Biomedical subjects

Christophe Legendre

Publications and source records attributed to Christophe Legendre.

46 records · Page 3Linked to original sources

PubMed2003

Prevalence and management of anemia in renal transplant recipients: a European survey.

The TRansplant European Survey on Anemia Management (TRESAM) documented the prevalence and management of anemia in kidney transplant recipients. Data from 72 transplant centers in 16 countries were screened, involving 4263 patients who had received transplants 6 months, 1, 3 or 5 years earlier. The mean age of transplant recipients was 45.5 years at transplantation. The most common etiology was chronic glomerulonephritis. The most common comorbidities were coronary artery disease, hepatitis B/C, and type 2 diabetes. The mean hemoglobin levels before transplantation were significantly higher in the more recently transplanted recipients. At enrollment, 38.6% of patients were found to be anemic. Of the 8.5% of patients who were considered severely anemic, only 17.8% were treated with epoetin. There was a strong association between hemoglobin and graft function; of the 904 patients with serum creatinine > 2 mg/dL, 60.1% were anemic, vs. 29.0% of those with serum creatinine <or= 2 mg/dL (p < 0.01). Therapy with angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists, mycophenolate mofetil (MMF) or azathioprine was also associated with a higher likelihood of anemia. The prevalence of anemia in the transplant recipients was remarkably high and appeared to be associated with impaired renal function and with ACE inhibitors and angiotensin II receptor antagonist use. Further studies should be carried out to interpret whether appropriate management of anemia after kidney transplantation may improve long-term outcome.

Adult↗

PubMed2003

Efficacy and safety of lowering immunosuppression to treat CMV infection in renal transplant recipients on valaciclovir prophylaxis: a pilot study.

BACKGROUND: Routine cytomegalovirus (CMV)-pp65 antigenaemia monitoring shows that some patients will develop pp65 antigenaemia during valaciclovir prophylaxis or after cessation of treatment. The aim of this pilot study was to evaluate the safety and efficacy of lowering immunosuppression in kidney transplant recipients who exhibit mildly symptomatic CMV infections while on valaciclovir prophylaxis. METHODS: We selected 12 patients who experienced mildly symptomatic CMV infections defined as a positive CMV-pp65 antigenaemia test associated with either neutropenia, asthenia or arthralgia, but no fever. All of them received prophylaxis with valaciclovir for at least 3 months. Testing for CMV-pp65 antigenaemia was performed weekly for 6 months. RESULTS: The mildly symptomatic infections occurred at a median interval of 69 days after transplantation-during prophylaxis in eight cases and after valaciclovir discontinuation in the other four cases. All of them were effectively managed by lowering immunosuppressive therapy, leading to the disappearance of symptoms and CMV antigenaemia reduction. No immunological complication or recurrence of CMV infection or disease was noted. I.v. ganciclovir never became necessary. CONCLUSION: The mildly symptomatic CMV infections occurring in valaciclovir-treated patients may be managed efficiently and without immunologic complication by lowering immunosuppressive therapy.

Acyclovir↗

PubMed2003

Pharmacokinetic interaction between corticosteroids and tacrolimus after renal transplantation.

BACKGROUND: Tacrolimus is an immunosuppressive drug that is a substrate of cytochrome P450 3A (CYP3A) enzymes and P-glycoprotein (P-gp). After transplantation, many pharmacological interactions have been described. Corticosteroids induce both CYP3A and P-gp activity. This study was designed to investigate the presence of a clinically significant interaction between steroids and tacrolimus after renal transplantation. METHODS: We studied 83 renal transplant recipients receiving tacrolimus after transplantation. Patients were divided into three groups, according to steroid dose (low: 0-0.15 mg/kg/day; intermediate: 0.16-0.25 mg/kg/day; and high: >0.25 mg/kg/day). All other medications, including those known to interact with CYP3A and/or P-gp, were recorded. Steroid dosage, tacrolimus dosage, tacrolimus trough concentration (C0) and tacrolimus concentration/dose ratio [C0 divided by the 24 h dosage (mg/kg)] were assessed for each dosage group after 1 and 3 months of tacrolimus treatment. RESULTS: The three groups were not different as regards the use of non-immunosuppressive treatments or clinical events. At 1 and 3 months, the tacrolimus doses and concentration/dose ratios differed significantly in the three steroid dosage groups. With the higher doses, higher tacrolimus doses were needed to achieve the blood tacrolimus targeted trough level. CONCLUSIONS: We demonstrated that pharmacokinetic interaction occurs between steroids and tacrolimus in renal transplant patients. The higher the steroid dosage, the higher the dosage of tacrolimus needed to achieve target trough levels in these patients. The most likely interaction mechanism is specific enzymatic induction of CYP3A and/or P-gp. Interaction is present, even when the steroid dosage is low. The clinical events liable to occur during steroid sparing or tapering must be taken into account because it may be associated with episodes of tacrolimus-related nephrotoxicity.

Adult↗

PubMed2003

Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients.

The immunosuppressive drug tacrolimus, whose pharmacokinetic characteristics display large interindividual variations, is a substrate for P-glycoprotein (P-gp), the product of the multidrug resistance-1 (MDR1) gene. Some of the single nucleotide polymorphisms (SNP) of MDR1 reported correlated with the in vivo activity of P-gp. Because P-gp is known to control tacrolimus intestinal absorption, it was postulated that these polymorphisms are associated with tacrolimus pharmacokinetic variations in renal transplant recipients. The objective of this study was to evaluate in a retrospective study of 81 renal transplant recipients the effect on tacrolimus dosages and concentration/dose ratio of four frequent MDR1 SNP possibly associated with P-gp function (T-129C in exon 1b, 1236C>T in exon 12, 2677G>T,A in exon 21, and 3435C>T in exon 26). As in the general population, the SNP in exons 12, 21, and 26 were frequent (16, 17.3, and 22.2% for the variant homozygous genotype, respectively) and exhibited incomplete linkage disequilibrium. One month after tacrolimus introduction, exon 21 SNP correlated significantly with the daily tacrolimus dose (P < or = 0.05) and the concentration/dose ratio (P < or = 0.02). Tacrolimus dose requirements were 40% higher in homozygous than wild-type patients for this SNP. The concentration/dose ratio was 36% lower in the wild-type patients, suggesting that, for a given dose, their tacrolimus blood concentration is lower. Haplotype analysis substantiated these results and suggested that exons 26 and 21 SNP may be associated with tacrolimus dose requirements. Genotype monitoring of the MDR1 gene reliably predicts the optimal dose of tacrolimus in renal transplant recipients and may predict the initial daily dose needed by individual patients to obtain adequate immunosuppression.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2003

[Use of a previously transplanted kidney for second transplantation].

The constant shortage of renal transplants has led to the selection of unusual donors. We report a case of renal transplantation using a renal transplant that had already been transplanted 29 months previously. To our knowledge, this constitutes the first case of retransplantation of the same organ after long-term implantation in a first recipient.

Cadaver↗

PubMed2002

The economic value of valacyclovir prophylaxis in transplantation.

Cytomegalovirus (CMV) infection and disease, with its extensive direct and indirect consequences, adds considerably to the cost of patient management in both solid organ and bone marrow transplantation. Antiviral prophylaxis for CMV infection can offer cost advantages over preemptive therapy and "wait-and-treat" approaches. Valacyclovir has demonstrated efficacy for CMV prophylaxis in renal, heart, and bone marrow transplantation and is cost-effective when compared with placebo in renal transplant recipients at high risk of CMV infection. In reducing CMV infection and disease, valacyclovir prophylaxis appears to be associated with reductions in indirect effects of CMV (acute graft rejection, other opportunistic infections) and, if these effects are considered, the potential exists for even greater savings to be made with valacyclovir therapy. Benefits of valacyclovir in transplantation extend beyond CMV to other herpesviruses and may be increased in some clinical situations by prolonging prophylaxis beyond 3 months.

Acyclovir↗

PubMed2002

Prognostic value of quantitative Kaposi sarcoma--associated herpesvirus load in posttransplantation Kaposi sarcoma.

Organ transplant recipients have a higher risk of Kaposi sarcoma (KS). A quantitative real-time polymerase chain reaction assay was developed to evaluate KS-associated herpesvirus (KSHV) as a prognostic tool in transplant recipients with KS. Forty-three patients who developed KS after transplantation were included in a cross-sectional study to correlate virus load with transplantation or KS parameters. Seventeen patients (40%) had KSHV viremia (>100 copies/microg of DNA; median, 6067 copies/microg of DNA). Factors associated with these levels of viremia by univariate analysis were progression of KS (P=.00002), time from KS diagnosis (P=.0007), actual stage of KS (P=.006), initial stage of KS (P=.22), graft loss (P=.013), and time from transplantation (P=.0246). Disease progression remained associated with KSHV viremia in a multivariate analysis (P=.01). Thus, quantification of KSHV load in peripheral blood mononuclear cells could represent a useful tool for monitoring transplant recipients with KS.

Cohort Studies↗

PubMed2002

Severe evolution of chronic hepatitis C in renal transplantation: a case control study.

BACKGROUND: To evaluate the impact of kidney transplantation on histopathological progression of hepatitis C virus (HCV)-related liver disease. METHODS: In a retrospective study, 28 HCV-positive renal transplant patients, who underwent two sequential liver biopsies with a mean of 7.1+/-4.0 years, were compared with 28 matched immunocompetent controls. RESULTS: According to the Metavir score, the initial and final activity scores (from 0 to 3) increased from 0.2+/-0.4 to 1.4+/-1.1 (P<0.001) and those of fibrosis (from 0 to 4) from 0.5+/-0.5 to 2.0+/-1.4 (P<0.001) in the transplanted group, respectively, whereas the respective differences were not significant in the control group. The yearly progression rate of activity and fibrosis was significantly higher in the renal transplant group as compared with the immunocompetent group: 0.26+/-0.41 vs 0.01+/-0.19 (P<0.01) and 0.26+/-0.35 vs 0.05+/-0.21 (P<0.03), respectively. Twenty (71.5%) and 14 (50.0%) of the renal allograft recipients had activity and fibrosis progression as compared with four (16%) (P<0.001) and four (16%) (P<0.01) in immunocompetent patients; six kidney recipients (21.4%) evolved to cirrhosis vs only one in the control group (3.6%) (P=0.07). Liver-related mortality was significantly higher during the follow-up period in renal transplant patients than in the control group (10 vs 0%) (P<0.05). CONCLUSION: Using conventional immunosuppressive regimen, renal transplantation is associated with a more severe evolution of chronic hepatitis C as compared with HCV-infected immunocompetent subjects. Thus, the histopathological evaluation should be performed and anti-viral therapy discussed before renal transplantation.

Adult↗

PubMed2002

Long-term renal allograft outcome after simultaneous kidney and pancreas transplantation.

BACKGROUND: In selected young patients with type 1 diabetes mellitus and end-stage renal failure, simultaneous pancreas and kidney (SPK) transplantation is the treatment of choice. We conducted a retrospective, case-controlled study to compare the function, survival and pathology of renal allografts after SPK and kidney-alone (KA) transplantations. METHODS: We studied 26 consecutive SPK patients and 67 KA controls matched for time of transplantation. Renal function was assessed by routine evaluation of serum creatinine and its course by the 1/serum creatinine vs time curve. Histologic evaluation of early biopsies (0-3 months post-transplantation, n=63), intermediate biopsies (3 months-1 year, n=75) and late biopsies (after 1 year, n=35) were performed by two independent reviewers. RESULTS: SPK and KA recipients differed significantly with regard to donor and recipient age, time on the waiting list, HLA sensitization, renal cold ischaemia time (CIT) and the incidence of delayed graft function. Acute rejection was more frequent after SPK than KA (54 vs 27%; P=0.01), despite higher trough levels of calcineurin inhibitors. After SPK and KA, actuarial patient and renal allograft survival and renal function were comparable at 1 and 4 years. Severe chronic lesions, especially vascular lesions, and calcineurin-inhibitor nephrotoxicity were more frequent in intermediate and late biopsies in the SPK group. CONCLUSIONS: We confirmed that patient and graft survival is comparable between SPK and KA recipients. Despite the use of optimal organs and shorter CIT in SPK, renal graft function was not different in the two groups. Histologic chronic lesions were more severe in SPK than in KA recipients. This might be caused by acute rejection episodes or be due to more severe nephrotoxicity after SPK, because of higher doses of calcineurin inhibitors, or higher sensitivity to calcineurin-inhibitor nephrotoxicity.

Adult↗

PubMed2001

Long-term results of TPMT activity monitoring in azathioprine-treated renal allograft recipients.

Thiopurine methyltransferase (TPMT) is implicated in the metabolism of azathioprine. The consequences of differential TPMT activity induction by azathioprine on the long-term results after renal transplantation were investigated. The erythrocyte TPMT activity in 82 patients on days 0, 7, and 30 was prospectively evaluated. Because various patterns of TPMT activity variation were noted, the population was subsequently divided between inductors (n = 47) and noninductors (n = 35). Data regarding patient and graft survival and acute rejection episodes were collected. Renal allograft assessment was performed at 3 mo and 2 yr to evaluate the renal function and the histologic lesions on routine biopsies. Data regarding azathioprine-related toxicity also were collected. In a subgroup of patients (n = 19), azathioprine blood levels were determined at day 7 and day 30. The graft survival censoring death was statistically improved in TPMT inductor patients when compared with non-TPMT inductors (P < 0.05). Among TPMT inductors, an acute rejection episode was observed in 34% of the patients versus 69% among non-TPMT inductors (P = 0.002). At 3 mo, serum creatinine was significantly lower among TPMT inductors when compared with non-TPMT inductors (123.1 +/- 7.6 and 161.4 +/- 13.9 micromol/L, respectively; P = 0.01). On routine allograft biopsies at 2 yr (n = 61), grade 2 or 3 chronic lesions were present in 19% versus 25%, respectively (P = NS). At days 7 and 30, the azathioprine blood levels were higher among patients who experienced acute rejection (P < 0.02). TPMT activity induction was observed in 57% of renal transplant recipients who received azathioprine. This induction was associated with better graft outcome. The appropriate conversion from azathioprine, which is a pro-drug, into 6-mercaptopurine could explain both better graft outcome and TPMT induction. Assessing the ability of azathioprine metabolism at an individualized level before transplantation may allow a more accurate choice among the different immunosuppressive treatments.

Acute Disease↗