Caracterización clínica de la Nefropatía por Poliomavirus BK en pacientes trasplantados renales / Clinical characterization of Polyomavirus BK nephropathy in kidney transplanted patients

INTRODUCCIÓN. La nefropatía por poliomavirus BK resulta un problema emergente en el trasplante renal, pues contribuye a la pérdida temprana de los injertos renales. OBJETIVO. Caracterizar clínicamente a los pacientes trasplantados renales con nefropatía por poliomavirus BK. MATERIALES Y MÉTODOS. Estudio observacional, descriptivo, realizado en el Hospital de Especialidades Carlos Andrade Marín en el período 2013-2022, se obtuvo una base de datos anonimizada, 479 pacientes trasplantados renales, de estos se identificaron 37 pacientes que corresponde a un 7,7% con nefropatía por poliomavirus BK, se realizó un análisis con el programa estadístico SPSS v26®. RESULTADOS. La población estuvo caracterizada por pacientes del sexo masculino (56,8%), con una edad media de 48,2 años, el donante cadavérico fue el más frecuente (94,5%), la mayor parte del tratamiento de la nefropatía por poliomavirus BK consistió en cambio de micofenolato sódico a everolimus y se mantuvo con 50% de Tacrolimus y Prednisona (40,5%); al valorar el cambio de los valores de creatinina, los niveles más elevados fueros a los 12 meses cuando la pérdida renal fue temprana (p: 0,042), y de la misma manera a los 12 meses, fueron más elevados los niveles de creatinina cuando el diagnóstico histopatológico fue Nefropatía por Poliomavirus Clase 3 (p: 0,01). DISCUSIÓN. La prevalencia de la nefropatía se mantuvo por debajo del 10% reportado a nivel global, la creatinina empeoró en pacientes con pérdida temprana del injerto renal y con una clase patológica avanzada, hecho reportado en la fisiopatología de la enfermedad. CONCLUSIÓN. La pérdida del injerto renal temprano presentó una creatinina más alta que la tardía. Es recomendable un tamizaje adecuado para la detección temprana del virus BK siendo crucial para prevenir el deterioro de la función renal y limitar la posterior pérdida del injerto.

INTRODUCTION: BK polyomavirus nephropathy is emerging as a significant concern in kidney transplantation, as it contributes to the early loss of renal grafts. OBJECTIVE: The aim of this study was to clinically characterize renal transplant recipients with BK polyomavirus nephropathy. MATERIALS AND METHODS: An observational and descriptive study was conducted at Carlos Andrade Marín Specialties Hospital during the period of 2013 to 2022. An anonymized database comprising 479 renal transplant patients was utilized. Among these, 37 patients, constituting 7.7%, were identified with BK polyomavirus nephropathy. Data analysis was performed using the statistical program SPSS v26®. RESULTS: The study population was predominantly composed of male patients (56.8%) with a mean age of 48.2 years. Deceased donors accounted for the majority (94.5%) of cases. The primary approach for managing BK polyomavirus nephropathy involved transitioning from mycophenolate sodium to everolimus, alongside maintaining a regimen of 50% tacrolimus and 40.5% prednisone. When assessing changes in creatinine values, the highest levels were observed at 12 months, coinciding with early renal loss (p: 0.042). Similarly, at the 12-month mark, elevated creatinine levels were associated with a histopathological diagnosis of Polyomavirus nephropathy Class 3 (p: 0.01). DISCUSSION: The prevalence of nephropathy remained below the globally reported threshold of 10%. Creatinine levels worsened in patients experiencing early graft loss and an advanced pathological classification, aligning with established disease pathophysiology. CONCLUSION: Early renal graft loss was associated with higher creatinine levels compared to delayed loss. Adequate screening for early detection of BK virus is recommended, as it plays a crucial role in preventing renal function deterioration and limiting subsequent graft loss.

Outpatient haploidentical hematopoietic stem cell transplant using post-transplant cyclophosphamide and incidence of hemorrhagic cystitis

Abstract Introduction Hemorrhagic cystitis (HC) is a common complication of haploidentical hematopoietic stem cell transplantation (haplo-HSCT), characterized by irritative symptoms of the urinary tract and a higher morbidity and mortality rate. The worldwide incidence is reported between 10% and 70%. The use of alkylating agents and BK viral infection are the most frequent etiologies. The aim of this study was to report the HC incidence in an outpatient haplo-HCST program with a reduced intensity-conditioning (RIC) regimen, cataloguing risk factors, complications and final outcomes. Methods The medical database of patients who received a haplo-HSCT between January 2012 and November 2017 was retrospectively analyzed. Demographic variables, general characteristics and HC incidence were included. Results One hundred and eleven patients were included, 30 (27%) of whom developed HC, most of them (70%) being grade II, with a 30-day (7-149) median time of post-transplant HC onset. The BK virus was detected in 71% of the urine samples analyzed. All HC patients responded to treatment, except two (6.6%), who died due to HC complications. Conclusions There was no difference in the HC incidence or severity, compared to that reported when performing haplo-HSCT in hospitalized patients, although the donor-recipient sex mismatch did relate to a higher HC incidence.

Modeling of covariates predicting renal allograft failure within six months after transplantation / Modelagem das covariáveis preditivas para falência do enxerto renal até seis meses do transplante

INTRODUCTION: Kidney transplantation (KT) is the renal replacement therapy (RRT) of choice for patients with chronic kidney disease (CKD). However, not every KT is successful and some patients persist on RRT. OBJECTIVE: To model a logistic regression with pre- and post-KT risk covariates capable of predicting secondary allograft dysfunction in need of RRT or reaching stage V of CKD until the first six months post-KT. METHODS: Cohort with KT recipients from Northeastern Brazil. Medical records of KT performed between 2011-2018 were analyzed. KT-recipients with insufficient data or who abandoned follow-up were excluded. The covariables analyzed were: demographic; infectious; pre- and post-KT comorbidities; panel reactive-antibodies; number of HLA mismatches; acute rejection episodes mediated by T-cell (ACR) or antibodies (AAR) six months after KT; and laboratory tests six months after KT. RESULTS: Covariates with higher risk for the analyzed outcomes six months after KT were: elderly KT recipients (OR:1.41; CI95%:1.01-1.99), time between onset of RRT and KT (ΔT-RRT&KT)>10years (OR:3.54; CI95%:1.27-9.87), diabetes mellitus (DM) pre-KT (OR:3.35; CI95%:1.51-7.46), pyelonephritis (OR:2.45; CI95%:1.24-4.84), polyomavirus nephropathy (OR:4.99; CI95%:1.87-13.3), AAS (OR:4.82; CI95%:1.35-17.2), 24h-proteinuria ≥300mg/24h (OR:5.05; CI95%:2.00-12.7) and serum calcium (Ca) <8.5mg/dL (OR:4.72; CI95%:2.00-11.1). The multivariate model presented an accuracy of 88.1% and the mean variance inflation factor is 1.81. CONCLUSION: Elderly-recipients, ΔT-RRT&KT>10 years, pre-KT DM, and post-KT aggressions until six months (pyelonephritis, polyomavirus nephropathy, ABMR, 24h-proteinuria≥300mg/24h, and Ca<8.5mg/dL) are associated with high predictive power for secondary allograft dysfunction in need of RRT or reaching CKD stage V until the first six months post-KT.

INTRODUÇÃO: Transplante renal (TR) é a terapia renal substitutiva (TRS) de escolha para pacientes com doença renal crônica (DRC). Entretanto, nem todo TR é bem-sucedido e alguns pacientes persistem em TRS. OBJETIVO: Modelar uma regressão logística com covariáveis de risco pré e pós-TR preditora da disfunção secundária do aloenxerto com necessidade de TRS ou alcance ao estágio V da DRC até os primeiros seis meses pós-TR. MÉTODOS: Coorte com receptores transplantados realizado em hospital no Nordeste brasileiro. Analisou-se registros médicos dos TR realizados entre 2011-2018. Receptores com dados insuficientes ou que abandonaram seguimento foram excluídos. Foram analisadas covariáveis: demográficas; infecciosas; comorbidades pré e pós-TR; painel de reatividade; incompatibilidades de HLA; episódios de rejeições agudas mediadas por células-T ou por anticorpos; exames laboratoriais seis meses pós-TR. RESULTADOS: Receptores idosos (OR:1,41; IC95%:1,01-1,99), tempo entre início da TRS e TR (∆T-TRS&TR)>10 anos (OR:3,54; IC95%:1,27-9,87), diabetes mellitus (DM) pré-TR (OR:3,35; IC95%:1,51-7,46), pielonefrite (OR:2,45; IC95%:1,24-4,84), nefropatia por poliomavírus (OR:4,99; IC95%:1,87-13,3), RAMA (OR:4,82; IC95%:1,35-17,2), proteinúria de 24h (Pt24h) ≥300mg/24h (OR:5,05; IC95%:2,00-12,7) e cálcio sérico (Ca)<8,5mg/dL (OR:4,72; IC95%:2,00-11,1) foram identificadas como covariáveis de maior risco para os desfechos analisados até seis meses pós-TR. O modelo multivariado apresentou acurácia de 88,1% e fator de inflação da variância médio de 1,81. CONCLUSÃO: Receptores idosos, ∆T-TRS&TR>10anos, DM pré-TR e agressões até seis meses pós-TR (pielonefrite, nefropatia por poliomavírus, RAMA, Pt24h≥300mg/24h e Ca<8,5mg/dL), apresentam alto poder preditivo para disfunção secundária do aloenxerto com necessidade de TRS ou alcance ao estágio V da DRC até os primeiros seis meses pós-TR.

Polyomaviruses BK and JC DNA infection in peripheral blood cells from blood donors

ABSTRACT Objectives: To investigate the prevalence of human polyomavirus (BK and JC viruses) infection in peripheral blood mononuclear cells of healthy blood donors. Methods: The study included 250 healthy blood donors. Five-milliliter blood was drawn into sterile EDTA tubes and PBMCs were isolated from whole blood. The isolated PBMCs were counted and stored at −70 °C for future investigation. DNA was extracted and subjected to simple, sensitive and specific semi-nested PCR as well as QPCR using both general and specific primers for different assays. Results: Of 250 blood samples, 66 (26.4%) were positive for BKV DNA (146-34,514 copies/106 cells). JC DNA was found in 45 (18%) blood samples (65-21,250 copies/106 cells). Co-infection with these viruses were found in 11 (4.4%) out of 250 blood samples. Discussion: Our study provides important data on polyomavirus infection in peripheral blood mononuclear leukocytes in immunocompetent individuals. These data indicate significant differences between the prevalence of BKV and JCV infection in healthy blood donors. The prevalence of BK and JC virus infection is higher in the age range 30-39 years compared to other age ranges.

Characteristics of BK polymavirus infection in kidney transplant recipients / 南方医科大学学报

OBJECTIVE@#To analyze the characteristics of BK polymavirus (BKV) infection and the optimal time window for intervention in kidney transplant recipients (KTRs).@*METHODS@#We retrospectively analyzed the clinical data and treatment regimens in 226 KTRs in our center between January, 2013 and January, 2018. Among the recipients, 157 had a urine BKV load ≥1.0×10 copy/mL after transplantation, and 69 had a urine BKV load below 1.0×10 copy/mL (control group).@*RESULTS@#Among the 157 KTRs, 60 (38.2%) recipients were positive for urine BKV, 66 (42.0%) had BKV viruria, and 31(19.7%) had BKV viremia. The incidence of positive urine occult blood was significantly higher in BKV-positive recipients than in the control group ( < 0.05). The change of urine BKV load was linearly related to that of Tacrolimus trough blood level (=0.351, < 0.05). In urine BKV positive group, the average estimated glomerular filtration rate (eGFR) was below the baseline level (60 mL·min·1.73 m) upon diagnosis of BKV infection reactivation, and recovered the normal level after intervention. In patients with BKV viruria and viremia, the average eGFR failed to return to the baseline level in spite of improvement of the renal function after intervention.@*CONCLUSIONS@#Positive urine occult blood after transplantation may be associated with BKV infection reactivation in some of the KTRs. BKV infection is sensitive to changes of plasma concentration of immunosuppressive agents. Early intervention of BKV replication in KTRs with appropriate dose reduction for immunosuppression can help to control virus replication and stabilize the allograft function.

Prognosis of BK polyomavirus nephropathy: 10-year analysis of 133 renal transplant recipients at a single center / 中华医学杂志(英文版)

BACKGROUND@#BK virus-associated nephropathy (BKVN) is an important cause of chronic allograft dysfunction. The objective of our study was to evaluate the prognosis of BKVN.@*METHODS@#We retrospectively reviewed the data of 133 renal transplant recipients with BKVN treated at the First Affiliated Hospital of Sun Yat-Sen University between July 2007 and July 2017. BK viral loads, graft function, and pathologic indexes were compared between initial diagnosis and last follow-up.@*RESULTS@#After a mean follow-up period of 14.4 (range, 0.3-109.6) months after diagnosis of BKVN, BK viruria, and BK viremia become negative in 19.5% and 90.2% of patients, respectively. The mean estimated glomerular filtration rate (eGFR) at last follow-up was lower than at diagnosis of BKVN (18.3 ± 9.2 vs. 32.8 ± 20.6 mL·min·1.73 m, t = 7.426, P < 0.001). Eight (6.0%) patients developed acute rejection after reducing immunosuppression. At last follow-up, the eGFR was significantly lower in patients with subsequent rejection than those without (21.6 ± 9.8 vs. 33.5 ± 20.9 mL·min·1.73 m, t = 3.034, P = 0.011). In 65 repeat biopsies, SV40-T antigen staining remained positive in 40 patients and became negative in the other 20 patients. The eGFR (42.6 ± 14.3 vs. 26.5 ± 12.3 mL·min·1.73 m), urine viral loads (median, 1.3 × 10vs. 1.4 × 10 copies/mL), and plasma viral load (median, 0 vs. 0 copies/mL) were all significantly lower in patients with negative SV40-T antigen staining than those with persistent BK involvement (all, P < 0.05). Five (3.8%) recipients lost their graft at diagnosis of BKVN, and 13 (9.8%) lost their graft during the follow-up period. The 1-, 3-, and 5-year graft survival rates after diagnosis of BKVN were 99.2%, 90.7%, and 85.7%, respectively. Higher pathologic stage correlated with lower allograft survival rate (χ = 6.341, P = 0.042).@*CONCLUSION@#Secondary rejection and persistent histologic infection in BKVN lead to poor prognosis.

Monitoring BK virus infection in pediatric kidney transplant recipients / 소아과

No abstract available.

Clinical manifestations of BK virus infection in pediatric kidney transplant patients / 소아과

BACKGROUND: Polyomavirus BK (BKV) infection is an important cause of graft loss in kidney transplant patients.PURPOSE: The purpose of this study was to evaluate clinical findings and risk factors for BKV in pediatric patients after kidney transplantation.METHODS: This retrospective single-center study included 31 pediatric kidney transplant recipients from January 2002 to December 2017. Two patients received 2 transplantations during the study period, and each transplant was analyzed independently. Total number of cases is 33 cases with 31 patients. BKV infection was confirmed from blood samples via periodic quantitative polymerase chain reaction.RESULTS: The mean age at kidney transplantation was 11.0±4.7 years, and the male-to-female ratio was 2.7:1. Three patients had a past medical history of high-dose chemotherapy and autologous stem-cell transplantation for solid tumors. Nine patients (27.3%) developed BKV infection. The median period from kidney transplantation to BKV detection in blood was 5.6 months. There was no statistically significant difference in estimated glomerular filtration rate between patients with and those without BKV infection. Among 9 patients with BKV viremia, 7 were treated by reducing their immunosuppressant dose, and BKV was cleared in 6 of these 7 patients. In the other 2 BKV-positive patients, viremia improved without immunosuppressant reduction.CONCLUSION: BKV infection is common in children with kidney transplantation and might not have affected short-term renal function in our patient sample due to early immunosuppressant reduction at the time of BKV detection.

BK virus salivary shedding and viremia in renal transplant recipients

Abstract Objectives: This study aimed to verify the presence of polyomavirus BK (BKPyV) in the saliva of kidney transplant recipients and to correlate it with blood viremia. Material and Methods: We have conducted a cross-sectional study with a sample involving 126 renal transplant recipients. 126 samples of saliva and 52 samples of blood were collected from these patients. Detection and quantification of BKPyV were performed using a real-time PCR. To compare the presence of BKPyV in blood and saliva, the binomial proportion test was used. To verify associations between salivary shedding BKPyV and post-transplant periods (in months), the Mann-Whitney test was used. Spearman's correlation was used to correlate the viral load in the saliva with blood of kidney transplant recipients. Results: The mean age of the study group was 51.11±12.45 years old, and 69 participants (54.8%) were female, with a mean post-transplantation time of 4.80±6.04 months. BKPyV was quantified in several samples of saliva and blood, with medians of 1,108 cp/mL and 1,255 cp/mL, respectively. Only 16/52 (30.8%) participants presented BKPyV in blood, and 59/126 (46.8%) excreted the virus in saliva (p=0.004). BKPyV shedding was found in patients at a shorter post-transplantation period (3.86±5.25, p=0.100). A weak correlation was observed between viral quantification in saliva and blood (Spearman's correlation coefficient=0.193). Conclusion: The results of this study suggested that, although saliva excretes more BKPyV than blood, there is no reliable correlation between salivary shedding and blood viremia, showing two independent compartments of viral replication.

Quantitative detection of BK virus in kidney transplant recipients: a prospective validation study / Detecção quantitativa de vírus BK em receptores de transplante renal: um estudo prospectivo de validação

Abstract Introduction: BK virus (BKV) infection in renal transplant patients may cause kidney allograft dysfunction and graft loss. Accurate determination of BKV viral load is critical to prevent BKV-associated nephropathy (BKVAN) but the cut-off that best predicts BKVAN remains controversial. Objective: To evaluate the performance of a commercial and an in-house qPCR test for quantitative detection of BK virus in kidney transplant recipients. Methods: This was a prospective study with kidney transplant recipients from two large university hospitals in Brazil. Patients were screened for BKV infection every 3 months in the first year post-transplant with a commercial and an in-house real time polymerase chain reaction (qPCR) test. BKVAN was confirmed based on histopathology. The area under the curve for plasma qPCR was determined from receiver operating characteristic analysis. Results: A total of 200 patients were enrolled. Fifty-eight percent were male, 19.5% had diabetes mellitus, and 82% had the kidney transplanted from a deceased donor. BKV viremia was detected in 32.5% and BKVAN was diagnosed in 8 patients (4%). BKVAN was associated with viremia of 4.1 log copies/mL, using a commercial kit. The cut-off for the in-house assay was 6.1 log copies/mL. The linearity between the commercial kit and the in-house assay was R2=0.83. Conclusion: Our study shows that marked variability occurs in BKV viral load when different qPCR methodologies are used. The in-house qPCR assay proved clinically useful, a cheaper option in comparison to commercial qPCR kits. There is an urgent need to make BKV standards available to the international community.

Resumo Introdução: A infecção pelo vírus BK (BKV) em pacientes de transplante renal pode levar a disfunção do aloenxerto renal e perda do enxerto. A determinação precisa da carga viral do BKV é fundamental para prevenir a nefropatia associada ao BKV (BKVAN), mas o ponto de corte de melhor valor preditivo para BKVAN ainda é foco de debates. Objetivo: Avaliar o desempenho de um teste de qPCR comercial e outro desenvolvido internamente para detecção quantitativa de vírus BK em receptores de transplante renal. Métodos: O presente estudo prospectivo incluiu receptores de transplante renal de dois grandes hospitais universitários no Brasil. Os pacientes foram testados para infecção por BKV a cada três meses no primeiro ano pós-transplante com um teste comercial de reação em cadeia de polimerase quantitativa em tempo real (qPCR) e outro desenvolvido internamente. A presença de BKVAN foi confirmada com base na histopatologia. A área sob a curva para o qPCR plasmático foi determinada a partir da análise da característica de operação do receptor. Resultados: Um total de 200 pacientes foram incluídos. Cinquenta e oito por cento eram do sexo masculino, 19,5% tinham diabetes mellitus e 82% tiveram seus rins transplantados de doadores falecidos. Viremia de BKV foi detectada em 32,5% dos pacientes e oito (4%) foram diagnosticados com BKVAN. BKVAN foi associada a viremia de 4,1 log cópias/mL usando o kit comercial. O corte para o ensaio interno foi de 6,1 log cópias/mL. A linearidade entre o kit comercial e o ensaio interno foi R2 = 0,83. Conclusão: Nosso estudo demonstrou uma acentuada variabilidade na carga viral de BKV quando diferentes metodologias de qPCR foram utilizadas. O ensaio interno de qPCR mostrou-se clinicamente útil, além de ser uma opção menos onerosa em relação aos kits comerciais de qPCR. Há uma necessidade urgente de se definir padrões de BKV para a comunidade internacional.

Research Progress on BK Virus Infection after Hematopoietic Stem Cell Transplantation--Review / 中国实验血液学杂志

BK virus infection is one of the common complications after hematopoietic stem cell transplantation(HSCT), which is also one of the reasons of the hemorrhagic cystitis．In recent years, although there are more studies of the risk factors related with human BK virus infection after hematopoietic stem cell transplantation, the risk factors related with BKV-associated hemorrhagio cystitis(BKV-HC) remain to be elucidated. Diagnosis of BK virus infection is mainly based on quantitative PCR of blood or urine. An effective strategy for treatment of these patients is the adoptive transfer of T lymphocytes specific to virus-associated antigens. In this review, the progressis of diagnosis and treatment of BK virus infection after hematopoietic stem cell transplantation are briefly summarized.

Common viral infections in kidney transplant recipients

Infectious complications have been considered as a major cause of morbidity and mortality after kidney transplantation, especially in the Asian population. Therefore, prevention, early detection, and prompt treatment of such infections are crucial in kidney transplant recipients. Among all infectious complications, viruses are considered to be the most common agents because of their abundance, infectivity, and latency ability. Herpes simplex virus, varicella zoster virus, Epstein–Barr virus, cytomegalovirus, hepatitis B virus, BK polyomavirus, and adenovirus are well-known etiologic agents of viral infections in kidney transplant patients worldwide because of their wide range of distribution. As DNA viruses, they are able to reactivate after affected patients receive immunosuppressive agents. These DNA viruses can cause systemic diseases or allograft dysfunction, especially in the first six months after transplantation. Pretransplant evaluation and immunization as well as appropriate prophylaxis and preemptive approaches after transplant have been established in the guidelines and are used effectively to reduce the incidence of these viral infections. This review will describe the etiology, diagnosis, prevention, and treatment of viral infections that commonly affect kidney transplant recipients.

Long-term prognosis of BK virus-associated nephropathy in kidney transplant recipients

BACKGROUND: The long-term prognosis of BK virus-associated nephropathy (BKVAN) in kidney transplant recipients (KTRs) is uncertain. We evaluated the long-term prognosis in KTRs with BKVAN and the clinical significance of BKVAN on post-transplant clinical outcome. METHODS: We retrospectively analyzed the medical records of 582 patients who underwent kidney transplant (KT) between 2001 and 2014. We divided the patients into a BKVAN group (15 patients) diagnosed by allograft biopsy and a control group (356 patients). RESULTS: The incidence of BKVAN was 4.0%, and the mean follow-up duration was 93.1 ± 52.3 months. Median time from KT to BKVAN diagnosis was 5.9 months (interquartile range [IQR], 4.4–8.7). In the BKVAN group, 9 (60.0%) KTRs with combined acute rejection progressed to graft failure, and the median time from BKVAN diagnosis to graft failure was 36.2 months (IQR, 9.7–65.5). Death-censored graft survival rate and patient survival rate in the BKVAN group were significantly lower than those in the control group. BKVAN and rejection were independent risk factors for graft failure. In the subgroup analysis, death-censored graft survival rate of KTRs with BKVAN with acute rejection was significantly worst in comparison with similar patients without BKVAN regardless of acute rejection (P < 0.001). CONCLUSION: The long-term prognosis of BKVAN with acute rejection was very poor because of graft failure caused by inadequate treatment for acute rejection considering BKVAN. Therefore, we should carefully monitor the allograft status of KTRs through regular surveillance tests after treatment for BKVAN with acute rejection.

Bortezomib Treatment for Refractory Antibody-Mediated Rejection Superimposed with BK Virus-Associated Nephropathy during the Progression of Recurrent C3 Glomerulonephritis / 대한이식학회지

A 38-year-old man, who underwent a second kidney transplantation (KT), was admitted because of antibody-mediated rejection (AMR) complicated by BK virus-associated nephropathy (BKVAN). He was placed on hemodialysis at the age of 24 years because of membranoproliferative glomerulonephritis. At the age of 28 years, he underwent a living donor KT from his father; however, 1 year after the transplantation, he developed a recurrence of the primary glomerular disease, resulting in graft failure 2 years after the first KT. Ten years later, he received a deceased-donor kidney with a B-cell-positive-cross-match. He received 600 mg of rituximab before the KT with three cycles of plasmapheresis and immunoglobulin (0.5 g/kg) therapy after KT. During the follow-up, the first and second allograft biopsies at 4 and 10 months after KT revealed AMR with a recurrence of primary glomerular disease that was reclassified as C3 glomerulonephritis (C3GN). He received a steroid pulse, rituximab, plasmapheresis, and immunoglobulin therapies. The third allograft biopsy demonstrated that the BKVAN was complicated with AMR and C3GN. As the azotemia did not improve after repeated conventional therapies for AMR, one cycle of bortezomib (1.3 mg/m²×4 doses) was administered. The allograft function stabilized, and BK viremia became undetectable after 6 months. The present case suggests that bortezomib therapy may be applicable to patients with refractory AMR, even in cases complicated with BKVAN.

Human polyomavirus infection: Cytological and molecular diagnosis / Infecção pelo poliomavírus humano: diagnóstico citológico e molecular

Summary Few studies directly compare urinary cytology with molecular methods for detecting BK and JC polyomaviruses. Reactivation of BKV infection is the main risk factor for the development of nephropathy in immunocompromised individuals. The limitation of the cytological method can be attributed to the stage where the infected cell does not have specific and sufficient morphological characteristics for a conclusive diagnosis and can be easily interpreted as degenerative alteration. Moreover, morphologically, it is not possible to differentiate the two types of viruses. Polymerase chain reaction (PCR), not only is a sensitive method, but also allows differentiation of viral types without quantification, and therefore is not indicative of nephropathy. According to the American Society of Nephrology, real-time PCR would be the gold standard to indicate nephropathy because it allows quantifying the number of viral copies.

Resumo Poucos estudos comparam diretamente a citologia urinária com métodos moleculares para detecção de poliomavírus BK e JC. A reativação da infecção por BKV é o principal fator de risco para o desenvolvimento de nefropatia em indivíduos imunocomprometidos. A limitação do método citológico pode ser atribuída ao estágio em que a célula infectada não possui características morfológicas específicas e suficientes para um diagnóstico conclusivo, podendo ser facilmente interpretada como alteração degenerativa. Além do mais, morfologicamente, não é possível diferenciar os dois tipos virais. A reação em cadeia pela polimerase (PCR), além de ser um método sensível, permite diferenciar os tipos virais sem quantificá-los, não sendo, portanto, indicativa de nefropatia. Segundo a American Society of Nephrology, a PCR em tempo real seria o padrão-ouro para indicar nefropatia, pois permite quantificar o número de cópias virais.

Distribution and genetic diversity of the human polyomaviruses JC and BK in surface water and sewage treatment plant during 2009 in Porto Alegre, Southern Brazil / Distribuição e diversidade genética dos poliomavírus humanos JC e BK em águas superficiais e de estação de tratamento de esgoto durante 2009 em Porto Alegre, sul do Brasil

Abstract The human polyomaviruses JC and BK (JCPyV and BKPyV) are ubiquitous, species-specific viruses that belong to the family Polyomaviridae. These viruses are known to be excreted in human urine, and they are potential indicators of human wastewater contamination. In order to assess the distribution of both JCPyV and BKPyV in urban water samples collected from a sewage treatment plant (STP) and from a canalized water stream of Porto Alegre, Brazil, two nested-PCR assays were optimized and applied to the samples collected. The amplicons obtained were submitted to sequencing, and the sequences were analyzed with sequences of human polyomaviruses previously deposited in GenBank. Twelve out of 30 water samples (40%) were JCPyV positive, whereas six samples (20%) were BKPyV positive. The sequencing results confirmed the presence of JCPyV subtypes 1 and 3, whereas only BKPyV Ia and Ib were found. This study shows for the first time the presence of human polyomaviruses in surface water and in samples collected in a sewage treatment plant in southern Brazil.

Resumo Os poliomavírus humanos JC e BK (JCPyV e BKPyV) são virus ubíquos, espécie-específicos, pertencentes à família Polyomaviridae. Estes vírus são conhecidos por serem excretados pela urina humana, sendo considerados potenciais indicadores de contaminação por águas residuais urbanas. Buscando acessar a distribuição de JCPyV e BKPyV em amostras de águas coletadas de uma estação de tratamento de esgoto e de um arroio canalizado de Porto Alegre, Brasil, duas técnicas de nested-PCR foram otimizadas e aplicadas às amostras coletadas. Os amplificados obtidos foram submetidos ao sequenciamento e suas sequências analisadas com base em sequências de poliomavírus humanos previamente depositadas no GenBank. Doze de 30 amostras de água (40%) foram positivas para JCPyV, enquanto 6 amostras (20%) foram positivas para BKPyV. Os resultados do sequenciamento confirmaram a presença dos subtipos 1 e 3 de JCPyV, enquanto apenas os BKPyV Ia e Ib foram encontrados. Este estudo demonstra pela primeira vez a presença de poliomavírus humanos em águas superficiais e em amostras coletadas em uma estação de tratamento de esgoto na região sul do Brasil.

Evaluation of the predisposition and clinical impact of BK virus replication in kidney transplant patients

ABSTRACT The BK virus (BKV) produces a subclinical kidney infection in immunocompetent individuals. However, viremia may occur in kidney transplant patients with ongoing immunosuppression. BKV-associated nephropathy (BKVN) has no specific treatment and is a leading cause of organ transplant loss. In this study, we evaluated the predisposition and the clinical impact of BKV replication in kidney transplant patients during post-transplant monitoring in a reference institution in Brazil. Demographic, clinical and laboratory data generated during routine outpatient follow-up were retrospectively collected. BK viremia was investigated using real-time polymerase chain reaction. Of the 553 participants, 7.4% (n = 41) presented BKV replication. Of these, 16 (39%) lost their kidney graft and interstitial nephritis was identified on kidney biopsy in 50% of the cases. Among the evaluated variables, only the use of the immunosuppressant mycophenolate sodium was identified as a risk factor for viremia (OR 7.96; 95% CI 2.35 to 26.98). The graft survival estimate in BKV-positive patients was significantly reduced (24.8% vs. 85.6%) after 10 years of transplantation. We concluded that defining predisposing factors remains an important challenge for the prevention and control of BKV activity following kidney transplantation, especially considering the development of BKVN and its strong effect on graft maintenance.

Poliomavirus en sistema nervioso central, una aproximación imagenológica / Polyomaviruses and central nervous system disease

The polyomavirus are a family of opportunistic virus, which belongs to the JC virus whose primary manifestation is the Progressive Multifocal Leukoencephalopathy and neuronopathy of granulosa cells. Recently given the use of PCR for BK virus in transplant patients have also been described CNS pathologies in relation to this, and most frequent encephalitis and leukoencephalopathy. Each entity has a compatible clinical and genetic testing have allowed a diagnosis of high specificity, however the RNM is the great diagnostic pillar in these pathologies, allowing differentiate the different entities, the progression of lesions and response to treatment, especially in cases where it is indicated antiretroviral therapy, as gadolinium enhancement and mass effect may suggest Syndrome Immune and worse prognosis.

Los Poliomavirus son una familia de virus oportunistas, al cual pertenece el virus JC cuya principal manifestación es la Leucoencefalopatía Multifocal Progresiva y la Neuronopatía de Células Granulosas. Recientemente, dada la utilización de PCR para virus BK en LCR en pacientes trasplantados, también se han descrito patologías de SNC en relación a éste, siendo lo más frecuente la Encefalitis y la Leucoencefalopatía. Cada entidad tiene un contexto clínico compatible y las pruebas genéticas han permitido un diagnóstico de alta especificidad, sin embargo, la RNM es el gran pilar diagnóstico en estas patologías, permitiendo diferenciar las distintas entidades, la progresión de las lesiones y la respuesta a tratamiento, especialmente en los casos en que está indicado la terapia antirretroviral, pues la captación de gadolinio y el efecto de masa pueden sugerir un Síndrome de Reconstitución Inmune y peor pronóstico.

Screening for BK virus nephropathy in kidney transplant recipients: comparison of diagnostic tests / Desempenho de métodos diagnósticos no rastreio de nefropatia pelo vírus BK em pacientes transplantados renais

Abstract Urine cytology and qPCR in blood and urine are commonly used to screen renal transplant recipients for polyomavirus-associated nephropathy (PVAN). Few studies, however, have directly compared these two diagnostic tests, in terms of their performance to predict PVAN. This was a systematic review in which adult (≥ 18 years old) renal transplant recipients were studied. A structured Pubmed search was used to identify studies comparing urine cytology and/or qPCR in urine and plasma samples for detecting PVAN with renal biopsy as the gold standard for diagnosis. From 707 potential papers, there were only twelve articles that matched the inclusion criteria and were analyzed in detail. Among 1694 renal transplant recipients that were included in the review, there were 115 (6.8%) patients with presumptive PVAN and 57 (3.4%) PVAN confirmed. In this systematic review, the qPCR in plasma had better performance for PVAN compared to urine cytopathology.

Resumo A citologia urinária e a reação da cadeia da polimerase em tempo real (qPCR) em amostras de sangue e/ou urina são comumente utilizados para rastrear nefropatia associada ao polyomavirus (PVAN), em pacientes transplantados renais. Entretanto, poucos estudos comparam diretamente esses testes diagnósticos quanto ao desempenho para predizer esta complicação. Aqui realizamos uma revisão sistemática na qual foram estudados pacientes transplantados renais adultos (≥ 18 anos). Uma pesquisa estruturada Pubmed foi utilizada para identificar estudos comparando citologia urinária e/ou qPCR em amostras de urina e plasma para detectar PVAN, utilizando a biópsia renal como padrão-ouro para o diagnóstico. Dentre os 707 artigos em potencial, apenas 12 atendiam aos critérios de inclusão e foram analisados em maior detalhe. Foram incluídos 1694 pacientes transplantados renais, entre os quais 115 (6,8%) classificados com PVAN presuntivo e 57 (3,4%) PVAN confirmado. Nessa revisão sistemática, o qPCR no plasma tive melhor desempenho para PVAN em comparação com citopatologia urinária.