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Clinical Significance of Microvascular Inflammation in the Absence of Anti-HLA DSA in Kidney Transplantation

Parajuli, Sandesh1; Redfield, Robert R.2; Garg, Neetika1; Aziz, Fahad1; Mohamed, Maha1; Astor, Brad C.1,3; Zhong, Weixong4; Djamali, Arjang1,2; Mandelbrot, Didier A.1

doi: 10.1097/TP.0000000000002487
Original Clinical Science—General
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Background. Limited information exists about outcomes of HLA donor-specific antibody (DSA) negative (DSA−) microvascular inflammation (MVI).

Methods. We report our experience with 25 DSA− patients with MVI compared to 155 DSA+ patients who met Banff 2013 criteria for antibody-mediated rejection (AMR). We also compared outcomes to 228 DSA+ patients whose biopsies were negative for rejection and served as a negative control.

Results. There were no significant differences in the baseline characteristics between the DSA− MVI and DSA+ AMR groups. At the time of diagnosis, both groups had similar graft function. The DSA− group had higher MVI scores but lower C4d scores. At last follow-up, renal function was similar between the groups. There were 12 (48%) graft failures in the DSA− group and 59 (38%) graft failures in the DSA+ group, which was not statistically different. Similar results were found after matching for the MVI scores, C4d, and treatment between 2 groups. We also found similar outcomes between DSA− and DSA+ patients when only including those who would have met Banff 2017 criteria for AMR. In univariate Cox regression analyses, estimated glomerular filtration rate at time of biopsy, glomerulitis, rituximab, diabetes, v score, allograft glomerulopathy, fibrous intimal thickening, tubular atrophy, and interstitial fibrosis scores were associated with graft failure. In multivariate analysis, only estimated glomerular filtration rate was protective. Both groups had significantly worse outcomes than the DSA+-negative controls without AMR.

Conclusions. Our findings suggest that outcomes and response to treatment with HLA DSA− MVI patients are similarly poor to those with DSA+ MVI patients, supporting a critical role for MVI in the diagnosis of AMR.

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

2 Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI.

3 Department of Population Health Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI.

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

Received 5 August 2018. Revision received 10 September 2018.

Accepted 8 October 2018.

The authors declare no conflicts of interest.

This work was supported by an unrestricted research grant from the Virginia Lee Cook Foundation.

S.P. participated in the concept, design, data collection, analysis, manuscript preparation, and editing. R.R.R. participated in the data collection, analysis, article preparation, and editing. N.G. participated in the data collection, analysis, article preparation, and editing. F.A. participated in the data collection, analysis, article preparation, and editing. M.M. participated in the analysis, article preparation, and editing. B.C.A. participated in the analysis, article preparation, and editing. W.Z. participated in the analysis, article preparation, and editing. A.D. participated in the analysis, article preparation, and editing. D.A.M. participated in the concept, design, analysis, article preparation, and editing.

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

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