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Subclinical Antibody-mediated Rejection After Kidney Transplantation

Treatment Outcomes

Parajuli, Sandesh1; Joachim, Emily1; Alagusundaramoorthy, Sayee1; Blazel, Justin1; Aziz, Fahad1; Garg, Neetika1; Muth, Brenda1; Mohamed, Maha1; Mandelbrot, Didier1; Zhong, Weixong2; Djamali, Arjang1,3

doi: 10.1097/TP.0000000000002566
Original Clinical Science—General
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Background. Antibody-mediated rejection (AMR) is a leading cause of morbidity and mortality after kidney transplantation. Early diagnosis and treatment of subclinical AMR based on the donor-specific antibody (DSA) testing may result in better outcomes.

Methods. We tested this hypothesis in 220 kidney transplant recipients who underwent an indication or DSA-based surveillance protocol biopsies between March 1, 2013 and December 31, 2016. Patients were divided into 3 groups: clinical AMR (n = 118), subclinical AMR (n = 25), or no rejection on protocol biopsy (controls; n = 77).

Results. Both clinical and subclinical AMR groups underwent similar treatment including plasmapheresis, pulse steroids, IVIG, and rituximab (P = ns). Mean follow-up after AMR was 29.5 ± 16.8 months. There were 2 (3%), 2 (8%), and 54 (46%) death-censored graft failures in the control, subclinical, and clinical AMR groups, respectively (P < 0.001). Graft outcomes were similar in the subclinical rejection and control groups. In adjusted Cox regression analysis, only clinical rejection (hazards ratio [HR], 4.31; 95% confidence interval [CI], 1.01-18.94; P = 0.05) and sum chronicity scores (HR, 1.16; 95% CI, 1.01-1.35; P = 0.03) were associated with increased risk of graft failure, while estimated glomerular filtration rate at time of biopsy (HR, 0.98; 95% CI, 0.96-0.99; P = 0.01) was associated with decreased risk of graft failure.

Conclusions. Our study suggests that early diagnosis and treatment of subclinical AMR using DSA monitoring may improve outcomes after kidney transplantation.

1 Division of Nephrology, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI.

2 Department of Pathology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

3 Division of Transplant Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Received 25 September 2018.

Accepted 6 November 2018.

S.P. conceptualized, designed, collected data, performed analysis, and prepared and edited the article. E.J., S.A., J.B., and F.A. collected data, performed analysis, and prepared and edited the article. N.G., B.M., M.M., D.M., and W.Z. performed analysis and prepared and edited the article. A.D. conceptualized, designed, performed analysis, and prepared and edited the article.

The authors declare no funding or conflicts of interest.

Correspondence: Sandesh Parajuli, MBBS, University of Wisconsin Medical Foundation Centennial Building 4175, 1685 Highland Avenue, Madison, WI 53705. (sparajuli@medicine.wisc.edu).

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