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Title: | Long-term graft survival in patients with chronic antibody-mediated rejection with persistent peritubular capillaritis treated with intravenous immunoglobulin and rituximab. | Authors: | Mulley W.R.;Nikolic-Paterson D.J. ;Ramessur Chandran S.;Longano A.;Amos L.A.R.;Kanellis J.;Huang L.L.;Polkinghorne K.R. | Institution: | (Mulley, Huang, Ramessur Chandran, Amos, Polkinghorne, Nikolic-Paterson, Kanellis) Department of Nephrology, Monash Medical Centre, Clayton, VIC, Australia (Mulley, Ramessur Chandran, Amos, Polkinghorne, Nikolic-Paterson, Kanellis) Department of Medicine, Centre for Inflammatory Diseases, Monash University, Clayton, VIC, Australia (Longano) Department of Anatomical Pathology, Monash Medical Centre, Clayton, VIC, Australia (Polkinghorne) Department of Epidemiology and Preventive Medicine, Monash University, Prahran, VIC, Australia | Issue Date: | 11-Sep-2017 | Copyright year: | 2017 | Publisher: | Blackwell Publishing Ltd (E-mail: customerservices@oxonblackwellpublishing.com) | Place of publication: | United Kingdom | Publication information: | Clinical Transplantation. 31 (9) (no pagination), 2017. Article Number: e13037. Date of Publication: September 2017. | Journal: | Clinical Transplantation | Abstract: | Chronic antibody-mediated rejection (cAMR) is the major cause of premature renal allograft loss and is resistant to therapy with 12-month graft failure of up to 50% reported. We examined the duration of graft survival and associates of graft failure in patients with donor-specific antibody-positive cAMR and treatment-resistant peritubular capillaritis between June 2007 and October 2010. Those with advanced interstitial fibrosis (n=5) were excluded. Included patients (n=24) received treatment with high-dose intravenous immunoglobulin and fixed-dose rituximab (500 mg). Compared with previous reports, the study group experienced prolonged graft survival (median 82.1 months). Graft loss was predicted by eGFR and degree of proteinuria at diagnosis but not by donor-specific HLA antibody class or intensity, nor individual or summed Banff scores. Allograft biopsies were further examined for infiltrating leukocyte subtypes and location with high numbers of glomerular leukocytes, particularly macrophages, independently associated with an increased risk of graft failure. This study suggests that patients with cAMR and persistent microcirculatory inflammation, excluding those with advanced histological damage, can expect prolonged graft survival when treated with IVIg and rituximab. Trial level evidence is required to validate this observation. Further examination of the role of macrophages in cAMR is warranted.Copyright © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1111/ctr.13037 | ORCID: | Mulley, William R.; ORCID: http://orcid.org/0000-0001-5109-165X | Link to associated publication: | Click here for full text options | PubMed URL: | 28640458 [http://www.ncbi.nlm.nih.gov/pubmed/?term=28640458] | ISSN: | 0902-0063 | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/38610 | Type: | Article | Subjects: | *kidney tubule disorder/co [Complication] *long term survival macrophage male neutrophil chemotaxis peritubular capillaritis/dt [Drug Therapy] priority journal proteinuria single drug dose azathioprine/cb [Drug Combination] cyclosporin/cb [Drug Combination] everolimus/cb [Drug Combination] HLA antibody/ec [Endogenous Compound] *immunoglobulin/cb [Drug Combination] *immunoglobulin/do [Drug Dose] *immunoglobulin/dt [Drug Therapy] *immunoglobulin/iv [Intravenous Drug Administration] methylprednisolone/cb [Drug Combination] methylprednisolone/dt [Drug Therapy] methylprednisolone/iv [Intravenous Drug Administration] mycophenolic acid/cb [Drug Combination] prednisolone/cb [Drug Combination] *rituximab/cb [Drug Combination] *rituximab/dt [Drug Therapy] tacrolimus/cb [Drug Combination] *peritubular capillaritis/co [Complication] *peritubular capillaritis/dt [Drug Therapy] prospective study adult *antibody mediated rejection article *capillaritis/co [Complication] *capillaritis/dt [Drug Therapy] capillaritis/dt [Drug Therapy] clinical article drug megadose estimated glomerular filtration rate female graft failure/co [Complication] *graft survival histology human human tissue immunosuppressive treatment inflammation inflammatory cell kidney biopsy kidney transplantation inflammatory cell kidney biopsy kidney transplantation *kidney tubule disorder / *complication *long term survival macrophage male neutrophil chemotaxis peritubular capillaritis / drug therapy priority journal prospective study proteinuria drug megadose clinical article capillaritis / drug therapy *capillaritis / *complication / *drug therapy Article *antibody mediated rejection adult single drug dose estimated glomerular filtration rate female graft failure / complication *graft survival histology human human tissue immunosuppressive treatment inflammation |
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