What are the timelines for renal transplant rejection?

Timelines for Renal Transplant Rejection

Renal transplant rejection follows specific timelines that can be categorized into hyperacute, acute, and chronic rejection periods, with acute rejection most commonly occurring from 1 week to 1 month after transplantation. 1

Types of Rejection by Timeline

Immediate Post-Transplant Period (< 1 week)

• Hyperacute rejection: Occurs within minutes to hours after transplantation
• Acute tubular necrosis (ATN): Most common cause of intrinsic dysfunction in this period, especially in deceased donor grafts 1
• Vascular complications: Renal artery thrombosis and renal vein thrombosis typically occur in the first week, usually due to technical surgical difficulties or clotting disorders 1

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

• Acute rejection: Most commonly occurs during this timeframe 1
• Clinical presentation: Manifests as declining kidney function, requiring biopsy confirmation
• Monitoring: Kidney allograft biopsy is recommended when there is a persistent, unexplained increase in serum creatinine 1

Intermediate Period (1-3 months)

• Calcineurin inhibitor toxicity: Most common in the second or third month when drugs are being titrated 1
• Late acute rejection: Can occur, especially in cases of medication non-compliance 2
• Monitoring: Continued surveillance of renal function is essential during this period

Late Period (> 3 months)

• Chronic rejection: Most common cause of late graft dysfunction, presenting at least 3 months following transplantation 1
• Late acute rejection: Often associated with patient non-compliance with immunosuppressive medications 2

Monitoring and Diagnosis

Recommended Monitoring Schedule

• Serum creatinine measurements 1:
  • Daily for 7 days or until hospital discharge
  • 2-3 times per week for weeks 2-4
  • Weekly for months 2 and 3
  • Every 2 weeks for months 4-6
  • Monthly for months 7-12
  • Every 2-3 months thereafter

Biopsy Recommendations

• Indications for biopsy 1:
  • Persistent, unexplained increase in serum creatinine
  • When serum creatinine has not returned to baseline after treatment of acute rejection
  • Every 7-10 days during delayed graft function
  • If expected kidney function is not achieved within the first 1-2 months
  • New onset of proteinuria or unexplained proteinuria >3.0 g per gram creatinine

Risk Factors and Outcomes

Risk Factors for Rejection

• Early acute rejection:
  • Younger recipient age 2
  • Delayed graft function 3
  • Sensitized recipients (high PRA) 3
  • Inadequate immunosuppression 2

Late Acute Rejection

• Primary risk factor: Patient non-compliance with immunosuppressive medications 2
• Impact: Significantly increases risk of graft loss (9% with first rejection, 38% with second rejection, and 50% with third rejection) 4

Chronic Rejection

• Risk factors: Prior acute rejection episodes, especially:
  • Multiple acute rejection episodes
  • Rejection episodes occurring more than 60 days post-transplant 5

Clinical Implications

Prognostic Significance

• Acute rejection episodes significantly increase the risk of developing biopsy-proven chronic rejection 5
• Steroid-resistant rejection has worse outcomes (58% one-year graft survival) compared to steroid-sensitive rejection (88%) 4
• The detrimental effect of acute rejection on graft survival extends beyond the early post-transplant period 3

Modern Immunosuppression Impact

• With tacrolimus-based immunosuppression, the incidence of subclinical rejection at 3 months has decreased to approximately 2.6% (compared to 30% with cyclosporine) 6
• The incidence of acute rejection has decreased over time with modern immunosuppressive regimens 3

Pitfalls and Caveats

• Rejection may be clinically silent (subclinical rejection), highlighting the importance of protocol biopsies in some cases
• Medication non-compliance is a major modifiable risk factor for late acute rejection 2
• Differentiating calcineurin inhibitor toxicity from rejection can be challenging without biopsy
• Delayed diagnosis and treatment of acute rejection significantly worsens long-term outcomes

Remember that early detection and prompt treatment of rejection episodes are critical for preserving long-term graft function and survival.