Chronic kidney disease prevention campaign: relationship between proteinuria and elderly people / Campanha de prevenção de doença renal crônica: relação entre proteinúria e idosos

ABSTRACT Objective: To verify the relationship between the presence of proteinuria as a renal injury marker in elderly without history of systemic arterial hypertension and cardiovascular diseases. A cross-sectional study was developed from January 2014 to December 2019, through kidney disease prevention campaigns promoted by the Federal University of Ceará in the city of Fortaleza. Methods: The sample consisted of 417 elderlies. A questionnaire was used to characterize individuals and assess previous diseases, and urinalysis reagent strips were used to assess proteinuria. Results: Statistically significant differences (p < 0.05) and moderate effect sizes were found for blood pressure levels (CI 0.53-0.93), systolic blood pressure, and diastolic blood pressure (CI 0.21-0.61). Significant differences in capillary glycemia were also found between groups (p = 0.033), but with a low effect size (0.02-0.42). The group with comorbidities was 2.94 times more likely to have proteinuria than those without comorbidities (OR 2.94, CI 1.55-4.01; p < 0.05). In the group without cardiovascular disease/high blood pressure, a statistically significant association was found for previous diabetes and proteinuria (p = 0.037), presenting 2.68 times higher risk of proteinuria in those with diabetes mellitus (OR 2.68, CI 1.05-6.85). Significant association was also found between age groups, with the older group having 2.69 times higher risk of developing proteinuria (75 to 90 compared to 60 to 74 years) (CI 1.01-7.16; p = 0.045). Conclusion: Even without systemic arterial hypertension or cardiovascular disease, diabetes and older age can be considered high risk factors for proteinuria.

Resumo Objetivo: Verificar a relação entre a presença de proteinúria como marcador de lesão renal em idosos sem histórico de hipertensão arterial sistêmica e doenças cardiovasculares. Um estudo transversal foi desenvolvido de Janeiro de 2014 a Dezembro de 2019, por meio de campanhas de prevenção a doenças renais promovidas pela Universidade Federal do Ceará, na cidade de Fortaleza. Métodos: A amostra foi composta por 417 idosos. Um questionário foi usado para caracterizar indivíduos e avaliar doenças prévias, e foram utilizadas tiras reagentes de urinálise para avaliar proteinúria. Resultados: Diferenças estatisticamente significativas (p < 0,05) e tamanhos de efeito moderados foram encontrados para níveis de pressão arterial (IC 0,53-0,93), pressão arterial sistólica e pressão arterial diastólica (IC 0,21-0,61). Também foram encontradas diferenças significativas na glicemia capilar entre grupos (p = 0,033), mas com um tamanho de efeito baixo (0,02-0,42). O grupo com comorbidades apresentou 2,94 vezes mais probabilidade de ter proteinúria do que aqueles sem comorbidades (OR 2,94; IC 1,55-4,01; p < 0,05). No grupo sem doença cardiovascular/hipertensão, foi encontrada uma associação estatisticamente significativa para diabetes anterior e proteinúria (p = 0,037), apresentando risco 2,68 vezes maior de proteinúria naqueles com diabetes mellitus (OR 2,68; IC 1,05-6,85). Também foi encontrada uma associação significativa entre faixas etárias, com o grupo mais velho apresentando risco 2,69 vezes maior de desenvolver proteinúria (75 a 90 em comparação com 60 a 74 anos) (IC 1,01-7,16; p = 0,045). Conclusão: Mesmo sem hipertensão arterial sistêmica ou doença cardiovascular, o diabetes e a idade avançada podem ser considerados fatores de alto risco para proteinúria.

Use of probiotics in patients with chronic kidney disease on hemodialysis: a randomized clinical trial / Uso de probióticos em pacientes com doença renal crônica em hemodiálise: um ensaio clínico randomizado

ABSTRACT Introduction: Supplementation with probiotics for patients with chronic kidney disease (CKD) may be associated with decreased systemic inflammation. Objective: To assess the impact of oral supplementation with probiotics for patients with CKD on hemodialysis. Method: This double-blind randomized clinical trial included 70 patients on hemodialysis; 32 were given oral supplementation with probiotics and 38 were in the placebo group. Blood samples were collected at the start of the study and patients were given oral supplementation with probiotics or placebo for three months. The probiotic supplement comprised four strains of encapsulated Gram-positive bacteria: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 and Bifidobacterium longum A101. Patients were given one capsule per day for 3 months. Blood samples were taken throughout the study to check for inflammatory biomarkers. Non-traditional biomarkers Syndecan-1, IFN-y, NGAL, and cystatin C were measured using an ELISA kit, along with biochemical parameters CRP, calcium, phosphorus, potassium, PTH, GPT, hematocrit, hemoglobin, glucose, and urea. Results: Patients given supplementation with probiotics had significant decreases in serum levels of syndecan-1 (239 ± 113 to 184 ± 106 ng/mL, p = 0.005); blood glucose levels also decreased significantly (162 ± 112 to 146 ± 74 mg/dL, p = 0.02). Conclusion: Administration of probiotics to patients with advanced CKD was associated with decreases in syndecan-1 and blood glucose levels, indicating potential improvements in metabolism and decreased systemic inflammation.

Resumo Introdução: A suplementação com probióticos na doença renal crônica (DRC) pode estar associada à redução do processo inflamatório sistêmico. Objetivo: Avaliar a suplementação oral com probióticos em pacientes com DRC em hemodiálise. Método: Ensaio clínico, duplo cego, randomizado com 70 pacientes em hemodiálise, sendo 32 do grupo que recebeu o suplemento de probióticos e 38 do grupo placebo. Inicialmente ocorreu a coleta de sangue e suplementação oral com probióticos ou placebo durante três meses. O suplemento probiótico foi composto pela combinação de 4 cepas de bactérias Gram-positivas encapsuladas: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 e Bifidobacterium longum A101, sendo 1 cápsula do suplemento ao dia, durante 3 meses. Após esse período foram feitas novas coletas de sangue para dosagem dos biomarcadores inflamatórios. Foram analisados os biomarcadores não tradicionais: Syndecan-1, IFN-y, NGAL e cistatina C pelo método ELISA, e os seguintes parâmetros bioquímicos: PCR, cálcio, fósforo, potássio, PTH, TGP, hematócrito, hemoglobina, glicose e ureia. Resultados: Os pacientes que receberam suplemento tiveram diminuição significativa dos níveis séricos de syndecan-1 (de 239 ± 113 para 184 ± 106 ng/mL, p = 0,005). Outro parâmetro que diminuiu significativamente nos pacientes que receberam suplemento foi a glicemia (de 162 ± 112 para 146 ± 74 mg/dL, p = 0,02). Conclusão: O uso de probióticos na DRC avançada esteve associado à redução dos níveis de syndecan-1 e glicemia, sinalizando possível melhora no metabolismo e redução do processo inflamatório sistêmico.

Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil.

BACKGROUND: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. METHODS: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. RESULTS: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. CONCLUSIONS: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Use of probiotics in patients with chronic kidney disease on hemodialysis: a randomized clinical trial.

INTRODUCTION: Supplementation with probiotics for patients with chronic kidney disease (CKD) may be associated with decreased systemic inflammation. OBJECTIVE: To assess the impact of oral supplementation with probiotics for patients with CKD on hemodialysis. METHOD: This double-blind randomized clinical trial included 70 patients on hemodialysis; 32 were given oral supplementation with probiotics and 38 were in the placebo group. Blood samples were collected at the start of the study and patients were given oral supplementation with probiotics or placebo for three months. The probiotic supplement comprised four strains of encapsulated Gram-positive bacteria: Lactobacillus Plantarum A87, Lactobacillus rhamnosus, Bifidobacterium bifidum A218 and Bifidobacterium longum A101. Patients were given one capsule per day for 3 months. Blood samples were taken throughout the study to check for inflammatory biomarkers. Non-traditional biomarkers Syndecan-1, IFN-y, NGAL, and cystatin C were measured using an ELISA kit, along with biochemical parameters CRP, calcium, phosphorus, potassium, PTH, GPT, hematocrit, hemoglobin, glucose, and urea. RESULTS: Patients given supplementation with probiotics had significant decreases in serum levels of syndecan-1 (239 ± 113 to 184 ± 106 ng/mL, p = 0.005); blood glucose levels also decreased significantly (162 ± 112 to 146 ± 74 mg/dL, p = 0.02). CONCLUSION: Administration of probiotics to patients with advanced CKD was associated with decreases in syndecan-1 and blood glucose levels, indicating potential improvements in metabolism and decreased systemic inflammation.

Subclinical signs of podocyte injury associated with Circulating Anodic Antigen (CAA) in Schistosoma mansoni-infected patients in Brazil

ABSTRACT Background: The long-term effects of schistosomiasis on the glomerulus may contribute to the development of chronic kidney disease. This study aimed to investigate baseline Schistosoma mansoni-Circulating Anodic Antigen (CAA) levels and their association with kidney biomarkers related to podocyte injury and inflammation in long-term follow-up after praziquantel (PZQ) treatment. Methods: Schistosoma infection was diagnosed by detecting CAA in urine using a quantitative assay based on lateral flow using luminescent up-converting phosphor reporter particles. A cutoff threshold of 0.1 pg/mL CAA was used to diagnose Schistosoma infection (baseline) in a low-prevalence area in Ceará, Northeast, Brazil. Two groups were included: CAA-positive and CAA-negative individuals, both of which received a single dose of PZQ at baseline. Urinary samples from 55 individuals were evaluated before (baseline) and at 1, 2, and 3 years after PZQ treatment. At all time points, kidney biomarkers were quantified in urine and adjusted for urinary creatinine levels. Results: CAA-positive patients had increased baseline albuminuria and proteinuria and showed greater associations between kidney biomarkers. CAA levels correlated only with Vascular Endothelial Growth Factor (VEGF) (podocyte injury) levels. Increasing trends were observed for malondialdehyde (oxidative stress), monocyte chemoattractant protein-1 (inflammation marker), and VEGF. In the follow-up analysis, no relevant differences were observed in kidney biomarkers between the groups and different periods. Conclusions: S. mansoni-infected individuals presented subclinical signs of glomerular damage that may reflect podocyte injury. However, no causal effect on long-term renal function was observed after PZQ treatment.

Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

ELMO CPAP: an innovative type of ventilatory support for COVID-19-related acute respiratory distress syndrome / ELMO-CPAP: um suporte ventilatório inovador para síndrome do desconforto respiratório agudo por COVID-19

ABSTRACT Objective: To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. Methods: This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. Results: ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. Conclusions: The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

RESUMO Objetivo: Avaliar se o uso do ELMO, um capacete para ventilação não invasiva criado no Brasil, teve impacto positivo no prognóstico de pacientes com insuficiência respiratória hipoxêmica por COVID-19 grave. Métodos: Estudo retrospectivo com 50 pacientes críticos com COVID-19. Dados epidemiológicos, clínicos e laboratoriais foram coletados na admissão na UTI e antes, durante e após o uso do ELMO. Os pacientes foram divididos em dois grupos (sucesso e falha) de acordo com o desfecho. Resultados: O uso do ELMO melhorou parâmetros de oxigenação como Pao2, Fio2 e relação Pao2/Fio2, e isso contribuiu para uma redução gradual da Fio2, sem aumento do CO2, conforme determinado pela gasometria arterial. Os pacientes do grupo sucesso apresentaram sobrevida significativamente maior (p < 0,001), conforme determinado pela análise de Kaplan-Meier, menor necessidade de intubação (p < 0,001), menos dias de hospitalização e menor incidência de lesão renal aguda em comparação com os do grupo falha. Conclusões: A significativa melhora nos parâmetros de oxigenação, a maior sobrevida, refletida pela menor necessidade de intubação e pela taxa de mortalidade, e a ausência de lesão renal aguda sugerem que o sistema ELMO CPAP é uma ferramenta promissora para o tratamento da SDRA e de condições clínicas semelhantes.

Use of non-conventional biomarkers in the early diagnosis of acute kidney injury in preterm newborns with sepsis / Biomarcadores não tradicionais de lesão renal aguda em recém-nascidos prematuros com sepse: diagnóstico precoce

Abstract Acute kidney injury (AKI) is a common finding in Neotatal Intensive Care Units (NICU). Sepsis is one the main causes of AKI in preterm newborns. AKI has been associated with significant death rates. Early detection of the condition is the first step to improving prevention, treatment, and outcomes, while decreasing length of hospitalization, care costs, and morbimortality. AKI may progress to chronic kidney disease (CKD), a condition linked with dialysis and greater risk of cardiovascular disease. This review article aims to discuss cases of AKI in preterm newborns with sepsis, the use of biomarkers in lab workup, and the use of non-conventional biomarkers for the early identification of AKI.

Resumo A lesão renal aguda (LRA) é comum na Unidade de Terapia Intensiva Neonatal (nUTI) e a sepse é uma de suas principais causas, especialmente em prematuros. Apresenta altas taxas de mortalidade e sua detecção precoce é o primeiro passo para a prevenção dessa condição, pois permite o tratamento adequado e melhora o desfecho, diminui o tempo de internação, os custos não médicos e a morbimortalidade. Destaca-se ainda que a LRA pode evoluir para doença renal crônica (DRC), havendo a necessidade de diálise, com maior risco de desenvolver doenças cardiovasculares. Este artigo de revisão tem como objetivo discutir a LRA em recém-nascidos (RNs) prematuros com sepse, abordando biomarcadores utilizados na rotina laboratorial e principalmente a utilização de biomarcadores não tradicionais para identificação precoce de LRA.

Kidney injury biomarkers and parasitic loads of Schistosoma mansoni in a highly endemic area in northeastern Brazil.

Schistosomiasis affects approximately 240 million people worldwide. In Brazil, it is estimated that 1.5 million people are infected with Schistosoma mansoni and up to 15% of diagnosed individuals develop kidney damage. Renal involvement in schistosomiasis mansoni is characterized by glomerular lesions, with a high incidence, especially in chronically infected patients living in areas of high endemicity. Renal damage occurs slowly and is often asymptomatic, with a long-term manifestation of chronic kidney disease, with progressive loss of kidney functions, and early detection of subclinical kidney disease is of great importance. The aim of this study was to investigate kidney damage in patients infected with S. mansoni through urinary biomarkers of kidney injury and their association with the different parasite loads found. The patients were divided into two groups based on the diagnosis of infection by S. mansoni by the Kato-Katz and IgG-ELISA-SEA method: group of individuals infected by S. mansoni, Kato-Katz positive (PG); and group of individuals not infected by S. mansoni, Kato-Katz-negative (NG). Urinary creatinine and albuminuria were determined by immunoturbidimetry and proteinuria by the colorimetric method. The urinary biomarkers of podocyte injury (VEGF and Nephrin) and glomerular inflammation (MCP-1) were quantified by immunoassay and expressed by the urinary creatinine ratio. Urinary VEGF showed significantly higher levels in PG compared to NG (p = 0.004), increasing at all intensities of infection including low parasite load (p = 0.020). Our results show increased signs of podocyte damage in patients with schistosomiasis mansoni regardless of the parasite load, evidenced by increased urinary VEGF levels. However, further studies are needed since data related to schistosomiasis glomerulopathy and its association with new urinary biomarkers of kidney injury are scarce in the literature.

Hypertriglyceridemia promotes dysfunctions in high-density lipoprotein increasing the cardiovascular risk

Abstract Hypertriglyceridemia is associated with several metabolic diseases. The triglycerides (TG) disrupt the cholesterol reverse transport and contribute to increased levels of low-density lipoprotein (LDL). High-density lipoprotein (HDL) acts in cholesterol reverse transport as an anti-inflammatory and antioxidant. This study aims to investigate the role of hypertriglyceridemia in the functionality of HDL. Individuals were divided into 4 groups based on high or low HDL-c and triglycerides levels. Biochemical and anthropometric analysis were performed. This study demonstrated that triglycerides promote dysfunctions on HDL, increasing the cardiovascular risk. Blood pressure was higher in subjects with low HDL. Women presented higher levels of HDL-c and low percentage of fat mass. The highest levels of triglycerides were observed in older age. In addition, high levels of triglycerides were associated with higher total cholesterol and LDL-c levels, non-HDL-c, non-esterified fatty acids, and blood glucose, increasing in the ratio of non-HDL-c/HDL-c and ApoB/ApoA-I. The increase of triglycerides levels progressively impairs the antioxidant capacity of HDL, probably due to a higher occurrence of fatty acid peroxidation in individuals with hypertriglyceridemia. Patients with high HDL and low TG levels increased the Lag Time. Furthermore, a positive correlation was found between TG versus HDL particle size, variables that depend on age and anthropometric parameters.

Intraoperative systemic biomarkers predict post-liver transplantation acute kidney injury.

OBJECTIVE: Liver transplant (LT) is a definitive therapeutic option for patients with chronic liver disease. However, acute kidney injury after LT (post-LT AKI) is a frequent complication that may lead to graft dysfunction and decrease life expectancy. Delay in AKI detection by traditional biomarkers boosted research with new biomarkers for post-LT AKI as neutrophil gelatinase-associated lipocalin (NGAL) and syndecan-1. We aim to evaluate associations of intraoperative systemic NGAL and syndecan-1 levels with post-LT AKI. METHODS: This is a prospective study conducted in 46 patients selected for LT. Patients were evaluated preoperatively and blood samples were collected intraoperatively: T1 (after induction of anesthesia), T2 (anhepatic phase) and T3 (2 h after reperfusion of the graft). RESULTS: The mean age was 54 ± 12 years and 60% were male. Post-LT AKI was observed in 24 (52%) patients of which 12% needed dialysis. Serum NGAL and syndecan-1 increased along surgical phases. Mostly, increment values of serum NGAL of T2 to T3 and syndecan-1 at T3 were importantly associated with post-LT AKI. Into a multivariate model with model for end-stage liver disease score, age, gender, warm ischemia, cold ischemia and surgery time, syndecan-1 levels at T3 remains capable to predict post-LT AKI. Serum NGAL had significance only with increment values calculated by the ratio of 'T3/T2'. Finally, serum syndecan-1 at T3 had a better diagnostic performance in receiver operating characteristic curve analysis. CONCLUSION: Serum syndecan-1 levels in 2 h after reperfusion were most useful in early post-LT AKI diagnosis and may be used to construct new risk groups in this context.

COVID-19 and Kidney: a narrative review / COVID-19 e os rins: uma revisão narrativa

Abstract COVID-19 is a pandemic associated with systemic clinical manifestations. In this study, we aimed to present a narrative review on kidney involvement in COVID-19. Kidney involvement could be derived from direct cytopathic effects, immunological mechanisms, indirect effects on renal tissue through other mediators, and dysfunction or injury of other organs. The evolution of COVID-19 may be complicated with acute kidney injury (AKI) in a significant percentage of patients, and renal dysfunction seems to be associated with worse prognosis. Patients with chronic kidney disease (CKD) seem to be more susceptible to the severe forms of COVID-19. Patients with renal replacement therapy (RRT) are also a vulnerable population as consequence of their advanced age, underlying comorbidities, impaired immune response, and clustering in hemodialysis centers, with requirements for frequent contact with healthcare services. Kidney transplant patients may be at high-risk due to long-term immunosuppression and comorbidities, hence, managing immunosuppression is imperative. Lastly, renal replacement therapy may be required during COVID-19, and different modalities are discussed based on clinical findings and laboratorial aspects. Therefore, COVID-19 seems to affect kidney by different mechanisms, which contributes for AKI development and increases the severity of the disease. Also, patients with CKD and kidney transplant recipients are at higher risk for COVID-19 and mortality.

Resumo COVID-19 é uma pandemia associada a manifestações clínicas sistêmicas. Neste estudo, apresenta-se revisão narrativa acerca do envolvimento renal na COVID-19. Envolvimento renal parece ser relacionado a efeitos citopáticos diretos, mecanismos imunológicos, efeitos indiretos de outros mediadores no tecido renal, além de disfunção e lesão de outros órgãos. A evolução da COVID-19 pode ser complicada por lesão renal aguda (LRA) em percentual significativo dos pacientes, e a disfunção renal parece ser associada a pior prognóstico. Pacientes com doença renal crônica (DRC) parecem ser mais suscetíveis a formas severas da COVID-19. Pacientes em terapia de substituição renal (TSR) contínua também constituem população vulnerável em razão de idade avançada, comorbidades subjacentes, resposta imune disfuncional e aglomeração em unidades de diálise, com necessidade de visitas frequentes aos serviços de saúde. Pacientes transplantados renais podem estar em alto risco dadas imunossupressão a longo prazo e comorbidades; assim, o manejo da imunossupressão é mandatório. Finalmente, TSR pode ser necessária durante a COVID-19, e diferentes modalidades são discutidas conforme manifestações clínicas e aspectos laboratoriais. Assim, COVID-19 parece acometer os rins por diferentes mecanismos, os quais contribuem para o desenvolvimento de LRA e aumento da severidade da doença. Ainda, pacientes com DRC e transplantados renais apresentam elevado risco para desenvolvimento de COVID-19 e de mortalidade.

Clinical assessment and pathophysiology of Bothrops venom-related acute kidney injury: a scoping review

Bothrops are one of the most common medically important snakes found in Latin America. Its venom is predominantly hemotoxic and proteolytic, which means that local lesion (edema and redness) and hemorrhagic symptoms are recurrent in envenoming by this snake. Although hemorrhage is usually the major cause of death, snakebite-related acute kidney injury is another potentially fatal clinical complication that may lead to chronic kidney disease. The present review highlights the main studies on Bothrops venom-related acute kidney injury, including observational, cross-sectional, case-control and cohort human studies available up to December 2019. The following descriptors were used according to Medical Subject Headings (MeSH): on Medline/Pubmed and Google Scholar "acute kidney injury" or "kidney disease" and "Bothrops"; on Lilacs and SciELO "kidney disease" or "acute kidney injury" and "Bothrops". Newcastle-Ottawa quality assessment scale was used to appraise the quality of the cross-sectional and cohort studies included. The selection of more severe patients who looked for health care units and tertiary centers is a risk of bias. Due to the methodological heterogeneity of the studies, a critical analysis of the results was performed based on the hypothesis that the design of the included studies influences the incidence of acute kidney injury. Fifteen human studies (total participants 4624) were included according to stablished criteria. The coagulation abnormalities (hemorrhagic symptoms, abnormal fibrinogen and activated partial thromboplastin time) were associated with acute kidney injury in the most recent studies reported. The findings observed in this review provide up-to-date evidence about the acute kidney injury pathogenesis following Bothrops syndrome. Studies pointed out that coagulation abnormalities comprise the major pathway for acute kidney injury development. This review may improve patient management by primary healthcare providers, allowing earlier diagnosis and treatment of Bothrops venom-related acute kidney injury.(AU)

Acute Kidney Injury Induced by Bothrops Venom: Insights into the Pathogenic Mechanisms.

Acute kidney injury (AKI) following snakebite is common in developing countries and Bothrops genus is the main group of snakes in Latin America. To evaluate the pathogenic mechanisms associated with Bothrops venom nephrotoxicity, we assessed urinary and blood samples of patients after hospital admission resulting from Bothrops snakebite in a prospective cohort study in Northeast Brazil. Urinary and blood samples were evaluated during hospital stay in 63 consenting patients, divided into AKI and No-AKI groups according to the KDIGO criteria. The AKI group showed higher levels of urinary MCP-1 (Urinary monocyte chemotactic protein-1) (median 547.5 vs. 274.1 pg/mgCr; p = 0.02) and urinary NGAL (Neutrophil gelatinase-associated lipocalin) (median 21.28 vs. 12.73 ng/mgCr; p = 0.03). Risk factors for AKI included lower serum sodium and hemoglobin levels, proteinuria and aPTT (Activated Partial Thromboplastin Time) on admission and disclosed lower serum sodium (p = 0.01, OR = 0.73, 95% CI: 0.57⁻0.94) and aPTT (p = 0.031, OR = 26.27, 95% CI: 1.34⁻512.11) levels as independent factors associated with AKI. Proteinuria showed a positive correlation with uMCP-1 (r = 0.70, p < 0.0001) and uNGAL (r = 0.47, p = 0.001). FENa (Fractional Excretion of sodium) correlated with uMCP-1 (r = 0.47, P = 0.001) and uNGAL (r = 0.56, p < 0.0001). sCr (serum Creatinine) showed a better performance to predict AKI (AUC = 0.85) in comparison with new biomarkers. FEK showed fair accuracy in predicting AKI (AUC = 0.92). Coagulation abnormality was strongly associated with Bothrops venom-related AKI. Urinary NGAL and MCP-1 were good biomarkers in predicting AKI; however, sCr remained the best biomarker. FEK (Fractional Excretion of potassium) emerged as another diagnostic tool to predict early AKI. Positive correlations between uNGAL and uMCP-1 with proteinuria and FENa may signal glomerular and tubular injury. Defects in urinary concentrations highlighted asymptomatic abnormalities, which deserve further study.

Renal involvement in paroxysmal nocturnal haemoglobinuria: a brief review of the literature.

INTRODUCTION: Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired genetic disorder characterized by complement-mediated haemolysis, thrombosis and variable cytopenias. Renal involvement may occur and causes significant morbidity to these patients. OBJECTIVE: To review the literature about pathophysiology and provide recommendations on diagnosis and management of renal involvement in PNH. METHODS: Online research in the Medline database with compilation of the most relevant 26 studies found. RESULTS: PNH may present with acute kidney injury caused by massive haemolysis, which is usually very severe. In the chronic setting, PNH may develop insidious decline in renal function caused by tubular deposits of hemosiderin, renal micro-infarcts and interstitial fibrosis. Although hematopoietic stem cell transplantation remains the only curative treatment for PNH, the drug Eculizumab, a humanized anti-C5 monoclonal antibody is capable of improving renal function, among other outcomes, by inhibiting C5 cleavage with the subsequent inhibition of the terminal complement pathway which would ultimately give rise to the assembly of the membrane attack complex. CONCLUSION: There is a lack of information in literature regarding renal involvement in PNH, albeit it is possible to state that the pathophysiological mechanisms of acute and chronic impairment differ. Despite not being a curative therapy, Eculizumab is able to ease kidney lesions in these patients.

Renal involvement in paroxysmal nocturnal haemoglobinuria: a brief review of the literature

SUMMARY INTRODUCTION: Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired genetic disorder characterized by complement-mediated haemolysis, thrombosis and variable cytopenias. Renal involvement may occur and causes significant morbidity to these patients. OBJECTIVE: To review the literature about pathophysiology and provide recommendations on diagnosis and management of renal involvement in PNH. METHODS: Online research in the Medline database with compilation of the most relevant 26 studies found. RESULTS: PNH may present with acute kidney injury caused by massive haemolysis, which is usually very severe. In the chronic setting, PNH may develop insidious decline in renal function caused by tubular deposits of hemosiderin, renal micro-infarcts and interstitial fibrosis. Although hematopoietic stem cell transplantation remains the only curative treatment for PNH, the drug Eculizumab, a humanized anti-C5 monoclonal antibody is capable of improving renal function, among other outcomes, by inhibiting C5 cleavage with the subsequent inhibition of the terminal complement pathway which would ultimately give rise to the assembly of the membrane attack complex. CONCLUSION: There is a lack of information in literature regarding renal involvement in PNH, albeit it is possible to state that the pathophysiological mechanisms of acute and chronic impairment differ. Despite not being a curative therapy, Eculizumab is able to ease kidney lesions in these patients.

RESUMO INTRODUÇÃO: A hemoglobinúria paroxística noturna (HPN) é uma doença genética adquirida, caracterizada por hemólise mediada pelo sistema complemento, eventos trombóticos e citopenias variáveis. Envolvimento renal pode ocorrer, contribuindo com morbidade significativa nesses pacientes. OBJETIVO: Realização de revisão de literatura sobre o envolvimento renal na HPN. MÉTODOS: Pesquisa on-line na base de dados Medline, com compilação e análise dos 26 estudos encontrados de maior relevância. RESULTADOS: A HPN pode se apresentar com insuficiência renal aguda induzida por hemólise maciça, que geralmente tem apresentação grave. Em quadros crônicos, declínio insidioso da função renal pode ocorrer por depósitos tubulares de hemossiderina, microinfartos renais e fibrose intersticial. Apesar de o transplante de células-tronco hematopoiéticas permanecer como a única terapia curativa para a HPN, a droga Eculizumab é capaz de melhorar a função renal, entre outros desfechos, por meio da inibição de C5 e a subsequente ativação da cascata do complemento, que culminaria com a formação do complexo de ataque à membrana. CONCLUSÃO: Há poucas informações na literatura no que concerne ao envolvimento renal na HPN, apesar de ser possível estabelecer que os mecanismos fisiopatológicos das lesões agudas e crônicas são distintos. Apesar de não ser uma terapia curativa, Eculizumab é capaz de amenizar o comprometimento renal nesses pacientes.

Urinary Syndecan-1 and acute kidney injury after pediatric cardiac surgery.

INTRODUCTION: Acute kidney injury (AKI) is a common occurrence after pediatric cardiac surgery. Plasma syndecan-1 is a biomarker of endothelial glycocalyx damage and it is associated with AKI. Syndecan-1 is also expressed in renal tubular cells but there is no study evaluating urinary syndecan-1 in predicting AKI. METHODS: Prospective cohort study with 86 patients ≤18 years submitted to cardiac surgery at one reference institution. Postoperative urinary syndecan-1 was collected within the first 2 h after cardiac surgery. Severe AKI - defined according to KDIGO as stage 2 or 3 - doubling of serum creatinine from the preoperative value or need for dialysis during hospitalization was the main outcome. Analyses were adjusted for clinical cofounders. RESULTS: Postoperative urinary syndecan-1 levels were higher in patients with severe AKI and even after adjustment for several clinical variables; the fourth quartile was significantly associated with severe AKI. The AUC-ROC for postoperative urinary syndecan-1 showed good discriminatory capacity (AUC-ROC = 0.793). The addition of urinary syndecan-1 improved the discrimination capacity of a clinical model (0.78 to 0.84). It also improved risk prediction, as measured by net reclassification improvement (NRI). CONCLUSION: Urinary syndecan-1 predicts severe AKI after pediatric cardiac surgery. Moreover, it appears to add capacity to predict severe AKI into a clinical model.

Fatores de risco pré-operatórios para lesão renal aguda após transplante hepático: resultados de um estudo transversal no Nordeste do Brasil / Preoperative risk factors for acute kidney injury after liver transplantation: results from a cross-sectional study in northeast of brazil

ABSTRACT BACKGROUND: Acute kidney injury (AKI) is a common complication in the immediate postoperative period of patients undergoing liver transplantation. OBJECTIVE: The aim of this study was to evaluate preoperative risk factors for AKI after liver transplantation. METHODS: A cross-sectional study was conducted with adults submitted to orthotopic liver transplantation at a reference hospital in Fortaleza, Northeast of Brazil, from January to December 2016. Preoperative risk factors were evaluated for AKI development in the immediate postoperative period. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. RESULTS: A total of 40 patients were included in the study. AKI was found in 85% of patients in the first 24 hours after transplantation, most of them (40%) classified in KDIGO stage 1. Preoperative data indicate that serum albumin levels were lower in the KDIGO stage 3 group compared to the non-AKI group, as well as the hematocrit levels. Direct bilirubin (DB) was higher in the KDIGO stage 3 group compared to the group without AKI, as well as alkaline phosphatase (AP) and gamma-glutamiltransferase (GGT). In a logistic regression analysis independent risk factors for AKI were increase levels of AP, GGT and DB and decrease level of serum albumin. CONCLUSION: Low levels of serum albumin, and elevated levels of DB, AP and GGT in the preoperative period are risk factors for AKI development after liver transplantation.

RESUMO CONTEXTO: Lesão renal aguda (LRA) é uma complicação comum no pós-operatório imediato do transplante hepático. OBJETIVO: O objetivo foi avaliar os fatores de risco pré-operatórios para LRA após o transplante hepático. MÉTODOS: Foi realizado estudo transversal com adultos submetidos a transplante hepático ortotópico em um hospital de referência em Fortaleza, Nordeste do Brasil, de janeiro a dezembro de 2016. Foram avaliados os fatores de risco pré-operatórios para o desenvolvimento de LRA no pós-operatório. LRA foi definida de acordo com os critérios do Kidney Disease: Improving Global Outcomes (KDIGO). RESULTADOS: Foram incluídos 40 pacientes no estudo. LRA foi encontrada em 85% dos casos nas primeiras 24 horas após o transplante, sendo a maioria deles (40%) classificados no estágio KDIGO 1. Os dados pré-operatórios indicaram que os níveis séricos de albumina eram menores nos pacientes no estágio KDIGO 3, em comparação com o grupo sem LRA, bem como os níveis de hematócrito. Os níveis de bilirrubina direta (BD) eram maiores nos pacientes no estágio KDIGO 3 em comparação ao grupo sem LRA, bem como os níveis de fosfatase alcalina (FA) e gama-glutamiltransferase (GGT). Em um modelo de regressão logística, os fatores de risco independentes para LRA foram: níveis elevados de FA, GGT e BD e níveis reduzidos de albumina. CONCLUSÃO: Níveis reduzidos de albumina sérica, e níveis elevados de BD, FA e GGT no período pré-operatório são fatores de risco para o desenvolvimento de LRA após o transplante hepático.

Nephroprotective effects of (-)-α-bisabolol against ischemic-reperfusion acute kidney injury.

BACKGROUND: Ischemia/reperfusion (I/R) in kidney is commonly related to acute kidney injury (AKI), essentially through oxidative stress. (-)-α-Bisabolol is a sesquiterpene isolated from the essential oil of a variety of plants, including chamomile, which has important antioxidant activity. STUDY DESIGN: This study intends to evaluate the nephroprotective activity of (-)-α-bisabolol (Bis) in both in vivo and in vitro models of kidney I/R. METHODS: Male Wistar rats were submitted to right nephrectomy, followed by ischemia by clamping of the renal artery in the left kidney for 60min. and 48h of reperfusion. The animals were treated orally with Bis (100mg/kg) or vehicle for 24h after reperfusion, and placed in metabolic cages, to evaluate water consumption, diuresis, urinary osmolality, classic biochemical markers and urinary KIM-1 (kidney injury molecule-1). Additionally, the left kidney was collected for histological evaluation and determination of glutathione (GSH) and Thiobarbituric Acid Reactive Substances (TBARS) levels. Tubular epithelial cells LLC-MK2 were used to assess Bis effect on in vitro I/R, by MTT assay. It was performed the cellular respiration tests by flow cytometry: evaluation of the production of cytoplasmic reactive oxygen species by DCFH-DA assay and mitochondrial transmembrane potential analysis with the dye rhodamine 123. RESULTS: I/R caused alterations in diuresis, water intake, urinary osmolality, plasmatic creatinine, urea and uric acid, creatinine clearance, proteinuria and microalbuminuria. Treatment with Bis ameliorated all of these parameters. Also, KIM-1 level enhanced by I/R was also diminished in groups treated with Bis. The histological examination showed that Bis attenuated the morphological changes caused by I/R, markedly vascular congestion and intratubular deposits of proteinaceous material. Additionally, Bis was able to reduce the changes observed in TBARS and GSH levels in kidney tissue. In in vitro assay, Bis was capable to partially protect the cell lineage against cell damage induced by I/R. CONCLUSION: (-)-α-Bisabolol has a nephroprotective effect in kidney I/R, with antioxidant effect. Moreover, this result seems to be associated to a direct protective effect on tubular epithelia.

Syndecan-1 improves severe acute kidney injury prediction after pediatric cardiac surgery.

OBJECTIVE: Acute kidney injury is a common occurrence after pediatric cardiac surgery and is associated with adverse patient outcomes. Syndecan-1 is a biomarker of endothelial glycocalyx damage, and its early increment after surgery can be associated with acute kidney injury. METHODS: We performed a prospective cohort study with 289 patients aged less than 18 years who underwent cardiac surgery at 1 reference institution. Postoperative plasma syndecan-1 was collected within the first 2 hours after cardiac surgery. Severe acute kidney injury, defined according to Kidney Disease: Improving Global Outcomes stage 2 or 3, doubling of serum creatinine from the preoperative value, or need for dialysis during hospitalization, was the main outcome. Analyses were adjusted for clinical variables and "renal angina index" components (early decrease in estimated creatinine clearance from baseline and increase in percent of intensive care unit fluid overload on the first postoperative day). RESULTS: Plasma syndecan-1 levels measured early in the postoperative period were independently associated with severe acute kidney injury. The accuracy of postoperative syndecan-1 for the diagnosis of severe acute kidney injury was moderate (area under the curve receiver operating characteristic, 0.77; 95% confidence interval, 0.68-0.85). The addition of syndecan-1 improved the discrimination capacity of a clinical model from 0.80 to 0.86 (P = .004) and improved risk prediction, as measured by net reclassification improvement and integrated discrimination improvement. Postoperative sundecan-1 levels also were independently associated with longer length of intensive care unit and hospital stay. CONCLUSIONS: Postoperative plasma syndecan-1 is associated with subsequent severe acute kidney injury and poor outcomes among children undergoing cardiac surgery. It may be useful to identify patients who are at increased risk for acute kidney injury after cardiac surgery.