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Kidney Week

Abstract: TH-PO773

A Single-Center Experience of Bortezomib in Pediatric Kidney Transplants With Long-Term Graft Outcome

Session Information

  • Pediatric CKD
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Vyas, Shefali, Saint Barnabas Medical Center, West Orange, New Jersey, United States
  • Nath, Nihaal, West Orange High School, West Orange, New Jersey, United States
  • Roberti, Isabel, Saint Barnabas Medical Center, West Orange, New Jersey, United States
Background


Acute antibody mediated rejection (aAMR) remains a challenge with poor renal allograft longterm outcome and unclear therapeutic efficacy of current therapies. We report the use of Bortezomib for treatment of persistent aAMR after failure of conventional therapy and long term graft and patient outcomes,.

Methods


Review of 118 kidney transplants (txp) from 2004-2019, noted - 4 had primary graft failure, 3 patients were deceased (2 with functioning grafts) and 3 were lost to follow up. 32 rejections- 12 with TCR and 20 with aAMR (biopsy proven by Banff criteria); All 20 aAMR received MP pulse, IVIG (1-2 g/Kg),10 PP treatments (1.5 to 2 plasma vol exchange/ rx) and Thymoglobulin (if ACR). On follow up 9/20 received Bortezomib 1.3mg/m2/dose IV x4 for persistent graft dysfunction with postivie DSA.. Mean DSA titers (pre and post rx), eGFR, graft outcome, adverse effects infections were tracked in Bortezomib group. Graft outcome was also followed in patients with no rejection and + rejection aAMR/TCR .

Results

9 received 10 doses of Bortezomib ; Ethnicity: AA/Wh/ His/ Asian=33%(3)/33%(3)/22% (2)/ 11%(1), male 8 (89%),
Age at txp :median 16.8 (3-20yrs), 7 (78%)received DDT, all received Induction ( 4 thymo for pre txp PRA >25%).
Time to rejection: median 2.5 yrs (8 days- 8 yrs), 2 neg C4D and DSA; 1 de novo anti GBM GN and 1 had AT1R abs+.
Infections:: 1 oral Herpes+ oral candidiasis+ pneumonia, 1 herpes + atypical mycobacteria+ candida, 3 gastroenteritis and 1 C. difficle colitis, 1 prolonged EBV viremia and 1 cellulitis.(1.4 infections/pt)
Follow up time: after txp 1-12 yr (median =3.8), postbortezomib = 0.5-9 yrs (median 1.5).
Post bortezomib: eGFR improved from 58 to 79 ml/min/1.73M2 (21%) and reduction in DSA = 36%.
Other therapies: 1 Rituximab; 1 Cytoxan (anti GBM GN); 4 Thymoglobulin for TCR.
Graft survival with Bortezomib: 100% at 1 and 3 yrs. 2 progressed to ESRD at 9 and 12 yrs (22% graft loss).
Graft survival with no rejection (86): 92 %
Graft loss overall: 24% (28/115): 4 primary non function, 2 expired with functioning grafts; Patient survival: 97.4%

Conclusion

Bortezomib was well tolerated well with few adverse effects; 36% reduction in DSA, 21% improvement in eGFR and graft loss 22%. Graft loss in children with no rejection was 8% compared to 47% with rejection ( aAMR and TCR). Overall, graft loss was 24% and patient survival 97.4% as of last follow up.