Immunology · Year 2 · from Immunology
Case 1: Acute Cellular Rejection in Kidney Transplant
Patient Demographics
- Age: 52 years old
- Sex: Male
- Ethnicity: African American
Chief Complaint
Decreased urine output and rising creatinine 3 weeks post-transplant
History of Present Illness
A 52-year-old man who received a deceased-donor kidney transplant 3 weeks ago presents with decreased urine output over the past 2 days. He had an uncomplicated early post-operative course with excellent initial graft function (creatinine nadired at 1.2 mg/dL by day 5). However, over the past 48 hours, his urine output has decreased from 2L/day to 800mL/day, and routine labs show a rising creatinine. He denies fever, graft site pain, urinary symptoms, diarrhea, or medication non-compliance.
Transplant Details
- Donor: Deceased donor, 45-year-old male
- HLA matching: 3/6 antigen mismatch (2 HLA-A, 1 HLA-DR mismatch)
- Crossmatch: Negative (CDC and flow cytometric)
- Induction: Basiliximab
- Maintenance immunosuppression: Tacrolimus, mycophenolate mofetil, prednisone
Past Medical History
- End-stage renal disease due to hypertensive nephrosclerosis
- Hemodialysis for 4 years prior to transplant
- Hypertension
- Previous blood transfusions (sensitized: cPRA 45%)
Physical Examination
- General: Well-appearing man in no distress
- Vital Signs: T 37.4C, HR 78, RR 14, BP 145/88
- Cardiovascular: Regular rhythm, no murmurs
- Lungs: Clear bilaterally
- Abdomen: Soft, non-tender; well-healed incision in right lower quadrant; graft non-tender, no bruit
- Extremities: Trace bilateral edema
Laboratory Workup
| Test | Result (Today) | Result (Day 7) | Reference |
|---|---|---|---|
| Creatinine | 2.8 mg/dL | 1.3 mg/dL | 0.7-1.3 mg/dL |
| BUN | 42 mg/dL | 22 mg/dL | 7-20 mg/dL |
| Potassium | 5.4 mEq/L | 4.2 mEq/L | 3.5-5.0 mEq/L |
| Tacrolimus trough | 8.2 ng/mL | 9.1 ng/mL | Target 8-12 ng/mL |
| WBC | 6,800/uL | 7,200/uL | 4,500-11,000/uL |
| Urinalysis | 1+ protein, no casts | Normal | Normal |
| CMV PCR | Not detected | -- | Not detected |
| BK virus PCR | Not detected | -- | Not detected |
| Donor-specific antibodies | Negative | Negative | Negative |
Imaging
- Renal ultrasound: Normal graft size and echogenicity; good arterial and venous flow; no hydronephrosis; no perinephric fluid collection
Kidney Biopsy Findings
- Light microscopy: Moderate interstitial inflammation with tubulitis (>4 lymphocytes per tubular cross-section); no arteritis
- Immunofluorescence: Negative for C4d
- Histology grading: Banff 1B acute T cell-mediated rejection
Clinical Image
Image illustrating concepts in transplant immunology including allorecognition and rejection mechanisms. The direct pathway involves recipient T cells recognizing intact donor MHC on donor APCs, while the indirect pathway involves processing of donor antigens by recipient APCs. Image source: Course lecture materials.
Diagnosis
Acute T Cell-Mediated Rejection (Banff 1B) in deceased-donor kidney transplant
Discussion
Acute cellular rejection is mediated by recipient T cells recognizing donor alloantigens:
Pathophysiology:
- Direct allorecognition: Recipient T cells recognize intact donor MHC on passenger leukocytes (predominates early)
- Indirect allorecognition: Recipient APCs process and present donor antigens to T cells (predominates later)
- Activated T cells infiltrate graft parenchyma
- CD8+ CTLs directly kill tubular epithelial cells
- CD4+ Th1 cells recruit macrophages via IFN-gamma
Banff classification of acute T cell-mediated rejection:
| Grade | Histological Findings |
|---|---|
| 1A | Interstitial inflammation >25%, tubulitis with 1-4 lymphocytes/tubular cross-section |
| 1B | Interstitial inflammation >25%, tubulitis with >4 lymphocytes/tubular cross-section |
| 2A | Mild intimal arteritis (<25% luminal narrowing) |
| 2B | Moderate intimal arteritis (>25% luminal narrowing) |
| 3 | Severe arteritis with fibrinoid necrosis or transmural inflammation |
Risk factors for rejection in this patient:
- African American race (higher immunological risk)
- HLA mismatch (3/6)
- Prior sensitization (cPRA 45%)
- Non-depleting induction (basiliximab vs ATG)
Why wasn't this antibody-mediated rejection?
- Donor-specific antibodies negative
- C4d staining negative on biopsy
- No microvascular inflammation
Treatment
- Pulse corticosteroids: Methylprednisolone 500mg IV daily x 3 days
- Continue maintenance immunosuppression: Ensure therapeutic tacrolimus levels
- Response assessment: Check creatinine daily; expect improvement within 3-5 days
- If steroid-resistant: Anti-thymocyte globulin (ATG) for Grade 2A and above or steroid-refractory Grade 1B
- Long-term: May need to intensify maintenance (increase tacrolimus target)
- Prognosis: Grade 1B generally responds well to steroids; however, rejection episodes increase chronic rejection risk