Renal Transplant Immunosuppression
Maintenance Regimen, Calcineurin Inhibitors, and Rejection Management
Standard Maintenance Triple Therapy
Calcineurin Inhibitor
Tacrolimus (preferred)
  • Binds FKBP12 → inhibits calcineurin
  • Blocks interleukin-2 transcription
  • Narrow therapeutic index — monitor trough
  • Risks: nephrotoxicity, diabetes, neurotoxicity
Antiproliferative
Mycophenolate Mofetil
  • Prodrug → mycophenolic acid
  • Inhibits IMPDH → blocks guanosine synthesis
  • Selective lymphocyte suppression
  • Risks: GI toxicity, leukopenia, teratogenicity
Corticosteroid
Prednisone (low dose)
  • Inhibits NF-kB → suppresses cytokines
  • Broad anti-inflammatory effect
  • Chronic toxicity: diabetes, osteoporosis, cardiovascular disease
  • Steroid minimization protocols used when possible
mTOR Inhibitor (alternative)
Sirolimus / Everolimus
  • Binds FKBP12 → inhibits mTORC1
  • Calcineurin-independent mechanism
  • Role: CNI minimization in nephrotoxicity
  • Risks: wound healing, pneumonitis, dyslipidemia
Calcineurin Inhibitor Comparison
Feature Tacrolimus Cyclosporine Both Agents
Binding protein FKBP12 Cyclophilin Both inhibit calcineurin
Distinct adverse effects Diabetes, neurotoxicity, tremor Gingival hyperplasia, hirsutism, hyperlipidemia Nephrotoxicity, hypertension, hyperuricemia
Key interactions CYP3A4 inhibitors ↑ levels (azoles, macrolides, diltiazem); CYP3A4 inducers ↓ levels (rifampin, phenytoin)
T-Cell Mediated Rejection
Tubulitis + Interstitial Inflammation
  • Mechanism: alloreactive T-cell infiltration
  • Biopsy: lymphocytic tubulitis, interstitial inflammation
  • Treatment: pulse methylprednisolone (500 mg IV x 3 days)
  • Steroid-resistant: antithymocyte globulin
  • Better prognosis than AMR
Antibody-Mediated Rejection
Donor-Specific Antibodies
  • Mechanism: donor-specific antibodies vs HLA antigens
  • Biopsy: peritubular capillaritis, C4d deposition
  • Treatment: plasmapheresis + IVIG + rituximab
  • More treatment-resistant than TCMR
  • Leading cause of late graft loss
Azathioprine + Allopurinol — Dangerous Combination

Allopurinol inhibits xanthine oxidase, the enzyme that inactivates 6-mercaptopurine (the active metabolite of azathioprine). Co-administration causes 6-mercaptopurine accumulation and life-threatening myelosuppression. If allopurinol is required in a transplant patient on azathioprine, reduce azathioprine dose by 75% or switch to mycophenolate mofetil, which does not interact with xanthine oxidase.