Electron microscopy in the evaluation of late dysfunction biopsies

A late dysfunction of a renal allograft involves to a progressive decline in renal function manifested >3 months after transplantation. A late dysfunction may have several parenchymal causes, such as chronic rejection (CR), chronic allograft nephropathy (CAN), chronic calcineurin inhibitor toxicity, de novo or recurrent renal disease and acute rejection. An allograft biopsy is necessary to establish a definitive diagnosis. The standard interpretation of the alterations is widely carried out on the basis of the "Banff 97 classification" [Kidney Int 55:713-723, 1999], which relies on the study of light microscopic stains (H&E, PAS, methenamine-silver, trichrome). In our department, late dysfunction biopsies are routinely evaluated via these stains, supplemented with the elastin stain, by immunofluorescence on frozen sections (IgG, IgA, IgM, fibrinogen, C3, C4d [linear staining along peritubular capillaries: a marker of humoral rejection], and HLA-DR [cytoplasmic staining in tubular epithelial cells: a marker of acute cellular rejection]), and by electron microscopy. The ultrastructural examination of peritubular and glomerular capillaries facilitates the recognition of microvascular indicator lesions of CR (see next).