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Am J Transplant. 2019 Feb 12. doi: 10.1111/ajt.15299. [Epub ahead of print]

Response to treatment and long-term outcomes in kidney transplant recipients with acute T cell-mediated rejection.

Author information

1
Paris Translational Research Center for Organ Transplantation, INSERM, UMR-S970, Paris, France.
2
Kidney Transplant Department, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
3
Pathology Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
4
Kidney Transplant Department, Necker Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.
5
Department of Immunology and Histocompatibility, Saint-Louis Hospital, Assistance Publique - Hôpitaux de Paris, Paris, France.

Abstract

The recent recognition of complex and chronic phenotypes of T cell-mediated rejection (TCMR) has fostered the need to better evaluate the response of acute TCMR-a condition previously considered to lack relevant consequences for allograft survival-to the standard of care. In a prospective cohort of kidney recipients (n = 256) with biopsy-proven acute TCMR receiving corticosteroids, we investigated clinical, histological, and immunological phenotypes at the time of acute TCMR diagnosis and 3 months posttreatment. Independent posttreatment determinants of allograft loss included the glomerular filtration rate (GFR) (HR = 0.94; 95% CI = 0.92-0.96; P < .001), proteinuria (HR = 1.40; 95% CI = 1.10-1.79; P = .007), time since transplantation (HR = 1.02; 95% CI = 1.00-1.03; P = .016), peritubular capillaritis (HR = 2.27; 95% CI = 1.13-4.55; P = .022), interstitial inflammation in sclerotic cortical parenchyma (i-IF/TA) (HR = 1.87; 95% CI = 1.08-3.25; P = .025), and donor-specific anti-HLA antibodies (DSAs) (HR = 2.67; 95% CI = 1.46-4.88; P = .001). Prognostic value was improved using a composite evaluation of response to treatment versus clinical parameters only (cNRI = 0.68; 95% CI = 0.41-0.95; P < .001). A classification tree for allograft loss identified five patterns of response to treatment based on the posttreatment GFR, i-IF/TA, and anti-HLA DSAs (cross-validated accuracy = 0.80). Compared with responders (n = 155, 60.5%), nonresponders (n = 101, 39.5%) had a higher incidence of de novo DSAs, antibody-mediated rejection, and allograft loss at 10 years (P < .001 for all comparisons). Thus, clinical, histological, and immunological assessment of response to treatment of acute TCMR revealed different profiles of the response to treatment with distinct outcomes.

KEYWORDS:

clinical research/practice; graft survival; kidney transplantation/nephrology; rejection: T cell mediated (TCMR)

PMID:
30748089
DOI:
10.1111/ajt.15299

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