Kidney Allograft Failure Workup
A comprehensive workup for kidney allograft failure should include biomarker assessment, histological evaluation, and immunological testing to identify the specific cause of failure and guide management decisions. 1
Definition of Kidney Allograft Failure
- Failing kidney allograft: Characterized by irreversible and progressive decline in kidney function with anticipated allograft survival of less than 1 year 1
- Failed kidney allograft: Graft that is either no longer functioning or working so poorly that meaningful functional improvement is not possible and additional kidney replacement therapy is required 1
Essential Biomarkers for Workup
Kidney Function Assessment
- Serial monitoring of serum creatinine and estimated glomerular filtration rate (eGFR) to establish trajectory of decline 1
- Consider using non-creatinine markers such as cystatin C for more accurate assessment of kidney function in transplant recipients 1
- Note that standard eGFR formulas have limitations in transplant recipients and may need adjustment 1
Proteinuria Assessment
- Quantitative measurement of proteinuria (spot urine protein-to-creatinine ratio or 24-hour urine collection) 1
- Proteinuria is a significant predictor of graft failure and helps identify glomerular pathologies 1
Immunological Testing
- Evaluation for circulating anti-human leukocyte antigen donor-specific antibodies (HLA-DSAs) 1
- Panel reactive antibody (PRA) testing to assess degree of sensitization 1
- Complement activation markers (C4d staining on biopsy) 1
Histological Evaluation
Kidney allograft biopsy is essential for definitive diagnosis of the cause of failure 1, 2
Biopsy should be performed when there is:
- Unexplained rise in serum creatinine
- New onset or worsening proteinuria
- Persistent decline in eGFR 1
Histopathological evaluation should include:
Common Causes to Evaluate
Glomerular diseases (36.6% of graft failures) including:
- Recurrent primary disease
- Transplant glomerulopathy
- De novo glomerular disease 2
Interstitial fibrosis/tubular atrophy (30.7% of graft failures) 2
Acute rejection (11.8% of graft failures) 2
Medical/surgical conditions (16.3% of graft failures) 2
Additional Workup Components
Evaluation for infection:
- Urinalysis and urine culture
- BK virus PCR in blood and urine
- Cytomegalovirus (CMV) PCR 1
Medication review:
- Assessment of immunosuppression adherence
- Evaluation for drug interactions
- Therapeutic drug monitoring of immunosuppressants 1
Vascular assessment:
- Doppler ultrasound to evaluate for vascular complications
- Consider CT angiography if transplant renal artery stenosis is suspected 1
Planning for Kidney Replacement Therapy
- Early identification of potential living donors to increase chances of preemptive retransplantation 1
- Assessment for arteriovenous (AV) access placement when eGFR declines to <20 ml/min 1
- Timing of dialysis initiation should be based on clinical factors and symptoms rather than eGFR alone 1
Common Pitfalls to Avoid
- Attributing graft dysfunction solely to calcineurin inhibitor toxicity without adequate investigation (accounts for <1% of graft losses as a sole cause) 2
- Delaying biopsy in cases of unexplained graft dysfunction 1
- Late referral for dialysis access placement or transplant evaluation 1
- Poor communication between transplant center and dialysis unit during transition to kidney replacement therapy 1
Management Considerations
- Immunosuppression management should be based on patient risks and plans for retransplantation 1
- Coordination of care between transplant center and dialysis unit is critical during transition 1
- Patient education and psychological support are essential during this difficult period 1
By following this comprehensive workup approach, clinicians can identify specific causes of kidney allograft failure and implement appropriate management strategies to optimize patient outcomes.