Treatment of Refractory Chronic Active Antibody-Mediated Rejection: Improvement in Histopathology are Delayed Compared to the Reduction in Donor Specific Antibodies

K. R. Degner¹, S. Parajuli¹, F. Aziz¹, N. Garg¹, M. Mohamed¹, D. A. Mandelbrot¹, S. E. Panzer¹, L. Hidalgo¹, N. A. Wilson¹, S. R. Reese¹, K. Van Hyfte¹, W. Zhong¹, P. Nickerson², A. Djamali¹

¹University of Wisconsin, Madison, WI, ²University of Manitoba, Winnipeg, MB, Canada

Meeting: 2021 American Transplant Congress

Abstract number: 1045

Keywords: Histology, Kidney transplantation, Rejection, Renal function

Topic: Clinical Science » Kidney » Kidney Chronic Antibody Mediated Rejection

Session Information

Session Name: Kidney Chronic Antibody Mediated Rejection

Session Type: Poster Abstract

Session Date & Time: None. Available on demand.

Location: Virtual

*Purpose: There are limited options for the treatment and management of refractory chronic active antibody-mediated rejection (cABMR) after kidney transplantation. Longitudinal histologic data in patients with refractory cABMR are also lacking. We hypothesized that clinical and histologic evidence of a treatment response may require longer than 3 months, our institutions standard follow up time for patients with rejection, in patients with refractory cABMR.

*Methods: Kidney transplant recipients (n=8) with refractory cABMR, defined as persistent rejection despite standard treatment, underwent serial biopsies at diagnosis (index biopsy), 3, 6, and 12 months. Banff 2017 pathology, donor-specific antibodies (DSA), and serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR) and urine protein creatinine ratio (UPC) were assessed at each biopsy. Treatment of rejection included pulse steroids, IVIG, and rituximab.

*Results: Participants were primarily white men (88%) at an average age of 40±14.5. Index biopsy was performed an average of 4.4±3.7 years after transplant. Index biopsies were performed primarily for changes in DSA, either rising DSA or development of de novo DSA (63%). One patient lost their allograft during the 12 month follow up period due to ongoing rejection. There was a significant decline in total (6,093±5,424 vs. 2,731±4,172, p=0.04) and Class II DSA (5,845±5,366 vs. 2,731±4,172, p=0.04) between index biopsy and 3 months after treatment. In parallel, there was a decline in C4d staining at 3 months post treatment compared to index biopsy (1.6±1.5 vs. 0.4±1.1, p=0.03). Sum microvascular inflammation (mvi) decreased significantly at 12 months, but not sooner (3.7±1.5 vs. 2.3±1.1, p=0.05). Chronic allograft pathology (ct, ci, cv, cg scores) and kidney function in patients with a functioning allograft were stable over the course of the study period.

*Conclusions: In patients with refractory cABMR, the decline in DSA precedes improvements in allograft inflammation, suggesting that benefits from therapy may not become evident upon repeat biopsy for at least one year. Larger studies of patients with refractory cABMR are needed to expand upon these observations.

To cite this abstract in AMA style:

Degner KR, Parajuli S, Aziz F, Garg N, Mohamed M, Mandelbrot DA, Panzer SE, Hidalgo L, Wilson NA, Reese SR, Hyfte KVan, Zhong W, Nickerson P, Djamali A. Treatment of Refractory Chronic Active Antibody-Mediated Rejection: Improvement in Histopathology are Delayed Compared to the Reduction in Donor Specific Antibodies [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/treatment-of-refractory-chronic-active-antibody-mediated-rejection-improvement-in-histopathology-are-delayed-compared-to-the-reduction-in-donor-specific-antibodies/. Accessed May 16, 2025.

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