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Nephrology - Kidney Transplant Immunosuppression - Fast Facts | NEJM Resident 360
| Drug | Description | Mechanism | Toxicity and Comments |
|---|---|---|---|
| Cyclosporine | 11-amino-acid cyclic peptide from Tolypocladium inflatum | Binds to cyclophilin; complex inhibits calcineurin phosphatase and T-cell activation | Nephrotoxicity, hemolytic–uremic syndrome, hypertension, neurotoxicity, gum hyperplasia, skin changes, hirsutism, post-transplantation diabetes mellitus, hyperlipidemia |
Requires trough monitoring or checking levels 2 hours after administration |
| Tacrolimus
(FK 506) | Macrolide antibiotic from Streptomyces tsukubaensis | Binds to FKBP12; complex inhibits calcineurin phosphatase and T-cell activation | Similar adverse effects as cyclosporine but with lower incidence of hypertension, hyperlipidemia, skin changes, hirsutism, and gum hyperplasia and a higher incidence of post-transplantation diabetes mellitus and neurotoxicity
Requires trough monitoring | | Sirolimus (rapamycin) | Triene macrolide antibiotic from S. hygroscopicus from Easter Island (Rapa Nui) | Binds to FKBP12; complex inhibits target of rapamycin and interleukin-2–driven T-cell proliferation | Hyperlipidemia, increased toxicity of calcineurin inhibitors, thrombocytopenia, delayed wound healing, delayed graft function, mouth ulcers, pneumonitis, and interstitial lung disease
Requires lipid monitoring; recipients at low-to-moderate risk for rejection can stop cyclosporine treatment 2−4 months after transplantation | | Everolimus | Derivative of sirolimus | | | | Mycophenolate mofetil and enteric-coated mycophenolate | Mycophenolic acid from penicillium molds | Inhibits synthesis of guanosine monophosphate nucleotides; blocks purine synthesis, prevents proliferation of T and B cells | Gastrointestinal symptoms (mainly diarrhea), neutropenia, mild anemia
Blood-level monitoring not required but may improve efficacy; absorption reduced by cyclosporine | | Azathioprine | Prodrug that releases 6-mercaptopurine | Converts 6-mercaptopurine to tissue inhibitor of metalloproteinase, which is converted to thioguanine nucleotides that interfere with DNA synthesis; thioguanine derivatives may inhibit purine synthesis | Leukopenia, bone-marrow depression, macrocytosis, liver toxicity (uncommon)
Requires blood-count monitoring | | Polyclonal anti-thymocyte globulin | Polyclonal IgG from horses or rabbits with human thymocytes; absorbed to reduce unwanted antibodies | Depletes CD4 lymphocytes through acting against human T-cell surface antigens; used for induction (off-label), and used to treat rejection | Cytokine-release syndrome (fever, chills, hypotension), thrombocytopenia, leukopenia, serum sickness | | Muromonab-CD3 | Murine monoclonal antibody against CD3 component of T-cell–receptor signal-transduction complex | Binds to CD3 associated with T-cell receptor, leading to initial activation and cytokine release, followed by blockade of function, lysis, and T-cell depletion | Severe cytokine-release syndrome, pulmonary edema, acute renal failure, gastrointestinal disturbances, changes in central nervous system | | Alemtuzumab | Humanized monoclonal antibody against CD52, a 25-to-29-kD membrane protein | Binds to CD52 on all B and T cells, most monocytes, macrophages, and natural killer cells, causing cell lysis and prolonged depletion | Mild cytokine-release syndrome, neutropenia, anemia, idiosyncratic pancytopenia, autoimmune thrombocytopenia, thyroid disease
Widely used for chronic lymphocytic leukemia and multiple sclerosis (FDA-approved); used off-label in some kidney transplant regimens
Alemtuzumab did not reduce calcineurin inhibitor exposure or improve transplant function or survival | | Rituximab | Chimeric monoclonal antibody against membrane-spanning four-domain protein CD20 | Binds to CD20 on B cells and mediates B-cell lysis | Infusion reactions, hypersensitivity reactions (uncommon) | | Basiliximab | Chimeric monoclonal antibody against CD25 (interleukin-2–receptor α chain) | Binds to and blocks the interleukin-2–receptor α chain (CD25 antigen) on activated T cells, depleting them and inhibiting interleukin-2–induced T-cell activation | Hypersensitivity reactions (uncommon); two doses required
No monitoring required
Used with calcineurin inhibitor and glucocorticoids
Used for transplant rejection prophylaxis and in induction regimens | | Daclizumab | Humanized monoclonal antibody against CD25 (interleukin-2–receptor α chain) | Has similar action to basiliximab | Hypersensitivity reactions (uncommon); five doses recommended but two may suffice
No monitoring required | | Abatacept | Protein combining B7-binding portion of CTLA-4 with IgG Fc region | Binds to B7 on T cells, preventing CD28 signaling and signal 2 | Hypersensitivity reactions, infections, malignancies | | Belatacept | Monoclonal antibody | Inhibits T-cell CD28 activation and proliferation through binding to costimulatory ligands (CD80, CD86) on antigen-presenting cells | Infections, lymphoproliferative disorders, malignancy, activation of latent viral infections
Used in combination with basiliximab induction, mycophenolate mofetil, and glucocorticoids for rejection prevention |