What is the timeline for renal transplant rejection?

Timeline for Renal Transplant Rejection

Renal transplant rejection typically follows a predictable timeline with hyperacute rejection occurring immediately post-transplant, acute rejection most commonly occurring from 1 week to 1 month after transplantation, and chronic rejection presenting at least 3 months following transplantation. 1

Types of Rejection by Timeline

Immediate Post-Transplant Period (<24 hours)

• Hyperacute rejection: Occurs within minutes to hours after transplantation
  • Caused by preformed donor-specific antibodies
  • Results in immediate graft failure
  • Rare in modern transplantation due to crossmatching

Early Post-Transplant Period (<1 week)

• Acute Tubular Necrosis (ATN): Most common cause of intrinsic dysfunction in this period 1
  • Common in deceased donor grafts
  • Less frequent in living donor transplants
  • Not technically rejection but can mimic its presentation

Early to Mid Post-Transplant Period (1 week to 1 month)

• Acute rejection: Peak incidence occurs during this timeframe 1
  • Characterized by rapid deterioration in graft function
  • Requires prompt diagnosis and treatment
  • 71% of all rejection episodes occur in the first 30 days post-transplant 2

Mid Post-Transplant Period (2-3 months)

• Calcineurin inhibitor toxicity: Most common in second or third month 1
  • Occurs during medication titration
  • Can mimic rejection symptoms

Late Post-Transplant Period (≥3 months)

• Chronic rejection: Most common cause of late graft dysfunction 1
  • Typically presents at least 3 months post-transplantation
  • Characterized by gradual deterioration in graft function over at least 6 months 3
  • Associated with previous acute rejection episodes

Risk Factors and Correlates

Acute Rejection Risk Factors

• Previous acute rejection episodes (especially multiple episodes)
• Rejection episodes occurring >60 days post-transplant 3
• Younger recipient age 4
• Medication non-compliance (particularly associated with late acute rejection) 4
• Delayed graft function 2
• High panel reactive antibody (PRA) levels 2

Chronic Rejection Risk Factors

• History of acute rejection episodes (strongest predictor)
• Multiple acute rejection episodes increase risk
• Late acute rejection (>60 days post-transplant) 3

Monitoring Recommendations

Surveillance Biopsies

• Consider surveillance biopsies during periods of delayed graft function every 7-10 days 1
• Biopsy if expected kidney function is not achieved within 1-2 months post-transplantation 1
• Biopsy for persistent, unexplained increases in serum creatinine 1

Laboratory Monitoring

• Measure serum creatinine 1:
  • Daily for first 7 days or until discharge
  • 2-3 times weekly for weeks 2-4
  • Weekly for months 2-3
  • Every 2 weeks for months 4-6
  • Monthly for months 7-12
  • Every 2-3 months thereafter

Rejection Monitoring

• Monitor for rejection episodes particularly in the first 90 days
• Patients rejection-free at 90 days tend to remain rejection-free for the entire first year 2

Clinical Implications

1. The risk of graft loss increases with each rejection episode:

   • 9% with first rejection
   • 38% with second rejection
   • 50% with third rejection 2

2. Modern immunosuppressive regimens have significantly reduced rejection rates:

   • With tacrolimus-based regimens, subclinical rejection at 3 months is now only 2.6% 5
   • This is much lower than the 30% reported with older cyclosporine-based regimens

3. Late acute rejection is often associated with non-compliance rather than inadequate immunosuppression 4

Treatment Considerations

• Corticosteroids are recommended as first-line treatment for acute cellular rejection 1
• For steroid-resistant rejections, consider lymphocyte-depleting antibodies 1
• For chronic rejection with CNI toxicity, consider reducing, withdrawing, or replacing the CNI 1

Understanding the timeline of renal transplant rejection is crucial for appropriate monitoring, early intervention, and improved long-term graft outcomes.