Rapid estimation of whole blood everolimus concentrations using architect sirolimus immunoassay and mathematical equations: comparison with everolimus values determined by liquid chromatography/mass spectrometry.

United States Food and Drug Administration (FDA) in 2010 approved the use of immunosuppressant drug everolimus, which requires therapeutic drug monitoring in whole blood. Taking advantage of structural similarity between sirolimus and everolimus we attempted to rapidly estimate everolimus concentration from apparent sirolimus concentration obtained by using Architect sirolimus immunoassay and mathematical equations (both polynomial and linear). Mathematical equations were derived by curve-fitting methods based on observed apparent sirolimus concentration and true everolimus concentration determined by a liquid chromatography combined with mass spectrometry (LC/MS) method using eight everolimus standards (concentration range 1-30 ng/mL) prepared in whole blood.

Comparing an early corticosteroid/late calcineurin-free immunosuppression protocol to a sirolimus-, cyclosporine A-, and prednisone-based regimen for pancreas-kidney transplantation.

Aim: A prednisone and calcineurin inhibitor (CNI)-free protocol was compared with a sirolimus, cyclosporine A (CsA), and prednisone-based immunosuppressive regimen for simultaneous pancreas-kidney transplantation (SPK).

Methods: A nonrandomized, single-center, sequential study enrolled low-immune responder SPK transplant recipients. The prednisone/CNI-free (minimization) group of 22 patients received thymoglobulin followed by sirolimus and reduced-dose CsA.

Risk factors for impaired wound healing in sirolimus-treated renal transplant recipients.

Aim: As sirolimus has been implicated in impaired wound healing, the aim of this study was to evaluate risk factors for wound complications after renal transplantation in patients treated with this drug de novo.

Methods: This single center retrospective review of wound complications included 194 renal transplant recipients, all of whom received sirolimus immunosuppression in combination with reduced doses of cyclosporine (CsA) and corticosteroids de novo. A wound complication was defined as an infection, incisional hernia, or lymphocele.

Long-term outcomes of single paediatric vs. ideal adult renal allograft transplants in adult recipients.

Aim: To compare the outcomes of single paediatric vs. adult kidneys transplanted into adult recipients.

Methods: A retrospective single-centre review of 38 single cadaver kidney transplants from donors less than five yr of age to wait-listed patients of low body mass index (BMI).

Pancreas transplantation utilizing thymoglobulin, sirolimus, and cyclosporine.

Background: This study aims to determine the impact of thymoglobulin-sirolimus-cyclosporine immunosuppression on the alloimune response of pancreas-kidney transplant recipients.

Methods: Thirty-six pancreas transplant recipients received an induction protocol of thymoglobulin, sirolimus, reduced-dose cyclosporine, and corticosteroids. Ten recipients were also enrolled in a study to measure immune responsiveness.

Low incidence of malignancy among sirolimus/cyclosporine-treated renal transplant recipients.

Background: Malignancies, a well-known complication of immunosuppressive therapy in renal transplant recipients, represent an important cause of long-term morbidity and mortality. One approach to addressing this problem is identifying agents that display antineoplastic properties concomitant with their immunosuppressive effects.

Methods: We examined the neoplasms among 1008 renal transplant recipients treated at a single center with sirolimus-cyclosporine +/- prednisone.

Increasing organ recovery from level I trauma centers: the in-house coordinator intervention.

Purpose: Daily presence of organ procurement organization staff in level I trauma centers combined with early family contact and interaction can increase donation rates.

Methods: A successful in-house coordinator program already in place at 2 level I trauma centers in Houston was replicated in 6 other level I trauma centers in New York City, Los Angeles, and Seattle. Organ procurement organization staff were placed inside the 8 trauma centers to provide early family support in potential donor situations and day-to-day donation system management.

The selective use of basiliximab versus thymoglobulin in combination with sirolimus for cadaveric renal transplant recipients at low risk versus high risk for delayed graft function.

Background: We previously reported that the use of basiliximab together with sirolimus permits a window of recovery from delayed graft function before the introduction of reduced-dose cyclosporine. The present study reviews our experience with the substitution of thymoglobulin for basiliximab as induction therapy for recipients at increased risk for early acute rejection episodes.

Methods: We retrospectively reviewed 145 cadaveric renal allograft recipients who received either basiliximab (n=115) or thymoglobulin (n=30) in combination with sirolimus and prednisone, followed by delayed introduction of reduced doses of cyclosporine.

Phase I and phase II safety and efficacy trial of intercellular adhesion molecule-1 antisense oligodeoxynucleotide (ISIS 2302) for the prevention of acute allograft rejection.

Background: ISIS 2302, an antisense oligonucleotide that inhibits the expression of human intercellular adhesion molecule (ICAM)-1, was evaluated in combination with a cyclosporine (CsA)-prednisone (Pred) regimen first in a phase I safety and pharmacokinetic study and then in a phase II assessment of prophylaxis of acute rejection episodes in deceased donor renal allografts.

Methods: Both phase I and phase II trials were double-blinded and placebo-controlled, including 17 stable and 39 de novo patients, respectively, in time-lagged, ascending-dose regimens. Each study compared the outcomes of 8 alternate-day intravenous infusions of four ISIS 2302 dose levels (0.

Location of in-house organ procurement organization staff in level I trauma centers increases conversion of potential donors to actual donors.

Background: Of 5810 acute care hospitals in the United States, only 3.9% (231) are Level 1 Trauma Centers (L1TCs). L1TCs have a significant number of potential organ donors (PODs).

Thymoglobulin, sirolimus, and reduced-dose cyclosporine provides excellent rejection prophylaxis for pancreas transplantation.

Background: We investigated a novel immunosuppressive protocol including thymoglobulin induction in combination with sirolimus and corticosteroids, followed by introduction of markedly reduced exposures to cyclosporine to prevent pancreas-transplant rejection.

Methods: A 7-day course of thymoglobulin (1.5 mg/kg per day) was begun on postoperative day (POD) 0, together with 15 mg of sirolimus on POD 1, and followed by 5 mg per day, targeting these doses to achieve a trough of 10 to 20 ng/mL.

De novo hemolytic uremic syndrome after kidney transplantation in patients treated with cyclosporine-sirolimus combination.

Objective: We sought to examine factors that predisposed 1.5% (10/672) of renal transplant recipients treated with a cyclosporine (CsA)/sirolimus (SRL)/steroid immunosuppressive regimen to develop hemolytic uremic syndrome (HUS).

Methods: Two cohorts of recipients were treated for 1-212 months (mean: 25.

Low intraindividual variability of cyclosporin A exposure reduces chronic rejection incidence and health care costs.

The present study applied a receiver operating characteristic (ROC) analysis to assess the role of intraindividual variability of cyclosporin A (CsA) drug exposure in predisposing renal transplant recipients to the occurrence of chronic rejection, as well as to increased health care costs using a resource-based economic analysis. Two hundred and four adult renal transplant recipients were treated with tapering doses of prednisone (Pred) and with a concentration-controlled strategy that selected doses of the olive oil-based formulations of CsA (Sandimmune(R)) that achieved target concentrations based on serial pharmacokinetic profiles. The ROC analysis revealed an inflection point of plots of the coefficient of variation (%CV) of CsA exposure versus the risk of chronic rejection at >/=28.