Answer: Moderate acute rejection, Banff 97 type 2A, and findings consistent with CSA nephrotoxicity

Histology: The low-power image (Image 1) shows mild glomerulitis, mild interstitial edema with mild scattered mononuclear cell inflammatory infiltrates, and an artery showing mild intimal arteritis. Glomerulitis (Image 2) involves infiltration of glomeruli by leukocytes (mainly lymphocytes) with associated endothelial swelling; while often associated with acute rejection it is not a specific or diagnostic lesion. Intimal arteritis (Image 3) is characterized by the presence of one or more lymphocytes and often edema fluid directly beneath the endothelium of an artery, often with reactive-type changes in the endothelial cells. Lymphocytes adherent to the endothelium do not represent a diagnostic lesion of intimal arteritis. Tubular findings on the biopsy include focal isometric vacuolization (many small cytoplasmic vacuoles of similar size) of proximal tubular epithelial cells (Image 4) and mild tubulitis, with occasional (fewer than 5 in any tubular cross-section) lymphocytes infiltrating tubules (Image 5). Tubulitis is best visualized on PAS and methenamine silver stains that highlight the tubular basement membrane; infiltrating lymphocytes often have a surrounding “halo” that allows them to be easily distinguished from tubular epithelial cell nuclei (arrow, Image 5).

Discussion: The widely used Banff 97 working classification of renal allograft pathology (Kidney International 55: 713-723, 1999) defines 3 major types, or grades, or acute rejection on renal transplant biopsy. Mild acute rejection (type 1) is characterized by mononuclear inflammatory cell infiltrates in >25% of the interstitium of the cortical tissue present, with 5-10 (type 1A) or >10 (type 1B) mononuclear cells within the most involved tubular cross-section (or group of 10 tubular epithelial cells for longitudinally cut tubules), without intimal artertitis. Atrophic tubules are not counted. Biopsies showing interstitial inflammation but only mild tubulitis (1-4 cells per tubular cross-section) and no intimal arteritis are classified as showing borderline infiltrates, the clinical significance of which vary according to different reports. A diagnosis of moderate acute rejection (type 2) requires the presence of intimal arteritis, with or without concurrent tubulitis. Cases showing severe intimal arteritis (occlusion of >25% of the lumen of the most involved artery by inflammatory cells and edema fluid) are classified as showing type 2B acute rejection; those with less severe intimal arteritis (as in this case) are classified as type 2A. Severe acute rejection (type 3) involves either transmural inflammation or fibrinoid necrosis in one or more arteries. The Banff types of acute rejection have been shown to correlate well with reversibility of the rejection episode with corticosteroids and other anti-rejection therapies: type 1A (most often reversible) > types 1B, 2A > type 2B > type 3 (often irreversible, even with anti-T cell antibodies). This biopsy also shows one of the 2 lesions described in association with acute cyclosporine (or tacrolimus) nephrotoxicity: isometric vacuolization of proximal tubular epithelium, and thrombotic microangiopathy. Hyaline arteriolopathy is typically seen in association with chronic cyclosporine or tacrolimus toxicity.