Non-Adherence and Late Acute Rejection in an Adolescent Transplant Recipient
A 17-year-old girl received a kidney transplant at age 12 for focal segmental glomerulosclerosis. She is now 5 years post-transplant with a baseline creatinine of 1.1 mg/dL. Her maintenance regimen is tacrolimus twice daily, mycophenolate mofetil, and low-dose prednisone. Over the past 3 months her creatinine has risen to 1.9 mg/dL, and her tacrolimus trough is undetectable. She admits to missing doses because she feels well and dislikes the side effects, including tremor and acne. She has missed two clinic appointments. Urinalysis shows 1+ protein and no cells. Donor-specific antibodies are now positive with a mean fluorescence intensity of 4,000 against HLA-DQ7. She has no fever or dysuria.
1. What is the likely diagnosis, and what are the immediate management priorities?
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The likely diagnosis is late acute rejection, probably antibody-mediated rejection given the new donor-specific antibodies against HLA-DQ7, combined with non-adherence and an undetectable tacrolimus level. The rising creatinine, proteinuria, and DSA positivity are concerning for active antibody-mediated injury. Immediate priorities: (1) Restore immunosuppression - resume therapeutic tacrolimus and mycophenolate with directly observed or supervised dosing, and consider intravenous or long-acting formulations to ensure adherence. (2) Graft biopsy to characterize rejection (Banff classification) and exclude other causes such as BK virus nephropathy or recurrent FSGS. (3) Check BK viral load and CMV because increased immunosuppression and non-adherence can unmask infection. (4) Assess for infection before escalating immunosuppression. (5) Involve the adolescent and family in a adherence plan with behavioral support, simplified dosing, and mental health assessment. (6) Consider plasmapheresis and IVIG if biopsy confirms antibody-mediated rejection, with or without rituximab, per center protocol.
2. How would you address the underlying adherence problem and the transition to adult care to reduce the risk of future graft loss?
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Adolescence is a high-risk period for non-adherence and graft loss, especially during transition to adult care. The approach should be structured and multidisciplinary: (1) Nonjudgmental assessment of barriers - side effects, pill burden, mental health, school stress, and health literacy. (2) Simplify the regimen where possible (once-daily tacrolimus, combination pills) and use reminders, pillboxes, and pharmacy refill monitoring. (3) Directly observed therapy or supervised dosing at school or home for a period. (4) Behavioral and psychological support, including counseling for depression and body-image concerns from acne and tremor. (5) Peer support and education about the consequences of missed doses. (6) Structured transition program with joint pediatric-adult clinic visits, a written transition plan, and a named adult provider before transfer. (7) Monitor DSA and renal function closely, with a low threshold for biopsy. (8) Document the plan and involve the family appropriately. The goal is to stabilize adherence before transfer, because late rejection and DSA are strong predictors of graft loss.