Why is organ transplantation clinically important?

Solid organ transplantations save lives in patients affected by terminal organ failures and improve quality of life. Organ transplantations have gradually ameliorated in the last two decades and usually provide excellent results in children and young adults, and are increasingly challenged by the growing proportion of elderly transplant patients with comorbidities. Renal transplantation increases patient survival over dialysis, and lifesaving transplants are indispensible to treat patients with liver, heart, or lung irreversible diseases.

Belatacept utilization recommendations: an expert position.

Introduction: There is a continuing need for an immunosuppressive therapy that offers a high benefit-risk profile for renal transplant recipients, supporting long-term patient and graft survival while minimizing cumulative nephrotoxicity and other side effects. Belatacept , the first biological agent developed for primary maintenance immunosuppression, was recently approved for use in Europe. Belatacept combined with corticosteroids and a mycophenolic acid is indicated for prophylaxis of graft rejection in adults receiving renal transplant.

Improvement in renal function in kidney transplant recipients switched from cyclosporine or tacrolimus to belatacept: 2-year results from the long-term extension of a phase II study.

Kidney transplant recipients who switched from a calcineurin inhibitor (CNI) to belatacept demonstrated higher calculated glomerular filtration rates (cGFRs) at 1 year in a Phase II study. This report addresses whether improvement was sustained at 2 years in the long-term extension (LTE). Patients receiving cyclosporine or tacrolimus were randomized to switch to belatacept or continue CNI.

Immunosuppression in the era of biological agents.

Immunosuppression is the mayor mechanism to prevent allograft rejection and to induce tolerance. Since the first solid organ transplant, the development of safe and effective immunosuppressive regimens was a constant over the last decades. A lot of immunosuppressants have been discovered, and today the immunosuppressive agents are classified in two broad groups: Xenobiotic immunosuppressants and biological immunosuppressants.

Clinical assessment and determinants of chronic allograft nephropathy in maintenance renal transplant patients.

Background: Current knowledge about the natural history, treatment and physicians' perception of chronic allograft nephropathy (CAN) is limited. The present study evaluated the prevalence and determinants of CAN in renal transplant patients.

Methods: Epidemiological, cross-sectional multi-centre study conducted in Spain.

Optimal immunosuppression to prevent chronic allograft dysfunction.

Prevention of chronic allograft dysfunction is currently one of the main goals in renal transplantation for the improvement of kidney graft survival. For this purpose, refinements in immunosuppressive regimens, both controlling alloimmune responses and avoiding calcineurin inhibitor (CNI)-derived nephrotoxicity, are mandatory. The majority of trials aiming to avoid CNI-related nephrotoxicity have only reported short-term data, with different rates of acute rejection depending on the strategy performed.

An integrated safety profile analysis of belatacept in kidney transplant recipients.

Background: Belatacept is associated with better renal function and an improved cardiovascular/metabolic risk profile versus cyclosporine in kidney transplant recipients. The current analysis examined pooled safety data for belatacept versus cyclosporine used in combination with basiliximab, mycophenolate mofetil, and steroids.

Methods: Patients enrolled in three core studies in de novo kidney transplantation were randomized to a more intensive (MI) or less intensive (LI) regimen of belatacept or cyclosporine.

Mycophenolate mofetil and calcineurin-inhibitor reduction: recent progress.

Mycophenolate mofetil (MMF) in combination with calcineurin inhibitors (CNIs) has greatly contributed to acute rejection rate reduction. Because of its immunosuppressive potency it was initially thought that MMF would help in reducing/avoiding CNI-related nephrotoxicity. Elective avoidance of CNI in induction and maintenance MMF-based immunosuppression has resulted in an increased risk for acute and chronic rejection.

The pharmacokinetics of mycophenolate mofetil in renal transplant recipients receiving standard-dose or low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus: the Symphony pharmacokinetic substudy.

Background: Exposure to mycophenolic acid (MPA), the primary active metabolite of mycophenolate mofetil (MMF), is correlated with therapeutic efficacy of MMF but varies depending on the concomitantly administered immunosuppressive drugs.

Methods: A 3-month pharmacokinetic substudy of the prospective, randomized, multicentre, open-label Symphony study was performed. Eighty-three adult renal transplant patients received standard-dose cyclosporine, MMF 2 g/day and corticosteroids, or daclizumab induction, MMF 2 g/day and corticosteroids plus low-dose cyclosporine, low-dose tacrolimus or low-dose sirolimus.