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Biomedical subjects

Y Lebranchu

Publications and source records attributed to Y Lebranchu.

At least 19 recordsLinked to original sources
PubMed2007

Urinary albumin excretion and the risk of graft loss and death in proteinuric and non-proteinuric renal transplant recipients.

BACKGROUND: Microalbuminuria and macroalbuminuria constitute risk factors for ESRD and death in non-transplanted populations. Whether microalbuminuria (especially in non-proteinuric patients) and macroalbuminuria constitute risk factors for graft loss and death is presently unknown in renal transplantation. METHODS: We retrospectively assessed the association between urinary albumin excretion (UAE) and ESRD and death in renal transplantation. RESULTS: UAE was measured in 616 (397 proteinuric; 219 non-proteinuric patients) renal transplant recipients. They were grafted for 62 months (range: 6-192). During the 40 months (3.7-99) thereafter, 31 patients underwent dialysis and 32 died. Microalbuminuria (vs. normoalbuminuria) and macroalbuminuria (vs. microalbuminuria) were powerful risk factors for graft loss [OR: 14.25 (2.88-52.3) and 16.41 (7.46-36.0), respectively, both p < 0.0001], even after adjustments on renal function and diabetes. Among the 219 non-proteinuric patients, microalbuminuria (vs. normoalbuminuria) was a significant risk factor for graft loss [OR: 23.09 (1.93-276.4), p = 0.0132]. Both microalbuminuria (vs. normoalbuminuria) [OR: 5.55 (2.43-12.66), p < 0.0001] and macroalbuminuria (vs. microalbuminuria) [OR: 4.12 (1.65-10.29), p = 0.0024] were predictive of death. CONCLUSIONS: Microalbuminuria and macroalbuminuria are powerful independent predictors of ESRD and death. Microalbuminuria is a risk factor for graft loss even in non-proteinuric patients. UAE provides additional information on renal and patient prognosis as compared to proteinuria and renal function.

Adult↗
PubMed2006

Low 1-year cyclosporine microemulsion doses are associated with better 5-year renal graft function: an insight from MOST, a multinational observational study.

BACKGROUND: In earlier registry analyses, cyclosporine at doses of < 3 mg/kg/d at 1 year post-renal transplantation has been associated with significant graft loss or reduction in renal function. Improvements in cyclosporine formulation with increased bioavailability, plus the use of more efficient comedications, may now confer better outcomes. To determine the effect of the 1-year cyclosporine microemulsion (CsA-ME) dose on renal allograft function at 5 years, we analyzed data collected from 2889 patients with documented graft survival to year 5 in a prospective, multinational, observational study-Neoral MOST. RESULTS: Glomerular filtration rate (GFR) at year 1 was 63 +/- 20 mL/min and 59 +/- 22 mL/min at year 5. The multivariate analysis including year 1 CsA-ME dose as factor and GFR at 1 year as covariate revealed the most significant factors affecting GFR at year 5 were 1-year GFR, donor age > 60 years, and CsA-ME dose at 1 year. Risk factors associated with reduction in 5-year GFR (<65 mL/min) included donor or recipient age >60 years, delayed graft function, cadaveric donor, previous graft, and acute rejection. CsA-ME dose <3 mg/kg/d was found to protect GFR. Analysis of GFR at each year posttransplantation (Wilcoxon model) found 1-year CsA-ME (cutoff 3 mg/kg/d) had a significant effect at each time point. CONCLUSIONS: Compared to higher doses, CsA-ME <3 mg/kg/d at year 1 posttransplantation is associated with increased preservation of renal allograft function at year 5.

Aged↗
PubMed2006

Early proteinuria is a strong indicator of donor renal lesions, ischemia-reperfusion injury and immunological aggression.

BACKGROUND: Early proteinuria is associated with reduced long-term graft survival. However, the determinants and mechanisms of proteinuria early after transplantation have not been identified. METHODS: Parameters associated with proteinuria within the first 3 months following transplantation were retrospectively assessed among 484 renal transplant recipients. RESULTS: Proteinuria was more abundant in patients with a history of two or more rejection episodes (0.42 +/- 0.68 vs 0.18 +/- 0.39 g/d; P = .02). Proteinuria was greater when donor age was 60 or more (OR: 4.43; P = .003), when recipient death was due to cardiovascular causes (OR: 1.98; P = .002), or when cold (OR: 1.77; P = .006) or warm (1.21; P = .09) ischemia times were prolonged. CONCLUSIONS: Proteinuria early after transplantation was related to pretransplant renal lesions, ischemia-reperfusion, and immunologic injuries.

Biomarkers↗
PubMed2006

Estimation of the glomerular filtration rate through different methods in kidney transplant recipients: correlation with the creatinine clearance measurement.

The measurement of the glomerular filtration rate (GFR) is an important tool for physicians to follow kidney transplant recipients. Indeed, renal function has been shown to be predictive of graft outcome in retrospective studies. Several methods have been proposed to measure GFR. In the present study we evaluated the correlation of GFR between a reference method (calculation through the urine to plasma ratio of creatinine [UV/P] formula) and three estimation equations (Cockcroft and Gault; Nankivell; modification of diet in renal disease) in 81 kidney transplant recipients at 3 and 12 months posttransplantation. We showed a significant correlation between the three predictive formulas and UV/P, but none of the predictive equations showed an excellent correlation. The best correlation between an estimation equation and the UV/P formula was the CG formula. Further studies are required to compare the estimated GFR with better reference methods, such as the use of isotopic markers in kidney graft recipients.

Creatinine↗
PubMed2006

Long-term results of monoclonal anti-Il2-receptor antibody versus polyclonal antilymphocyte antibodies as induction therapy in renal transplantation.

We compared the influence of induction therapy on 5-year patient and graft survival as well as on renal function in 100 kidney graft recipients at low immunological risk treated with antilymphocyte globulin (n = 50) versus anti-IL-2R monoclonal antibody (n = 50) in a prospective multicenter study. Long-term immunosuppressive treatment included cyclosporine, mycophenolate mofetil, and a short course of steroids in all patients. Five year graft (86% vs 86%) and patient (94% vs 94%) survivals were identical in both study arms. Moreover, neither serum creatinine or proteinuria were significantly different between the two groups. Our results showed that the choice of the induction therapy seemed to not have a major impact on long-term outcomes among renal recipients at low immunological risk.

Antibodies, Monoclonal↗
PubMed2006

Tolerability of enteric-coated mycophenolate sodium to 1 year in combination with cyclosporine and corticosteroids in renal transplant recipients.

Enteric-coated mycophenolate sodium (EC-MPS) is therapeutically equivalent to mycophenolate mofetil, but delays release of mycophenolic acid until it reaches the small intestine. De novo renal transplant patients taking part in a 12-month, multicenter, randomized study received cyclosporine microemulsion (CsA-ME, early or delayed to day 6), EC-MPS, steroids, and interleukin-2 antagonist induction. Tolerability data relating to EC-MPS are reported. Ninety-seven patients were randomized to early CsA-ME and 100 patients to delayed CsA-ME. Median daily dose of EC-MPS was 1440 mg at all time points throughout the 12-month period. The most frequently reported adverse events were constipation, anemia, urinary tract infection, abdominal pain, leukopenia, and cytomegalovirus infection; there were four malignancies. Fifty patients (24.6%) discontinued EC-MPS prematurely by 12 months, including 42 patients (84%) who discontinued owing to adverse events. No patient discontinued treatment because of gastrointestinal adverse events. Two-thirds of patients (137 [67.5%]) maintained full EC-MPS dose throughout the 12-month study and did not require any dose reduction or dose interruption. EC-MPS is well tolerated in de novo renal transplant recipients when administered in combination with CsA-ME and steroids, with low rates of dose reductions or interruptions. Gastrointestinal adverse events were responsible for dose reduction or interruption in only 5% of patients.

Adrenal Cortex Hormones↗
PubMed2005

[Cyclosporin-induced toxic neuromyopathy].

INTRODUCTION: Cyclosporine is an immunosuppressive treatment whose side effects limit its usefulness. Among neurological side effects, neuropathies or myopathies have been reported, specially inpatients given combinations of cyclosporine with co-enzyme A reductase inhibitors. CASE REPORT: We report here the case of a 67-year-old woman who developed few months after a kidney graft sensorimotor disorders which progressed rapidly. Since all etiologies of such a disorder were ruled out, the hypothesis of toxicity exclusively induced by cyclosporine was suggested and confirmed by the improvement observed after its withdrawal. CONCLUSION: This observation highlights the fact that cyclosporine may induce neuromyopathies even when given alone at the therapeutic dosage.

Coenzyme A↗
PubMed2004

Relationship between calcineurin inhibition and plasma endothelin concentrations in cyclosporine-A-treated kidney transplant patients.

OBJECTIVE: The inter-individual variability of cyclosporine (CsA) pharmacokinetics is well known. However, there is obviously also an inter-individual pharmacodynamic variability, which might be explored by the measurement of biomarkers of CsA effects. METHODS: In 11 renal transplant patients, blood CsA concentrations, calcineurin inhibition in peripheral blood mononuclear cells and endothelin plasma concentrations were measured over a 4-h period after CsA intake. RESULTS: Mean plasma endothelin concentrations were higher than those of healthy subjects (3.66+/-0.46 pg ml(-1) versus 3.15+/-0.40 pg ml(-1), P<0.01) but were not related to CsA dose or blood concentrations. There was a linear relationship between calcineurin inhibition at t (0) and mean endothelin concentrations (r (2)=0.51, P<0.05). Patients with gingival hypertrophy had higher mean endothelin concentrations than patients without this complication (4.0 pg ml(-1) versus 3.4 pg ml(-1), P<0.01), although CsA doses and concentrations were not different between these two groups. CONCLUSION: We observed a correlation between calcineurin inhibition and endothelin concentrations. Endothelin plasma concentrations is a biomarker of CsA effect, which may provide more information than CsA blood concentrations.

Adult↗
PubMed2004

Cost-minimization study comparing Simulect vs. Thymoglobulin in renal transplant induction.

PURPOSE: Based on the data of clinical trial CHI-F-02 comparing the efficacy and safety of basiliximab (Simulect) vs. anti-thymocyte globulin (Thymoglobulin) in renal transplant induction, we carried out an economic evaluation. METHOD: This pharmacoeconomic study was a cost-minimization study, i.e. given the equivalent efficacy of the products, the strategy that minimized the cost of care was considered better. The cost of care was analyzed from the hospital perspective. MATERIAL: This 'piggyback' study of 100 patients estimated the direct medical costs incurred over 6 months of use of two strategies for renal transplant induction therapy. Direct medical costs are those of utilized medical resources: medications, hospital stays, dialysis, and physician visits and investigations not scheduled in the protocol. RESULTS: In the Simulect arm, significant reductions were found in the initial hospital stay duration and number of infectious episodes. Therefore, although the average cost of treatment was slightly higher with Simulect) than with Thymoglobulin (2964 vs. 2298 Euros), the cost of the initial hospitalization was significantly lower in the Simulect arm (10 907 vs. 11 967 Euros; p = 0.02). Furthermore the mean cost of infectious episodes was significantly lower in the Simulect arm (1056 vs. 1790 Euros, p = 0.03). Cytomegalovirus infection accounted for a significantly smaller proportion of this cost in the Simulect arm than in the Thymoglobulin arm (30% vs. 53%, p = 0.001). CONCLUSION: This study showed direct medical cost savings of 1159 Euros per patient in the Simulect arm, which more than compensated for the higher price of this immunosuppressive drug.

Adult↗
PubMed2003

One-year posttransplant renal function is a strong predictor of long-term kidney function: results from the Neoral-MOST Observational Study.

BACKGROUND: Peritransplant risk factors influence short-term and long-term graft survival, and 1-year serum creatinine is known to predict long-term graft survival. To examine interrelationships between risk factors, renal function at 1 year, and long-term graft function in patients maintained on cyclosporine, we analyzed data collected from 10,692 de novo or maintenance renal transplant recipients in an ongoing international, prospective, observational study--Neoral-MOST (Multinational Observational Study in renal Transplantation). The effect of donor age, delayed graft function, acute rejection, donor type, panel-reactive antibodies, and previous graft on 1- and 5-year renal function and their relationship to 1-year serum creatinine was assessed. RESULTS: Donor age, delayed graft function, acute rejection, and donor type significantly increased the risk for serum creatinine > 130 micromol/L at 1 year posttransplant, and 1-year serum creatinine was the strongest predictor of 5-year renal function. After adjustment for 1-year serum creatinine, an ongoing influence was observed for donor age, donor type, and previous graft. Delayed graft function and acute rejection had a significant effect on serum creatinine at year 1 but no additional impact on long-term graft function. CONCLUSIONS: Serum creatinine at 1 year is influenced by risk factors known to affect overall graft survival and is predictive of 5-year renal graft function. The effects of delayed graft function and acute rejection appear to be limited to their influence on serum creatinine at 1 year, whereas donor type and previous graft predominantly affect later stages of graft life.

Creatinine↗
PubMed2001

Induction versus noninduction in renal transplant recipients with tacrolimus-based immunosuppression.

BACKGROUND: The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. METHODS: This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mg/kg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. RESULTS: At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P<0.001), fever (25.2% vs. 10.1%, P=0.001), herpes simplex (17.9% vs. 5.7%, P=0.001), and thrombocytopenia (11.3% vs. 3.2%, P=0.007). In the induction group, serum sickness was observed in 10.6% of patients. The incidence of new onset diabetes mellitus was 3.4% (induction) and 4.5% (noninduction). CONCLUSION: Low incidences of acute rejection were found in both treatment arms. Induction treatment with ATG has the advantage of a lower incidence of acute rejection, but it significantly increases adverse events, particularly CMV infection.

Adult↗
PubMed2001

[Allorecognition].

TWO TYPES OF RECOGNITION: Direct recognition occurs when the recipient's T cells recognize allogenic antigens presented by the donor antigen presenting cells. Indirect recognition occurs when donor antigens on recipient antigen presenting cells are recognized. DIRECT RECOGNITION: Direct recognition occurs during the first days or weeks after transplantation when naive recipient cells recognize donor dendritic cells that have migrated to secondary lymphoid organs. This explains why acute rejection occurs mainly during the first weeks after transplantation. INDIRECT RECOGNITION: This is certainly a less intense mechanism than direct recognition. It probably is involved in acute rejection but is known to play a major role in chronic rejection. CD4 cells that have been activated by indirect recognition play an essential role in activating B cells, leading to the formation of anti-HLA antibodies as well as in activating macrophages and monocytes, endothelial cells and smooth muscle cells. INDUCTION OF TOLERANCE: Three mechanisms of action for regulating the allo-immune response leading to graft tolerance have been put forward: consumption of interleukin-2, production of suppressive cytokins, direct or indirect suppressive contact. T CELL ACTIVATION: Knowledge of the intracellular signals induced by T cell receptor activation makes it possible to target key proteins that could be blocked leading to better immunosuppression than with calcineurin inhibition.

Acute Disease↗
PubMed2001

[Microalbuminuria in hypertensive, non-proteinuric renal transplant recipients: role of previous acute rejection episodes and sodium intake].

UNLABELLED: Microalbuminuria (Malb: albuminuria: 30-299 mg/24 h) is associated with many cardiovascular parameters (high systolic (SAP) and diastolic (DAP) arterial pressure, total cholesterol, triglycerides, fasting glucose and body weight, low HDL-cholesterol) and may be a marker of cardiovascular and renal risk in the general population. Whether MAlb could be an integrated marker of cardiovascular and renal risk in transplant recipients is unknown. PATIENTS AND METHODS: 75 hypertensive non-proteinuric renal transplant recipients were selected. Antihypertensive medications were stopped for a month prior to the studies. MAlb (on a 24-hour urine collection), cyclosporine trough levels (CsA-L), fasting glucose and lipids were measured. SAP and DAP were determined with a semi-automatic device. RESULTS: 29 patients (12 W/17M) had normal levels of albuminuria (Nalb: albuminuria < 30 mg/24 h) and 46 had MAlb. As compared to Nalb patients, those with Malb were younger (M +/- SD: 44.3 +/- 13 vs 51.2 +/- 9.7 respectively, p = 0.009), had higher SAP (152 +/- 16 vs 146 +/- 15 mmHg, p = 0.09) et DAP (86 +/- 11 vs 81 +/- 10 mmHg, p = 0.01). No difference in smoking habits, serum creatinine (125 +/- 27 vs 119 +/- 28 mumol/L), total-, HDL- and LDL-cholesterol, triglycerides, fasting glucose, CsA-L (142 +/- 29 vs 144 +/- 26 ng/mL), 24 h-urine urea excretion was observed. History of acute rejection episodes (45.7% vs 17.2%, p = 0.01) was more frequent and 24-hour natriuresis (192 +/- 70 vs 152 +/- 79 mmol/24 h, p < 0.01) was higher in Malb than in Nalb. CONCLUSION: The determinants of microalbuminuria in renal transplant recipients are different from those found in the general population. History of acute rejection episodes was more frequent in renal transplant recipients with Malb than in those with NAlb despite similar renal function, suggesting that Malb may a marker of subclinical renal lesions due to immunological aggression. The relationship between natriuresis and Malb suggests that sodium intake modulates target-organ damage associated with hypertension.

Adult↗
PubMed2000

[Regulation and dysfunction of endothelium-dependent vasomotricity. What can be applied to clinical practice?].

FUNCTIONS OF THE ENDOTHELIUM: The endothelium plays a pivotal role in regulating vasomotor tone, vessel permeability, blood cell extravasation, and antiatherogenic, antithrombogenic and antiadhesive processes. DYSFUNCTION OF THE ENDOTHELIUM: Demonstrated, in particular, by endothelium-dependent vasomotricity disorders, endothelium dysfunction occurs in many psysiological and pathological situations that lead to atherosclerosis: advanced age, menopause, high blood pressure, dyslipidemia, diabetes, smoking, elevated homocysteinemia, chronic renal failure.... These dysfunctions of the endothelium constitute the fundamental and very early step in the development of atherosclerosis. PREVENTION: Specific treatment of functional anomalies of the endothelium can be an essential element in the prevention of atherosclerosis. In certain cases, he cause of endothelial dysfunction may be related to the presence of radical oxygen species, nitric oxide inhibitors, or increased synthesis or release of endothelin. Potential treatments should be adapted to the specific cause of the underlying endothelial anomaly: antioxidants, statins, anti-endothelins, or converting enzyme inhibitors. In clinical practice, it may be important to recognize the cause of endothelial dysfunction for adapted early drug therapy.

Arteriosclerosis↗