Glomerular Parietal Epithelial Cells Infection Is Associated With Poor Graft Outcome in Kidney Transplant Recipients With BK Polyomavirus–Associated Nephropathy

Chen, Xu-Tao; Yang, Shicong; Chen, Wenfang; Li, Jun; Deng, Shijie; Qiu, Jian; Fei, Ji-guang; Deng, Ronghai; Chen, Yan-Yang; Chen, Peisong; Huang, Yang; Wang, Changxi; Huang, Gang

doi:10.1093/infdis/jiz022

Cited by 9 publications

(11 citation statements)

References 20 publications

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“…(40,41). Similarly, in our previous study, we also found that BKPyV could infect glomerular parietal epithelial cells, and this phenomenon often indicated more serious pathological damage and worse prognosis of transplanted kidney function (42). Moreover, our results showed that BKPyV infection in renal tubular epithelial cell is concurrent in all patients with glomerular BKPyV involvement.…”

Section: Discussionsupporting

confidence: 82%

Non-invasive urinary sediment double-immunostaining predicts BK polyomavirus associated-nephropathy in kidney transplant recipients

Chen¹,

Chen²,

Hou

et al. 2020

Ann Transl Med

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Background: The positive predictive value (PPV) of urinary decoy cells for diagnosing BK polyomavirus associated-nephropathy (BKPyVAN) is low. This study was designed to increase the PPV of urinary decoy cells for diagnosing BKPyVAN in kidney transplant recipients.Methods: A total of 105 urine sediment samples from 105 patients with positive BK viruria and decoy cells were evaluated by automatic double-immunostaining with anti-HGD (a renal tubular marker) antibody + anti-SV40-T antibody or anti-S100P (an urothelial marker) antibody + anti-SV40-T antibody.Results: Of the 105 patients, 76 (72.4%) had both HGD(+)/SV40-T(+) cells and S100P(+)/SV40-T(+) cells (group A), 24 (22.9%) had only S100P(+)/SV40-T(+) cells (group B), and 5 (4.6%) had only S100P(−)/ HGD(−)/SV40-T(+) cells (group C). Seventy patients in group A (92.1%), 3 patients in group B (12.5%), and no patients in group C were diagnosed with BKPyVAN. The area under the ROC curve of predicting BKPyVAN by decoy cells was 0.531 (0.431-0.630), with an optimal cut-off value of 29 (per 10 high power field), a sensitivity of 45.8% (95% CI: 34.0-58.0%), and a specificity of 68.8% (95% CI: 50.0-83.9%).Besides, the area under the ROC curve of predicting BKPyVAN by plasma BKPyV load was 0.735 (95% CI: 0.632-0.822), with an optimal cut-off value of 1,000 copies/mL, a sensitivity of 61.1% (95% CI: 48.9-72.4%) and a specificity of 84.2% (95% CI: 60.4-96.6%). In contrast, the PPV, negative predictive value, sensitivity, and specificity of HGD(+)/SV40-T(+) cells for diagnosing BKPyVAN were 92.1% [95% confidence interval (CI): 83.0-96.7%], 89.7% (95% CI: 71.5-97.3%), 95.9% (95% CI: 87.7-98.9%), and 81.3% (95% CI: 63.0-92.1%) respectively.Conclusions: Double-immunostaining with anti-HGD or anti-S100P and anti-SV40-T antibodies helps to identify the origin of decoy cells and diagnose BKPyVAN.

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Section: Discussionsupporting

confidence: 82%

Non-invasive urinary sediment double-immunostaining predicts BK polyomavirus associated-nephropathy in kidney transplant recipients

Chen¹,

Chen²,

Hou

et al. 2020

Ann Transl Med

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“…Drachenberg CB et al reported that the extent of SV40-T staining was positively associated with BKPyVAN stages (12). Our previous study has demonstrated that BKPyV infection in glomerular parietal epithelial cells is a risk factor for accelerated renal graft failure, indicating the infection depth of BKPyV in allograft has an adverse effect on prognosis (9). Thus, if the depth and extent of BKPyV infection in allograft could be determined non-invasively, it may provide some useful information for risk stratification and prognosis evaluation of BKPyVAN.…”

Section: Introductionmentioning

confidence: 78%

“…Similarly, the findings from the Banff working group showed that BKPyV only infected the medulla at class 1 of BKPyVAN but extended from medulla to cortex at class 2 and class 3 of BKPyVAN ( 28 ). Our previous study proved that BKPyV involvement in glomerular parietal epithelial cells is an independent risk factor for renal allograft failure ( 9 ). The results of this study showed that 69 (90.8%) of 76 biopsy-proved BKPyVAN recipients had urinary HGD(+)/SV40-T(+) cells, which was consistent with our previous study ( 6 ).…”

Section: Discussionmentioning

confidence: 94%

“…During the progression of BKPyVAN, BK polyomavirus (BKPyV) usually infects the pelvis, collecting ducts, distal tubules, and subsequently proximal tubules ( 5 – 8 ). In some cases of severe infection, BKPyV can spread to the glomerular parietal epithelial cells ( 9 – 11 ). Drachenberg CB et al reported that the extent of SV40-T staining was positively associated with BKPyVAN stages ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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

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“…The presence of viral cytopathic changes in the glomeruli has also been associated with a poor prognosis (5). Similarly, we have found BKPyV infection in glomerular parietal epithelial cells (GPECs) in some kidney transplant (KT) recipients, and these patients had rapid deterioration of renal function and even graft loss (6). BKPyVAN with glomerular involvement exhibits specific pathological features.…”

Section: Introductionmentioning

confidence: 79%

Pathological characteristics of BK polyomavirus-associated nephropathy with glomerular involvement

et al. 2020

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Background: This study aimed to investigate the pathological characteristics of BK polyomavirus (BKPyV)-associated nephropathy (BKPyVAN) with glomerular involvement in kidney transplant recipients.Methods: Forty-four patients with glomerular BKPyV infection were retrospectively included for analysis. Immunohistochemical (IHC) staining was performed on paraffin sections using monoclonal mouse anti-SV40 large T antigen antibody.Results: In BKPyV-infected glomeruli, the glomerular parietal epithelial cells (GPECs) were swollen, hyperchromatic, and enlarged, with an increased nuclear to cytoplasm (N/C) ratio and smudgy basophilic intra-nuclear viral inclusions. IHC staining revealed the distribution of BKPyV involvement in GPECs, podocytes, and shedding cells within Bowman's space. Notably, BKPyV affected GPEC proliferation and caused crescent formation (7 biopsies, 15.9%). Three biopsies exhibited fibrous crescents and the absence of viral inclusions. The other 4 biopsies exhibited cellular and fibro-cellular crescents, with viral cytopathic changes and positive IHC staining in the proliferative GPECs. Electron microscopy showed viral particles in both GPECs and podocytes. BKPyV-infected GPECs were degenerative, with mitochondrial swelling, endoplasmic reticulum expansion, and multi-layered membranous structure formation. Twelve (27.3%) patients received repeat biopsies within 1.6 to 39.5 months (median: 13.5 months), but none revealed persistent glomerular BKPyV infection.Conclusions: Distinct glomerular changes in BKPyVAN biopsies should raise the possibility of glomerular involvement.

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Glomerular Parietal Epithelial Cells Infection Is Associated With Poor Graft Outcome in Kidney Transplant Recipients With BK Polyomavirus–Associated Nephropathy

Cited by 9 publications

References 20 publications

Non-invasive urinary sediment double-immunostaining predicts BK polyomavirus associated-nephropathy in kidney transplant recipients

Non-invasive urinary sediment double-immunostaining predicts BK polyomavirus associated-nephropathy in kidney transplant recipients

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

Pathological characteristics of BK polyomavirus-associated nephropathy with glomerular involvement

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