Renal changes in COVID-19 infection

SUMMARY The COVID-19 (SARS-CoV-2) infection started in China, Wuhan City, Hubei Province, in December 2019, and it was declared a pandemic in mid-March 2020, caused by a new coronavirus strain called SARS-CoV-2. The pathogenesis of kidney injury attributed to SARS- CoV-2 is not well defined yet. Observations show that the kidney damage caused by the new virus mutation is mainly tubular, with impairment of glomerular filtration and high levels of urea and creatinine. A study with seriously ill patients with COVID-19 showed that acute kidney injury was present in 29%. In the face of this evidence, based on recent studies, we can see the great renal contribution as an impact factor in the evolution of COVID-19, not just as a complicator of severity, but maybe part of the initial cascade of the process, requiring a deeper analysis using conventional biomarkers of kidney injury and more aggressive clinical intervention in patients at risk, in an attempt to reduce mortality.

RESUMO Infecção pelo COVID-19 (SARS-CoV-2) começou na China, cidade de Wuhan, província de Hubei, em dezembro de 2019, e foi declarada pandemia em meados de março de 2020, causada por uma nova cepa de coronavírus chamada SARS-CoV-2. A patogênese da lesão renal atribuída à SARS-CoV-2 ainda não está bem definida. Observações mostram que o dano renal causado pela nova mutação viral é principalmente tubular, com comprometimento da filtração glomerular e apresentação de altos níveis de uréia e creatinina. Estudo com pacientes gravemente enfermos com COVID-19 mostrou que a lesão renal aguda estava presente em 29%. Diante dessas evidências, com base em estudos recentes, podemos ver a grande contribuição renal como um fator de impacto na evolução do COVID-19, não apenas como um complicador da gravidade, mas talvez como parte da cascata inicial do processo, exigindo uma investigação de análise mais profunda usando biomarcadores convencionais de lesão renal e intervenção clínica mais agressiva em pacientes em risco, na tentativa de reduzir a mortalidade.

Presencia de trombosis y hallazgos anatomopatológicos post mortem en 109 pacientes con COVID-19 / Presence of thrombosis and post-mortem pathological findings in 109 patients with COVID-19

INTRODUCCIÓN: En 6 meses se notificaron más de 400 mil fallecidos por COVID-19. Han surgido múltiples investigaciones para comprender su etiopatogenia, siendo la autopsia médica uno de los mejores procedimientos para obtener información. Presentamos una revisión respecto a hallazgos post mortem publicados hasta mayo, 2020. RESULTADOS: Se recolectaron 12 estudios, de un total de 109 pacientes cuyo deceso fue por complicación respiratoria, predominó el sexo masculino, edad avanzada y con múltiples comorbilidades. El estudio PCR se realizó principalmente para diagnóstico. Se demostró ARN viral en riñón, hígado, corazón, cerebro y otros órganos. Los autores relataron presencia de micro y/o macro trombosis, en 50 de 109 casos, sobre todo a nivel pulmonar y renal, de tipo microscópica y relacionados a signos de shock. Desde la perspectiva anatomopatológica, se centra en alteraciones pulmonares y renales: daño alveolar difuso, injuria tubular aguda, microtrombos y otros signos de alteración microcirculatoria. Los estudios inmunohistoquímicos, de inmunofluoresencia y microscopía electrónica sugieren tropismo del virus por células epiteliales y estromales a nivel pulmonar y renal. En otros órganos se encuentran elementos morfológicos inespecíficos, atribuibles a patologías de base o shock. CONCLUSIÓN: El patrón histopatológico de daño alveolar difuso es frecuente, principalmente en fase exudativa o temprana. En el tejido renal destaca la injuria tubular aguda y daño microcirculatorio. El número y la descripción de muestras en otros órganos es reducida, siendo necesaria mayor casuística. La trombosis, es un trastorno prevalente en pulmones y riñones de pacientes con signos de shock. El tipo de trombo con más frecuencia descrito, es el microtrombo. Si bien se puede explicar como gatillante del fenómeno trombótico la interacción entre agente y huésped, otros factores deben ser estudiados para dilucidar la patogenia.

Pathogenicity of an FAdV-4 isolate to chickens and its genomic analysis / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Fowl adenovirus serotype 4 (FAdV-4) strain SD1511 was isolated from chickens with severe inclusion body hepatitis and hydropericardium syndrome in Shandong Province, China. The isolate was cultured in primary chicken embryo kidney cells. A study of pathogenicity indicated that SD1511 readily infected 7-35-d-old chickens by intramuscular injection and intranasal and oral routes, causing 50%-100% mortality. The 35-d-old chickens suffered more severe infection than 7- and 21-d-old chickens with mortality highest in the intramuscular injection group. The serum from surviving chickens showed potent viral neutralizing capability. The complete genome of SD1511 was sequenced and analyzed. The strain was found to belong to the FAdV-4 cluster with more than 99% identity with the virulent FAdV-4 strains isolated in China in recent years except for some distinct variations, including deletions of open reading frame 27 (ORF27), ORF48, and part of ORF19. Our findings suggest that SD1511 might be used as a prototype strain for the study of pathogenesis and vaccine development.

Association Between Hepatitis B Virus and Chronic Kidney Disease: a Systematic Review and Meta-analysis

Abstract: Background. Hepatitis B virus infection and chronic kidney disease are prevalent and remain a major public health problem worldwide. It remains unclear how infection with hepatitis B virus impacts on the development and progression of chronic kidney disease. Aim. To evaluate the effect of infection with HBV on the risk of chronic kidney disease in the general population. Material and methods. We conducted a systematic review of the published medical literature to determine if hepatitis B infection is associated with increased likelihood of chronic kidney disease. We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for chronic kidney disease (defined by reduced glomerular filtration rate and/or detectable proteinuria) with hepatitis B virus across the published studies. Meta-regression and stratified analysis were also conducted. Results. We identified 16 studies (n = 394,664 patients) and separate meta-analyses were performed according to the outcome. The subset of longitudinal studies addressing ESRD (n = 2; n = 91,656) gave a pooled aHR 3.87 (95% CI, 1.48; 6.25, P < 0.0001) among HBV-infected patients and no heterogeneity was recorded. In meta-regression, we noted the impact of male (P = 0.006) and duration of follow-up (P = 0.007) upon the adjusted hazard ratio of incidence of chronic kidney disease (including end-stage renal disease). No relationship occurred between HBV positive status and prevalent chronic disease (n = 7, n = 109,889 unique patients); adjusted odds ratio, were 1.07 (95% CI, 0.89; 1.25) and 0.93 (95% CI, 0.76; 1.10), respectively. Conclusions. HBV infection is possibly associated with a risk of developing reduced glomerular filtration rate in the general population; no link between HBV sero-positive status and frequency of chronic kidney disease or proteinuria was noted in cross-sectional surveys.

Detección de antígenos del virus del dengue en tejidos post mórtem / Detection of dengue virus antigen in post-mortem tissues

El panorama epidemiológico del dengue ha empeorado durante la última década. Las dificultades para prevenir su transmisión, así como la ausencia de una vacuna o tratamiento específico, lo convierten en un riesgo que desafía las medidas de salud pública y desborda la capacidad de los centros de salud y los sistemas de investigación a muchos niveles. Actualmente, la mayoría de los estudios sobre la patogenia de la infección centran su atención en la respuesta inmunitaria de las células T casi exclusivamente en infecciones secundarias y están dirigidos a identificar los mecanismos implicados en el desarrollo de la permeabilidad vascular y de los eventos hemorrágicos que lo acompañan. En este reporte se describe el caso de una menor de 45 días de edad con signos clínicos de dengue grave, cuyo diagnóstico se confirmó por reacción en cadena de la polimerasa de transcripción inversa en muestras de tejido post mórtem y por herramientas de apoyo diagnóstico de inmunohistoquímica, las cuales detectaron antígenos virales en todos los órganos obtenidos en la necropsia. Este caso subraya la importancia del estudio de las infecciones primarias asociadas a dengue grave, particularmente en niños, en quienes es más probable el desarrollo de la forma grave de la enfermedad sin una infección previa, y, además, pone de relieve la importancia de un diagnóstico que no se limite a las muestras de tejido hepático en el estudio de la patogenia de la infección viral.

The epidemiological situation of dengue has worsened over the last decade. The difficulties in preventing its transmission and the absence of a vaccine or specific treatment have made dengue a serious risk to public health, health centers and research systems at different levels. Currently, most studies on the pathogenesis of dengue infection focus on the T-cell immune response almost exclusively in secondary infections and are aimed at identifying the mechanisms involved in the development of vascular permeability and bleeding events that accompany the infection. This report describes the case of a baby girl less than 45 days of age with clinical signs of severe dengue, whose diagnosis was confirmed by reverse transcription polymerase chain reaction in post-mortem tissue samples and by the ancillary diagnostic use of immunohistochemistry, which detected viral antigens in all organs obtained at autopsy. This case highlights the importance of studying primary infections associated with severe dengue, particularly in children, who are more likely to develop the severe form of the disease without previous infection, and it further stresses the importance of a diagnosis that should not be based solely on the examination of liver tissue samples when studying the pathogenesis of the viral infection.

Impact of Combined Acute Rejection on BK Virus-Associated Nephropathy in Kidney Transplantation

BK virus-associated nephropathy (BKVAN) is one of the major causes of allograft dysfunction in kidney transplant (KT) patients. We compared BKVAN combined with acute rejection (BKVAN/AR) with BKVAN alone in KT patients. We retrospectively analyzed biopsy-proven BKVAN in KT patients from 2000 to 2011 at Seoul National University Hospital. Among 414 biopsies from 951 patients, biopsy-proven BKVAN was found in 14 patients. Nine patients had BKVAN alone, while 5 patients had both BKVAN and acute cellular rejection. BKVAN in the BKVAN alone group was detected later than in BKVAN/AR group (21.77 vs 6.39 months after transplantation, P=0.03). Serum creatinine at diagnosis was similar (2.09 vs 2.00 mg/dL). Histological grade was more advanced in the BKVAN/AR group (P=0.034). Serum load of BKV, dose of immunosuppressants, and tacrolimus level showed a higher tendency in the BKVAN alone group; however it was not statistically significant. After anti-rejection therapy, immunosuppression was reduced in the BKVAN/AR group. Renal functional deterioration over 1 yr after BKVAN diagnosis was similar between the two groups (P=0.665). These findings suggest that the prognosis of BKVAN/AR after anti-rejection therapy followed by anti-BKV therapy might be similar to that of BKVAN alone after anti-BKV therapy.

Factores de riesgo de enfermedad renal crónica / Chronic renal disease risk factors / Fatores de risco de doença renal crônica

La enfermedad renal crónica es una patología muy frecuente asociado con múltiples coomorbilidades. La fisiopatología del daño endotelial es diferente en los pacientes con enfermedad renal crónica y en este es un campo de investigación en la actualidad. El propósito de esta revisión es analizar la evidencia actual alrededor de los diferentes factores de riesgo asociados con la aparición de enfermedad renal crónica...

The chronic renal disease is a very frequent pathology associated with multiple comorbidities. The pathophysiology of the endothelial damage is different in chronic renal disease patients and this is presently a research domain. The aim of this review is to analyze the current evidence around the different risk factors associated with the appearing of chronic renal disease...

A doença renal crônica é uma patologia muito frequente associada com múltiplas coomorbilidades. A fisiopatologia do dano endotelial é diferente nos pacientes com doença renal crônica e este é um campo de pesquisa na atualidade. O propósito desta revisão é analisar a evidência atual ao redor dos diferentes fatores de risco associados com a aparição de doença renal crônica...

Experimental infection of chickens, ducks and quails with the highly pathogenic H5N1 avian influenza virus

Highly pathogenic avian influenza viruses (HPAIV) of the H5N1 subtype have spread since 2003 in poultry and wild birds in Asia, Europe and Africa. In Korea, the highly pathogenic H5N1 avian influenza outbreaks took place in 2003/2004, 2006/2007 and 2008. As the 2006/2007 isolates differ phylogenetically from the 2003/2004 isolates, we assessed the clinical responses of chickens, ducks and quails to intranasal inoculation of the 2006/2007 index case virus, A/chicken/Korea/IS/06. All the chickens and quails died on 3 days and 3-6 days post-inoculation (DPI), respectively, whilst the ducks only showed signs of mild depression. The uninoculated chickens and quails placed soon after with the inoculated flock died on 5.3 and 7.5 DPI, respectively. Both oropharyngeal and cloacal swabs were taken for all three species during various time intervals after inoculation. It was found that oropharyngeal swabs showed higher viral titers than in cloacal swabs applicable to all three avian species. The chickens and quails shed the virus until they died (up to 3 to 6 days after inoculation, respectively) whilst the ducks shed the virus on 2-4 DPI. The postmortem tissues collected from the chickens and quails on day 3 and days 4-5 and from clinically normal ducks that were euthanized on day 4 contained the virus. However, the ducks had significantly lower viral titers than the chickens or quails. Thus, the three avian species varied significantly in their clinical signs, mortality, tissue virus titers, and duration of virus shedding. Our observations suggest that duck and quail farms should be monitored particularly closely for the presence of HPAIV so that further virus transmission to other avian or mammalian hosts can be prevented.

Vírus rábico em morcego Nyctinomops laticaudatus na Cidade do Rio de Janeiro, RJ: isolamento, titulação e epidemiologia / Rabies virus in Nyctinomops laticaudatus bats in the City of Rio de Janeiro: isolation, titration and epidemiology

Apresenta-se o primeiro relato de raiva em morcego da espécie Nyctinomops laticaudatus, na Cidade do Rio de Janeiro, RJ. Foram realizados isolamento e titulação viral em diferentes tecidos, encontrando-se altos títulos no cérebro e glândulas salivares. A ocorrência de raiva em uma espécie pouco freqüente neste estado sugere que a doença pode ser mais prevalente do que aparenta.

The first case report of rabies in bats of the species Nyctinomops laticaudatus, in the city of Rio de Janeiro City, is presented. Virus isolation and titration were performed in different tissues, and high titers were found in the brain and salivary glands. Rabies occurrence in such an infrequent species in this state suggests that the disease may be more prevalent than it appears to be.