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

Background Limited information exists about outcomes of HLA 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 ABMR. 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+ ABMR 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 two groups. We also found similar outcomes between DSA- and DSA+ patients when only including those who would have met Banff 2017 criteria for ABMR. In univariate Cox regression analyses, eGFR at time of biopsy, glomerulitis, rituximab, diabetes, v score, cg, cv, ct, and ci scores were associated with graft failure. In multivariate analysis, only eGFR was protective. Both groups had significantly worse outcomes than the DSA+ negative controls without ABMR. 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 ABMR. Corresponding author's address, phone, and email: Sandesh Parajuli, MBBS, 4175 UW Medical Foundation Centennial Building, 1685 Highland Avenue, Madison, WI 53705, Tel: (608) 265-0152, Email: sparajuli@medicine.wisc.edu Author contribution statement. 1. Parajuli: concept, design, data collection, analysis, manuscript preparation, editing 2. Redfield: data collection, analysis, manuscript preparation, editing 3. Garg: data collection, analysis, manuscript preparation, editing 4. Aziz: data collection, analysis, manuscript preparation, editing 5. Mohamed: analysis, manuscript preparation, editing 6. Astor: analysis, manuscript preparation, editing 7. Zhong: analysis, manuscript preparation, editing 8. Djamali: analysis, manuscript preparation, editing 9. Mandelbrot: concept, design, analysis, manuscript preparation, editing Disclosure: The Authors have no financial disclosures or conflicts of interest Sources of Funding: This work was supported by an unrestricted research grant from the Virginia Lee Cook Foundation. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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