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Clinical Trial
. 2018 Sep;18(9):2189-2199.
doi: 10.1111/ajt.14933. Epub 2018 Jun 27.

Subclinical inflammation phenotypes and long-term outcomes after pediatric kidney transplantation

Michael E Seifert  1 , Megan V Yanik  1 , Daniel I Feig  1 , Vera Hauptfeld-Dolejsek  2   3 , Elizabeth C Mroczek-Musulman  4   5 , David R Kelly  4   5 , Frida Rosenblum  5 , Roslyn B Mannon  2   3   6
Affiliations
Clinical Trial

Subclinical inflammation phenotypes and long-term outcomes after pediatric kidney transplantation

Michael E Seifert et al. Am J Transplant. 2018 Sep.

Abstract

The implementation of surveillance biopsies in pediatric kidney transplantation remains controversial. Surveillance biopsies detect subclinical injury prior to clinical dysfunction, which could allow for early interventions that prolong allograft survival. We conducted a single-center retrospective cohort study of 120 consecutive pediatric kidney recipients, of whom 103 had surveillance biopsies ≤6 months posttransplant. We tested the hypothesis that subclinical inflammation (borderline or T cell-mediated rejection without clinical dysfunction) is associated with a 5-year composite endpoint of acute rejection and allograft failure. Overall, 36% of subjects had subclinical inflammation, which was associated with increased hazard for the composite endpoint (adjusted hazard ratio 2.89 [1.27, 6.57]; P < .01). Subjects with treated vs untreated subclinical borderline rejection had a lower incidence of the composite endpoint (41% vs 67%; P < .001). Subclinical vascular injury (subclinical inflammation with Banff arteritis score > 0) had a 78% incidence of the composite endpoint vs 11% in subjects with no major surveillance abnormalities (P < .001). In summary, we showed that subclinical inflammation phenotypes were prevalent in pediatric kidney recipients without clinical dysfunction and were associated with increased acute rejection and allograft failure. Once prospectively validated, our data would support implementation of surveillance biopsies as standard of care in pediatric kidney transplantation.

Keywords: biopsy; clinical research/practice; graft survival; kidney transplantation/nephrology; pathology/histopathology; pediatrics; protocol biopsy; rejection: subclinical; rejection: vascular.

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Conflict of interest statement

DISCLOSURE

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Figures

FIGURE 1
FIGURE 1
CONSORT diagram
FIGURE 2
FIGURE 2
Kaplan-Meier plot of 5-year incidence of primary (A) and secondary (B, C) outcomes between the subclinical inflammation and no major abnormalities groups. (A) Composite endpoint of acute rejection after surveillance and death-censored graft loss. (B) Acute rejection after surveillance component of the composite endpoint. (C) Death-censored graft loss component of the composite endpoint. Comparisons of time-to-event data between groups were made using the log-rank test. NOMOA, no major abnormalities
FIGURE 3
FIGURE 3
Kaplan-Meier plots of the 5-year incidence of the primary composite endpoint between the borderline and subclinical TCMR subgroups and the no major abnormalities group. (A) Five-year incidence of acute rejection after surveillance and graft loss between groups. (B) Five-year incidence of acute rejection after surveillance and graft loss between treated B-TCMR (n = 8), untreated B-TCMR (n = 16), SC-TCMR (all were treated, n = 13), and NOMOA (n = 66) groups. Comparisons of time-to-event data between groups were made using the log-rank test. In (B), the P-values for the overall trend plus key between-group comparisons are presented. B-TCMR, borderline T cell–mediated rejection; NOMOA, no major abnormalities; SC-TCMR, subclinical T cell–mediated rejection
FIGURE 4
FIGURE 4
Kaplan-Meier plots of 5-year incidence of the primary composite endpoint (A), the acute rejection after surveillance component (B), and the death-censored graft failure component (C) between subjects with subclinical inflammation (SCI) and v > 0, SCI and v = 0, and no major abnormalities (NOMOA). Comparisons of time-to-event data between groups were made using the log-rank test
See this image and copyright information in PMC

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