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. 2021 Apr;21(4):1391-1401.
doi: 10.1111/ajt.16161. Epub 2020 Jul 31.

Factors associated with kidney graft survival in pure antibody-mediated rejection at the time of indication biopsy: Importance of parenchymal injury but not disease activity

Gunilla Einecke  1 , Jeff Reeve  2   3 , Gaurav Gupta  4 , Georg A Böhmig  5 , Farsad Eskandary  5 , Jonathan S Bromberg  6 , Klemens Budde  7 , Philip F Halloran  2   8 ; INTERCOMEX investigators
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Free article

Factors associated with kidney graft survival in pure antibody-mediated rejection at the time of indication biopsy: Importance of parenchymal injury but not disease activity

Gunilla Einecke et al. Am J Transplant. 2021 Apr.
Free article

Abstract

We studied the relative association of clinical, histologic, and molecular variables with risk of kidney transplant failure after an indication biopsy, both in all kidneys and in kidneys with pure antibody-mediated rejection (ABMR). From a prospective study of 1679 biopsies with histologic and molecular testing, we selected one random biopsy per patient (N = 1120), including 321 with pure molecular ABMR. Diagnoses were associated with actuarial survival differences but not good predictions. Therefore we concentrated on clinical (estimated GFR [eGFR], proteinuria, time posttransplant, donor-specific antibody [DSA]) and molecular and histologic features reflecting injury (acute kidney injury [AKI] and atrophy-fibrosis [chronic kidney disease (CKD)] and rejection. For all biopsies, univariate analysis found that failure was strongly associated with low eGFR, AKI, CKD, and glomerular deterioration, but not with rejection activity. In molecular ABMR, the findings were similar: Molecular and histologic activity and DSA were not important compared with injury. Survival in DSA-negative and DSA-positive molecular ABMR was similar. Multivariate survival analysis confirmed the dominance of molecular AKI, CKD, and eGFR. Thus, at indication biopsy, the dominant predictors of failure, both in all kidneys and in ABMR, were related to molecular AKI and CKD and to eGFR, not rejection activity, presumably because rejection confers risk via injury.

Keywords: basic (laboratory) research / science; biopsy; graft survival; kidney failure / injury; kidney transplantation / nephrology; microarray / gene array; rejection: antibody-mediated (ABMR).

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REFERENCES

    1. Einecke G, Sis B, Reeve J, et al. Antibody-mediated microcirculation injury is the major cause of late kidney transplant failure. Am J Transplant. 2009;9(11):2520-2531.
    1. Sellares J, de Freitas DG, Mengel M, et al. Non-adherence is a major factor in kidney allograft failure because it triggers antibody-mediated rejection. Am J Transplant. 2011;11(s2):298-299.
    1. Venner JM, Famulski KS, Reeve J, Chang J, Halloran PF. Relationships among injury, fibrosis, and time in human kidney transplants. JCI Insight. 2016;1(1):e85323.
    1. Furness PN, Taub N. International variation in the interpretation of renal transplant biopsies: report of the CERTPAP Project. Kidney Int. 2001;60(5):1998-2012.
    1. Furness PN, Taub N, Assmann KJM, et al. International variation in histologic grading is large, and persistent feedback does not improve reproducibility. Am J Surg Pathol. 2003;27(6):805-810.

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