ABSTRACT In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 – 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 – 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Abstract This study aimed to evaluate the hematological and coagulation parameters according to the clinical outcomes of coronavirus disease (COVID-19). We analyzed the hematological and coagulation parameters of hospitalized patients with COVID-19 at admission, and two and three weeks during hospitalization. To assess the performance of these parameters in predicting poor outcomes, receiver operating characteristic (ROC) curves were created. We studied 128 patients with COVID-19 (59.2±17.7 years, 56% male). Non-survivors (n=54, 42%) presented significant alterations in hematological and coagulation parameters at admission, such as increased in white blood cells (WBC), neutrophil, and band cell counts, as well as elevated prothrombin time (PT), activated partial thromboplastin time, and D-dimer levels. During follow-up, the same group presented a gradual increase in D-dimer and PT levels, accompanied by a reduction in PT activity, hemoglobin, and red blood cell count (RBC). ROC curves showed that WBC, neutrophil, and band cell counts presented the best area under the curve (AUC) values with sensitivity and specificity of >70%; however, a logistic regression model combining all the parameters, except for RBC, presented an AUC of 0.89, sensitivity of 84.84%, and specificity of 77.41%. Our study shows that significant alterations in hematological and coagulation tests at admission could be useful predictors of disease severity and mortality in COVID-19.

Abstract Introduction: Members of the Herpesviridae family have been described in patients with systemic lupus erythematous (SLE), but the clinical impact on renal function is not well known. Methods: HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, and HHV-8 were evaluated by molecular biology on admission in blood samples from 40 consecutive SLE patients hospitalized for lupus activity. Results: Patients were 90.0% female, 77.5% non-white, with average age of 32.7 ± 13.6 years. We found positivity for EBV (65.0%), CMV (30.0%), HSV-1 (30.0%), HHV-6 (12.5%), and HHV-7 (7.5%). For all viruses, age, SLEDAI, hematological tests, ferritin, LDH, C-reactive protein, and erythrocyte sedimentation rate (ESR) were not significant. However, EBV positivity was a significant factor for higher serum creatinine (3.0 ± 2.8 vs. 0.9 ± 0.8; P = 0.001) and urea (86 ± 51 vs. 50 ± 46; P = 0.03). Moreover, positive cases for EBV only or with combined co-infections (66.7%-CMV; 58.3%-HSV-1) or negative for EBV only were evaluated by Kruskal-Wallis test again showed statistical significance for serum creatinine and urea (both P ≤ 0.01), with posttest also showing statistical differences for renal dysfunction and EBV presence (alone or in combined co-infections). The presence of EBV viral load was also significant for nephrotic-range proteinuria, renal flare, and the need for hemodialysis. Conclusion: Members of the Herpeviridae family (mainly EBV, HSV-1 and CMV) are common on hospital admission of SLE patients, reaching 65% for EBV, which seems to be associated with renal dysfunction and could reflect a previous association or overlapping disease, which is not well understood.

Resumo Introdução: Membros da família Herpesviridae tem sido descritos em pacientes com lúpus eritematoso sistêmico (LES), mas o impacto clínico na função renal não é bem conhecido. Métodos: Avaliou-se HSV1, HSV2, VZV, EBV, CMV, HHV-6, HHV-7, HHV-8 por biologia molecular na admissão em amostras sanguíneas de 40 pacientes com LES consecutivos hospitalizados por atividade lúpica. Resultados: Pacientes 90,0% mulheres, 77,5% não brancos, idade média 32,7 ± 13,6 anos. Encontramos positividade para EBV (65,0%), CMV (30,0%), HSV-1 (30,0%), HHV-6 (12,5%), HHV-7 (7,5%). Para todos os vírus, idade, SLEDAI, exames hematológicos, ferritina, LDH, proteína C reativa, velocidade de hemossedimentação não foram significativos. Entretanto, positividade para EBV foi estatisticamente significativo para creatinina (3,0 ± 2,8 vs. 0,9 ± 0,8; P = 0,001) e ureia (86 ± 51 vs. 50 ± 46; P = 0,03) séricas mais elevadas. Ademais, casos positivos para EBV isolado ou com coinfecções combinadas (66,7%-CMV; 58,3%-HSV-1) ou negativos apenas para EBV foram avaliados pelo teste Kruskal-Wallis e novamente mostraram significância estatística para creatinina e ureia séricas (ambas P ≤ 0,01), com pós-teste mostrando também diferenças estatísticas para disfunção renal e presença de EBV (sozinho ou em coinfecções combinadas). A presença de carga viral do EBV também foi significativa para proteinúria de faixa nefrótica, inflamação aguda, necessidade de hemodiálise. Conclusão: Membros da família Herpeviridae (principalmente EBV, HSV-1, CMV) são comuns na admissão de pacientes com LES, chegando a 65% para EBV, que parece associar-se à disfunção renal podendo refletir associação prévia ou doença sobreposta, o que não é bem compreendido.

Resumo Introdução No Brasil, algumas cidades adotaram várias medidas que provavelmente tiveram um impacto positivo no controle da Covid-19. Objetivo Relatar a distribuição dos casos de Covid-19 no Brasil, no estado do Rio de Janeiro e na cidade de Niterói. Paralelamente, buscamos demonstrar as estratégias preventivas adotadas pela cidade de Niterói para o controle da Covid-19. Método Dados fornecidos pelo Ministério da Saúde e Fundação Municipal de Saúde de Niterói foram usados para relatar o número de casos e óbitos causados pela Covid-19. Para algumas análises, os dados foram agrupados por semana e normalizados para 100.000 habitantes. Resultados Até 18 de julho de 2020, o Brasil registrou 2.074.860 casos e 78.772 mortes e o estado do Rio de Janeiro registrou 135.230 casos e 11.919 mortes; ambos ainda apresentando curvas ascendentes para mortes por Covid-19. Em contrapartida, a taxa de novos óbitos/100.000 habitantes é consistentemente menor na cidade de Niterói. Estimamos que 712 mortes foram evitadas pelas medidas adotadas pela cidade de Niterói, em comparação com o que foi observado no Rio de Janeiro. Conclusão As medidas preventivas adotadas pela cidade de Niterói foram eficazes na redução tanto da disseminação do vírus quanto da taxa de óbitos. Portanto, esta discussão se mostra relevante para a tomada de decisões futuras durante o surto de Covid-19 no Brasil.

Abstract Background In Brazil, some local city government’s adopted several measures, which probably had a positive impact on COVID-19 control. Objective To report the distribution of COVID-19 cases in Brazil, Rio de Janeiro state and Niterói city. In parallel, we aimed to demonstrate the preventive strategies adopted by Niterói city. Method Data provided by the Brazilian Ministry of Health and Municipal Health Foundation of Niterói were used to report COVID-19 cases and deaths. For some analysis, data were grouped by week and normalized for 100,000 inhabitants. Results By July 18th, 2020, Brazil reported 2,074,860 cases and 78,772 deaths and Rio de Janeiro state registered 135,230 cases and 11,919 deaths; both still presenting ascendant curves for COVID-19 deaths. In contrast, the rate of new deaths per 100,000 inhabitants is consistently lower in Niterói city. Importantly, we estimated that 712 deaths were prevented by the measures adopted by Niterói city, in comparison to which was observed in Rio de Janeiro. Conclusion The early preventive measures adopted in Niterói city were effective in reducing both the viral spread and rate of deaths. In this regard, this discussion could be relevant for making future decisions during the COVID-19 outbreak in Brazil.

ABSTRACT Introduction: Some COVID-19 patients have higher mortality and the responsible factors for this unfavorable outcome is still not well understood. Objective: To study the association between ferritin levels at admission, representing an inflammatory state, and hospital mortality in COVID-19 patients. Methods: From May through July 2020, SARS-CoV-2 positive patients with moderate to severe clinical symptoms were evaluated at admission, regarding clinical and laboratory data on renal and hepatic function, hematologic parameters, cytomegalovirus co-infection, and acute phase proteins. Results: A total of 97 patients were included; mean age = 59.9 ± 16.3 years, 58.8% male, 57.7% non-white, in-hospital mortality = 45.4%. Age, ferritin, C-reactive protein, serum albumin and creatinine were significantly associated with mortality. Ferritin showed area under the curve (AUC) of 0.79 (p < 0.001) for the cut-off of 1873.0 ng/mL, sensitivity of 68.4% and specificity of 79.3% in predicting in-hospital mortality. Age ≥60 years had an odds ratio (OR) of 10.5 (95% CI = 1.8–59.5; p = 0.008) and ferritin ≥1873.0 ng/mL had an OR of 6.0 (95% CI = 1.4–26.2; p = 0.016), both independently associated with mortality based on logistic regression analysis. Conclusion: The magnitude of inflammation present at admission of COVID-19 patients, represented by high ferritin levels, is independently predictive of in-hospital mortality.

Resumo A linfohistiocitose hemofagocítica (LHH) é uma condição incomum e potencialmente fatal, caracterizada por importante ativação imunológica e produção maciça de citocinas por células mononucleares inflamatórias, devido a defeitos na função linfocitária citotóxica. É ainda mais incomum em receptores de transplante renal, nos quais está freqüentemente associada a infecções não controladas. A mortalidade da LHH é alta, e o diagnóstico diferencial com sepse é um desafio. A abordagem e o tratamento dependem do gatilho e das comorbidades subjacentes. Relatamos o caso de uma paciente transplantada renal com 50 anos de idade, admitida com febre e mal-estar 3 meses após o transplante, apresentando anemia, febre, hipertrigliceridemia, níveis elevados de ferritina sérica e antigenemia positiva para CMV. A urina mostrou positividade para células decoy e BKV-DNA. A biopsia do enxerto mostrou nefrite por CMV. Ambas as culturas de sangue e urina foram positivas para E. coli. A hemofagocitose foi confirmada pelo aspirado de medula óssea. A imunossupressão foi reduzida e a paciente recebeu altas doses de imunoglobulina intravenosa e dexametasona, com resposta completa após 3 semanas. Destaca-se a importância do diagnóstico precoce e do manejo adequado de uma condição rara e grave em um paciente transplantado renal, o que pode permitir um curso clínico favorável e melhorar a taxa de sobrevida.

Abstract Hemophagocytic lymphohistiocytosis (HLH) is an uncommon and life-threating condition characterized by major immune activation and massive cytokine production by mononuclear inflammatory cells, due to defects in cytotoxic lymphocyte function. It is even more unusual in renal transplant recipients, in which it is often associated with uncontrolled infection. The mortality is high in HLH and differential diagnosis with sepsis is a challenge. The approach and management depend on the underlying trigger and comorbidities. We report a case of a 50-year-old renal transplant female admitted with fever and malaise 3 months post-transplant and presenting anemia, fever, hypertriglyceridemia, high levels of serum ferritin, and positive CMV antigenemia. Urine was positive for decoy cells and BKV-DNA. Graft biopsy showed CMV nephritis. Both blood and urine cultures where positive for E. coli. Hemophagocytosis was confirmed by bone marrow aspiration. Immunosuppression was reduced, and the patient received high-dose intravenous immunoglobulin and dexamethasone, with complete response after 3 weeks. We highlight the importance of early diagnosis and proper management of a rare and serious condition in a renal transplant patient, which can allow a favorable clinical course and improve survival rate.

RESUMO Introdução: Diferentemente do transplante de órgãos, poucos estudos correlacionam o monitoramento da antigenemia pp65 com o diagnóstico de citomegalovírus (CMV) em pacientes com lúpus eritematoso sistêmico (LES). Objetivo: De modo a destacar a importância do CMV para além do transplante, monitorizamos a antigenemia pp65 em uma série de pacientes com LES. Métodos: De março de 2015 a março de 2016, pacientes com LES que apresentaram acometimento renal, febre e infecção indeterminada na internação foram monitorados através da antigenemia pp65. O ensaio de antigenemia, revelada por imunofluorescência, foi correlacionado com achado clínicos e laboratoriais. Resultados: Foram incluídos 19 pacientes com suspeita de infecção indeterminada. Positividade para antigenemia pp65 foi encontrada em sete pacientes (36,8%). A idade média foi de 33,5 ± 11,2 anos; 16 (84%) eram do sexo feminino e 16 (84%) eram negros. Linfopenia, anemia e escore de SLEDAI mais elevado foram significativamente mais comuns em pacientes pp65 positivos. Cinco pacientes receberam terapia antiviral com ganciclovir. Apesar de receber tratamento específico para CMV, um paciente com suspeita de doença por CMV veio a óbito. Conclusões: Antigenemia pp65 pode ser relevante em pacientes com LES, e estudos com maior número de pacientes são necessários para estabelecer a sensibilidade e a especificidade da antigenemia pp65 em diferentes contextos clínicos envolvendo pacientes com LES.

ABSTRACT Introduction: In contrast to organ transplantation, few studies correlate the monitoring of pp65 antigenemia with a diagnosis of cytomegalovirus (CMV) in patients with systemic lupus erythematosus (SLE). Objective: To highlight the importance of CMV outside transplantation, we monitored pp65 antigenemia in a series of SLE patients. Methods: From March 2015 to March 2016, SLE patients presenting kidney involvement, fever, and an unclear infection at hospital admission were monitored through pp65 antigenemia. The pp65 antigenemia assay, revealed by immunofluorescence, was correlated with clinical and laboratory findings. Results: We included 19 patients with a suspected unclear infection. A positivity for pp65 antigenemia was found in seven patients (36.8%). The mean age was 33.5 ± 11.2 years, 16 (84%) were females, and 16 (84%) were black. Lymphopenia, anemia, and higher scores of SLEDAI were significantly more common in pp65-positive patients. Five patients received antiviral therapy with ganciclovir. Although receiving specific CMV treatment, one patient died because of suspected CMV disease. Conclusions: Pp65 antigenemia might be relevant in SLE patients, and studies with a greater number of patients are needed in order to establish sensitivity and specificity of pp65 antigenemia in different clinical contexts of SLE patients.

Abstract Introduction: Human cytomegalovirus is a major cause of morbidity in kidney transplant patients. Objectives: We aimed to study viral replication and serological response in the first months post kidney transplant in patients undergoing universal prophylaxis or preemptive therapy and correlate the findings with the clinical course of Human cytomegalovirus infection. Patients and methods: Independent from the clinical strategy adopted for managing Human cytomegalovirus infection, prophylaxis versus preemptive therapy, the pp65 antigenemia assay and serological response were assessed on the day of transplantation, and then weekly during the first three months of post-transplant. Results: From the 32 transplant recipients, 16 were positive for pp65 antigenemia, with a similar incidence rate in each group. There were no positive results in the first three weeks of monitoring; the positivity rate peaked at week eight. There was a trend for a higher and earlier frequency of positivity in the universal prophylaxis group in which the course of the Human cytomegalovirus infection was also more severe. Despite the differences in clinical picture and in the initial immunosuppressant schedule, the serological response was similar in both groups. Conclusion: Routine monitoring during the first three post-transplant months has a positive impact on the early detection of Human cytomegalovirus viral replication allowing for timely treatment in order to reduce morbidity of the disease. The strategy of universal therapy employing intravenous ganciclovir was associated to a worse clinical course of the Human cytomegalovirus infection suggesting that the use of >10 cells/2 × 105 leukocytes as a cut-off in this setting may be inappropriate.

BK Poliomavírus (BKPyV) é um agente causal de nefropatia, estenose ureteral e cistite hemorrágica em receptores de transplante renal, sendo considerado uma importante doença emergente na transplantação. Rastreamento regular para reativação do BKPyV, principalmente nos dois primeiros anos pós-transplante, com subsequente redução preemptiva da imunossupressão é considerada a melhor conduta para evitar a progressão da doença, já que a eliminação ou redução da viremia é alcançada na grande maioria dos pacientes dentro de 6 meses. O uso de drogas com propriedades antivirais para os pacientes com viremia persistente tem sido tentado, embora sem benefícios claros. As manifestações clínicas da nefropatia por BKPyV, as estratégias para o diagnóstico e monitoramento da infecção por BKPyV, o manejo do regime de imunossupressão após a detecção da reativação do BKPyV e o uso de drogas antivirais são discutidas nesta revisão.

BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.

Introdução: Hipomagnesemia familiar com hipercalciúria e nefrocalcinose, com grave envolvimento ocular, por mutação no gene da claudina-19, é uma doença rara autossômica recessiva. Seu espectro inclui perda renal de magnésio, nefrocalcinose medular e doença renal progressiva em crianças e adolescentes. Objetivo: Relatar um caso de transplante renal pai para filha em uma ocorrência familiar de nefrocalcinose bilateral grave associada com comprometimento ocular em uma família brasileira não consangüínea, na qual duas filhas apresentavam nefrocalcinose e retinopatia severa. Métodos: O caso índice, uma mulher de 19 anos de idade, tinha longa história pregressa de infecção urinária de repetição, o raio-X abdominal revelava calcificações renais múltiplas bilaterais, bem como litíase ureteral, e estava sob hemodiálise. Havia um diagnóstico prévio de retinite pigmentosa no período neonatal precoce. A outra filha (13 anos de idade) também apresentava nefrocalcinose com função renal preservada, retinopatia com grave deficiência visual, e além disso, ela exibia hipomagnesemia = 0,5 mg/dL e hipercalciúria. Os outros membros da família (mãe, pai e filho) não tinham nenhuma manifestação clínica da doença. A análise mutacional no gene da claudin-19 revelou duas mutações heterozigotas (P28L e G20D) em ambas as filhas afetadas. Os outros membros da família apresentavam estado mutante monoalélico. Apesar disso, o caso índice foi submetido a transplante de rim com doador vivo intrafamiliar (pai). Conclusão: Em conclusão, a doença foi caracterizada por um estado heterozigoto recessivo composto autossômico e após cinco anos de doação a função do enxerto renal manteve-se estável, sem recidiva de distúrbios metabólicos ou nefrocalcinose. Além disso, a homeostasia do Mg2+ e Ca2+ associado ao estado monoalélicos do doador e seu rim único não afetou a segurança da doação intervivos e o curso clínico usual pós-transplante.

Introduction: Familial Hypomagnesaemia with hypercalciuria and nephrocalcinosis, with severe ocular impairment secondary to claudin-19 mutation, is a rare recessive autossomic disorder. Its spectrum includes renal Mg2+ wasting, medullary nephrocalcinosis and progressive chronic renal failure in young people. Objective: To report a case of kidney transplantation father to daughter in a familial occurrence of severe bilateral nephrocalcinosis associated with ocular impairment in a non-consanguineous Brazilian family, in which two daughters had nephrocalcinosis and severe retinopathy. Methods: The index case, a 19 years-old female, had long-lasting past medical history of recurrent urinary tract infections, and the abdominal X-ray revealed bilateral multiple renal calcifications as well as ureteral lithiasis, and she was under haemodialysis. She had the diagnosis of retinitis pigmentosa in the early neonatal period. The other daughter (13 years-old) had also nephrocalcinosis with preserved kidney function, retinopathy with severe visual impairment, and in addition, she exhibited hypomagnesaemia = 0.5 mg/dL and hypercalciuria. The other family members (mother, father and son) had no clinical disease manifestation. Mutation analysis at claudin-19 revealed two heterozygous missense mutations (P28L and G20D) in both affected daughters. The other family members exhibited mutant monoallelic status. In despite of that, the index case underwent intrafamilial living donor kidney transplantation (father). Conclusion: In conclusion, the disease was characterized by an autosomal recessive compound heterozygous status and, after five years of donation the renal graft function remained stable without recurrence of metabolic disturbances or nephrocalcinosis. Besides, donor single kidney Mg2+ and Ca2+ homeostasis associated to monoallelic status did not affect the safety and the usual living donor post-transplant clinical course.

O Brasil tem o terceiro maior contingente de pacientes em hemodiálise (HD) no mundo. Todavia, pouco conhece-se sobre a taxa de sobrevida e os preditores do risco de mortalidade nessa população, que são os objetivos deste estudo. Um total de 3.082 pacientes incidentes em HD, de 2000 a 2004, em 25 unidades de diálise distribuídas por 7 dos 26 estados do Brasil, foi acompanhado até 2009. Os pacientes tinham entre 52 ± 16 anos de idade, 57,8% eram homens e 20,4%, diabéticos. O desfecho primário foi de mortalidade por todas as causas. Os dados foram censurados aos cinco anos de seguimento. A taxa global de sobrevida em cinco anos foi de 58,2%. No modelo proporcional de Cox, as variáveis associadas ao risco de óbito foram: a idade (risco relativo - RR = 1,44 por década; p < 0,0001), diabetes (RR = 1,51; p < 0,0001), albumina sérica (RR = 0,76 por g/dL; p = 0,001), creatinina (RR = 0,92 por mg/dL; p < 0,0001) e fósforo (RR = 1,06 por mg/dL; p = 0,04). Os resultados mostram que a taxa de mortalidade em HD nesta coorte brasileira foi relativamente baixa, mas a população é mais jovem e com prevalência de diabetes mais baixa do que aquela descrita nos países desenvolvidos.

Brazil has the third largest contingent of patients on maintenance hemodialysis (HD) worldwide. However, little is known regarding survival rate and predictors of mortality risk in that population, which are the purposes of this study. A total of 3,082 patients incident on HD, from 2000 to 2004, at 25 dialysis facilities distributed among 7 out of 26 states of Brazil were followed-up until 2009. Patients were 52 ± 16 years-old, 57.8% men, and 20.4%, diabetics. The primary outcome was all causes of mortality. Data were censored at five years of follow-up. The global five-year survival rate was 58.2%. In the Cox proportional model, variables associated with risk of death were: age (hazard ratio - HR = 1.44 per decade, p < 0.0001), diabetes (HR = 1.51, p < 0.0001), serum albumin (HR = 0.76 per g/dL, p = 0.001), creatinine (HR = 0.92 per mg/dL, p < 0.0001), and phosphorus (HR = 1.06 per mg/dL, p = 0.04). The present results show that the mortality rate on HD in this Brazilian cohort was relatively low, but the population is younger and with a lower prevalence of diabetes than the ones reported for developed countries.