What is the likelihood of recurrent Immunoglobulin A (IgA) nephropathy in a transplanted kidney?

Recurrent IgA Nephropathy in Transplanted Kidneys

Recurrent IgA nephropathy occurs in approximately 23% of transplanted kidneys within 15 years post-transplantation and significantly increases the risk of graft loss. 1

Incidence and Timeline

• The recurrence rate of IgA nephropathy varies from 1% to 10% per year, with cumulative incidence reaching 23% at 15 years post-transplantation 2, 1
• Median time to recurrence is approximately 6.75 years after transplantation, though this can vary widely 3
• Studies using protocol biopsies (rather than symptom-triggered biopsies) report higher and earlier recurrence rates 2

Risk Factors for Recurrence

Patient-Related Factors

• Younger recipient age at transplantation (mean difference of 4.27 years younger in those with recurrence) 3, 4
• Male gender (17% increased risk of recurrence) 4
• Shorter time from IgA nephropathy diagnosis to end-stage kidney disease 4
• Shorter time on dialysis before transplantation 4
• Higher serum IgA levels post-transplantation 5
• Retransplantation (43% increased risk) 4

Transplant-Related Factors

• Pre-emptive kidney transplantation (3.45-fold higher risk) 1
• Living related donor transplants (53% increased risk compared to unrelated or deceased donors) 5, 3, 4
• Presence of preformed donor-specific antibodies (2.59-fold higher risk) 1
• Development of de novo donor-specific antibodies post-transplantation (6.65-fold higher risk) 1
• Lower HLA mismatches, particularly HLA-DR mismatches 4
• Absence of HLA-A2 in recipients (appears protective when present) 5
• Presence of HLA-B46 antigen (appears protective) 4

Monitoring and Diagnosis

Screening Recommendations

• Screen for microhematuria in kidney transplant recipients with history of IgA nephropathy 6:
  • Once in the first month post-transplant to establish baseline
  • Every 3 months during the first year
  • Annually thereafter

Biopsy Indications

• Kidney allograft biopsy is recommended when 6:
  • There is persistent, unexplained increase in serum creatinine
  • New onset of proteinuria is detected
  • Unexplained proteinuria >3.0 g per gram creatinine or >3.0 g/24h
  • When screening suggests possible recurrent disease

Outcomes and Prognosis

• Graft loss is 3.69 times higher in patients with recurrent IgA nephropathy compared to those without recurrence 1
• Approximately 32% of grafts are lost within 8 years after diagnosis of recurrence 1
• Progressive graft dysfunction occurs in approximately 29% of patients with recurrent IgA nephropathy 5
• Mean allograft survival is reduced in those with recurrence (6.5 years) compared to those without recurrence (10.4 years) 3
• At 6 years post-transplant, allograft failure occurs in 52% of patients with recurrence versus 10% in those without recurrence 3

Treatment Approaches

• The KDIGO guidelines suggest using an ACE inhibitor or ARB for patients with recurrent glomerulonephritis and proteinuria 6
• However, more recent data suggests ACE inhibitors/ARBs may be associated with a 63% increased risk of IgA recurrence 4
• Immunosuppressive regimens associated with lower recurrence rates include 4:
  • Anti-IL-2-R antibody induction (32% reduced risk)
  • Mycophenolate mofetil (31% reduced risk)
  • Pretransplant tonsillectomy (57% reduced risk)
• mTOR inhibitors may increase recurrence risk by 51% 4

Clinical Implications

• Regular monitoring for microhematuria and proteinuria is essential for early detection 6
• Patients with risk factors for recurrence should receive more vigilant monitoring 6
• The choice between living related versus unrelated donors should be carefully considered given the higher recurrence risk with related donors 5, 3, 4
• Management of donor-specific antibodies is crucial as they significantly increase recurrence risk 1