Abstract: TH-PO954

Endothelin-1 Type A Receptor Antibodies Are Associated with Arteritis and Functional Decline in Pediatric Renal Transplantation

Session Information

Category: Transplantation

  • 1702 Transplantation: Clinical and Translational

Authors

  • Pearl, Meghan, UCLA, Los Angeles, California, United States
  • Grotts, Jonathan, UCLA, Los Angeles, California, United States
  • Rossetti, Maura, UCLA, Los Angeles, California, United States
  • Zhang, Qiuheng Jennifer, UCLA, Los Angeles, California, United States
  • Weng, Patricia L., UCLA, Los Angeles, California, United States
  • Reed, Elaine F., UCLA, Los Angeles, California, United States
  • Tsai, Eileen W., Duke University, Durham, North Carolina, United States
Background

We recently found that the non HLA antibody, Angiotensin II Type 1 Receptor Antibody (AT1R-Ab) is associated with poor outcomes in pediatric kidney transplant recipients (KTRs); however, the role and clinical impact of other non-HLA antibodies such as endothelin-1 Type A receptor Antibody (ETAR-Ab) remains unknown.

Methods

65 pediatric patients were monitored for 2 years after transplantation from August 2005 to November 2014. ETAR-Ab (ELISA), AT1R-Ab (ELISA), and HLA DSA (Luminex bead assay) were measured pre-transplant, 6 months (m), 12m, 24m post-transplant and during episodes of rejection. Based on a receiver operating curve analysis, > 10 and >17 units/ml was considered positive for ETAR-Ab and AT1R-Ab respectively while MFI cut off >1000 was considered positive for HLA DSA. Biopsies were performed at 6m, 12m, 24m post-transplant per protocol and for clinical suspicion of rejection and evaluated by 2013 Banff criteria. Clinical risk factors and renal function (MDRD for >18 and updated Schwartz Equation for <18 years old) were assessed.

Results

The prevalence of ETAR-Ab was 32%. Risk factors for ETAR-Ab included younger age (p=0.038), steroid free immunosuppression (p=0.038), and AT1R-Ab (p<0.001), but not HLA DSA (Figure 1a). ETAR-Ab was associated with greater median declines in renal function (p=0.034, Figure 1b) and arteritis on biopsy (p=0.011), but not acute rejection (data not shown).

Conclusion

In pediatric KTRs, ETAR-Ab is highly prevalent and associated with AT1R- Ab, vascular inflammation, and worsening renal function. This suggests that ETAR-Ab and AT1R-Ab monitoring may be warranted in children, especially those on steroid-free immunosuppression. Dual blockade may attenuate allograft injury and improve renal function.

Funding

  • NIDDK Support