Abstract
Immunosuppressive therapy is a key component for successful kidney transplantation. It is commonly believed that more intensive immunosuppression is needed initially to prevent rejection episodes and less immunosuppression is subsequently maintained to minimize the overall risk of infection and malignancy. The selection of drugs should be guided by a comprehensive assessment of the immunologic risk, patient comorbidities, financial cost, drug efficacy and adverse effects. Lymphocyte-depleting antibody induction is recommended for patients with high immunologic risk, while IL-2R antibody can be used for low or moderate risk patients. Patients with very low risk may be induced with intravenous steroids without using an antibody. A maintenance regimen typically consists of a low-dose of steroid combined with two of the four class drugs: calcineurin inhibitor (tacrolimus or cyclosporine), antimetabolite (mycophenolate mofetil or enteric coated mycophenolate sodium), mTOR inhibitor (sirolimus or everolimus) and costimulation blocker (belatacept). Currently in the USA, the most popular maintenance is the combination of corticosteroid, mycophenolic acid and tacrolimus. Steroid minimization, or calcineurin inhibitor free or withdrawal should be limited to the highly selected patients with low immunological risk. Recently, the novel biological agent belatacept-based maintenance has demonstrated a significantly better renal function and improved cardiovascular and metabolic profile, which may provide hope for an ultimate survival benefit.
Highlights
The discovery and clinical application of potent immunosuppressive agents have successfully reduced the risk of acute rejection and graft loss from rejection
Lymphocyte-depleting antibody induction is recommended for patients with high immunologic risk, while IL-2R antibody can be used for low or moderate risk patients
A maintenance regimen typically consists of a low-dose of steroid combined with two of the four class drugs: calcineurin inhibitor, antimetabolite, Mammalian Target-of-Rapamycin (mTOR) inhibitor and costimulation blocker
Summary
The discovery and clinical application of potent immunosuppressive agents have successfully reduced the risk of acute rejection and graft loss from rejection. Kidney transplant has become the preferred therapy for treating patient with ESRD. Modern immunosuppressive protocol typically includes an induction therapy and a long-term maintenance. Antibody induction is recommended in patients with immunologic risk, but the choice of antibody remains controversial. In the USA, about 60% of kidney transplant patients in the year of 2011 were given a T-cell depleting antibody induction, predominately the antithymocyte globulin (ATG). Other 40% of patients received either IL-2 receptor antibody (IL-2R Ab) or no antibody induction [1]. Maintenance immunosuppression is required for the lifetime of functioning allograft to prevent rejection of transplanted kidney. In the USA, the most popular maintenance either at beginning of transplant or at 1 year after transplant remains the combination of corticosteroid, mycophenolic acid (MFA) and tacrolimus [1]
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