Kidney transplantation

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Indications & Evaluation - The Kidney Waitlist

  • Indication: End-Stage Renal Disease (ESRD), typically with GFR < 20 mL/min/1.73m².
  • Evaluation: A multidisciplinary team assesses suitability, focusing on contraindications.
  • Absolute Contraindications:
    • Active malignancy (requires disease-free interval).
    • Active, untreated systemic infection.
    • Severe, irreversible extra-renal organ damage (e.g., severe CAD, advanced liver disease).
    • Active substance abuse.
    • Persistent non-adherence to medical care.
  • Relative Contraindications:
    • Morbid obesity (BMI > 40).
    • Active smoking.
    • Poorly controlled psychiatric conditions.

⭐ Most solid-organ cancers require a 2-5 year disease-free interval before a patient can be listed, as immunosuppression can accelerate recurrence.

Immunosuppression - Taming the Defenses

  • Goal: Prevent and treat rejection while minimizing drug toxicity and infection risk.
  • Phases:
    • Induction: High-dose agents (e.g., basiliximab, anti-thymocyte globulin) at time of transplant.
    • Maintenance: Lifelong triple therapy is common (e.g., CNI + antimetabolite + steroid).
    • Rejection Treatment: High-dose steroids (pulses) or antibody therapy.
ClassMechanism of Action (MOA)Key Adverse Effects (AEs)
Calcineurin Inhibitors (Tacrolimus, Cyclosporine)Block IL-2 transcription → ↓ T-cell activationNephrotoxicity, neurotoxicity, hypertension, hyperglycemia
Antimetabolites (Mycophenolate, Azathioprine)Inhibit purine synthesis → ↓ lymphocyte proliferationGI distress (diarrhea), bone marrow suppression
mTOR Inhibitors (Sirolimus, Everolimus)Block IL-2 signal transduction → ↓ T-cell proliferationHyperlipidemia, proteinuria, poor wound healing, pancytopenia
Corticosteroids (Prednisone)Broad anti-inflammatory; inhibit cytokine genesCushingoid features, osteoporosis, hyperglycemia, avascular necrosis

Transplant Rejection - The Body Fights Back

TypeTimingPathophysiologyKey Histologic FindingsManagement
HyperacuteMins-hoursPre-formed anti-donor Abs (Type II HSR)Widespread thrombosis, fibrinoid necrosisImmediate graft removal
Acute< 6 monthsCellular (T-cell) or Antibody-mediated (B-cell)Cellular: Lymphocytic infiltrate, tubulitis
Antibody: C4d deposition
Corticosteroids, anti-lymphocyte Abs
Chronic> 6 monthsMixed cellular/humoral; chronic inflammationInterstitial fibrosis, tubular atrophy (IF/TA)Supportive, eventual re-transplantation

⭐ C4d deposition in peritubular capillaries is a key marker for antibody-mediated rejection, indicating complement activation against the graft endothelium.

Post-Transplant Complications - More Than Just Rejection

  • Infections: Prophylaxis for CMV is key. Screen for BK virus to prevent graft loss.
  • Malignancies: ↑ risk of skin cancers (SCC > BCC) and PTLD (EBV-driven).
  • Cardiovascular Disease: The primary cause of long-term mortality.

⭐ BK virus nephropathy presents with a rising creatinine, mimicking acute rejection. Biopsy is required to differentiate as treatment differs (reduce immunosuppression vs. increase).

High‑Yield Points - ⚡ Biggest Takeaways

  • Standard triple immunosuppression includes a calcineurin inhibitor (e.g., tacrolimus), an antimetabolite, and corticosteroids.
  • Acute rejection, the most common type, is T-cell mediated and typically responds to high-dose steroids.
  • Chronic allograft nephropathy is the primary cause of late graft failure, marked by irreversible fibrosis.
  • Calcineurin inhibitors are highly effective but carry a major risk of nephrotoxicity and hypertension.
  • Post-transplant risks include opportunistic infections (CMV, BK virus) and malignancy (skin cancer, PTLD).

Practice Questions: Kidney transplantation

Test your understanding with these related questions

A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney?

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Flashcards: Kidney transplantation

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Reactivation of CMV occurs in the immunosuppressed, such as _____ and AIDS patients

TAP TO REVEAL ANSWER

Reactivation of CMV occurs in the immunosuppressed, such as _____ and AIDS patients

organ transplant

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