Effect of sirolimus on malignancy and survival after kidney transplantation: systematic review and meta-analysis of individual patient data.

Objective: To examine risk of malignancy and death in patients with kidney transplant who receive the immunosuppressive drug sirolimus.

Design: Systematic review and meta-analysis of individual patient data.

Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials from inception to March 2013.

Tacrolimus-based, steroid-free regimens in renal transplantation: 3-year follow-up of the ATLAS trial.

Background: Long-term use of corticosteroids is associated with considerable morbidity, including cardiovascular and metabolic adverse effects.

Methods: This study evaluated the long-term efficacy and safety of two steroid-free regimens compared with a triple immunosuppressive therapy in renal transplant recipients. This was a 3-year follow-up to a 6-month, open-label, randomized, multicenter study.

Everolimus plus early tacrolimus minimization: a phase III, randomized, open-label, multicentre trial in renal transplantation.

There is increasing interest in tacrolimus-minimization regimens. ASSET was an open-label, randomized, 12-month study of everolimus plus tacrolimus in de-novo renal-transplant recipients. Everolimus trough targets were 3-8 ng/ml throughout the study.

Belatacept-versus cyclosporine-based immunosuppression in renal transplant recipients with pre-existing diabetes.

Background And Objectives: Renal transplant recipients with pre-existing diabetes (PD) have reduced graft survival and increased risk of mortality and ischemic heart disease compared with nondiabetic transplant recipients. To assess the effect of belatacept in this high-risk group, we evaluated outcomes of the subpopulation with PD from previously published BENEFIT and BENEFIT-EXT trials.

Design, Setting, Participants, & Measurements: A post hoc analysis evaluated pooled data from BENEFIT (living donors or standard criteria donors) and BENEFIT-EXT (extended criteria donors).

[Long-term follow-up of the first 500 liver transplant recipients transplanted at the Institute for Clinical and Experimental Medicine in Prague].

Background: Between April 1995 and November 2005, 500 liver transplantations were performed in 476 patients of age from 3, till 70, at the Transplantation center of the Institute of Clinical and Experimental Medicine (IKEM) in Prague. The most common indications for liver transplantation were alcoholic liver cirrhosis (23%), hepatitis C cirrhosis (17%), and cholestatic cirrhosis (PBC and PSC, 9% each). Mean MELD score of recipients at the transplantation was 15-18 for each year of transplantation.

[Kidney transplantation at the Institute for Clinical and Experimental Medicine].

Background: Kidney transplantation represents the method of choice of end stage renal disease.

Methods And Results: The program of kidney transplantation was established in 1966 in our centre. In recent years, roughly 200 patients have undergone kidney transplantation annually, and 20-30 of them have received a graft from the living donor.

Primary liver transplantation for autoimmune hepatitis: a comparative analysis of the European Liver Transplant Registry.

The principal aim of this study was to compare the probability of and potential risk factors for death and graft loss after primary adult and pediatric liver transplantation in patients undergoing transplantation for autoimmune hepatitis (AIH) to those in patients undergoing transplantation for primary biliary cirrhosis (PBC; used as the reference group) or alcoholic cirrhosis (used as an example of a nonautoimmune liver disease). The 5-year survival of patients undergoing transplantation for AIH (n = 827) was 0.73 [95% confidence interval (CI) = 0.

Interchangeability of ciclosporin formulations in stable adult renal transplant recipients: comparison of Equoral and Neoral capsules in an international, multicenter, randomized, open-label trial.

The cost of immunosuppression following transplantation can be reduced by using generic ciclosporin (for example, Equoral) rather than innovator ciclosporin drugs such as Neoral. Thus, this study aims to evaluate the interchangeability, safety, and tolerability of Equoral, a generic ciclosporin, with Neoral in stable adult renal transplant recipients. This was a multicenter, randomized, open-label, parallel-group clinical trial in stable renal transplant patients, comparing 6 months of treatment with Equoral with the same treatment period on Neoral.

Tacrolimus combined with two different corticosteroid-free regimens compared with a standard triple regimen in renal transplantation: one year observational results.

Side effects of steroid use have led to efforts to minimize their use in transplantation. Two corticosteroid-free regimens were compared with a triple immunosuppressive therapy. Data from the original intent-to-treat (ITT) population (153 tacrolimus/basiliximab [Tac/Bas], 151 tacrolimus/MMF [Tac/MMF], and 147 tacrolimus/MMF/steroids [control]) were analyzed in a 12-month follow-up.

Acute rejection in low-toxicity regimens: clinical impact and risk factors in the Symphony study.

The Symphony study assessed whether mycophenolate mofetil (MMF)-based regimens containing reduced doses of adjunct immunosuppressants could reduce toxicity while maintaining efficacy. Here, we examined the impact of acute rejection and associated risk factors. The incidence of biopsy-proven acute rejection in the low-dose tacrolimus group was approximately half that of the standard-dose cyclosporine and low-dose cyclosporine groups, and a third of that in the low-dose sirolimus group.

Conversion to sirolimus of patients with chronic allograft nephropathy--a retrospective analysis of outcome and influencing factors.

Purpose: The purpose of this study was to analyse the outcome and its influencing factors in patients whose therapy was converted from calcineurin inhibitors (CNI) to sirolimus (SRL) due to chronic allograft nephropathy (CAN).

Materials And Methods: Therapies of 78 patients (44 men) with CAN from three European transplant centres were converted from CNI therapy to SRL and followed 24 months. Slopes for creatinine clearance before and after conversion were calculated.

Asymmetric dimethylarginine in obesity after renal transplantation.

Objective: We have assessed in obese renal transplant recipients a course of selected proinflammatory factors liable to influence the long-term outcome of transplant patients and kidney grafts.

Design And Patients: In a prospective cohort study, we examined a total of 68 obese renal transplant recipients (body mass index [BMI] >or= 30 kg/m(2)) for a period of 12 months (Group I). A control group consisted of 72 comparable non-obese renal transplant recipients (Group II).

Metabolic syndrome after renal transplantation.

Obesity and hyperlipidemia are common findings after kidney transplantation (Tx), and may represent independent risk factors for development of atherosclerosis and chronic allograft nephropathy. In a prospective metabolic study, we monitored a total of 68 obese transplant patients (body mass index > 30 kg/m2) with dyslipidemia. We compared findings of a new therapeutic regimen 1 year (at baseline) and 2 years after renal transplantation.

Early bone mineral density loss after renal transplantation and pre-transplant PTH: a prospective study.

Background: Post-transplant osteopathy is a known complication of kidney transplantation (KTx). The aim of this study was to assess bone mineral density (BMD) in a large cohort of patients with treatment depending on pre-transplant parathormone (PTH) and baseline BMD.

Patients And Methods: 347 consecutive KTx recipients (222 M, 125 F) finished all follow-up measurements of BMD at lumbar spine, femur and radius using DEXA Lunar (at baseline and at 6 and 18 months).

Reduced exposure to calcineurin inhibitors in renal transplantation.

Background: Immunosuppressive regimens with the fewest possible toxic effects are desirable for transplant recipients. This study evaluated the efficacy and relative toxic effects of four immunosuppressive regimens.

Methods: We randomly assigned 1645 renal-transplant recipients to receive standard-dose cyclosporine, mycophenolate mofetil, and corticosteroids, or daclizumab induction, mycophenolate mofetil, and corticosteroids in combination with low-dose cyclosporine, low-dose tacrolimus, or low-dose sirolimus.

Asymmetric dimethylarginine and adiponectin after renal transplantation: role of obesity.

Background: In obese renal transplant recipients, we assessed the course of selected proinflammatory factors liable to influence long-term outcomes of transplant patients and kidney grafts.

Methods: In a prospective cohort study, we examined a total of 140 renal transplant recipients for a period of 12 months. Based on body mass index (BMI), patients were divided into Group I (BMI > or = 30 kg/m2, 68 patients) and Group II (BMI < or = 30 kg/m2, 72 patients).

Intrarenal cytokine and chemokine gene expression and kidney graft outcome.

Aims: Proinflammatory cytokines are thought to play an important role in various kidney graft diseases resulting in interstitial fibrosis and tubular atrophy frequently found in case biopsies. To explore the role of various cytokines and chemokines in the long-term graft outcome, the transcription patterns of their genes in kidney allograft biopsies were evaluated.

Methods: The real-time RT-PCR was used to identify intragraft mRNA expression of cytokines and chemokines in 74 kidney graft recipients and the results were correlated with histological and clinical parameters and long-term graft outcome.

Soluble CD30 in patients with antibody-mediated rejection of the kidney allograft.

Unlabelled: The aim of our retrospective study was to evaluate the clinical significance of measurement of the soluble CD30 (sCD30) molecule for the prediction of antibody-mediated (humoral) rejection (HR). Sixty-two kidney transplant recipients (thirty-one C4d-positive and thirty-one C4d-negative patients) were included into the study. Soluble CD30 levels were evaluated before transplantation and during periods of graft function deterioration.

Ischaemic heart disease is a risk factor for renal failure after heart transplantation.

Background: The improvement of a long-term outcomes of heart transplantation (HTx) has resulted in a new phenomenon; specifically, the development of renal dysfunction secondary to calcineurin inhibitor toxicity. This study was designed to assess the participation of risk factors in the development of renal dysfunction in HTx.

Methods: Data from 310 patients undergoing HTx in our center between 1988-1998 with a post-operation survival period for minimum 5 years (n=155) were analyzed retrospectively.

12-month safety and efficacy of everolimus with reduced exposure cyclosporine in de novo renal transplant recipients.

The proliferation signal inhibitor everolimus (Certican), has demonstrated efficacy with full-dose cyclosporine (CsA) (Neoral). Two multicenter randomized controlled studies were performed to compare 12-month efficacy and safety of everolimus 1.5 and 3.

Association between heat shock protein 70s and toll-like receptor polymorphisms with long-term renal allograft survival.

Long-term renal allograft survival has not improved significantly in recent years and only a minority of grafts survives for more than 15 years. To evaluate the association between HSPA1A G(190)C, HSPA1B A(1267)G and TLR4 A(299)G polymorphisms and allograft survival we analyzed DNA of patients with long-term renal graft function over 15 years (Tx15), consecutively transplanted recipients (Tx), patients with acute rejection and healthy controls. HSPA1B (1267)AA was less prevalent in Tx versus Tx15 (P = 0.

Two corticosteroid-free regimens-tacrolimus monotherapy after basiliximab administration and tacrolimus/mycophenolate mofetil-in comparison with a standard triple regimen in renal transplantation: results of the Atlas study.

Background: The side effects associated with corticosteroids have led to efforts to minimize their use in renal transplant patients. In this study we compared two corticosteroid-free tacrolimus-based regimens with a standard triple therapy.

Methods: This was a 6-month, phase III, open-label, parallel-group, multicenter study.

Three-year efficacy and safety results from a study of everolimus versus mycophenolate mofetil in de novo renal transplant patients.

Everolimus 1.5 or 3 mg/day was compared with mycophenolate mofetil (MMF) 2 g/day in a randomized, multicenter 36-month trial in de novo renal allograft recipients (n = 588) receiving cyclosporine microemulsion (CsA) and corticosteroids. The study was double-blind until all patients had completed 12 months, then open-label.