Detection of Proximal Tubule Involvement by BK Polyomavirus in Kidney Transplant Recipients With Urinary Sediment Double-Immunostaining

Abstract

Background: The extent and depth of BK polyomavirus (BKPyV) infection in renal allograft correlate with prognosis. This study was designed to evaluate the value of urinary sediment double-immunostaining for predicting BKPyV infection in proximal tubular epithelium. Materials and methods: A total of 76 urine sediment cell blocks, as well as the corresponding transplanted kidney tissues with BK polyomavirus associatednephropathy (BKPyVAN), were evaluated by automatic double-immunostaining with anti-58-kDa Golgi protein (58K, a proximal renal tubular marker) + anti-SV40-T and anti-homogentisate 1, 2-dioxygenase (HGD, a renal tubular marker) + anti-SV40-T. Results: Immunohistochemical staining demonstrated that 58K was expressed in proximal tubular epithelium but not in distal tubular epithelium or transitional epithelium. Of the 76 patients, 28 (36.8%) had urinary 58K(+)/SV40-T(+) cells and HGD(+)/SV40-T(+) cells, 41 (53.9%) had only HGD(+)/SV40-T(+) cells, one (1.3%) had only 58K(+)/SV40-T(+) cells, and six (7.9%) had only 58K(−)/HGD(−)/SV40-T(+) cells. The presence of urinary 58K(+)/SV40-T(+) cells was correlated with BKPyV infection in proximal tubular epithelium (P < 0.001, r = 0.806). The mean extent of SV40-T staining was significantly more extensive in patients with urinary 58K(+)/SV40-T(+) cells than those without urinary 58K(+)/SV40-T(+) cells (21.4 vs. 12.0%, P < 0.001). The positive predictive value, negative predictive value, sensitivity, and specificity of urinary 58K(+)/SV40-T(+) cells for predicting BKPyV infection in proximal tubular epithelium

Current Status, Prevention and Treatment of BK Virus Nephropathy

“…Transmission is ongoing from person-to-person, foecal-oral transmission via wastewater is also possible. Furthermore, leukocyte-containing blood transfusion and transplacental transmission has been also reported (4,6). BKV replicates itself in the nucleus of renal tubular proximal epithelial cells that are also the natural host cells (6).…”

“…Furthermore, leukocyte-containing blood transfusion and transplacental transmission has been also reported (4,6). BKV replicates itself in the nucleus of renal tubular proximal epithelial cells that are also the natural host cells (6). Daughter viruses are delivered to other cells to spread infection (7), which is followed by necrosis, inflammation and local tissue damage which enables the virus to penetrate into the intertubular space, peritubular capillaries and adjacent cells (8).…”

Polyomavirus nephropathy: diagnosis, histologic features, and differentiation from acute rejection

“…An additional suggested urinary test is double staining of shed epithelial cells with anti-58-kDa Golgi protein, expressed on proximal tubules, and SV40. The presence of urinary 58-kDa+/SV40+ cells is strongly correlated with BKVN, with a positive predictive value of 89.7% (95% confidence interval [CI], 71.5%-97.3%) and a negative predictive value of 91.5% (95% CI, 78.7%-97.2%) [73].…”

High Incidence and Early Onset of Urinary Tract Cancers in Patients with BK Polyomavirus Associated Nephropathy

“…An epidemiologic study demonstrated that approximately 80% of the general population was infected by BKPyV in their childhood [ 14 ]. Following primary infection, BKPyV is persistently hidden in the renourinary tract, and when the immunity of the organ transplant recipients is suppressed, BKPyV rapidly replicates to cause renal inflammation, the occurrence of BKPy-viruria and BKPy-viremia, and sometimes BKPyV-associated nephropathy (BKPyVAN) [ 15 , 16 , 17 , 18 ]. Potent immunosuppressants reduce acute rejection episodes but increase the risk of BKPyVAN and its associated allograft loss.…”