Cluster analysis of lesions in nonselected kidney transplant biopsies: Microcirculation changes, tubulointerstitial inflammation and scarring

B. Sis, G. Einecke, J. Chang, L. G. Hidalgo, M. Mengel, B. Kaplan, P. F. Halloran

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


Banff classification empirically established scoring of histologic lesions, but the relationships of lesions to each other and to underlying biologic processes remain unclear. We hypothesized that class discovery tools would reveal new relationships between individual lesions, and relate lesions to C4d staining, anti-HLA donor-specific antibody (DSA) and time posttransplant. We studied 234 nonselected renal allograft biopsies for clinical indications from 173 patients. Silhouette plotting and principal component analysis revealed three groups of lesions: microcirculation changes, including inflammation (glomerulitis, capillaritis) and deterioration (double contours, mesangial expansion); scarring/hyalinosis; and tubulointerstitial inflammation. DSA and C4d grouped with microcirculation inflammation, whereas time posttransplant grouped with scarring/hyalinosis lesions. Intimal arteritis clustered with DSA, C4d and microcirculation inflammation, but also showed correlations with tubulitis. Fibrous intimal thickening in arteries clustered with scarring/hyalinosis. Capillary basement membrane multilayering showed intermediary relationships between microcirculation deterioration and time-dependent scarring. Correlation analysis and hierarchical clustering confirmed the lesion relationships. Thus, we propose that the pathologic lesions in biopsies are not independent but are members of groups that represent distinct pathogenic forces: microcirculation changes, reflecting the stress of DSA; scarring, hyalinosis and arterial fibrosis, reflecting the cumulative burden of injury over time; and tubulointerstitial inflammation. Interpretation of lesions should reflect these associations.

Original languageEnglish (US)
Pages (from-to)421-430
Number of pages10
JournalAmerican Journal of Transplantation
Issue number2
StatePublished - Feb 2010
Externally publishedYes


  • Antibody
  • Antibody-mediated rejection
  • Banff classification
  • C4d
  • Class discovery
  • Donor-specific antibody
  • Endothelium
  • HLA
  • Humoral rejection
  • Informatics
  • Kidney
  • Panel reactive antibody
  • Pathology
  • Renal allograft rejection
  • Transplant glomerulopathy

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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