A kidney transplant recipient on tacrolimus, mycophenolate mofetil, and prednisolone develops gradually rising creatinine 8 months post-transplant. Renal biopsy shows 'chronic allograft nephropathy' with interstitial fibrosis/tubular atrophy (IF/TA) and intimal fibrosis of vessels. What is the most likely immunological mechanism?
- A Hyperacute rejection mediated by preformed donor-specific antibodies (DSA) against HLA
- B Calcineurin inhibitor (tacrolimus) nephrotoxicity causing striped interstitial fibrosis
- C CMV nephritis causing tubular inflammation and atrophy
- D Chronic antibody-mediated rejection (cAMR) driven by de novo donor-specific HLA antibodies causing endothelial injury and transplant vasculopathy ✓
Explanation
Chronic antibody-mediated rejection (cAMR) is the leading cause of late kidney allograft failure. It is driven by de novo donor-specific antibodies (DSA) against donor HLA class I or II antigens that develop after transplantation due to alloantigen sensitization. DSA bind endothelial cells activating complement (C4d deposition, a key diagnostic marker on biopsy) and ADCC, causing progressive transplant vasculopathy (arterial intimal fibrosis) and glomerulitis. IF/TA pattern with peritubular capillaritis and C4d positivity supports cAMR diagnosis. Tacrolimus toxicity also causes IF/TA but in a striped, centrolobular pattern without C4d or glomerulitis.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
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Written and medically reviewed by the StethoPrep medical team.