Search

Background: The complexity of treatment after solid organ transplantation has been related to non-adherence to therapy prescriptions and to reduced graft survival. The aim of this study was to evaluate the middle-term effects of the conversion from Prograf (TAC), to extended-release tacrolimus (Advagraf) (ADV) in stable kidney transplant recipients., Methods: Conversion from TAC to ADV (dose, 1:1 mg/mg) was planned in 78 kidney transplant patients with stable renal function 71±48 months after renal transplantation. Before conversion, 1 week after conversion, and every 6 months up to 3 years, patients were evaluated clinically and by means of the usual blood chemistry and pharmacologic parameters., Results: Twenty patients (26%) refused to change their pre-existing immunosuppressive therapy; therefore, 58 patients entered the study and 45 (77%) completed the 3-year follow-up. Patient survival was 98% and allograft survival was 96%. Significant reduction in serum creatinine levels and increased glomerular filtration rate were observed after conversion (3-year creatinine: before TAC 1.67±0.47 mg/dL vs after ADV 1.47±0.62 mg/dL, P<.001; glomerular filtration rate, MDRD abbreviated: before TAC 49±15 mL/min vs after ADV 59±24 mL/min, P<.001). The daily dose and C0 blood levels of tacrolimus were stable before and after conversion (dose before vs 3 years after conversion: TAC 3.79±1.81 mg/day vs ADV 3.54±1.86 mg/day, P=ns; C0 tacrolimus blood levels, before vs 3 years after conversion: TAC 6.03±1.75 ng/mL vs ADV: 5.58±1.38 ng/mL, P = NS). One patient in the ADV group had an episode of acute rejection (2%)., Conclusions: Our data support the safety and efficacy of converting from Prograf to Advagraf in stable kidney transplant patients in the middle term. We suggest that the observed improvement in renal function after conversion to ADV is related to the reduction of the 24-hour tacrolimus area under the curve exposure., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Encapsulating peritoneal sclerosis is a serious complication of peritoneal dialysis and can occur even after transplant. The gut is partially or totally enveloped by a thick fibrous membrane that leads to the formation of multiple sections containing intestinal loops contracted and reduced in volume. Exacerbation after renal transplantation is a very rare but sometimes dramatic condition. We report a patient who developed intestinal obstruction due to encapsulating peritoneal sclerosis 1 year after a deceased-donor kidney transplant. Treatment included laparotomy, small-bowel lengthening by release of adhesions, and high doses of corticosteroids. The patient received immunosuppressive therapy with a combination of low-dose cyclosporine, everolimus, and prednisone, unchanged except for a temporary steroid increase in the postoperative period. We report success with this combined surgical plus medical therapy, with no recurrence after 81 months of follow-up., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Cardiovascular (CV) disease is the first cause of death after kidney transplantation. Left ventricular hypertrophy (LVH) is one of the main CV risk factors. It has been reported that the antiproliferative properties of everolimus (EVE) treatment may decrease left ventricular mass. The aim of this study was to evaluate the evolution of LVH in two groups of kidney transplant recipients receiving immunosuppressive treatment with low-dose calcineurin inhibitor (CNI) + EVE or CNI + mycophenolate mofetil (MMF)., Methods: We evaluated 104 patients of mean age 47.5 ± 13.1 years who underwent kidney transplantation between January 2006 and December 2009 pretransplant by echocardiography, which was repeated every year for 3 years during which all patients continued the initial therapy. Over the 3-year period 76 subjects were treated with MMF, and 28 with EVE. We recorded left ventricular end-diastolic diameter (LVEDD), interventricular septum thickness in diastole (IVSTD), left ventricular posterior wall thickness in diastole (LVPWD), left ventricular end-diastolic volume and end-systolic volume during the follow-up echocardiographic evaluations., Results: No differences in the evolution of the echocardiographic parameters were observed between the two groups-MMF versus EVE group: LVEDD, 50.3 ± 5.1 versus 51.2 ± 6.7 mm; IVSTD, 11.2 ± 1.9 versus 11.3 ± 2 mm; LVPWD, 10.2 ± 1.9 versus 10.5 ± 1.7 mm; relative wall thickness, 0.041 ± 0.08 versus 0.42 ± 0.08; ejection fraction, 63 ± 6% versus 61 ± 5%; and left ventricular mass index, 113 ± 28.9 versus 121.9 ± 39.4 g/m(2), respectively. Compared with pretransplant echocardiographic evaluations, similar reductions in left ventricular mass index were noted in both groups after transplantation., Conclusions: We observed that after renal transplantation there was a reduction of the LVH respect to the pretransplant dialytic status. The two immunosuppressive regimen did not influence the evolution of post-transplant LVH., (Copyright © 2013. Published by Elsevier Inc.)

We compared in kidney transplantation two immunosuppressive regimens: tacrolimus plus mycophenolate mofetil (MMF) (TAC) and everolimus plus low-dose cyclosporine (EVE). Sixty consecutive patients received TAC (30 patients) or EVE (30 patients) as immunosuppressive regimen; all subjects also received induction with basiliximab and corticosteroids. After three-yr follow-up, no difference was found in patient and graft survival (PTS: TAC: 97% vs. EVE: 100%; GS: TAC: 93% vs. EVE: 93%). The incidence of acute rejection was higher in the EVE group but the difference was not statistically significant (17% vs. 23%, p = ns). Patients in EVE showed higher serum cholesterol (205 ± 41 vs. 235 ± 41 mg/dL, p = 0.0012) and lower hemoglobin concentration (13.6 ± 1.4 vs. 12.4 ± 1.9, p = 0.01). Renal function was not significantly different in the two groups (3 Y creatinine: TAC 1.4 ± 0.8 vs. EVE 1.6 ± 0.8 mg/dL, p = ns). Treatment discontinuation was higher in the EVE group (TAC 17 vs. EVE 36%, p = ns). Our data show that in the middle-term follow-up, an immunosuppressive regimen with tacrolimus plus MMF has a similar efficacy and safety profile in comparison with the combination of low-exposure cyclosporine plus everolimus. Further follow up could evidence the benefits related to the anti-proliferative effects of everolimus., (© 2013 John Wiley & Sons A/S.)

Introduction: The half-life of everolimus is approximately 28 hours, but everolimus is generally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day everolimus (OD) with the standard twice a day administration regimen (BID) as immunosuppressive therapy in renal transplantation., Methods: Forty-one de novo renal transplant recipients prospectively assigned to OD (n=21) or BID (n=20) treatment were followed for 1 year. In the OD group, everolimus was orally administered targeting a trough blood level of 2 to 5 ng/mL. In the BID group, everolimus was given twice a day targeting a trough blood level of 3 to 12 ng/mL. All patients also received induction with basiliximab and low-dose calcineurin inhibitor immunosuppression., Results: At 1 year follow-up patient and graft survivals were 100%. The intention-to-treat analysis showed similar renal function between the two regimens: serum creatinine values for OD 1.54 ± 0.6 versus BID 1.48 ± 0.53 mg/dL (P=NS). Also the occurrence of acute rejection episodes was not significantly different: 4.8% in the OD versus 15% in the BID group, (P=NS). The median trough blood levels were significantly lower among the OD group: OD 4.5 versus BID 7.2 ng/mL (P<.001)., Discussion: This study demonstrated that once a day administration of everolimus achieved excellent patient and graft survival and good renal function without an increased incidence of acute rejection episodes., (Copyright © 2011. Published by Elsevier Inc.)

Introduction: The half-life of everolimus is approximately 28 hours, but everolimus is normally administered twice a day. The aim of this prospective, single-center, exploratory study was to compare the efficacy and safety of a once a day (OD) everolimus regimen versus the standard twice a day regimen (BID) for immunosuppressive therapy in renal transplantation., Methods: Forty de novo renal transplant recipients prospectively assigned to OD (n = 21) or BID (n = 19) were followed for 6 months. In the OD group, everolimus was given orally once a day to target a trough blood level of 2-6 ng/mL. In the BID, group everolimus was given twice a day to target a trough blood level of 3-12 ng/mL. All patients also received induction treatment with basiliximab and low-dose calcineurin inhibitors., Results: At 6 months follow-up, patient and graft survivals were 100%; renal function and acute rejection rates were similar between the 2 regimens. Patients in the OD group showed significantly lower cholesterol and triglyceride levels compared with those in the BID group, namely, total cholesterol level, OD 212 +/- 54 versus BID 249 +/- 59 mg/dL (P < .05), and serum triglycerides, OD 162 +/- 72 versus BID 245 +/- 133 mg/dL (P < .02)., Discussion: This study showed that OD administration of everolimus provided excellent patient and graft survivals and good renal function without an increased incidence of acute rejection episodes. The lipid profile was significantly better among patients receiving everolimus OD. These findings suggested that everolimus can be safely administered once a day., (Copyright (c) 2010. Published by Elsevier Inc.)

Objective: The aim of this prospective study was to compare the cardiovascular risk (CVR) profile in patients treated with 2 different immunosuppressive regimens: tacrolimus and mycophenolate mofetil (TAC) compared with everolimus and low-dose cyclosporine (EVL)., Patients and Methods: Sixty consecutive renal transplant recipients prospectively assigned to TAC (n = 30) or to EVL (n = 30) were followed for 6 months. TAC group immunosuppression consisted of basiliximab, tacrolimus, mycophenolate mofetil (MMF), and steroid. EVL group immunosuppression consisted of basiliximab, everolimus, and low doses of cyclosporine and steroid. Main CVR factors analyzed were: hypertension, dyslipidemia, posttransplant diabetes mellitus, and weight gain., Results: Six months posttransplantation, patients in the EVL group showed significantly higher mean serum cholesterol (P < .003) and serum triglyceride levels (P < .027), as well as a greater number of patients were receiving statin treatment (P < .05). Mean systolic blood pressure, mean diastolic blood pressure, number of patients treated for hypertension, number of antihypertensive medications prescribed per patient, posttransplant weight gain, and posttransplant diabetes mellitus were not significantly different among the EVL and TAC groups after 1, 3, and 6 months posttransplantation., Conclusions: This study showed that at 6 months posttransplantation, patients on EVL displayed significantly greater dyslipidemia with respect to the TAC group. A longer follow-up will be necessary to discover whether the presence of everolimus in the immunosuppressive regimen provides significant benefits for the CVR of renal transplant recipients.

Sirolimus (SRL) in combination with Cyclosporine A (CsA) and steroids has been shown to lower the incidence of acute renal allograft rejection episodes, allowing CsA sparing. We retrospectively compared the incidence of posttransplant diabetes mellitus (PTDM) among kidney transplant recipients (KTx) immunosuppressed with SRL + CsA versus CsA alone. Patients were divided into two groups: SRL + CsA (n = 38) versus CsA (n = 48). Mean follow-up was 53.9 +/- 17.1 months. Seventeen/86 subjects (19.8%) developed diabetes after transplantation (7 IFG, 8.1%; 10 PTDM, 11.6%). The incidence was significantly higher in SRL + CsA (12/38 patients, 31.6%) compared with CsA (5/43 patients, 10.4%) (P = .0144, odds ratio 3.97). More patients required treatment in the SRL + CsA compared to CsA alone cohort (13.2% vs 2.1%, P = .051): 4 pts (10.5%) became insulin- dependent among SRL+CsA, vs none in the CsA group. Use of OHD was similar in both groups (2.6% SRL + CsA vs 2.1% CsA). There were no significant differences between the two groups in terms of age, sex distribution, BMI, or serum creatinine at 1 to 3 and 5 years from transplantation. All PTDM patients are alive at follow-up, while two grafts were lost due to chronic renal allograft dysfunction. Within the limits of a small retrospective study, we observed that SRL in combination with CsA increased the diabetogenic potential of CsA. A possible explanation of our findings is that higher CsA doses were used in the early experience with SRL + CsA; therefore the higher incidence of PTDM that we observed in the SRL + CsA combination may be a sign of toxicity. Careful monitoring of blood levels is mandatory in the SRL + CsA combination to avoid pleiotropic toxicity.