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Biomedical subjects

Bertrand Dussol

Publications and source records attributed to Bertrand Dussol.

At least 19 recordsLinked to original sources
PubMed2006

Influence of haemodialysis and left ventricular failure on peripheral A(2A) adenosine receptor expression.

BACKGROUND: Haemodialysis (HD) sometimes accelerates left ventricular failure (LVF). As adenosine (ADO) is strongly implicated in cardiovascular functions, particularly via A(2A) receptor activation and as changes of peripheral A(2A) receptors mirror changes occurring in the cardiovascular system, we examined the influence of HD and LVF on both ADO plasma concentration and the expression of A(2A) receptors (i.e. Bmax, K(D) and mRNA amount) of peripheral blood mononuclear cells. METHODS: This cross-sectional study included 61 chronic renal failure (CRF) patients: 41 without LVF (24 haemodialysed and 17 undialysed) and 20 with LVF (9 haemodialysed and 11 undialysed). Ten LVF patients without CRF and 10 healthy subjects were also examined. RESULTS: (i) Bmax values of CRF patients without LVF were significantly decreased in undialysed patients compared with haemodialysed patients, and compared with controls (69 +/- 25 vs 98 +/- 33 vs 180 +/- 60 fmol/mg of protein, P < 0.05). Bmax values of CRF patients with LVF were lower in undialysed patients than in haemodialysed patients (60 +/- 27 vs 101 +/- 27 fmol/mg of protein, P < 0.05). Bmax values of LVF patients without CRF were lower than in controls (51 +/- 19 vs 180 +/- 60 fmol/mg of protein). (ii) A(2A) mRNA expression was increased in haemodialysed patients compared with controls (20.2 +/- 0.75 vs 17.6 +/- 1.3, P < 0.05). (iii) ADO plasma levels were high in haemodialysed patients and further increased during the HD sessions. CONCLUSION: The number of A(2A) receptors was decreased by CRF with or without LVF. However, this decrease was less important in haemodialysed patients. The changes in peripheral A(2A) receptor expression suggest a significant inflammatory response to HD and heart or kidney failure. Whether these changes do reflect alterations in cardiomyocytes needs further investigation.

Adenosine↗
PubMed2006

[About two cases of hypokaliemic periodic paralysis].

We report on two cases of hypokaliemic periodic paralysis due to a potassium shift from the extracellular to the intracellular compartment of skeletal muscle cells. The first case occurred in a 15-year-old boy who experienced rapid onset flaccid tetraplegia without neurological abnormalities. Physical exam revealed facial dysmorphy, and EKG a long QT. Biology evidenced shift hypokalemia that was quickly reversible after administration of intravenous potassium. After exclusion of Andersen-Tawil syndrom, hypokalemic familial paralysis (Westphall disease) was diagnosed by molecular genetic testing (disease-causing mutation in CACNA1S) in the proband and in three other family members. The second case occurred in a 24-year-old male who experienced rapid onset flaccid tetraplegia due to intracellular potassium shift that was quickly reversible after administration of intravenous potassium. Biology revealed thyrotoxicosis due to Grave's disease. To the best of our knowledge, this is the first case described in a people from pacific origin. The clinical, biological, and electromyographic findings of the most frequent causes of periodic paralysis are underlined as well as the molecular genetic diagnosis in familial forms.

Adolescent↗
PubMed2006

A randomized trial of saline hydration to prevent contrast nephropathy in chronic renal failure patients.

BACKGROUND: Contrast nephropathy (CN) is a common cause of renal dysfunction that may be prevented by saline hydration and by drugs such as theophylline or furosemide. Whether oral saline hydration is as efficient as intravenous saline hydration is unknown. The preventive efficacy of theophylline and furosemide for CN remains controversial. The purpose of the current study was to evaluate the efficacy of oral saline hydration and of intravenous saline hydration plus theophylline or furosemide for the prevention of CN. METHODS: We prospectively studied 312 patients with chronic renal failure (serum creatinine 201+/-81 micromol/l, Cockcroft clearance 37+/-12 ml/min/1.73 m(2)), who were undergoing various radiological procedures with a non-ionic, low osmolality contrast agent. Patients were randomly assigned to four arms. In arm A, patients received 1 g/10 kg of body weight/day of sodium chloride per os for 2 days before the procedure. In arm B, patients received 0.9% saline intravenously at a rate of 15 ml/kg for 6 h before the procedure. In arm C, patients received the same saline hydration as in arm B plus 5 mg/kg theophylline per os in one dose 1 h before the procedure. In arm D, patients received the same saline hydration as in arm B plus 3 mg/kg of furosemide intravenously just after the procedure. RESULTS: Patients were well-matched with no significant differences at baseline in any measured parameters. Acute renal failure, defined as an increase in serum creatinine of 44 micromol/l (0.5 mg/dl), occurred in 27 out of 312 patients (8.7%). There was no significant difference between the rate of renal failure in the different arms of the study: five out of 76 (6.6%) in arm A, four out of 77 (5.2%) in arm B, six out of 80 (7.5%) in arm C and 12 out of 79 (15.2%) in arm D. No patient had fluid overload or a significant increase in blood pressure in the 2 days following the radiological procedure. The independent predictors of CN were diabetes mellitus, high baseline serum creatinine and high systolic blood pressure. CONCLUSIONS: Oral saline hydration was as efficient as intravenous saline hydration for the prevention of CN in patients with stage 3 renal diseases. Furosemide and theophylline were not protective.

Administration, Oral↗
PubMed2006

[What do large clinical trials learn us about cardiovascular and renal prevention in patients with type 2 diabetes mellitus and hypertension?].

Type 2 diabetes mellitus and hypertension are frequently associated. Cardiovascular morbidity is a major burden in these patients. Furthermore a renal disease appears in 40% of them that may lead to chronic terminal renal failure. Whatever the stage of the renal disease, it increases the cardiovascular risk. A majority of type 2 diabetic patients will eventually died of cardiovascular complications before having reached chronic terminal renal failure. Many large clinical trials including type 2 diabetic patients with hypertension have been performed in the last 20 years with cardiovascular morbidity and mortality as primary outcomes. These trials mainly evaluated the role of glycemic control, of hypertension as well as the decrease of LDL-cholesterol. Based on these trials, the prescription type of hypertensive type 2 diabetic patient should include, besides hygienic and dietary advices, antidiabetic treatment, thiazide and/or betablocker and platelet inhibitor. Statin should be prescribed for secondary prevention if serum LDL-cholesterol is above 1,3 g/l and for primary prevention depending on serum LDL-cholesterol and on the number of cardiovascular risk factors. The objectives are an HbA1c below 6,5%, a LDL-cholesterol below 1g/l and a blood pressure below 150/80 mmHg. The appearance of diabetic nephropathy alters the treatment and the therapeutic objectives. Many large trials aimed at preventing microalbuminuria (primary prevention), macroproteinuria (secondary prevention), and chronic renal failure (tertiary prevention) have been conducted. For primary prevention, angiotensin-converting-enzyme inhibitors should be prescribed in case of hypertension because they delay the appearance of microalbuminuria. For secondary prevention, angiotensin-converting-enzyme inhibitors and angiotensin-receptor blockers decrease albuminuria excretion rate and delay the appearance of macroproteinuria whatever the blood pressure. Tertiary prevention is based on angiotensin-receptor blockers since they slow down the decrease of renal function. The objectives are a blood pressure below 130/80 mmHg and the regression or the reduction of albuminuria excretion rate. Intensified and target-driven interventions aimed at multiple risk factors implicated in cardiovascular and renal lesions, as successfully performed in the STENO-2 study, reduce the risk of cardiovascular and renal morbidity and mortality. In this article, large clinical trials having the prevention of cardiovascular and renal risks as primary outcomes were analyzed.

Cardiovascular Diseases↗
PubMed2006

Estimated one-year glomerular filtration rate is the best predictor of long-term graft function following renal transplant.

BACKGROUND: Long-term success of renal transplantation depends upon the quality of the donor organ, avoidance of peritransplant and early posttransplant damage (rejection), and optimal maintenance of graft function after the first 6-12 months. Glomerular filtration rate (GFR) at 1 year is a standard way to evaluate short-term success, whereas calculated GFR at 5 years gives a better appreciation of long-term outcomes. The objective of this study was to assess the effect of various demographic and transplant-related parameters on renal function via GFR at 1 year and 5 years post transplantation, using univariate and multivariate data analysis. METHODS: Data on 1-year GFR were available from 10,397 patients, whereas 2,889 patients provided data on both 1-year and 5-year GFR. All patients were enrolled in the Neoral Multinational Observational Study in Transplantation (Neoral-MOST), an ongoing, prospective, observational study of adult renal transplant recipients. RESULTS: One-year GFR was the most relevant predictor for 5-year GFR. In a multifactorial analysis (ANCOVA) using 1-year GFR as a continuous variable, the effects of several highly relevant parameters from univariate analysis (such as acute rejection and delayed graft function) on 5-year GFR appeared to be fully mediated by their influence on 1-year GFR, whereas immunological risk factors like HLA match or previous transplantation had an ongoing effect on graft function beyond year 1. CONCLUSIONS: The findings of this study corroborate and augment data from previous registry surveys, and confirm the importance of observational studies in investigating the role of peritransplant parameters on long-term graft outcome.

Adult↗
PubMed2006

Artificial neural networks for assessing the risk of urinary calcium stone among men.

The pathophysiology of idiopathic calcium oxalate nephrolithiasis involves metabolic abnormalities. Previous studies gave conflicting results about the metabolic factors in stone formers. Artificial neural networks (ANN) are new methods based on computer programming that have outperformed conventional methods in prediction of outcomes in different medical applications. The aim of our study was to compare with ANN the clinical and biochemical parameters implicated in urinary calcium stone between stone formers (SF) and controls (C). We compared 11 clinical and biochemical variables among 119 male idiopathic calcium oxalate SF and 96 C by univariate and multivariate statistical analyses. Univariate analyses included discriminant analysis, logistic regression analysis, and ANN. For multivariate analyses, stepwise discriminant analysis and ANN were performed. Variables included age, body mass index (BMI), family history of nephrolithiasis, supersaturation with respect to calcium oxalate, calcemia, and 24-h urinary calcium, oxalate, uric acid, urea, sodium, and citrate. With univariate and multivariate analyses, ANN were as efficient as classical statistical analyses in discriminating the different parameters. The sensitivity, the specificity, and the percentage of correctly classified patients were similar in all analyses. With ANN, supersaturation (receiver operating characteristic, ROC curves index 0.73) and urea (ROC 0.72) were the most discriminant followed by family history and urinary calcium (ROC 0.67). ROC index was 0.63 for citrate, 0.61 for oxalate and urate, 0.60 for sodium and calcemia, 0.58 for age, and 0.56 for BMI, but these parameters were not statistically different between SF and C. ANN gave additional information since they made it possible to determine the cut-off values of the parameters and their predictive power. Cut-off values for being a stone former were 8.9 for supersaturation and 363 mmol/day for urinary urea with a predictive power of 0.69 and 0.70, respectively. Univariate and multivariate analysis evidenced supersaturation and 24-h urinary urea excretion as the most discriminant parameters between the two populations. In addition to high supersaturation, the negative impact of protein intake was confirmed.

Adolescent↗
PubMed2006

Follow-up after renal transplantation with organs from donors after cardiac death.

Kidneys obtained from donors after cardiac death (DCD) are known to have higher rates of primary nonfunction and delayed graft function (DGF) than heart beating cadaveric donor (CAD) kidneys, but little is known about long-term function of DCD grafts that survive to 1 year. To investigate the outcomes of renal transplant recipients whose DCD graft functioned for at least 1 year, this study analyzed data collected from 326 DCD graft recipients and 340 CAD-matched controls enrolled in a prospective, multinational, observational study--Neoral-MOST (Multinational Observational Study in Transplantation) (Novartis, Basel, Switzerland). No differences were found in the demographics or immunosuppression between the two groups. All patients received a Neoral-based immunosuppressive regimen. Donors after cardiac death graft recipients had a higher incidence of DGF (40% vs. 27% CAD; P < 0.001). One year glomerular filtration rate (GFR) and GFR-decline after 1 year were similar in DCD and CAD recipients (GFR 56 ml/min DCD vs. 59 ml/min CAD; GFR-decline -1.3 ml/min DCD vs. -1.4 ml/min CAD; P = not significant). Multifactorial analyses confirmed that GFR at 1 year was significantly influenced by donor age and gender, DGF, and acute rejection; however, DCD status was not an independent risk factor in cyclosporine-treated patients with grafts that had functioned for at least 1 year.

Adult↗
PubMed2006

Population pharmacokinetics of ceftriaxone and pharmacodynamic considerations in haemodialysed patients.

OBJECTIVES: To determine the pharmacokinetic parameters of ceftriaxone following an infusion in haemodialysed outpatients and to use these parameters for an optimisation of dosing based on pharmacodynamic indices. METHODS: Fifty haemodialysed patients were enrolled in a single-centre, prospective, open-label study. They received short intravenous infusions of ceftriaxone 1 or 2 g every 48 hours for bronchopneumonia immediately after the dialysis session. Total plasma concentrations of ceftriaxone were analysed with a population pharmacokinetic approach using nonlinear mixed-effects modelling. Free drug concentrations were derived from published binding parameters in order to estimate the time when they exceed the minimum inhibitory concentration (MIC). RESULTS: The pharmacokinetics were best described by a two-compartment model. None of the covariates tested (age, bodyweight, height, sex, body mass index, albumin) influenced the pharmacokinetic parameters. The estimated population pharmacokinetic parameters (interindividual variability [percentage of coefficient of variation]) were clearance 0.36 L/h (48%), volume of distribution of the central compartment 4.53 L (47%), intercompartmental clearance 10.8 L/h and volume of distribution of the peripheral compartment 9.54 L (63%). The terminal elimination half-life (t(1/2)beta) from plasma was 27.5 hours. The mean (range) times when the free drug concentration exceeded the MIC (T>MIC) following ceftriaxone 1 g infusion were 60.3 (53.0-67.7) hours and 2.5 (1.0-3.9) hours for the breakpoints 1 and 8 mg/L (based on free drug concentration), respectively. After administration of ceftriaxone 2 g, the T>MIC was 88.5 (78.8-98.3) hours and 17.7 (13.3-22.0) hours for the breakpoints 1 and 8 mg/L, respectively. The simulated free drug concentrations (median, first and third quartile) for 48 and 72 hours following the first dose of ceftriaxone 1g were 1.11, 0.63 and 1.89 mg/L, and 0.63, 0.28 and 1.18 mg/L, respectively. For ceftriaxone 2g infusion, the simulated free concentrations (median, first and third quartile) at 48 and 72 hours were 2.50, 1.40 and 4.52 mg/L, and 1.37, 0.60 and 2.70 mg/L, respectively. CONCLUSIONS: On the basis of decreased clearance in haemodialysed patients, it can be argued that the dose of ceftriaxone should be decreased or the delay between doses should be increased. However, taking into account pharmacodynamic considerations, this study showed that following intravenous administration of ceftriaxone 1 g after each dialysis session, some patients were at risk of achieving a concentration below the MIC (1 mg/L), particularly if the second administration occurred 72 hours after the first dosing. Thus, a dose of ceftriaxone 2 g intravenously is recommended immediately following dialysis, particularly in patients with severe infections or when the dosing interval will be higher than 48 hours.

Adult↗
PubMed2006

Influence of the dialysis membrane on markers of tissue ischemia.

BACKGROUND: Hemodialysis (HD) is often accompanied by adverse effects, such as tissue ischemia. We have already observed an increase in plasma adenosine (ADO) levels during HD sessions, which may be the result of tissue ischemia. Here we evaluate the influence of the dialysis membrane on two sensitive and early markers of ischemia: ADO and ischemia-modified albumin (IMA). METHODS: We included in the study 50 patients with end-stage renal failure, 39 hemodialyzed (mean age 61+/-24 years; 24 male; membranes: 23 synthetic and 16 cellulose based) and 11 undialyzed (mean age 55+/-12 years; 6 male), and 10 healthy subjects (mean age 47+/-11 years; 4 male). We compensated for hemoconcentration during HD by measuring either the IMA to albumin (Alb) or the ADO to Alb ratio. RESULTS: Under basal conditions, the IMA to Alb ratio was not significantly different in patients and controls and HD did not significantly modify this ratio. Conversely, the ADO to Alb ratio (mean+/-SD in micromol/g) was higher in patients before HD compared with either undialyzed patients or controls (before HD: 0.077+/-0.02; undialyzed patients: 0.026+/-0.11; controls: 0.022+/-0.01). During HD, there was a significant increase in the ADO to Alb ratio (before HD: 0.077+/-0.02; after HD: 0.09+/-0.029; p<.01). We found no significant difference in the IMA to Alb or ADO to Alb ratio using either synthetic or cellulose-based membranes. CONCLUSIONS: We concluded that ADO is a more sensitive marker of ischemia than IMA and that, under our HD conditions, the ischemia caused by HD was very weak, independent of the dialysis membrane.

Adenosine↗
PubMed2006

Relationship between A2A adenosine receptor expression and intradialytic hypotension during hemodialysis.

BACKGROUND: Intradialytic hypotension (IDH) is a common complication of hemodialysis sessions (HDSs). Adenosine may contribute to the drop in blood pressure during IDH events because it has hypotensive effects. As A(2A) adenosine receptor expression is essential for blood pressure control, we compared the expression of A(2A) receptors (Bmax, K(D), and messenger ribonucleic acid [mRNA] levels) in peripheral blood mononuclear cells from IDH and non-IDH patients and from controls. We also evaluated adenosine plasma levels (APLs). METHODS: We included 10 hemodialyzed patients with at least three IDH events per month. We also included 11 hemodialyzed patients with no history of IDH events and 10 healthy subjects as controls. RESULTS: IDH patients had higher Bmax values than non-IDH patients (mean before HDS, +86%; after HDS, +112%), whereas non-IDH patients had lower Bmax values than controls (mean -72%). K(D) values were not significantly different between patients and controls. The levels of mRNA increased significantly during HDS but without an increase in receptor expression on the cell membranes. APLs were higher in hemodialyzed patients than in controls. CONCLUSION: We found that A(2A) receptors are more expressed in IDH patients than in non-IDH patients, whereas APL was high in all patients. Both high APL and a relative increase in A(2A) receptor expression may favor IDH events.

Adenosine↗
PubMed2005

A randomized trial of low-protein diet in type 1 and in type 2 diabetes mellitus patients with incipient and overt nephropathy.

OBJECTIVE: The efficacy of a low-protein diet in the secondary prevention of diabetic nephropathy is not established in patients with type 1 or type 2 diabetes mellitus. To determine whether a low-protein diet slows the decrease in glomerular filtration rate (GFR) and decreases the albumin excretion rate (AER) in diabetic patients with incipient and overt nephropathy, we performed a 2-year prospective, randomized controlled trial comparing the effects of a low-protein diet (0.8 g/kg/day) with a usual-protein diet. SETTING AND PATIENTS: The study was conducted in a University hospital and included 63 type 1 and type 2 diabetic patients with either incipient or overt nephropathy and mild renal failure (prestudy GFR, 80 +/- 20 mL/min). The primary outcome measures were decreased in GFR and 24-hour AER. RESULTS: In the low-protein-diet group, patients were younger (52 +/- 12 versus 63 +/- 9 years old) and more often were type 2 diabetic. During the follow-up period, according to dietary records the low-protein-diet group consumed 16% +/- 3% of total caloric intakes as compared with 19% +/- 4% in the usual-protein-diet group (P < .02), but 24-hour urinary urea excretions did not differ between the two groups. The 2-year GFR decrease was 7 +/- 11 mL/min in the low-protein-diet group and 5 +/- 15 mL/min in the usual-protein-diet group (P = not significant). AER did not increase significantly in the two diet groups during the follow-up period. Blood pressure and glycemic control were similar in the two groups all along the study. The decrease in GFR and AER were also similar in 6 compliant patients according to dietary records and to 24-hour urinary urea excretions from the low-protein-diet group and in 12 patients from the usual-protein-diet group. CONCLUSIONS: A 2-year low-protein diet did not alter the course of GFR or of AER in diabetic patients with incipient or overt nephropathy receiving renin-angiotensin blockers with strict blood pressure control.

Adult↗
PubMed2004

A randomized trial of furosemide vs hydrochlorothiazide in patients with chronic renal failure and hypertension.

BACKGROUND: Loop diuretics are the drugs of choice for the treatment of hypertension in chronic renal failure patients. However, the adaptive changes in the distal nephron and the short half-life of these drugs may decrease their long-term efficacy. Thiazides are not believed to be efficient in advanced renal failure, but this is debated. METHODS: We compared the efficacy of long-acting furosemide (60 mg/day) and hydrochlorothiazide (25 mg/day) in a double-blind, randomized crossover trial in seven patients with severe renal failure and hypertension (seven men, 54+/-10 years old). The primary end-points were sodium and chloride fractional excretions after 1 month of each diuretic and then after their combination. During the trial, other treatments and the diet were controlled. RESULTS: A trend towards an increase in the fractional excretion of sodium and of chloride was observed with furosemide, but the difference did not reach the level of statistical significance (P = NS). Hydrochlorothiazide significantly increased fractional excretion of sodium and chloride from 3.7+/-0.9 to 5.5+/-0.3 and from 3.9+/-0.19 to 6.5+/-0.3, respectively (P<0.05). The combination of the two diuretics had no additional effect on the increase in sodium and chloride fractional excretion. Furosemide, hydrochlorothiazide and the combination of the two diuretics decreased mean arterial blood pressure by the same extent from 112 to 97, 99 and 97 mmHg, respectively (P<0.05). CONCLUSIONS: Hydrochlorothiazide increased the fractional excretion of sodium and chloride more than furosemide did in hypertensive severe renal failure patients. Mean arterial blood pressure decreased by the same amount with both diuretics. Combining furosemide and hydrochlorothiazide did not increase the efficacy of hydrochlorothiazide.

Adult↗
PubMed2004

Sequential development of perinuclear ANCA-associated vasculitis and anti-glomerular basement membrane glomerulonephritis.

A 75-year-old man suffered from perinuclear antineutrophil cytoplasm antibody (p-ANCA)-associated vasculitis with mild renal involvement. Three years later, he suddenly experienced an anuric acute renal failure due to anti-glomerular basement membrane (GBM) disease. Antibodies to myeloperoxydase were continuously present at a high titer in the patient's serum while serum anti-GBM antibodies were only detected at the time of the acute renal failure. A substantial proportion of patients with anti-GBM glomerulonephritis simultaneously display ANCAs whose pathogenic role is not clear. In our case, ANCAs were supposed to be of pathogenic importance because they may have uncovered the Goodpasture antigen. This case report lends further support to the concept that p-ANCA vasculitis may trigger anti-GBM disease.

Aged↗
PubMed2004

Prognostic value of inducible myocardial ischemia in predicting cardiovascular events after renal transplantation.

BACKGROUND: The aims of the present study were to determine the prevalence of inducible myocardial ischemia (IMI) in renal transplant recipients (RTR) more than 50 years old, to identify predictors of IMI, and to search for its prognostic value. METHODS: Among the 377 renal transplantations performed between 1989 and 1998 in a single institution, 120 were done in patients > or =50 years old, and 97 were recruited for the study. During the last quarter of 1998, all of them underwent an exercise test (EST), an exercise-thallium 201 single photon emission computed tomography coupled with dipyridamole (SPECT), and 81% of them had a dobutamine stress echocardiography (DSE). Patients with IMI subsequently underwent coronary angiography to detect coronary stenosis. RESULTS: IMI was present in 12 of the 97 patients (10%). The diagnosis was evidenced by EST in four cases, by SPECT in 11 cases, and DSE in three cases. Five of these 12 patients (42%) had significant coronary artery stenosis (> or =50%). Multivariate analysis of several pre- and post-transplant variables evidenced acute rejection and left ventricular hypertrophy as significant correlates of IMI (both P < 0.03). Patients were prospectively followed-up for 48 months for the occurrence of major cardiovascular events. Kaplan-Meier analysis revealed a significant increase in cardiovascular events in the IMI group (P < 0.0001). In addition, the Cox proportional hazards model revealed that IMI and diabetes mellitus had an independent significant effect on the occurrence of major cardiovascular events. CONCLUSION: IMI was present in 10% of RTR aged > or =50 years, and was predicted by acute rejection and left ventricular hypertrophy. IMI had a strong effect on major cardiovascular events in this population.

Acute Disease↗
PubMed2004

Kinetic study of adenosine concentrations and the expression of adenosine deaminase in mononuclear cells during hemodialysis.

BACKGROUND: We previously showed that high intralymphocytic adenosine (Ado) concentrations are found in hemodialyzed patients due to the reduced activity of mononuclear cell adenosine deaminase (MCADA). These abnormalities contribute to the immune defect observed in HD patients. The kinetics of these abnormalities and the causes of the low MCADA activity, however, have not been investigated. Here, we addressed this question. Since interferon gamma (IFNgamma) partially modulates MCADA, we also evaluated the effect of IFNgamma on MCADA activity in vitro. METHODS AND RESULTS: The study included 12 patients (eight men and four women) who were observed from the first to the 36th hemodialysis (HD) session, and eight healthy subjects (controls). MCADA activity and Ado concentrations were normal before the first HD session. Ado concentrations progressively increased from the first (10.5 +/- 3.1 pmol/10(7) cells) to the fourth session (26.7 +/- 3 pmol/10(7) cells), before stabilizing at a high level. MCADA activity increased transiently until the second session (2.2 +/- 0.5 IU/10(7) cells before HD vs. 2.8 +/- 0.6 IU/10(7)cells), and then decreased and stabilized at a low level (1.0 +/- 0.5 IU/10(7)cells). The amount of MCADA mRNA transiently increased until the third session (mRNA MCADA/mRNA beta-actin: 0.6 +/- 0.2 vs. 0.8 +/- 0.2), and then decreased to 0.3 +/- 0.1 at the 36th session. MCADA activity underwent a dose-dependent increase after IFNgamma stimulation. CONCLUSION: HD affects the transcription of the gene encoding MCADA after just three HD sessions, leading to decreased MCADA activity and increased plasma concentration of Ado.

Adenosine↗