Risk Factors for Recurrent IgA Nephropathy in Renal Transplant
Younger recipient age at transplantation is the most consistently identified risk factor for IgA nephropathy recurrence, along with living related donor transplantation, rapid progression of original disease, and shorter time to end-stage renal disease. 1
Primary Risk Factors
Recipient-Related Factors
Age is the strongest predictor of recurrence:
- Younger recipients face significantly higher recurrence risk (mean age difference of 4.27 years younger in those with recurrence, RR=0.96 per year increase). 1
- Pediatric and young adult recipients (ages 0-25 years) demonstrate elevated risk, with 5.4% experiencing graft loss specifically from recurrent disease. 2
Disease progression characteristics:
- Rapid progression from IgA nephropathy diagnosis to ESRD (mean difference of 1.84 years shorter) strongly predicts recurrence. 1
- Shorter time on dialysis before transplantation (mean difference of 3.14 months less) increases recurrence risk. 1
Gender:
- Male recipients have 17% higher risk of recurrence (RR=1.17). 1
Donor-Related Factors
Living related donor (LRD) transplantation carries the highest recurrence risk:
- LRD transplantation increases recurrence risk by 53% (RR=1.53) compared to other donor types. 1, 3
- Younger donor age (mean difference of 2.19 years younger) correlates with higher recurrence rates. 1
- Parental living donors specifically show higher rates of graft loss from recurrence compared to non-parental living donors (aHR=0.52 for non-parental). 2
Important caveat: Despite higher recurrence rates, LRD transplants do not show inferior overall graft survival compared to deceased donor transplants, likely due to lower rates of chronic allograft nephropathy. 3 This reflects the competing risks between recurrence and other causes of graft dysfunction.
Immunologic Factors
HLA matching:
- Lower total HLA mismatches (mean difference of 0.11 fewer mismatches) paradoxically associate with higher recurrence. 1
- Lower HLA-DR mismatches (mean difference of 0.13 fewer mismatches) similarly correlate with increased recurrence. 1
- HLA-B46 antigen presence reduces recurrence risk by 61% (RR=0.39). 1
Retransplantation:
- Second or subsequent transplants increase recurrence risk by 43% (RR=1.43). 1
Immunosuppression-Related Risk Factors
Induction therapy:
- Absence of induction therapy increases recurrence risk by 73% (RR=1.73). 1
- Anti-IL-2 receptor antibody induction reduces recurrence by 32% (RR=0.68). 1
Maintenance immunosuppression:
- mTOR inhibitor use increases recurrence risk by 51% (RR=1.51). 1
- Mycophenolate mofetil reduces recurrence risk by 31% (RR=0.69). 1
- Corticosteroid use shows no protective effect on graft survival in pediatric/young adult populations. 2
Dialysis modality:
- Hemodialysis increases recurrence risk by 68% (RR=1.68) compared to peritoneal dialysis. 1
Protective Factors
Pretransplant tonsillectomy:
- Reduces recurrence risk by 57% (RR=0.43), though this remains controversial and requires validation. 1
Clinical Implications and Monitoring
Recurrence timeline:
- Recurrent IgA nephropathy rarely manifests clinically before 3 years post-transplantation. 4
- Cumulative 10-year recurrence rate reaches 30.8% with considerable variation across centers (13-50% depending on biopsy policies). 3, 5
Impact on graft survival:
- Recurrence increases graft loss risk by 119% (RR=2.19). 1
- 10-year graft survival drops to 61.0% with recurrence versus 85.1% without (P<0.01). 3
Screening recommendations per KDIGO guidelines:
- Screen for microhematuria once in the first month to establish baseline. 6, 7
- Continue screening every 3 months during the first year. 6, 7
- Annual screening thereafter. 6, 7
Common pitfall: Chronic allograft nephropathy may affect graft survival more significantly than recurrence itself, emphasizing the need for comprehensive monitoring beyond just recurrence detection. 3