Glomerular inflammation in renal allografts biopsies after the first year: Cell types and relationship with antibody-mediated rejection and graft outcome

John C. Papadimitriou, Cinthia B. Drachenberg, Raghava Munivenkatappa, Emilio Ramos, Joseph Nogueira, Charles Sailey, David K. Klassen, Abdolreza Haririan

Research output: Contribution to journalArticle

Abstract

Background. Antibody-mediated rejection manifests with glomerular and peritubular capillary inflammation and transplant glomerulopathy (TG). The role of glomerular inflammation (GI) components in the development of TG and their impact on outcome are incompletely understood. Methods. GI was quantified on hematoxylin-eosin, CD3+ CD+20, and CD68 stains on biopsies from 240 patients with grafts functioning more than or equal to 1 year. Results. A predominance of CD+68 cells followed by less numerous CD3+ cells was found in TG and glomerulitis. CD68+ cells more than 12 in the most inflamed glomerulus were strongly associated with TG, donor-specific antibody (DSA), and C4d staining. Glomerular CD68+ cells correlated with peritubular capillary multilamellation, and similarly, the Banff g score correlated with light and electron microscopic indexes of chronic microvascular damage. Overall, GI components correlated with the g score, DSA, and peritubular capillary C4d. The Banff cg 1, 2, and 3 scores showed high levels of GI composed mostly of CD68 cells, similar to but not higher than cases of g2 and g3 glomerulitis. Glomerular T cells and neutrophils followed similar trends as the predominant macrophages. T-cell-mediated rejection in this cohort did not significantly affect the composition of GI. Prognostically, all types of pronounced GI, g scores, DSA, C4d, and capillaropathy were associated with worse prognosis; however, only high level of macrophages was an independent predictor of graft failure. Conclusions. GI in more than or equal to 1 year grafts is mostly antibody-mediated rejection related, correlates with chronic microvascular damage, and consists predominantly of macrophages. The latter seem to represent a pivotal pathogenetic, diagnostic, and prognostic factor in this setting.

Original languageEnglish (US)
Pages (from-to)1478-1485
Number of pages8
JournalTransplantation
Volume90
Issue number12
DOIs
Publication statusPublished - Dec 27 2010
Externally publishedYes

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Keywords

  • CD68
  • Diabetes mellitus
  • Glomerulitis
  • Glomerulonephritis
  • Graft failure
  • Hepatitis C
  • Ischemia
  • Macrophages
  • Thrombotic microangiopathy
  • Transplant glomerulopathy

ASJC Scopus subject areas

  • Transplantation

Cite this

Papadimitriou, J. C., Drachenberg, C. B., Munivenkatappa, R., Ramos, E., Nogueira, J., Sailey, C., ... Haririan, A. (2010). Glomerular inflammation in renal allografts biopsies after the first year: Cell types and relationship with antibody-mediated rejection and graft outcome. Transplantation, 90(12), 1478-1485. https://doi.org/10.1097/TP.0b013e3181ff87f5