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G Mourad

Publications and source records attributed to G Mourad.

At least 19 recordsLinked to original sources
PubMed2006

New onset dyslipidemia after renal transplantation: is there a difference between tacrolimus and cyclosporine?

UNLABELLED: Lipid abnormalities including increased total cholesterol (TC), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) have been frequently reported in renal transplantation and could be involved in the high frequency of cardiovascular diseases in this population. PATIENTS AND METHODS: Two hundred ninety-five patients were transplanted between January 1995 and October 2000 in our center. Two hundred two patients were included in this study. Seventy-six patients received tacrolimus (Tac), and 126 patients cyclosporine (CsA). Lipid parameters were assessed the day of transplantation and 1 year posttransplantation. RESULTS: Serum lipids were similar between the two groups at D0. At M12, TC and LDL-C were significantly higher in the CsA group (6.14 +/- 1.37 vs 5.28 +/- 1.32 mmol/L; P < .05 and 3.98 +/- 1.05 vs 3.26 +/- 1.03 mmol/L; P < .05 CsA vs Tac, respectively). TG were comparable in both groups (1.86 +/- 1.07 vs 1.62 +/- 0.92 mmol/L; P = .55; CsA vs Tac). Incidence of de novo hypercholesterolemia was significantly higher in the CsA group (28 vs 8%) whereas incidence of hyperTG was similar in both groups. Prevalence of LDL-C was significantly higher in the CsA group (65% vs 31%; P < .001), whereas there was no difference in high density lipoprotein (HDL)-C levels. DISCUSSION: Mean serum lipid levels and incidence and prevalence of hyperTC, especially LDL-C, was significantly higher in patients receiving CsA when compared with Tac. TG and HDL-C levels were similar. Although the study was retrospective, our results confirm that CsA increases lipid levels, whereas Tac does not. CONCLUSION: Lipid disorders are frequently observed in renal transplant recipients. CsA, but not Tac, significantly increases incidence and prevalence of high TC and LDL-C.

Adult↗
PubMed2006

Renal transplantation decreases osteoprotegerin levels.

Vascular calcifications are an important risk factor for cardiovascular mortality and morbidity in patients with chronic renal failure. Osteoprotegerin, a soluble decoy receptor for receptor activator NFkB ligand, has emerged as an independent predictive factor of atherosclerosis and vascular calcification in hemodialysis patients. Sparse data are available on the evolution of osteoprotegerin after renal transplantation. The aim of this study was to follow the evolution of serum osteoprotegerin levels and biochemical risk factors after renal transplantation. Forty patients were included. Blood samples for analysis were collected before and 3 months after renal transplantation. Besides the expected diminution in calcium-phosphate product, we have shown an early normalization of osteoprotegerin (10.05 +/- 4.77 pmol/L to 4.59 +/- 2.26 pmol/L). This study demonstrates that kidney transplantation improves this risk factor for vascular calcifications. However, these preliminary results should be confirmed and extended by the follow-up of vascular calcifications in the long term.

Adult↗
PubMed2006

Evaluation of an immunoassay (Abbott-IMX Analyzer) allowing routine determination of sirolimus: comparison with LC-MS method.

BACKGROUND: The use of the immunosuppressive agent sirolimus is increasing in renal transplantation but its monitoring often requires high-performance liquid chromatography (HPLC) with ultra-violet (UV) or tandem mass spectrometric (MS-MS) detection. The aim of this study was to compare a new microparticle enzyme immunoassay (MEIA, Microparticle Enzyme Immunoassay) on IMx Abbott Analyser with a liquid chromatography-mass spectometry (LC-MS) method. METHOD: The accuracy of immunoassay analytical performance including within run and between run imprecision and linearity was tested. For comparison studies, sirolimus level was then determined with the two methods on 98 samples from 52 transplant patients. RESULTS: Total intra-assay and inter-assay variation coefficients were below 10% at the three levels tested, and the coefficient of linearity was r = 0.99. The values obtained were highly correlated with the LC-MS method (MEIA = 1.02LC-MS + 0.91; r(2) = 0.87). As a result, the immunoassay showed good performance, and clinical sample measurements were not affected by the method. The MEIA may be a useful alternative for routine monitoring of sirolimus.

Chromatography, High Pressure Liquid↗
PubMed2006

Small dense low-density lipoprotein in renal transplant recipients: a potential target for prevention of cardiovascular complications?

BACKGROUND: Immunosuppressive therapy is frequently associated with dyslipidemia, which is involved in cardiovascular morbidity and mortality in transplant patients. Beyond classical factors, such as low-density lipoprotein (LDL) cholesterol (LDL-C), qualitative abnormalities of lipoproteins, such as presence of the atherogenic factor, small dense LDL, may be of interest for a cardiovascular risk assessment. This study was designed to explore LDL size in renal transplant recipients in relation to quantitative lipid parameters and apolipoprotein (apo) CIII polymorphism. METHODS: Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), LDL-C, apoA1, apoB, apoCIII, and LDL size were measured in 62 patients of mean age 45 +/- 13 years including 71% men at 2 +/- 0.5 years after renal transplantation. Thirty-two patients received cyclosporine (CsA), while 30 received tacrolimus (FK). ApoCIII Sstl genotype was determined by restriction fragment length polymorphism. RESULTS: The CsA group exhibited higher TC (P = .001), LDL-C (P = .004), non-HDL-C (P = .009), HDL-C (P = .03), apoB (P = .008), and apoCIII (P = .002) levels than the FK group. However, LDL-C (CsA: 3.7 +/- 1.2, FK: 3.0 +/- 0.6 mmol/L) and triglyceride levels (CsA: 1.55 mmol/L, FK: 1.37 mmol/L) were near the normal range in both groups. Allelic frequency of the sparse A2 allele associated with hypertriglyceridemia was 6%, similar to the general population. LDL size, which was comparable in the CsA and FK groups (25.87 +/- 0.89 vs 25.75 +/- 0.62 nm, respectively), inversely correlated with TG/HDL ratio (P = 10(-4)). Prevalence of small dense LDL (defined as <25.5 nm) was 26% in the CsA group and 33% in the FK group. CONCLUSION: After LDL-C goal has been achieved, LDL size modulation may be taken into account in order to prevent cardiovascular complications.

Adult↗
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↗
PubMed2006

Impact of early or delayed cyclosporine on delayed graft function in renal transplant recipients: a randomized, multicenter study.

The benefit of delayed cyclosporine in reducing risk of delayed graft function (DGF) is not clearly established. This study compared early vs. delayed cyclosporine microemulsion (CsA-ME) inde novorenal transplant patients. Patients were randomized to early (day 0, n=97) or delayed (day 6, n=100) CsA-ME at an initial dose of 8 mg/kg/day with dose adjusted according to C2 level. All patients received enteric-coated mycophenolate sodium (EC-MPS), steroids and an anti-interleukin-2 receptor antibody. In both groups, 33% of patients were at high risk of DGF; 26 patients (26.8%) in the early CsA-ME group and 23 patients (23.0%) in the delayed CsA-ME group experienced DGF (n.s.). Renal function at 3 months was comparable (creatinine clearance 51.1 mL/min with early CsA-ME and 53.8 mL/min with delayed CsA-ME), and remained similar to 12 months. Treatment failure, defined as biopsy-proven acute rejection, graft loss or death, did not differ significantly at 12 months (23.7% with early CsA-ME vs. 29.0% with delayed CsA-ME). Biopsy-proven acute rejection occurred in 15.5% of early CsA-ME and 26.5% of delayed CsA-ME patients (n.s.). Both regimens were well tolerated. These data suggest that early or delayed introduction of CsA-ME results in similar renal function in renal transplant patients regardless of DGF risk level.

Adult↗
PubMed2005

Assessment of two strategies of neoral administration, early versus delayed, on renal function and efficacy in de novo renal transplant patients receiving myfortic, steroids, and anti-IL2R antibodies: 12-month results of a randomized, multicentre, open, prospective controlled study.

UNLABELLED: The optimal immunosuppressive strategy and benefit of delaying Neoral to prevent delayed graft function (DGF) have not been clearly established. Renal function was assessed by estimated creatinine clearance (Cockcroft-Gault) at 3 months, and efficacy by treatment failure and BPAR at 6 and 12 months after renal transplantation. Two hundred three patients were enrolled after stratification according to DGF risk (USRDS criteria). One hundred ninety-seven were randomized to receive either early (E; day 0; n = 97) or delayed (D; day 6; n = 100) Neoral in combination with myfortic, steroids, and anti-IL2R antibodies. Neoral was adjusted using C2. Six patients who were not randomized have been excluded from the intention-to-treat (ITT) analysis. RESULTS: There was no significant difference in the demographic or baseline parameters between the two groups. The risk of DGF(score > or = 5) was similar in both groups: 32 of 97 in E-Neoral versus 33 of 100 in D-Neoral. In the group at high risk for DGF, the incidence of DGF was 13 of 32 pts in E-Neoral versus 14 of 33 in D-Neoral. Renal function was not statistically different between the two groups in both the ITT and per-protocol (PP) populations at 3, 6, or 12 months. Over 12 months, the evidence of treatment failure and BPAR were not statistically different: 24 of 97 (24.7%) versus 27 of 100 (27%) and 18 of 97 (18.6%) versus 24 of 100 (24%) for E-Neoral and D-Neoral, respectively. The severity of acute rejection was mild in 83% patients. CONCLUSION: These data suggest that there is no significant impact on renal function and immunosuppressing efficacy of early versus delayed introduction of Neoral, in combination with myfortic and steroids among renal transplant patients with or without a risk of DGF.

Acute Disease↗
PubMed2005

Sirolimus-based therapy with or without cyclosporine: long-term follow-up in renal transplant patients.

This open-label, phase 3b, extension trial in renal transplant recipients (Sirolimus Study 311) assessed the long-term safety of sirolimus (SRL) administered with cyclosporine (CsA) (SRL + CsA group, n = 98) or without CsA (SRL group, n = 69). Renal transplant recipients who had either completed one of seven previous SRL studies sponsored by Wyeth Research or had participated for > or =3 months and reached a protocol-designated endpoint were eligible for enrollment. Data were available for 167 patients, all of whom initially received steroids. Mean total SRL exposure was 1526 days, including previous study participation. After enrollment in the extension study, there were significantly more acute rejections in the SRL + CsA group (6.1% vs 0%, P < .05). Differences in rates of graft loss (3.1% vs 1.4%) and death (6.1% vs 1.4%) were not significantly different between SRL + CsA and SRL groups, respectively. At 48 months after transplantation, calculated GFR (53.4 vs 70.9 mL/min) and hemoglobin (124.9 vs 136.6 g/L) were significantly better in the SRL group. Lipid values were not significantly different between groups at 48 months. The incidence of treatment-emergent increased creatinine, anemia, hypertension, headache, epistaxis, abnormal kidney function, and upper respiratory infection were significantly higher in the SRL + CsA group, whereas no adverse events were significantly higher in the SRL group. Malignancies were reported more frequently (11.2% vs 0%) with SRL + CsA. Results from this extension study indicate that SRL-based therapy without CsA is a safe alternative to combination therapy with CsA, offering long-term improvement in renal function with no increased risk of late acute rejection.

Adult↗
PubMed2005

Blood cyclosporine level soon after kidney transplantation is a major determinant of rejection: insights from the Mycophenolate Steroid-Sparing Trial.

Target organs express antigens directly recognized by antigen-specific T cells, thereby precipitating rejection. When early T-cell activation is inhibited, there is a low risk of rejection. We sought to determine the predictive values of serial posttransplant blood cyclosporine trough (C(0)) concentrations to minimize the risk for a first rejection episode compared with 2-hour postdose (C(2)) drug concentrations. The final aim of the study was to identify a concentration range for the best predictive pharmacokinetic parameter that should be targeted to reduce the risk of rejection. This possibility was explored in 334 de novo kidney transplant recipients who participated in the prospective, multicenter Mycophenolate Steroid-Sparing Trial. Among measurements performed during the first 6 months postsurgery, cyclosporine C(0) levels measured early after transplantation were the strongest predictor of acute graft rejection. Levels within 300 to 440 ng/mL were associated with the lowest risk of rejection, while patients with levels lower than 300 ng/mL showed a more than double risk. Cyclosporine trough values predicted allograft rejection with an accuracy of 74%, while C(2) levels had no predictive value. These findings underline the need to target cyclosporine therapy early posttransplant to modulate T-cell activation.

Adrenal Cortex Hormones↗
PubMed2004

[Nocardiosis--is it frequently observed after the introduction of new immunosuppressive agents in renal transplantation?].

In our series of 1374 renal transplantations performed between February 1970 and December 2002, we observed 6 cases of infection due to Nocardia asteroides. There were 4 males and 2 females, aged 49.8 +/- 12 years (29 to 63 years). One patient received his first transplantation and the 5 others retransplants. Three patients had PRA > 80%, one 28% and one 40%. One patient was diabetic and two had HCV infection. Two of 6 patients experienced acute rejection episodes. Nocardiosis localisation was pulmonary in 5 cases, cerebral in two and mediastinal in one. All patients recovered after reduction of immunosuppression and appropriate antibiotherapy with trimethoprim-sulfamethoxasole (TMP-SMX). When we analyzed the role of immunosuppression, we observed that only two cases were observed in the 933 recipients transplanted between 1985 and 2002 and receiving cyclosporin, contrasting with 4 cases among 174 recipients transplanted between 1996 and 2002 and receiving tacrolimus. Our data suggest that high immunologic risk patients, heavy immunosuppression, and perhaps tacrolimus-based immunosuppression are risk factors of nocardial infection. Early diagnosis of this severe infection, reduction of immunosuppression and appropriate therapy with TMP-SMX resulted in complete recovery in all our patients.

Adrenal Cortex Hormones↗
PubMed2004

[Sequential protocols with thymoglobuline and delayed introduction of calcineurin: effects on renal function in renal transplant recipients with non immunological risk and low risk of delayed graft function].

Induction therapy with thymoglobuline significantly decreases the risk of acute rejection, particularly in high immunological risk patients, in combined transplantations and in pediatric renal transplantation. After the introduction of cyclosporin in the 1980's and the recognition of its potential nephrotoxicity, induction therapy with delayed introduction of cyclosporin (sequential protocols) have became very popular in many transplant centers and are now used even in low-immunological risk patients. The aim of the present study was to assess the recovery of renal function in low-immunological risk patients receiving a sequential protocol versus those receiving a calcineurin inhibitor at day 1. Among patients receiving their first transplant in our center between January 1999 and June 2000, we selected 72 recipients with no immunological risk and no risk of delayed graft function (DGF). 35 patients (group I) have received a sequential protocol whereas 37 patients (group II) have received a calcineurin inhibitor (Neoral or prograf) at day 1. We analysed creatinine reduction ratio, 24-hour creatinine excretion on post-transplant day 2, and serum creatinine and creatinine clearance at day 15, 30, 45, 60 and 90 post-transplant. There was no difference between groups concerning demographic, immunological or surgical parameters. The percentage of patients with immediate graft function was similar between the two groups (10 versus 9). The number of patients requiring dialysis in the first post-transplant week was also similar (8/35 versus 6/37). The day serum creatinine reached 200 micromol/l was 15 +/- 11 versus 14 +/- 12 in groups I and II respectively. Serum creatinine and creatinine clearance were similar at all time intervals. CMV disease was significantly higher in the group 1 (42% versus 18.5%; p < 0.005). Our data suggest that in patients with low immunological risk and low-risk of DGF, introduction of calcineurin inhibitors as early as the post-transplant day 1 is not deleterious for renal function recovery. These data should be confirmed by a prospective randomised trial.

Adult↗
PubMed2002

Necrotic skin lesions in a dialysis patient: a multifactorial entity.

A female dialysis patient with a consistently high serum calcium phosphate product presented with large necrotic skin lesions with ulcers. The clinical course was highly suggestive of calciphylaxis. Parathyroidectomy was followed by the healing of the lesions. New skin lesions appeared following relapse of hyperparathyroidism. Her clinical records included a long past of hypertension, which was the cause of her renal failure. She had a limited walking range and previously had presented bilateral ulcers of vascular origin. This case presents a type of lesion which bears a serious prognosis in dialysis patients. The clinical context and the presentation of the lesions are compatible with multiple etiology: vascular lesions and calciphylaxis. The documented longitudinal follow-up illustrates the importance of treating the different factors known to participate in the appearance of skin lesions in dialysis patients. Particularly, it stresses the benefit of performing parathyroidectomy, even if the parathyroid hormone level is not in the range normally accepted as requiring surgical removal of parathyroid glands.

Aged↗
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

Nocardiosis revealed by thyroid abscess in a liver--kidney transplant recipient.

Nocardiosis is a life-threatening infection, particularly among immunocompromised patients, which usually affects lungs, skin and central nervous system. We report a case of disseminated nocardiosis revealed by suppurative thyroiditis in a liver-kidney transplant recipient with poor nutritional status at the time of infection. Nocardia Asteroides was isolated from fine-needle aspiration material of the thyroid abscess. Clinical manifestations resolved after surgical drainage of the thyroid abscess, prolonged antibiotherapy and diminution of immunosuppressive regimen. Clinicians should be aware of this entity, as Nocardia Asteroides may need more than 5 days of culture to be isolated.

Abscess↗