What is the appropriate workup for a patient with a history of kidney transplantation suspected of having a rejection episode?

Workup for Kidney Transplant Rejection

Perform an ultrasound with Doppler as the initial imaging study, followed by image-guided renal biopsy before initiating treatment for suspected rejection, unless biopsy will substantially delay therapy. 1

Initial Laboratory Assessment

• Measure serum creatinine immediately and estimate glomerular filtration rate (GFR) using validated formulas to establish baseline dysfunction 2
• Check calcineurin inhibitor (CNI) blood levels (tacrolimus or cyclosporine trough levels) to distinguish rejection from drug toxicity or subtherapeutic dosing 1, 2
• Quantify urine protein excretion as new or worsening proteinuria suggests rejection or recurrent disease 2
• Assess medication adherence through patient history and pharmacy records, as non-compliance is a major cause of late acute rejection 2, 3

Imaging Studies

First-Line Imaging

• Renal ultrasound with Doppler is the initial imaging modality to evaluate for vascular complications (renal artery stenosis, thrombosis), hydronephrosis, and perinephric collections 1, 2
• Calculate the resistive index (RI) from intrarenal arteries: RI >0.90 has 100% positive predictive value for acute rejection, while RI <0.70 makes rejection unlikely (94% negative predictive value) 4

Advanced Imaging (If Ultrasound Indeterminate or Suggests Vascular Complications)

• CT angiography (CTA) or MR angiography (MRA) should be performed when ultrasound is non-diagnostic or suggests renal artery stenosis, with both modalities showing sensitivity >93% and specificity ~80% for detecting transplant renal artery stenosis 1
• MRA of abdomen/pelvis with contrast can identify areas of infarction and vascular stenosis while avoiding radiation 1

Renal Allograft Biopsy

Indications for Biopsy

• Persistent unexplained elevation in serum creatinine 2
• Creatinine not returning to baseline after treatment of prior rejection 2
• Failure to achieve expected renal function within 1-2 months post-transplant 2
• New-onset or unexplained proteinuria 2

Biopsy Protocol

• Image-guided (ultrasound) core needle biopsy of the renal cortex is mandatory before treating suspected acute rejection, unless biopsy would substantially delay treatment 1
• Pathologic classification using Banff criteria determines whether rejection is cellular, antibody-mediated, or mixed, which directly impacts treatment selection 1, 5
• Biopsy altered management in ~40% of cases where presumptive diagnosis was made clinically, with complication rates extremely low (0.4-1.0%) 1

Immunologic Evaluation

• Monitor CNI levels more frequently (every other day) when dysfunction suggests nephrotoxicity or rejection 1
• Consider testing for donor-specific antibodies (DSA) if antibody-mediated rejection is suspected, though this is not explicitly required for initial workup 1

Common Pitfalls to Avoid

• Do not assume rejection based on imaging alone: acute rejection cannot be distinguished from acute tubular necrosis or CNI toxicity without biopsy 1
• Do not delay biopsy for additional imaging when clinical suspicion is high and ultrasound shows no surgical complications 1
• Do not treat empirically with corticosteroids before obtaining tissue diagnosis, as this violates guideline recommendations and may mask other treatable causes 1, 5
• Avoid assuming steroid resistance before day 5 of pulse steroid therapy, though vascular rejection on biopsy may warrant earlier escalation 6

Timing Considerations

• Early rejection (first 90 days): occurs in ~50% of patients, with 71% of episodes in the first 30 days; often related to inadequate immunosuppression 7
• Late rejection (>90 days): strongly associated with medication non-compliance rather than inadequate immunosuppression 3
• Patients rejection-free at 90 days typically remain rejection-free through the first year 7