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

Rachel M Engen*, Giulia E. Park, Cooper S. Schumacher, Idoia Gimferrer, Paul Warner, Laura S. Finn, Noel S. Weiss, Jodi M. Smith

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2072-2079
Number of pages8
JournalTransplantation
Volume102
Issue number12
Early online dateMay 31 2018
DOIs
StatePublished - Dec 1 2018

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Tissue Donors
Pediatrics
Transplants
Kidney
Antibodies
Confidence Intervals
Kidney Transplantation
Transplant Recipients
Biopsy
Graft Rejection
Glomerular Filtration Rate
Creatinine
Staining and Labeling
Inflammation
Research

ASJC Scopus subject areas

  • Transplantation

Cite this

Engen, R. M., Park, G. E., Schumacher, C. S., Gimferrer, I., Warner, P., Finn, L. S., ... Smith, J. M. (2018). Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients. Transplantation, 102(12), 2072-2079. https://doi.org/10.1097/TP.0000000000002310
Engen, Rachel M ; Park, Giulia E. ; Schumacher, Cooper S. ; Gimferrer, Idoia ; Warner, Paul ; Finn, Laura S. ; Weiss, Noel S. ; Smith, Jodi M. / Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients. In: Transplantation. 2018 ; Vol. 102, No. 12. pp. 2072-2079.
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abstract = "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.",
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Engen, RM, Park, GE, Schumacher, CS, Gimferrer, I, Warner, P, Finn, LS, Weiss, NS & Smith, JM 2018, 'Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients', Transplantation, vol. 102, no. 12, pp. 2072-2079. https://doi.org/10.1097/TP.0000000000002310

Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients. / Engen, Rachel M; Park, Giulia E.; Schumacher, Cooper S.; Gimferrer, Idoia; Warner, Paul; Finn, Laura S.; Weiss, Noel S.; Smith, Jodi M.

In: Transplantation, Vol. 102, No. 12, 01.12.2018, p. 2072-2079.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Donor-specific Antibody Surveillance and Graft Outcomes in Pediatric Kidney Transplant Recipients

AU - Engen, Rachel M

AU - Park, Giulia E.

AU - Schumacher, Cooper S.

AU - Gimferrer, Idoia

AU - Warner, Paul

AU - Finn, Laura S.

AU - Weiss, Noel S.

AU - Smith, Jodi M.

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

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