Renal Failure Associated with Human Polyomavirus BK and Human Adenovirus in a Child with Acute Lymphoblastic Leukaemia

Immunocompromised patients are susceptible to multiple severe viral infections. This paper describes a 4-year-old boy with newly diagnosed B-cell precursor acute lymphoblastic leukaemia. The 4-year-old patient developed haemorrhagic cystitis, obstructive nephropathy and renal failure due to human polyomavirus BK and human adenovirus co-infection. Cidofovir should be used only in life-threatening cases.

Prevalence of Human Polyomavirus BK Virus in Prostate Cancer Patients and Benign Prostatic Hyperplasia: A Cross-Sectional Study on Prostate Patients Referred to Imam Khomeini Hospital in Ahvaz Between 2015 and 2017

Background: Human polyomavirus BK virus (BKV) belongs to the Polyomaviridae family and seems to be a drastic virus in prostate cancer (PCa) etiology. BKV induces oncogenesis via the expression of large tumor antigen (LTAg) and small tumor antigen (stAg). Also, BKV infection seems to play an essential role in prostate cancer development. Objectives: In this study was aimed to study the prevalence of BKV in benign and cancerous prostate tissues. Methods: In this study, 100 formalin-fixed paraffin-embedded tissues of PCa specimens and benign prostatic hyperplasia (BPH) were collected. The DNA was extracted from tissue samples, and the BKV DNA was investigated using a semi-nested polymerase chain reaction (PCR). The MEGA 6.0 software was used for phylogenetic analysis to assemble the viral genome. A phylogenetic tree was constructed by neighbor-joining analysis with 1,000 replicates of the bootstrap resampling test using Mega 6.0. Statistical analysis was done by SPSS version 22. Results: The BKV DNA was found in 66% (33/50) of patients with PCa and 36% (18/50) of patients with benign prostatic hyperplasia (BPH) (P = 0.003). The frequency of BKV DNA in different classes of Gleason score (5 - 10) was not significant (0.094). The distribution of BKV DNA among different age groups was not significant (P = 0.086). Conclusions: High frequency of BKV infection was detected in patients with PCa compared to patients with BPH (P = 0.003), and the coexistence of BKV DNA was confirmed in 51% (51/100) of tissue samples, which were confirmed to be subtype 1 of BKV infection.

NGHIÊN CỨU TÌNH TRẠNG NHIỄM MỘT SỐ VIRUS VÀ MỐI LIÊN QUAN ĐẾN ĐÁI THÁO ĐƯỜNG SAU GHÉP THẬN

Mục tiêu: Phân tích tỉ lệ nhiễm một số virus đánh giá mối mối liên quan đến đái tháo đường sau ghép trên đối tượng 3 tháng sau ghép thận. Đối tượng và phương pháp nghiên cứu: Gồm 508 bệnh nhân có thời gian sau ghép thận ≥ 3 tháng được theo dõi và điều trị sau ghép tại BV Việt Đức, từ 09/2017 đến 04/2018. Tất cả các bệnh nhân đều tự nguyện tham gia nghiên cứu. Bệnh nhân được lấy máu, và nước tiểu vào buổi sáng trước khi ăn và uống thuốc ức chế miễn dịch. Xét nghiệm sinh học phân tử (Realtime PCR) phát hiện sự có mặt của các loại virus viêm gan B (hepatitis B virus - HBV), virus viêm gan C (hepatitis C virus - HCV), cytomegalovirus (CMV), BK polyomavirus (BK) trong máu của bệnh nhân, riêng virus BK còn được đánh giá sự có mặt trong nước tiểu. Chẩn đoán đái tháo đường sau ghép tạng dựa trên tiêu chuẩn của Hiệp hội Đái tháo đường Hoa Kỳ (ADA - American Diabetes Association). Kết quả: Trong 508 đối tượng nghiên cứu, trong máu có: 28/436 bệnh nhân (6,42%) có HBV-DNA dương tính; 24/444 (5,54%) bệnh nhân HCV-RNA dương tính; 35/395 (8,86%) bệnh nhân CMVdương tính; 30/493 (6,09%) BK máu dương tính; Trong nước tiểu có 150/500 (30 %) BK dương tính; 40/508 (7,87%) bệnh nhân đồng nhiễm ít nhất 2 loại virus. Không có sự khác biệt về tỉ lệ NODAT giữa những người bị nhiễm các loại virus kể trên với người không bị nhiễm. Kết luận: Kết quả của nghiên cứu này cung cấp số liệu về tỉ lệ nhiễm các loại virus HBV, HCV, CMV và BK trên một số lớn đối tượng và cho thấy chưa có mối liên quan với NODAT ở bệnh nhân 3 tháng sau ghép thận.

Routine immunohistochemistry study for polyomavirus BK nephropathy in transplanted kidney biopsies, is it recommended?

Background Early diagnosis and treatment of Polyomavirus BK Nephropathy (PVBKN) is a challenging issue in the management of patients with kidney transplantation. Currently, histopathologic diagnosis is the gold standard method for diagnosis of PVBKN. However, typical viral inclusions may not be found in early stages of the PVBKN and should, instead, be diagnosed using immunohistochemistry (IHC) study. There is no clear consensus about routine IHC tests in the pathologic evaluation of transplanted kidney biopsy samples. Material and methods The current study was conducted on transplanted kidney biopsy samples, since 2016 to 2019. The patients who have presented with new onset of allograft dysfunction, at least 2 weeks after transplantation surgery, were included in our study. All these biopsy samples were evaluated with routine renal biopsy stains as well as IHC for SV40 (Simvian Virus 40) antigen. The identification of typical nuclear virus inclusion body and any nuclear positive staining on IHC (≥1+ positive result) were considered as definite evidence of PVBKN. Sensitivity, specificity, Positive Predictive and Negative Predictive Values (PPV and NPV) of histopathologic assessment without IHC study were evaluated. Results Among 275 included cases, 18 (6.5%) patients with PVBKN were diagnosed. In patients with PVBKN, typical viral inclusions were detected in 14 samples (77.7%), on primary histopathological examination. However, virus-infected cells were identified just after IHC study in 4 (22.2%) of patients. Sensitivity, Specifity, PPV and NPV of morphologic histopathological assay without IHC for detection of PVBKN was 77.7, 100, 100 and 98.4% respectively. Conclusion Routine IHC study for SV40 in all transplanted kidney biopsy samples with new onset of allograft dysfunction, will enhance the diagnostic sensitivity of early stage disease detection.

Infektionen unter Immunsuppression nach Nierentransplantation

ZUSAMMENFASSUNGUnter immunsuppressiver Therapie besteht ein deutlich erhöhtes Infektionsrisiko nach Nierentransplantation (NTx), insbesondere für virale Infektionen. Bereits vor einer geplanten NTx sollte auf einen aktuellen Impfstatus geachtet werden, da nach einer Transplantation unter immunsuppressiver Therapie einerseits Lebendimpfstoffe nicht mehr gegeben werden dürfen und andererseits eine adäquate Impfantwort schwieriger zu erreichen ist. Die saisonale Influenzaimpfung kann bereits einen Monat nach Transplantation gegeben werden, für alle anderen Impfungen wird ein Abwarten von 3–6 Monaten empfohlen. Eine prophylaktische Therapie kann das Auftreten bestimmter Infektionen effektiv verhindern. Nach NTx sollte für die ersten 6 Monate eine PjP-Prophylaxe (PjP: Pneumocystis-jirovecii-Pneumonie) mit Trimethoprim/Sulfamethoxazol verabreicht werden. Eine CMV-Prophylaxe (CMV: Zytomegalievirus) mit Valganciclovir erfolgt in Abhängigkeit vom Sero-Status von Empfänger und Spender i. d. R. für 3 bzw. 6 Monate. Im Falle einer Infektion kann in Abhängigkeit vom Schweregrad der Antimetabolit (meist MMF: Mycophenolatmofetil) dosishalbiert oder pausiert werden, jedoch ist dies mit einem erhöhten Rejektionsrisiko verbunden. Insbesondere bei Infektionen mit CMV und BKV (Polyomavirus BK) kann anstelle von MMF ein mTOR-Inhibitor (mTOR: „mechanistic target of rapamycin“) eingesetzt werden in Kombination mit einem niedrigdosierten Calcineurininhibitor (CNI). Bei einer COVID-19-Erkrankung (COVID-19: Coronavirus Disease 2019) nach NTx sollte wie bei anderen Infektionen in einer Kombinationstherapie zunächst der Antimetabolit bzw. der mTOR-Inhibitor dosisreduziert oder pausiert werden. Ein Absetzen des CNIs bei COVID-19 erscheint aus unserer Sicht nicht regelhaft indiziert, sondern bleibt schweren Verläufen im Einzelfall vorbehalten. Im Falle einer antiviralen Therapie bei COVID-19 muss immer an mögliche Interaktionen mit den Immunsuppressiva (v. a. mit CNI und mTOR-Inhibitoren) gedacht werden.

Renal Allograft Biopsies with Polyomavirus BK Nephropathy: Turin Transplant Center, 2015–19

Background: In kidney transplant patients, polyomavirus-associated nephropathy (PVAN) represents a serious complication; the key factor for the development of PVAN is immunosuppression level and modulation of anti-rejection treatment represents the first line of intervention. Allograft biopsy and histology remain the criterion standard for diagnosing PVAN. Methods: All consecutive renal biopsies with the diagnosis of PVAN carried out at the University Hospital City of Health and Science of Turin over a five-years period were studied. Renal allograft biopsy was performed due to renal function alterations associated to medium-high polyomavirus BK (BKV)-DNA levels on plasma specimen. Results: A total of 21 patients underwent a first biopsy to diagnose a possible BKV nephropathy, in 18, a second biopsy was made, in eight, a third biopsy, and finally, three underwent the fourth renal biopsy; following the results of each biopsies, immunosuppressant agents dosages were modified in order to reduce the effect of PVAN. Conclusions: In this study, the clinical and histological features of 21 kidney transplant recipients with BKV reactivation and development of PVAN are described. To date, the only treatment for PVAN consists in the reduction of immunosuppressive agents, constantly monitoring viral load.

Complete Genome Sequence of Original Material Used To Derive the WHO International Standard for Human Polyomavirus BK DNA

The complete genomic sequence was determined for the original biological material used to derive the WHO international standard for BK polyomavirus (BKV) DNA. The entire coding sequence and noncoding regions were assigned BKV subtype 1, subgroup 1b-1. This information will aid development and evaluation of human BKV DNA amplification assays.