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The Impact of Early Clinical and Subclinical T Cell–mediated Rejection After Kidney Transplantation

Hoffman, William MD1; Mehta, Rajil MD1; Jorgensen, Dana R. PhD1; Sood, Puneet MD1; Randhawa, Parmjeet MD2; Wu, Christine M. MD1; Puttarajappa, Chetan MD1; Shah, Nirav A. MD1; Tevar, Amit D. MD3; Hariharan, Sundaram MD1

doi: 10.1097/TP.0000000000002560
Original Clinical Science—General
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Background. We investigated the effect of clinical and subclinical T cell–mediated rejection (C-TCMR and SC-TCMR) on allograft histology, function, and progression.

Methods. Adult kidney recipients with 2 protocol biopsies were divided into No-TCMR on biopsies (n = 104), SC-TCMR (n = 56), and C-TCMR (n = 32) in at least 1 biopsy. Chronicity (ci + ct + cg + cv) scores, renal function, and the burden of renal disease measured by area under the curve (serum creatinine, mg mo/dL) were compared.

Results. Baseline characteristics were similar except for mean donor age and Kidney Donor Profile index scores. Patients with C-TCMR had higher mean serum creatinine, lower mean estimated glomerular filtration rate, and higher area under the curve with 95% confidence interval (75.2 [67.7-82.7]) as opposed to patients with SC-TCMR and No-TCMR (58.3 [53.6-62.9], 65.1 [58.8-71.5]), P = 0.0004. Chronicity scores were higher at 3 months in C-TCMR (2.30 ± 1.58) compared with SC-TCMR (2.02 ± 1.42) and No-TCMR (1.31 ± 1.18), P = 0.0001 and also at 12 months. At last follow-up, 18.8% patients with C-TCMR had ≥50% decline in estimated glomerular filtration rate from 3 months compared with 7% and 1% among No-TCMR and SC-TCMR groups (P = 0.038). Multivariate analyses revealed higher odds of Δ-creatinine ≥ 0.5 mg/dL from 3 months to last follow-up for C-TCMR (3.39 [95% confidence interval, 1.25-9.20]) versus No-TCMR (P = 0.016).

Conclusions. Kidney transplant recipients with C-/SC-TCMR have heightened early allograft chronicity and worse renal function compared with those with No-TCMR. Progressive renal dysfunction was noted among patients with C-TCMR as opposed to SC-TCMR and No-TCMR.

1 Department of Medicine, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA.

2 Department of Pathology, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA.

3 Department of Surgery, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA.

Received 11 September 2018. Revision received 11 November 2018.

Accepted 14 November 2018.

W.H. participated in analyzing and writing the manuscript. R.M. participated in data collection and verification. D.R.J. and C.P. participated in data analysis. P.S. participated in analysis and interpretation. P.R. participated in interpretation of renal histology. C.M.W. and N.A.S. participated in writing the manuscript. A.D.T. participated in analysis. S.H. participated in research design, analysis, interpretation, and writing the manuscript.

The authors declare no funding or conflicts of interest.

Correspondence: Sundaram Hariharan, MD, Department of Medicine, Thomas E Starzl Transplantation Institute, University of Pittsburgh Medical Center, 3459 Fifth Avenue, 7S, Pittsburgh, PA 15213. (hariharans@upmc.edu).

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