Induction therapy options in kidney transplantation include several distinct pharmacologic strategies used to mitigate early rejection risk. IL-2 receptor antagonists, most commonly basiliximab, provide selective, non-depleting immunosuppression and are typically used in standard-risk recipients due to their favorable safety profile. Polyclonal lymphocyte-depleting antibodies, such as rabbit antithymocyte globulin (rATG) and ATG-Fresenius, produce broader T- and B-cell depletion and are preferentially used in high-immunologic-risk patients, those at risk for delayed graft function, or in steroid-minimization protocols, though at the cost of increased infection and malignancy risk. Alemtuzumab, a CD52-directed monoclonal antibody, provides prolonged lymphocyte depletion and has been associated with lower acute rejection rates but carries a higher infectious risk and variable effects on donor-specific antibody development. In ABO-incompatible and HLA-sensitized transplantation, induction therapy is combined with desensitization strategies such as plasma exchange, rituximab, and intravenous immunoglobulin. Imlifidase, a novel IgG-cleaving enzyme, facilitates transplantation in highly sensitized or crossmatch-positive recipients by rapidly removing circulating donor-specific antibodies, although antibody rebound and early antibody-mediated rejection remain important considerations. [1]
Maintenance immunosuppression following kidney transplantation typically consists of triple therapy with a calcineurin inhibitor (CNI; tacrolimus or cyclosporine), an antiproliferative agent (most commonly mycophenolate), and corticosteroids. Tacrolimus-based regimens are preferred over cyclosporine due to lower rates of acute rejection and graft loss, though intrapatient pharmacokinetic variability and metabolic adverse effects remain important considerations. Belatacept, a selective costimulation blocker, has emerged as a key CNI-sparing alternative and is associated with superior long-term renal function and reduced chronic allograft injury despite higher early acute rejection rates. A 2022 multidisciplinary consensus report endorsed by major transplant societies supports tacrolimus as the preferred CNI across solid organ transplantation, recognizes extended-release formulations as equivalent to immediate-release forms, affirms the central role of mycophenolate derivatives, and emphasizes steroid minimization when feasible. The consensus also acknowledges belatacept and mTOR inhibitors as appropriate alternatives in selected patients to reduce CNI-related toxicity, reinforcing the need for individualized maintenance immunosuppression strategies. [1], [2]
A 2023 publication offers a detailed review of current therapies for kidney transplant rejection, focusing on acute T-cell-mediated rejection (TCMR) and antibody-mediated rejection (ABMR). The primary treatment for TCMR involves corticosteroids, specifically intravenous methylprednisolone, which is often followed by an oral prednisone taper. In severe or steroid-resistant cases of TCMR, T-cell-depleting agents such as thymoglobulin are recommended, which target various receptors on T cells to induce lymphocyte depletion through complement-dependent lysis and apoptosis. For ABMR, the publication highlights the significant role of antibody interaction with graft endothelial cells, often treated with plasmapheresis to remove circulating donor-specific antibodies, although the efficacy of this method is debated. The review discusses additional therapies, including intravenous immunoglobulins (IVIG), anti-CD20 antibodies like rituximab, complement inhibitors (eculizumab), and proteasome inhibitors (bortezomib), each with variable efficacy in managing ABMR. The management decisions are underscored by the necessity to assess the timing of the rejection episode and the presence of chronic changes, aiming to optimize immunosuppression and address adherence issues. [3]
Post-transplant infectious complications in kidney transplantation involve viral, bacterial, and fungal pathogens, with management largely guided by the type and severity of infection. Epstein-Barr virus-associated post-transplant lymphoproliferative disorder is primarily managed with immunosuppression reduction, with rituximab, chemotherapy, or radiation used as indicated. Cytomegalovirus is treated with oral valganciclovir or intravenous ganciclovir in severe cases. BK virus infection and nephropathy are managed mainly through immunosuppression reduction, with adjunctive therapies such as intravenous immunoglobulin, leflunomide, or cidofovir used selectively. Clostridioides difficile infection is treated with oral vancomycin or fidaxomicin, with high-dose vancomycin plus intravenous metronidazole reserved for fulminant disease, and bezlotoxumab considered for recurrence prevention. Fungal infections, including blastomycosis, coccidioidomycosis, and histoplasmosis, are typically treated with lipid-formulation amphotericin for severe disease, followed by step-down azole therapy, whereas mild cases may be managed with primary azole therapy. [4]