title: Microcirculation inflammation associates with outcome in renal transplant patients with de novo donor-specific antibodies.
abstract: In renal transplant patients with de novo donor-specific antibodies (dnDSA) we studied the value of microcirculation inflammation (MI; defined by the addition of glomerulitis (g) and peritubular capillaritis (ptc) scores) to assess long-term graft survival in a retrospective cohort study. Out of all transplant patients with standard immunological risk (n = 638), 79 (12.4%) developed dnDSA and 58/79 (73%) had an indication biopsy at or after dnDSA development. Based on the MI score on that indication biopsy patients were categorized, MI0 (n = 26), MI1 + 2 (n = 21) and MI ≥ 3 (n = 11). The MI groups did not differ significantly pretransplantation, whereas posttransplantation higher MI scores developed more anti-HLA class I + II DSA (p = 0.011), showed more TCMR (p < 0.001) and showed a trend to C4d-positive staining (p = 0.059). Four-year graft survival estimates from time of indication biopsy were MI0 96.1%, MI1 + 2 76.1% and MI ≥ 3 17.1%; resulting in a 24-fold increased risk of graft failure in the MI ≥ 3 compared to the MI0 group (p = 0.003; 95% CI [3.0-196.0]). When adjusted for C4d, MI ≥ 3 still had a 21-fold increased risk of graft failure (p = 0.005; 95% CI [2.5-180.0]), while C4d positivity on indication biopsy lost significance. In renal transplant patients with de novo DSA, microcirculation inflammation, defined by g + ptc, associates with graft survival.
authors.affiliation: Department of Histopathology, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: H
authors.initials: H
authors.lastname: de Kort
authors.forename: M
authors.initials: M
authors.lastname: Willicombe
authors.forename: P
authors.initials: P
authors.lastname: Brookes
authors.forename: K M
authors.initials: KM
authors.lastname: Dominy
authors.forename: E
authors.initials: E
authors.lastname: Santos-Nunez
authors.forename: J W
authors.initials: JW
authors.lastname: Galliford
authors.forename: K
authors.initials: K
authors.lastname: Chan
authors.forename: D
authors.initials: D
authors.lastname: Taube
authors.forename: A G
authors.initials: AG
authors.lastname: McLean
authors.forename: H T
authors.initials: HT
authors.lastname: Cook
authors.forename: C
authors.initials: C
authors.lastname: Roufosse
mesh_terms: D000328:Adult; D000906:Antibodies / Q000276:immunology*; D001706:Biopsy; D015935:Complement C4b / Q000032:analysis; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation; D007668:Kidney / Q000276:immunology*; D016030:Kidney Transplantation / Q000276:immunology* / Q000379:methods*; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D015233:Models, Statistical; D010446:Peptide Fragments / Q000032:analysis; D051437:Renal Insufficiency / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D007166:Immunosuppressive Agents; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d