Genes and Beans
Maintenance immunosuppressive therapy in renal transplantation is typically initiated at the time of transplant and may or may not be used with induction therapy. Dual or triple immunosuppressive regimens are often used to attain adequate immunosuppression, while reducing the toxicity associated with higher doses of a single agent used as monotherapy. As shown in Table 1, the combination of immunosuppressants currently recommended by the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines include a CNI and an antimetabolite agent, with or without CS.
Tacrolimus and mycophenolate derivatives have largely replaced the use of cyclosporine and azathioprine (AZA), respectively, and are the preferred CNI and antimetabolite agent for maintenance therapy in renal transplantation as well as other organ transplant populations. Tacrolimus has demonstrated decreased risk of AR and enhanced graft survival during the first year of transplantation versus cyclosporine. Mycophenolate derivatives, either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium, in combination with a CNI have demonstrated clinical benefit over AZA by diminishing the risk of early and late allograft rejection and possibly prolonging graft survival in several types of transplant. Based on these data, mycophenolate derivatives have become the standard of care in most immunosuppressive regimens. However, this clinical difference has not borne out in some randomized trials, suggesting that AZA should be considered as a reasonable alternative in specific patients.
CS have conventionally been the backbone of maintenance immunosuppression in renal transplantation. However, toxicities from CS have led to current efforts to minimize or avoid their use in immunosuppression regimens. Consensus guidelines recommend the discontinuation of CS during the first week after transplantation for low immunological risk patients who receive induction therapy; however, prednisone use beyond the first week should continue as late discontinuation (>1 year post-transplant) may be associated with increased risk of rejection.
mTOR inhibitors may be considered as an alternative therapy for patients who cannot tolerate a CNI or an antiproliferative; however, several concerning adverse effects limit their use.
Generally, higher concentrations of immunosuppressants are targeted in the early post-transplant period when the risk of AR is greatest. CNI target drug concentrations are typically reduced over time as the risk of AR decreases, although this is largely determined by patient-specific risk factors for rejection. Furthermore, higher levels of chronic maintenance immunosuppression have not improved patient or graft outcomes, and can be detrimental owing to the adverse effect profiles of some of the medications commonly used in transplant.
Standard Renal Transplant Immunosuppressive Therapy
Maintenance immunosuppressive therapy in renal transplantation is typically initiated at the time of transplant and may or may not be used with induction therapy. Dual or triple immunosuppressive regimens are often used to attain adequate immunosuppression, while reducing the toxicity associated with higher doses of a single agent used as monotherapy. As shown in Table 1, the combination of immunosuppressants currently recommended by the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines include a CNI and an antimetabolite agent, with or without CS.
Tacrolimus and mycophenolate derivatives have largely replaced the use of cyclosporine and azathioprine (AZA), respectively, and are the preferred CNI and antimetabolite agent for maintenance therapy in renal transplantation as well as other organ transplant populations. Tacrolimus has demonstrated decreased risk of AR and enhanced graft survival during the first year of transplantation versus cyclosporine. Mycophenolate derivatives, either mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium, in combination with a CNI have demonstrated clinical benefit over AZA by diminishing the risk of early and late allograft rejection and possibly prolonging graft survival in several types of transplant. Based on these data, mycophenolate derivatives have become the standard of care in most immunosuppressive regimens. However, this clinical difference has not borne out in some randomized trials, suggesting that AZA should be considered as a reasonable alternative in specific patients.
CS have conventionally been the backbone of maintenance immunosuppression in renal transplantation. However, toxicities from CS have led to current efforts to minimize or avoid their use in immunosuppression regimens. Consensus guidelines recommend the discontinuation of CS during the first week after transplantation for low immunological risk patients who receive induction therapy; however, prednisone use beyond the first week should continue as late discontinuation (>1 year post-transplant) may be associated with increased risk of rejection.
mTOR inhibitors may be considered as an alternative therapy for patients who cannot tolerate a CNI or an antiproliferative; however, several concerning adverse effects limit their use.
Generally, higher concentrations of immunosuppressants are targeted in the early post-transplant period when the risk of AR is greatest. CNI target drug concentrations are typically reduced over time as the risk of AR decreases, although this is largely determined by patient-specific risk factors for rejection. Furthermore, higher levels of chronic maintenance immunosuppression have not improved patient or graft outcomes, and can be detrimental owing to the adverse effect profiles of some of the medications commonly used in transplant.
Source...