Transplant Glomerulopathy: Ultrastructural Abnormalities Occur Early in Longitudinal Analysis of Protocol Biopsies
| Autor: | Moses Wavamunno, Jeremy R. Chapman, Caroline L.-S. Fung, Brian J. Nankivell, M. Vitalone, Richard D. M. Allen, Philip J. O'Connell |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Time Factors Endothelium Biopsy Kidney Glomerulus Kaplan-Meier Estimate Peritubular capillaries Ultrastructural Pathology Podocyte Complement C4b Humans Immunology and Allergy Medicine Pharmacology (medical) Longitudinal Studies Basement membrane Transplantation Podocytes business.industry Transplant glomerulopathy Middle Aged medicine.disease Kidney Transplantation Peptide Fragments Capillaries Endothelial stem cell medicine.anatomical_structure Case-Control Studies Mesangial Cells Female Endothelium Vascular business |
| Zdroj: | American Journal of Transplantation. 7:2757-2768 |
| ISSN: | 1600-6135 |
| DOI: | 10.1111/j.1600-6143.2007.01995.x |
| Popis: | Transplant glomerulopathy (TXG) presents a distinctive pattern of glomerular abnormalities. The aim of this study was to describe its sequential ultrastructural pathology. A paired cohort study of 228 protocol biopsies, from our longitudinal database (n = 1345), compared TXG (7 patients, 95 biopsies) and controls (8 patients, 133 biopsies). Ultrastructural morphometry and C4d immunoperoxidase were evaluated from implantation to 5 years after transplantation against sequential histology and functional changes. TXG was predated by early glomerular endothelial cell activation; typified by vacuolation, hypertrophy, serration and expansion of lamina rara interna from 39 +/- 23 days after transplantation. Endothelial cells were transformed into an activated phenotype, containing numerous mitochondria, Golgi and ribosomes. Transition from fenestrated to continuous endothelium, mesangial matrix expansion and podocyte fusion occurred late. Endothelial cell activation also occurred in peritubular capillaries (PTC) followed by basement membrane multi-lamination (p < 0.05-0.001). Light microscopy changes of TXG occurred at 2.3 years. PTC C4d deposition was intermittently expressed over time, correlating with endothelial abnormalities, glomerular C4d and donor-specific antibodies (DSA) (p < 0.05-0.001). In summary, endothelial and subendothelial ultrastructural abnormalities in glomerular and peritubular capillaries are sensitive, early markers of TXG, likely due to stimulation of endothelial cells into an activated phenotype by antibody-mediated sub-lytic complement deposition. |
| Databáze: | OpenAIRE |
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