BK polyomavirus nephropathy in two kidney transplant patients with distinct diagnostic strategies for BK virus and similar clinical outcomes: two case reports

A 37-year-old white man underwent kidney transplant in July 2013 due to hypertension nephropathy. In the first postoperative (PO) 5 months, his glomerular filtration rate estimated by the Modification of Diet in Renal Disease Study equation (MDRD) [18] ranged between 45 and 49 mL/minute per 1.73 m² (Fig. 1). In PO month 6, he was administered prednisone 5 mg/day, mycophenolate mofetil (MMF) 1440 mg/day, and tacrolimus 6 mg twice a day. The tacrolimus was reduced from 12 mg to 6 mg/day and MMF was substituted with sirolimus (3 mg/day). In PO month 10, there were clinical signs of tacrolimus nephrotoxicity and the dosage was further decreased to 4 mg/day. A graft biopsy was performed in PO month 14, due to continuous decreasing renal function. The biopsy revealed stage B BKVAN characterized by: epithelial tubular necrosis foci; many epithelial cells with basophilic intranuclear inclusions presenting diffusely in the core, especially in the medulla; patchy and moderate interstitial infiltrate with predominance of lymphocytes; a microabscess of neutrophils involving medullar tubules; edema, especially in the medulla; patchy stromal bleeding; few foci of mild tubulitis (maximum two inflammatory cells per tubular cross-section); tubular atrophy; interstitial fibrosis in <10% of renal cortex (Fig. 2a); and arteriolosclerosis with some hyalinosis. Many tubular epithelial cells were positive for Simian virus 40 large T antigen (SV40 T-ag). There were no signs of transplant glomerulopathy or vasculopathy/vasculitis. Tacrolimus was substituted with MMF 720 mg/day. Our patient presented episodes of bacterial infection in his respiratory tract (PO month 27) and skin (PO month 29), when two sessions of hemodialysis were required. A second graft biopsy was performed in PO month 30, showing extensive interstitial fibrosis (>90% renal cortex) and inflammatory cell infiltration (>50% renal cortex), mainly composed of lymphocytes (Fig. 2b). Some tubular cells in the medulla showed basophilic intranuclear inclusions. There were no signs of transplant glomerulopathy or vasculopathy and complement component 4d (C4d) was negative. There was weak nuclear positivity for SV40 T-ag in a few tubular epithelial cells in the cortex and medulla. The diagnosis was stage C BKVAN. He was returned to the hemodialysis program.

A 49-year-old mulatto man underwent kidney transplant in June 2015 due to autosomal dominant polycystic kidney disease. He underwent a previous kidney transplant in 2011 and spent 3 years on dialysis between the two transplants. In PO month 2, his serum tacrolimus level was 26.7 ng/mL. He was administered prednisone (15 mg/day), sirolimus (3 mg/day), and tacrolimus (2 mg twice a day). Tacrolimus was decreased from 4 mg to 2 mg/day (Fig. 3). He was submitted to biweekly urinary monitoring for BKV (screening for DC in urine sediment). Urinary DC were detected in PO month 3. From then on, all urine samples were strongly positive for DC, >10/high power field (HPF), with the smears presenting a dirty background, cellular debris, many leukocytes and, in some samples, cellular casts with nuclei showing features of polyomavirus infection (Fig. 4). An ultrastructural study of urine sediment revealed abundant icosahedral viral particles measuring approximately 40 nm in diameter, either intranuclear or in the cytosol, as single particles, small aggregates, or forming typical crystalline arrays, free or membrane-bound, or extracellular in continuity with the cell membrane (Fig. 5). In PO month 12, there was a sharp drop in renal function and a graft biopsy was performed. The histology revealed stage B BKVAN characterized by tubular cellular necrosis associated with many nuclear inclusions expressing SV40 T-ag (Fig. 6), present in both cortex and medulla, minimal interstitial inflammatory infiltrate, fibrosis and tubular atrophy, no tubulitis, and no transplant glomerulopathy or vasculopathy. There were no typical morphological signs of nephrotoxicity by tacrolimus. He returned to the hemodialysis program in PO month 15.