title: Acute renal endothelial injury during marrow recovery in a cohort of combined kidney and bone marrow allografts.
abstract: An idiopathic capillary leak syndrome ('engraftment syndrome') often occurs in recipients of hematopoietic cells, manifested clinically by transient azotemia and sometimes fever and fluid retention. Here, we report the renal pathology in 10 recipients of combined bone marrow and kidney allografts. Nine developed graft dysfunction on day 10-16 and renal biopsies showed marked acute tubular injury, with interstitial edema, hemorrhage and capillary congestion, with little or no interstitial infiltrate (≤10%) and marked glomerular and peritubular capillary (PTC) endothelial injury and loss by electron microscopy. Two had transient arterial endothelial inflammation; and 2 had C4d deposition. The cells in capillaries were primarily CD68(+) MPO(+) mononuclear cells and CD3(+) CD8(+) T cells, the latter with a high proliferative index (Ki67(+) ). B cells (CD20(+) ) and CD4(+) T cells were not detectable, and NK cells were rare. XY FISH showed that CD45(+) cells in PTCs were of recipient origin. Optimal treatment remains to be defined; two recovered without additional therapy, six were treated with anti-rejection regimens. Except for one patient, who later developed thrombotic microangiopathy and one with acute humoral rejection, all fully recovered within 2-4 weeks. Graft endothelium is the primary target of this process, attributable to as yet obscure mechanisms, arising during leukocyte recovery.
authors.affiliation: Pathology Service, Massachusetts General Hospital (MGH), Boston, MA, USA. abfarri@emory.edu
authors.forename: A B
authors.initials: AB
authors.lastname: Farris
authors.forename: D
authors.initials: D
authors.lastname: Taheri
authors.forename: T
authors.initials: T
authors.lastname: Kawai
authors.forename: L
authors.initials: L
authors.lastname: Fazlollahi
authors.forename: W
authors.initials: W
authors.lastname: Wong
authors.forename: N
authors.initials: N
authors.lastname: Tolkoff-Rubin
authors.forename: T R
authors.initials: TR
authors.lastname: Spitzer
authors.forename: A J
authors.initials: AJ
authors.lastname: Iafrate
authors.forename: F I
authors.initials: FI
authors.lastname: Preffer
authors.forename: S A
authors.initials: SA
authors.lastname: Locascio
authors.forename: B
authors.initials: B
authors.lastname: Sprangers
authors.forename: S
authors.initials: S
authors.lastname: Saidman
authors.forename: R N
authors.initials: RN
authors.lastname: Smith
authors.forename: A B
authors.initials: AB
authors.lastname: Cosimi
authors.forename: M
authors.initials: M
authors.lastname: Sykes
authors.forename: D H
authors.initials: DH
authors.lastname: Sachs
authors.forename: R B
authors.initials: RB
authors.lastname: Colvin
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000473:pathology; D019559:Capillary Leak Syndrome / Q000209:etiology* / Q000473:pathology; D003404:Creatinine / Q000097:blood; D005260:Female; D006084:Graft Rejection / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male
chemical_list: D003404:Creatinine