Sandesh Parajuli1, Robert R Redfield2, Neetika Garg1, Fahad Aziz1, Maha Mohamed1, Brad C Astor1,3, Weixong Zhong4, Arjang Djamali1,2, Didier A Mandelbrot1. 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.
Abstract
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.
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.
Authors: Kin Yee Shiu; Dominic Stringer; Laura McLaughlin; Olivia Shaw; Paul Brookes; Hannah Burton; Hannah Wilkinson; Harriet Douthwaite; Tjir-Li Tsui; Adam Mclean; Rachel Hilton; Sian Griffin; Colin Geddes; Simon Ball; Richard Baker; Candice Roufosse; Catherine Horsfield; Anthony Dorling Journal: Front Immunol Date: 2020-02-05 Impact factor: 7.561
Authors: Alexandre Loupy; Mark Haas; Candice Roufosse; Maarten Naesens; Benjamin Adam; Marjan Afrouzian; Enver Akalin; Nada Alachkar; Serena Bagnasco; Jan U Becker; Lynn D Cornell; Marian C Clahsen-van Groningen; Anthony J Demetris; Duska Dragun; Jean-Paul Duong van Huyen; Alton B Farris; Agnes B Fogo; Ian W Gibson; Denis Glotz; Juliette Gueguen; Zeljko Kikic; Nicolas Kozakowski; Edward Kraus; Carmen Lefaucheur; Helen Liapis; Roslyn B Mannon; Robert A Montgomery; Brian J Nankivell; Volker Nickeleit; Peter Nickerson; Marion Rabant; Lorraine Racusen; Parmjeet Randhawa; Blaise Robin; Ivy A Rosales; Ruth Sapir-Pichhadze; Carrie A Schinstock; Daniel Seron; Harsharan K Singh; Rex N Smith; Mark D Stegall; Adriana Zeevi; Kim Solez; Robert B Colvin; Michael Mengel Journal: Am J Transplant Date: 2020-05-28 Impact factor: 8.086