338.1 🎓 醫孞生版

338.1.0.1 📌 䞀頁重點

338.1.0.1.1 Indications + Benefits

338.1.1 Indications

  • ESKD (eGFR < 20 + planning RRT)
  • Preemptive (before dialysis) ideal
  • Failed allograft (re-transplant)

338.1.2 Benefits vs Dialysis

  • Better survival (50-70% reduction in mortality vs continued dialysis)
  • Better quality of life
  • Cost-effective long-term (after 2-3 years)
  • Better metabolic control
  • Better fertility, growth (pediatric)

338.1.3 Pre-Emptive Transplant

  • Before dialysis start
  • Best outcomes
  • Need early referral + workup
338.1.3.0.1 Donor Selection

338.1.4 Living Donor (LD) — Preferred

  • Related (parent, sibling, child)
  • Unrelated (spouse, friend)
  • Paired exchange programs (incompatible donor-recipient pairs)
  • Altruistic (anonymous donor)

Living Donor Evaluation: - Medical: extensive (BP, DM, kidney function, imaging, no significant comorbidity) - Psychosocial - Genetic counseling (if hereditary disease) - Long-term donor follow-up

Living Donor Outcomes: - Better graft survival than deceased - Long-term kidney function preserved in donor (mostly) - Minimal increase in ESKD risk (small)

338.1.5 Deceased Donor (DD)

Categories: - Donation after brain death (DBD) — standard - Donation after circulatory death (DCD) — expanding - Expanded criteria donors (ECD) — older, comorbid — for older / less ideal recipients - PHS Increased Risk (HBV, HCV history) — modern era, with treatment

Allocation: UNOS (US) / NHS (UK) / Eurotransplant systems - Wait time - HLA matching - Sensitization (PRA) - ABO, size, comorbidities - Highly sensitized + pediatric priority

338.1.6 Crossmatch + HLA Matching

ABO Compatibility: - Critical to match - O can give to all (universal donor) - AB can receive from all

HLA Matching: - Class I: A, B, C - Class II: DR, DQ, DP - Better match → better outcome - Importance: DR > B > A

Crossmatch: - Donor cells + recipient serum - Positive: pre-formed antibodies, contraindication - T-cell crossmatch: HLA Class I + II - B-cell crossmatch: HLA Class II - Flow vs CDC crossmatch

Panel Reactive Antibodies (PRA): - % of population with which recipient has antibodies - High PRA = sensitized (challenging match)

Donor-Specific Antibodies (DSA): - Pre-existing antibodies against donor HLA - Risk for hyperacute or AMR

338.1.7 Sensitization Sources

  • Prior transplant
  • Pregnancy
  • Transfusions
338.1.7.0.1 Immunosuppression

338.1.8 Induction Therapy

Indications: at time of transplant

Basiliximab (IL-2 Receptor Antagonist): - 20 mg IV day 0 + day 4 - Low-risk patients - Less immunosuppressive

Antithymocyte Globulin (rATG, Thymoglobulin): - 1-1.5 mg/kg × 4-7 doses - Higher-risk patients (sensitized, AMR history, DCD) - Profound T-cell depletion - Side effects: cytopenia, CMV, infection

Alemtuzumab (Campath): - Anti-CD52 - B + T cell depletion - Used selectively - Pre-medication with steroids, antihistamine

338.1.9 Maintenance Triple Therapy

Calcineurin Inhibitor (CNI) — Anchor: - Tacrolimus (Prograf, Astagraf XL, Envarsus XR) — preferred - Trough 5-10 ng/mL (early), 4-7 (long-term) - Cyclosporine — alternative (older) - Less commonly used now

Antiproliferative: - Mycophenolate mofetil (MMF) — preferred - 1-2 g daily divided - Side effects: GI, leukopenia - Mycophenolic acid (Myfortic) — enteric-coated - Azathioprine — older, alternative

Corticosteroids: - Prednisone, tapered - Some advocate steroid-free regimens (sensitized considerations)

338.1.10 Alternative Regimens

mTOR Inhibitors: - Sirolimus (rapamycin) - Everolimus - For specific indications (CNI nephrotoxicity, malignancy reduction, CAV) - Side effects: hyperlipidemia, edema, oral ulcers, wound healing

Belatacept (Nulojix): - Fusion protein (CTLA-4 + IgG Fc) - IV monthly - CNI-sparing (avoids nephrotoxicity) - Approved 2011 - BENEFIT trials - EBV-positive only (PTLD risk in EBV-naive)

338.1.10.0.1 Complications

338.1.11 Surgical / Early

Delayed Graft Function (DGF): - Need for dialysis within first week - Risks: cold ischemia time, donor age, DCD - Most recover

Perioperative: - Bleeding - Vascular complications (thrombosis, stenosis) - Urological (ureteral leak, stricture) - Wound issues

338.1.12 Acute Rejection

Acute Cellular Rejection (ACR): - T-cell mediated - Banff classification (1A, 1B, 2A, 2B, 3) - ↑ Cr + sometimes pain/fever - Treatment: pulse methylprednisolone 500-1000 mg × 3 days; rATG for refractory

Antibody-Mediated Rejection (AMR): - Donor-specific antibodies (DSAs) - Microvascular inflammation, C4d deposition on biopsy - Treatment: plasmapheresis + IVIG + rituximab + bortezomib + IS optimization - Refractory cases challenging

Hyperacute Rejection: - Pre-formed antibodies - Within minutes-hours - Now rare with crossmatch screening - Graft loss

338.1.13 Chronic Allograft Injury

Chronic Active T-Cell Rejection: - Inflammation in tubulitis - Treatment: pulse steroids + IS optimization

Chronic Active AMR: - Microvascular inflammation + glomerulopathy - Difficult to treat

Interstitial Fibrosis and Tubular Atrophy (IFTA): - Common late finding - Multifactorial (rejection, CNI toxicity, infection, recurrence) - Progressive function loss

338.1.14 Infections

CMV (most common viral): - D+/R- highest risk - Prophylaxis valganciclovir 6-12 months - Tissue invasive: pneumonia, colitis, hepatitis, retinitis - Treatment: ganciclovir IV → valganciclovir oral

BK Virus Nephropathy: - 1-10% of transplants - BK PCR (blood, urine) - Reduction of IS - Cidofovir, IVIG for severe (limited)

PCP: - Prophylaxis: TMP-SMX (also for toxoplasma)

Fungal: - Candida, Aspergillus - Antifungal prophylaxis in select

Bacterial: - UTIs common - Sepsis at any time

338.1.15 Malignancy

Skin Cancer: - SCC most common (vs BCC in general population) - UV protection - Annual dermatology - Voriconazole long-term ↑ SCC risk

Post-Transplant Lymphoproliferative Disorder (PTLD): - EBV-driven (especially in D+/R- mismatch) - B-cell predominant - Treatment: reduce IS + rituximab (CD20+) + chemo

Kaposi Sarcoma: HHV-8

Solid Organ: lung, GI, others

Renal Cell Carcinoma: in native kidneys

338.1.16 CV Risk

  • HTN, hyperlipidemia, DM (often new-onset, NODAT)
  • ↑ Cardiovascular events vs general population
  • Top cause of death post-transplant

338.1.17 Recurrence of Original Disease

  • FSGS (especially primary) — recurs 20-30%
  • MN — anti-PLA2R antibodies risk
  • MPGN / C3G — recurs
  • IgA — recurs but often mild
  • HUS / aHUS — eculizumab
  • DKD — recurs but slow

338.1.18 CNI Toxicity

  • Nephrotoxicity (acute + chronic)
  • Hypertension
  • Hyperkalemia
  • Tremor
  • Glucose intolerance (new-onset DM)
  • Neurotoxicity (PRES)
338.1.18.0.1 Outcomes

338.1.19 Survival

  • 1-year graft: 95%+
  • 5-year graft: 80-85%
  • 10-year graft: 60-70%

338.1.20 Patient Survival

  • 1-year: 97%+
  • 5-year: 90%
  • 10-year: 70-80%

338.1.21 Half-Life of Graft

  • ~ 10-15 years (improving)
  • LD better than DD
338.1.21.0.1 Special Considerations

338.1.22 Pediatric Transplant

  • Smaller donor pool
  • Living donor preferred
  • Growth + development
  • Long-term issues

338.1.23 Pregnancy After Transplant

  • Possible
  • Wait 1-2 years post-transplant
  • Stable function
  • IS adjustment (avoid MMF — teratogenic)
  • Multidisciplinary

338.1.24 Recurrence Prevention

  • Identify high-risk recurrence diseases
  • Use specific regimens (e.g., complement inhibitors for aHUS)

338.1.24.1 🩺 床邊速查

  • Renal transplant: best for ESKD (vs dialysis)
  • Donors: LD > DD (DBD or DCD)
  • HLA matching: DR > B > A
  • Crossmatch + DSA: critical pre-transplant
  • Induction: basiliximab or rATG
  • Maintenance: tacrolimus + MMF + prednisone
  • Belatacept: CNI-sparing option
  • PTLD: EBV-driven; reduce IS + rituximab
  • Skin cancer: SCC most common; voriconazole ↑ risk
  • CMV: D+/R- highest; valganciclovir prophylaxis 6-12 mo