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Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients

Engen, Rachel M., MD1; Park, Giulia E.2; Schumacher, Cooper S., MS3; Gimferrer, Idoia, MD, PhD4; Warner, Paul, PhD4; Finn, Laura S., MD5; Weiss, Noel S., MD, PhD6; Smith, Jodi M., MD1

doi: 10.1097/TP.0000000000002310
Original Clinical Science—General

Background The development of de novo donor-specific antibodies (dnDSA) has been associated with rejection and graft loss in kidney transplantation, and DSA screening is now recommended in all kidney transplant recipients. However, the clinical significance of dnDSA detected by screening patients with a stable creatinine remains unclear.

Methods One hundred three patients younger than 18years receiving a first, kidney alone transplant between December 1, 2007, and December 31, 2013, underwent DSA screening every 3months for 2years posttransplant, with additional testing as clinically indicated. No treatment was given for DSAs in the absence of biopsy-proven rejection.

Results Twenty (19%) patients had dnDSA first detected on a screening test, and 13 (13%) patients had dnDSA first detected on a for-cause test. Mean follow-up time posttransplant was 4.4years. Screening-detected dnDSA was associated with an increased risk of rejection within 3years, microvascular inflammation, and C4d staining on a 2-year protocol biopsy. In a Cox proportional hazards regression, screening-detected dnDSA was not associated with time to 30% decline in estimated glomerular filtration rate (adjusted hazard ratio, 0.88; 95% confidence interval [CI], 0.30-2.00; P=0.598) or graft loss. dnDSA first detected on for-cause testing was associated with a 2.8 times increased risk of decline in graft function (95% CI, 1.08-7.27; P=0.034) and a 7.34 times increased risk of graft loss (95% CI, 1.37-39.23 P=0.020) compared with those who did not develop dnDSA.

Conclusions The clinical setting in which dnDSA is first detected impacts the association between dnDSA and graft function. Further research is needed to clarify the role of dnDSA screening in pediatric kidney transplantation.

In 103 kidney transplant children recipients of a first kidney, dnDSA detected for cause is associated with an increased risk of ABMR and graft failure which was not the case when dnDSA are detected on a routine basis.

1 Department of Pediatrics, University of Washington, Seattle, WA.

2 Division of Nephrology, Seattle Children’s Hospital, Seattle, WA.

3 Department of Biostatistics, University of Washington Seattle, WA.

4 Bloodworks Northwest, Seattle, WA.

5 Department of Pathology, University of Washington Seattle, WA.

6 Department of Epidemiology, University of Washington Seattle, WA.

Received 17 January 2018. Revision received 3 May 2018.

Accepted 18 May 2018.

R.M.E. was supported by National Institute of Health grant 5 T32 DK007662. C.S.S. was supported by National Institute of Health grant NIEHS T32ES015459.

The authors declare no conflicts of interest.

R.M.E. participated in the research design, performance of the research, data analysis, and writing of the article. G.E.P. participated in the performance of the research. C.S. participated in data analysis. I.G. participated in the performance of the research and the writing of the article. P.W. participated in the performance of the research. L.S.F. participated in performance of the research. N.S.W. participated in the research design and writing of the article. J.M.S. participated in the research design and writing of the article.

Correspondence: Rachel M Engen, 225 E Chicago Avenue, Box 37, Chicago, IL 60611. (rengen@luriechildrens.org).

Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.