free fraction of phenytoin), high-flux dialysis may be a valuable alternative or adjuvant to hemoperfusion.

Epilepsy↗

The use of low dose octreotide prophylaxis in pancreatic transplants with enteric drainage. Results of a prospective randomized single center trial.

AIM: The aim of this study was to investigate the effect of octreotide in the perioperative course of pancreas transplants drained into the bowel in terms of fistula formation, pancreatitis, hemorrhage and thrombosis, and to compare the results to patients not receiving octreotide in a prospectively, randomized single center trial. PATIENTS AND METHODS: Forty pancreas transplant recipients were prospectively randomized to either receive or not to receive octreotide 0.1 mg subcutaneously at the time of operation and 3x/d there after until post-operative day 7. The incidence of pancreatic leakage from the anastomosis and the content of peritoneal fluid drainage regarding amylase and lipase concentrations collected by abdominal drains were registered on day 0-10. Both groups were comparable for age, sex, onset of diabetes, surgical procedure and immunosuppressive regimen. RESULTS: There were 35 simultaneous pancreas-kidney transplants and five solitary pancreas transplants, two in the octreotide and three in the control group two pancreas after kidney, one pancreas after liver pancreas, one pancreas after simultaneous pancreas kidney transplantation, one pancreas transplant alone. All had enteric drainage. Twenty patients received octreotide and 20 did not. In one patient, receiving octreotide the pancreas had to be removed for septic complications because of an enteric fistula arising from the anastomosis (1/20 = 5%). The incidence in patients on octreotide vs. non-octreotide was 1 vs. 0 for pancreatitis, 2 vs. 3 for hemorrhage, 2 vs. 1 for thrombosis and 2 vs. 0 for pancreatic fistulae resulting in an actual overall 12 months patient survival of 100% in both groups and a pancreas survival of 85% vs. 95%. For primary simulaneous pancreas kidney the pancreas graft survival was 93%. The amylase and lipase concentrations of fluid collections drained into the peritoneum on day 0 to 10 post-operatively indicating pancreatic fistulization was comparable in both groups. CONCLUSION: The use of octreotide following pancreas transplantation did not prevent pancreatic fistula formation from the anastomosis neither from the pancreatic capsule in pancreas transplantation with enteric drainage. Further studies are required to finally evaluate the benefit of this prophylactic treatment.

Adult↗

Open prospective multicenter study of conversion to tacrolimus therapy in renal transplant patients experiencing ciclosporin-related side-effects.

The hyperlipidemic and hypertensive effects of ciclosporin constitute a cardiovascular risk. Cosmetic side-effects are known to reduce patients' quality of life. This was a 6-month, open, prospective, multicentre study in 296 adult kidney transplant patients to evaluate the conversion from ciclosporin to a tacrolimus-based regimen. Primary indications for conversion were hyperlipidemia (n =77), hypertension (n = 72), hypertrichosis (n = 32) and gingival hyperplasia (n = 115). At month 6, hyperlipidemia and hypertension were at least moderately improved in 59.1% and 63.5% of patients, and strongly or completely resolved in 29% and 25%. Gingival hyperplasia and hypertrichosis were strongly or completely resolved in 73% and 72% of patients. Mean total cholesterol was reduced from 255 to 218 mg/dl. Mean systolic blood pressure (SBP) was reduced from 152.9 to 137.5 mmHg and mean diastolic blood pressure (DBP) from 90.7 to 85.8 mmHg. Ciclosporin-related side-effects resolved or improved after conversion to tacrolimus.

Adult↗

Kinetic behavior of urea is different from that of other water-soluble compounds: the case of the guanidino compounds.

BACKGROUND: Although patients with renal failure retain a large variety of solutes, urea is virtually the only currently applied marker for adequacy of dialysis. Only a limited number of other compounds have up until now been investigated regarding their intradialytic kinetics. Scant data suggest that large solutes show a kinetic behavior that is different from urea. The question investigated in this study was whether other small water-soluble solutes, such as some guanidino compounds, show a kinetic behavior comparable or dissimilar to that of urea. METHODS: This study included 7 stable conventional hemodialysis patients without native kidney function undergoing low flux polysulphone dialysis (F8 and F10HPS). Blood samples were collected from the inlet and outlet bloodlines immediately before the dialysis session, after 5, 15, 30, 120 minutes, and immediately after discontinuation of the session. Plasma concentrations of urea, creatinine (CTN), creatine (CT), guanidinosuccinic acid (GSA), guanidinoacetic acid (GAA), guanidine (G), and methylguanidine (MG) were used to calculate corresponding dialyzer clearances. A two-pool kinetic model was fitted to the measured plasma concentration profiles, resulting in the calculation of the perfused volume (V(1)), the total distribution volume (V(tot)), and the intercompartmental clearance (K(12)); solute generation and overall ultrafiltration were determined independently. RESULTS: No significant differences were observed between V(1) and K(12) for urea (6.4 +/- 3.3 L and 822 +/- 345 mL/min, respectively) and for the guanidino compounds. However, with respect to V(tot), GSA was distributed in a smaller volume (30.6 +/- 4.2 L) compared to urea (42.7 +/- 6.0L) (P < 0.001), while CTN, CT, GAA, G, and MG showed significantly higher volumes (54.0 +/- 5.9 L, 98.0 +/- 52.3 L, 123.8 +/- 66.9 L, 89.7 +/- 21.4 L, 102.6 +/- 33.9 L, respectively; P= 0.004, = 0.033, = 0.003, < 0.001, = 0.001, respectively). These differences resulted in divergent effective solute removal: 67% (urea), 58% (CTN), 42% (CT), 76% (GSA), 37% (GAA), 43% (G), and 42% (MG). CONCLUSION: The kinetics of the guanidino compounds under study are different from that of urea; hence, urea kinetics are not representative for the removal of other uremic solutes, even if they are small and water-soluble like urea.

Aged↗

Dialysate partitioning in the Genius batch hemodialysis system: effect of temperature and solute concentration.

BACKGROUND: The Genius batch system contains a 75-L closed reservoir from which fresh dialysate is extracted at the top, and to which spent dialysate is returned at the bottom. In vivo studies have demonstrated that almost the entire amount of dialysate can be used before contamination of fresh with spent dialysate occurs. The question is raised whether density differences cause this separation, and what the relative contributions of temperature and solute content are. METHODS: As patient substitute, a container filled with dialysate was loaded with various amounts of urea. Temperature differences between spent and fresh dialysate were imposed by not heating the dialysate at the outlet line from the dialyzer (A), heating the outlet to obtain continuously equal temperatures at inlet and outlet (B), or to temperatures as in vivo (C). With a dialysate flow set at 300 mL/min, urea is not expected at the inlet before 250 minutes. RESULTS: With a urea concentration of 33 mg/dL, urea contamination at the dialysate inlet line occurred after 185 +/- 20 (A), 122 +/- 11 (B), and 175 +/- 12 minutes (C) of dialysis, whereas with 67 mg/dL, this happened at 219 +/- 5 (A), 162 +/- 11 (B), and 202 +/- 8 minutes (C). With 100 and 150 mg/dL, urea contamination appeared at 224 +/- 2 (A) and 204 +/- 14 minutes (B), and 227 +/- 5 (A) and 232 +/- 3 minutes (B), respectively. CONCLUSION: Both temperature differences between spent and fresh dialysate and solute content of spent dialysate contribute to dialysate partitioning in the Genius dialysis system.

Dialysis Solutions↗

Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death. A simple definition and classification of kidney disease is necessary for international development and implementation of clinical practice guidelines. Kidney Disease: Improving Global Outcomes (KDIGO) conducted a survey and sponsored a controversies conference to (1) provide a clear understanding to both the nephrology and nonnephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI), (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD. The K/DOQI definition and classification were accepted, with clarifications. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause. Kidney damage in many kidney diseases can be ascertained by the presence of albuminuria, defined as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens. GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. Kidney disease severity is classified into five stages according to the level of GFR. Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed.

Albuminuria↗

Chronic kidney disease: a European perspective.

There is an exponential growth worldwide of patients with end-stage renal disease (ESRD). Prevalences, outcomes, and underlying causes of ESRD are relatively well documented through different organizations. It is, however, clear that a large part of the bad outcome of ESRD patients is due to deficient follow-up during the earlier chronic kidney disease (CKD) stages. Data on CKD, prevalence of the different stages, and the evolution to ESRD are rather scant, and available data are conflictive. This is at least partly due to the lack of an international standard for measurement of renal function. In addition, there is compiling evidence that presence of proteinuria, even with a normal renal function, predisposes to ESRD. Most authors now prefer the term "kidney injury" rather than "kidney failure" to indicate people at risk for evolution to ESRD or for complications of CKD. Detection of these patients at risk is important to implement measures to slow down progression of CKD and avoid secondary complications. As it is clear that most of these CKD patients die before they reach ESRD, it might be that by taking the necessary preventive measures, the number of ESRD patients might still further increase exponentially.

Adult↗