Reducing Adverse Effects of Immunosuppressive Agents in Kidney Transplant Recipients

Abstract

Success in solid organ transplantation with minimal complications can now be achieved for most patients, and a remarkable rate of graft and patient survival can also be expected. However, the potential for adverse events and comorbid conditions increases with longer graft survival. Although the immunosuppressive regimen is central to the outcome of the transplant recipient and directly impacts the survival of the graft, chronic use of immunosuppressive agents is associated with metabolic disturbances such as hypertension, hyperlipidemia, loss of bone density, nephrotoxicity, and diabetes, which may contribute to other comorbid conditions. In addition, changes in appearance, gingival hyperplasia, hirsutism, alopecia, and weight gain disrupt quality of life and may lead to noncompliance with the immunosuppressive regimen. New immunosuppressive medications, including mycophenolate mofetil, sirolimus, basiliximab, and daclizumab, have allowed for experimentation with new regimens designed to reduce or allow discontinuation of corticosteroids and calcineurin inhibitors. This review highlights the impact and cost of immunosuppressive side effects and the potential for new immunosuppressive regimens to reduce this substantial clinical burden in transplantation.

Role of CXCL9/CXCR3 Chemokine Biology during Pathogenesis of Acute Lung Allograft Rejection

“…Calcineurin inhibitors such as CsA have led to improved survival of solid organ transplants (29). However, with significant side effects related to these reagents, any reduction in their dose would be important for the diminution of transplant recipient morbidity (29).…”

“…However, with significant side effects related to these reagents, any reduction in their dose would be important for the diminution of transplant recipient morbidity (29). For these reasons, we titrated (0.5, 1.0, 1.50, 1.75, and 1.85 mg/kg/day) the lowest dose of CsA required to inhibit allograft rejection at day 6, the time when anti-CXCL9 therapy maximally decreased acute lung allograft rejection scores.…”

First Experience with de novo Calcineurin-Inhibitor-Free Immunosuppression Following Cardiac Transplantation

“…All of these strategies have been based on the use of calcineurin inhibitors (CNIs) (cyclosporine or tacrolimus) as primary immunosuppressants. CNIs are, however, associated with specific adverse effects, such as renal impairment, diabetes, hypertension, hyperlipidemia, neurotoxicicty and cosmetic side effects (gingival hyperplasia, hirsutism, alopecia) (6,7).…”

Therapy in the Course of Kidney Graft Rejection—Implications for the Cardiovascular System—A Systematic Review

“…The rationale behind the use of Basiliximab relies on the crucial role in triggering rejection being played by IL-2 [117]. Consequently, it may lead to the potential suspension of steroid administration and reduced dosages of calcineurin inhibitors, thereby diminishing the deleterious side-effects associated with the use of steroids and CNIs, including infections, metabolic abnormalities, cardiovascular complications and nephrotoxicity following transplantation [57,58,118,119].…”