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Renal-transplant Recipients (renal-transplant + recipient)
Selected AbstractsEverolimus Plus Reduced-Exposure CsA versus Mycophenolic Acid Plus Standard-Exposure CsA in Renal-Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010H. Tedesco Silva Jr. Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3,8 and 6,12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab ± corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m2 in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: ,1.7, 6.4 and ,5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA. [source] Sotrastaurin, a Novel Small Molecule Inhibiting Protein Kinase C: First Clinical Results in Renal-Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010K. Budde Sotrastaurin, a novel protein-kinase-C inhibitor, blocks early T-cell activation. In this 12-month, Phase II study, de novo renal-transplant patients were randomized to sotrastaurin (200 mg b.i.d.) + standard-exposure tacrolimus (SET) or reduced-exposure tacrolimus (RET) (SET: n = 76; RET: n = 66), or control (SET + mycophenolic acid [MPA, 720 mg b.i.d.]; n = 74). In both sotrastaurin groups, patients were converted from tacrolimus to MPA after Month 3, achieving calcineurin inhibitor-free immunosuppression. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up). The key secondary endpoint was glomerular filtration rate (GFR). Composite efficacy failure rates were: 4.1%, 5.4% and 1.5% at Month 3 (preconversion) and 7.8%, 44.8% and 34.1% at study end in the control, sotrastaurin + SET and sotrastaurin + RET groups, respectively; these results led to premature study discontinuation. Median GFR at Month 6 was: 57.0, 53.0 and 60.0 mL/min/1.73 m2, respectively. Study-drug discontinuations due to adverse events occurred in 16.2%, 18.4% and 12.1%, respectively. Leukopenia and neutropenia occurred more frequently preconversion in control versus sotrastaurin groups: 13.7%, 5.6%, and 4.6%; and 11.1%, 4.3% and 3.1%, respectively. The initial sotrastaurin + tacrolimus regimen was efficacious and well tolerated but the postconversion sotrastaurin + MPA regimen showed inadequate efficacy. Longer-term evaluation of sotrastaurin + tacrolimus is warranted. [source] Low recurrence of preexisting extrahepatic malignancies after liver transplantationLIVER TRANSPLANTATION, Issue 6 2008Daniel Benten The incidence of de novo malignancies is increased in organ transplant recipients, and patients with hepatic carcinomas are at high risk for tumor recurrence after liver transplantation. Data about recurrent cancer after orthotopic liver transplantation (OLT) in patients with a history of nonhepatic malignancy are very limited. We retrospectively analyzed data from 606 adult OLT recipients and identified 37 patients (6.1%) with a preexisting extrahepatic malignancy. In the same group, 43 patients (7.0%) developed de novo cancer. Preexisting malignancies included 26 solid tumors and 11 hematological malignancies, including 7 patients with Budd-Chiari syndrome due to myeloproliferative disorders (MPDs). Patients had been selected for OLT because of the expected good prognosis of their preexisting malignancy. Except for 3 patients, recipients were tumor-free at OLT. The median interval from tumor diagnosis to OLT was 44 months (range, <1-321). After a median follow-up of 66 months post transplantation (range, 4-131), all but 1 recipient with incidental colon carcinoma were free of recurrence. No patient with MPD showed leukemic transformation, whereas a patient with neurofibromatosis experienced growth of skin fibromas. Our data and an included review of published OLT recipients with preexisting malignancies have enabled us to show that recurrence rates are comparable for nontransplanted patients and renal-transplant recipients. In conclusion, cancer recurrence is low if OLT recipients are carefully selected. Therefore, previous extrahepatic malignancy should not be considered a contraindication for OLT per se, but the oncologic/hematologic prognosis should be considered, particularly with respect to the current 5-year survival rate of OLT. Liver Transpl, 2008. © 2008 AASLD [source] Prospective monitoring of lipid profiles in children receiving pravastatin preemptively after renal transplantationPEDIATRIC TRANSPLANTATION, Issue 6 2005Lavjay Butani Abstract:, Hyperlipidemia is common after renal transplantation (Tx) and contributes to the increased cardiovascular morbidity seen in the post-transplant period. Limited data are available on the utility of the statins in children after renal Tx. This 12-month prospective study was undertaken to determine the efficacy of pravastatin in reducing dyslipidemia after renal Tx in children and to determine predictors of dyslipidemia after Tx. From August 2001 to April 2004, all 17 newly transplanted pediatric renal transplant recipients at our center were preemptively treated with pravastatin from the immediate post-transplant period. Fasting lipid profiles were obtained at 1, 3, 6 and 12 months after Tx. Trends in the lipid profile were analyzed using the repeated measures general linear model (GLM). A historical cohort of pediatric renal-transplant recipients not treated with pravastatin was used as the control population. The mixed effects GLM was used for multivariable logistic regression analyses to determine the independent effect of age, pretransplant cholesterol (Chol), body mass index (BMI), creatinine clearance (CrCl), and corticosteroid and tacrolimus doses on the development of dyslipidemia. The mean age of the children at Tx was 8.7 yr. The GLM analysis showed that with time, there was a significant decline in the total Chol, serum triglyceride (TG), LDL and also HDL-Chol (p-value <0.05 for each). Compared with the controls, the mean serum Chol was lower at all time points post-transplant in the treated patients. However, despite treatment, the prevalence of hypercholesterolemia increased from 31% pretransplant to 53% at 1-month, but declined thereafter to 6% at 3 and 6 months and 0% at 1 yr. Multivariable regression analyses showed the prednisone dose, pretransplant Chol and age to be the most important risk factors for the development of dyslipidemia. No child developed complications related to therapy. In summary, pravastatin is safe in the post-transplant period in children and reduces serum Chol, LDL-Chol and TG. An unexpected finding in our study was the decline in HDL-Chol after Tx. Whether the preemptive use of the statins will result in lower cardiovascular morbidity, especially considering the concomitant reduction in HDL-Chol remains to be determined. [source] Everolimus Plus Reduced-Exposure CsA versus Mycophenolic Acid Plus Standard-Exposure CsA in Renal-Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010H. Tedesco Silva Jr. Everolimus allows calcineurin-inhibitor reduction without loss of efficacy and may improve renal-transplant outcomes. In a 24-month, open-label study, 833 de novo renal-transplant recipients were randomized to everolimus 1.5 or 3.0 mg/day (target troughs 3,8 and 6,12 ng/mL, respectively) with reduced-exposure CsA, or mycophenolic acid (MPA) 1.44 g/day plus standard-exposure CsA. Patients received basiliximab ± corticosteroids. The primary endpoint was composite efficacy failure (treated biopsy-proven acute rejection, graft loss, death or loss to follow-up) and the main safety endpoint was renal function (estimated glomerular filtration rate [eGFR], by Modification of Diet in Renal Disease [MDRD]) at Month 12 (last-observation-carried-forward analyses). Month 12 efficacy failure rates were noninferior in the everolimus 1.5 mg (25.3%) and 3.0 mg (21.9%) versus MPA (24.2%) groups. Mean eGFR at Month 12 was noninferior in the everolimus groups versus the MPA group (54.6 and 51.3 vs 52.2 mL/min/1.73 m2 in the everolimus 1.5 mg, 3.0 mg and MPA groups, respectively; 95% confidence intervals for everolimus 1.5 mg and 3.0 mg vs MPA: ,1.7, 6.4 and ,5.0, 3.2, respectively). The overall incidence of adverse events was comparable between groups. The use of everolimus with progressive reduction in CsA exposure, up to 60% at 1 year, resulted in similar efficacy and renal function compared with standard-exposure CsA plus MPA. [source] Cardiac diastolic dysfunction in renal-transplant recipients is associated with increased circulating AdrenomedullinCLINICAL TRANSPLANTATION, Issue 3 2006Bernard Geny Abstract:, Background:, Renal transplantation is an excellent therapeutic alternative for end-stage renal diseases. Nevertheless, the cardiac function is often impaired in renal-transplant patients (RTR) and importantly determines their prognosis. Adrenomedullin (ADM), a peptide involved in cardiovascular homeostasis, is believed to protect both cardiac and renal functions , by increasing local blood flows, attenuating the progression of vascular damage and remodelling and by reducing glomerular injury , and might be involved in renal-transplantation physiopathology. This work was performed to investigate whether an increase in circulating ADM might be related to RTR cardiac function. Methods:, Twenty-nine subjects, 19 RTR and 10 healthy subjects, participated in the study. After 15 min rest in supine position, heart rate and systemic blood pressure were measured together with cyclosporine through levels, creatinine and ADM. Systolic and diastolic cardiac functions were assessed, using Doppler echocardiography. Results:, Subjects were similar concerning age, weight, heart rate and blood pressure. Creatinine and ADM (53.8±6.9 vs. 27.2±4.1 pmol/L, p = 0.02) were significantly increased in RTR (73±10 months after transplantation). Cardiac systolic function was normal, but a reduced mitral E:A ratio was observed in RTR (0.90±0.06 vs. 1.38±0.10, p<0.001), reflecting their impaired left ventricular relaxation. Such a ratio was negatively correlated with ADM (r = ,0.55, p = 0.002). Conclusions:, RTR present with an increased ADM is likely related to cardiac diastolic dysfunction. In view of its protective effect on the cardiovascular system, these data support further studies to better define the role and the therapeutic potential of ADM after renal transplantation. [source] | ||||||||||