An analysis of transplant glomerulopathy and thrombotic microangiopathy in kidney transplant biopsies

Transpl Int. 2014 Aug;27(8):784-92. doi: 10.1111/tri.12331. Epub 2014 May 24.

Abstract

Glomerular diseases of the transplanted kidney are the most important cause of poor long- term outcome. The estimation of the magnitude of this problem and an elucidation of pathogenic mechanism is essential for improvement of graft survival. This study from the Indian subcontinent aims (i) to determine the incidence of transplant glomerulopathy (TG) and thrombotic microangiopathy (TMA) in a large cohort of indicated renal transplant biopsies, (ii) to evaluate the histological and ultrastructural features of TG and TMA, and (iii) to assess the relationship between the two glomerular lesions. Of a total of 1792 indication renal transplant biopsies received over 5 years (2006-2010), 266 biopsies (of 249 patients) had significant glomerular pathology and were further analyzed along with immunofluorescence, electron microscopy (EM), and C4d immunohistochemistry. TG is the most common glomerular lesion followed by TMA seen in 5.97% and 5.08% of allograft biopsies, respectively, which constitutes 40.23% and 34.2% of biopsies with significant glomerular lesions. Pathologic antibody-mediated rejection (AMR) is associated with both TG and TMA in 71% and 46.5%, respectively. A coexistent TG was found in 18.4% of biopsies with TMA. Endothelial swelling with subendothelial widening, a feature of TMA, is also seen in early TG by EM. Our findings support the concept that TG evolves from a smoldering TMA of various causes.

Keywords: Antibody-mediated rejection; C4d; renal allograft biopsies; thrombotic microangiopathy; transplant glomerulopathy.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Biopsy
  • Complement C4b / analysis
  • Female
  • Humans
  • Kidney Glomerulus / pathology*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Peptide Fragments / analysis
  • Thrombotic Microangiopathies / pathology*

Substances

  • Peptide Fragments
  • Complement C4b
  • complement C4d