Mioclonías positivas y negativas en paciente con enfermedad renal crónica / Positive and negative myoclonus in a patient with end stage renal disease

Introducción: Las mioclonías son contracciones musculares paroxísticas de corta duración o pérdida abrupta del tono muscular, denominadas mioclonías positivas y negativas, respectivamente. Se presenta un caso clínico de mioclonías positivas y negativas generalizadas y se pretende describir los múltiples mecanismos fisiopatológicos y etiologías que lo desencadenan. Presentación del caso: Hombre de 35 años, con diabetes mellitus tipo 1 complicada con enfermedad renal diabética en hemodiálisis, desarrolló una bacteriemia asociada a catéter por Staphylococcus aureus y presentó mioclonías positivas y negativas. Se identificaron como posibles desencadenantes la uremia, la infección y los fármacos con potencial promioclónico; el hallazgo incidental de una lesión isquémica en núcleo caudado no explicaba la semiología encontrada en el paciente. Se hizo el control y retiro de todos los factores promioclónicos enunciados, junto a manejo farmacológico con levetiracetam, y con ello se logró el control de los síntomas. Discusión: Los pacientes con enfermedad renal crónica son susceptibles a la acumulación de productos tóxicos de tipo guanidinas, que tienen potencial para producir mioclonías. Además, las infecciones, el uso de fármacos con potencial promioclónico y lesiones estructurales como las isquemias corticales son etiologías que deben considerarse en el diagnóstico diferencial. El mayor impacto en los síntomas se observa con el control del factor desencadenante, y, en caso de persistir, la terapia farmacológica proporciona buenos resultados. Conclusión: Las mioclonías son trastornos del movimiento relativamente comunes en la enfermedad renal crónica. La identificación del desencadenante es crucial para su manejo junto al uso de fármacos con actividad antimioclónica.

Introduction: Myoclonus are paroxysmal muscle contractions of short duration or abrupt loss of muscle tone, called positive and negative myoclonus respectively. A clinical case of generalized positive and negative myoclonus is presented and the aim is to describe the multiple pathophysiological mechanisms and etiologies that trigger it. Case presentation: A 35-year-old man with type 1 diabetes mellitus complicated by diabetic kidney disease on hemodialysis developed catheter-associated bacteremia due to Staphylococcus aureus and presented positive and negative myoclonus. Uremia, infection, and drugs with pro-myoclonic potential were identified as possible triggers; The incidental finding of an ischemic lesion in the caudate nucleus did not explain the semiology found in the patient. The control and removal of all the pro-myoclonic factors mentioned was carried out, along with pharmacological management with levetiracetam, thus achieving control of the symptoms. Discussion: Patients with chronic kidney disease are susceptible to the accumulation of guanidine-type toxic products, which have the potential to produce myoclonus. Furthermore, infections, the use of drugs with pro-myoclonic potential and structural lesions such as cortical ischemia are etiologies that should be considered in the differential diagnosis. The greatest impact on symptoms is observed with the control of the triggering factor and if it persists, pharmacological therapy provides good results. Conclusion: Myoclonus are relatively common movement disorders in chronic kidney disease. Identification of the trigger is crucial for its management along with the use of drugs with anti-myoclonic activity.

Performance of the Pandemic Medical Early Warning Score (PMEWS), Simple Triage Scoring System (STSS) and Confusion, Uremia, Respiratory rate, Blood pressure and age ≥ 65 (CURB-65) score among patients with COVID-19 pneumonia in an emergency department triage setting: a retrospective study

ABSTRACT BACKGROUND: Healthcare institutions are confronted with large numbers of patient admissions during large-scale or long-term public health emergencies like pandemics. Appropriate and effective triage is needed for effective resource use. OBJECTIVES: To evaluate the effectiveness of the Pandemic Medical Early Warning Score (PMEWS), Simple Triage Scoring System (STSS) and Confusion, Uremia, Respiratory rate, Blood pressure and age ≥ 65 years (CURB-65) score in an emergency department (ED) triage setting. DESIGN AND SETTING: Retrospective study in the ED of a tertiary-care university hospital in Düzce, Turkey. METHODS: PMEWS, STSS and CURB-65 scores of patients diagnosed with COVID-19 pneumonia were calculated. Thirty-day mortality, intensive care unit (ICU) admission, mechanical ventilation (MV) need and outcomes were recorded. The predictive accuracy of the scores was assessed using receiver operating characteristic curve analysis. RESULTS: One hundred patients with COVID-19 pneumonia were included. The 30-day mortality was 6%. PMEWS, STSS and CURB-65 showed high performance for predicting 30-day mortality (area under the curve: 0.968, 0.962 and 0.942, respectively). Age > 65 years, respiratory rate > 20/minute, oxygen saturation (SpO2) < 90% and ED length of stay > 4 hours showed associations with 30-day mortality (P < 0.05). CONCLUSIONS: CURB-65, STSS and PMEWS scores are useful for predicting mortality, ICU admission and MV need among patients diagnosed with COVID-19 pneumonia. Advanced age, increased respiratory rate, low SpO2 and prolonged ED length of stay may increase mortality. Further studies are needed for developing the triage scoring systems, to ensure effective long-term use of healthcare service capacity during pandemics.

Digital radiography as an alternative method in the evaluation of bone density in uremic rats / Radiografia digital como método alternativo na avaliação da densidade óssea em ratos urêmicos

ABSTRACT Introduction: Digital radiography (DRx) may provide a suitable alternative to investigate mineral and bone disorder (MBD) and loss of bone density (BD) in rodent models of chronic kidney disease (CKD). The objective of this study was to use DRx to evaluate BD in CKD rats, and to evaluate the correlation between DRx findings and serum MBD markers and bone histomorphometry. Methods: Uremia was induced by feeding Wistar rats an adenine-enriched diet (0.75% for 4 weeks/0.10% for 3 weeks); outcomes were compared to a control group at experimental weeks 3, 4, and 7. The following biochemical markers were measured: creatinine clearance (CrC), phosphate (P), calcium (Ca), fractional excretion of P (FeP), alkaline phosphatase (ALP), fibroblast growth factor-23 (FGF-23), and parathyroid hormone (PTH). DRx imaging was performed and histomorphometry analysis was conducted using the left femur. Results: As expected, at week 7, uremic rats presented with reduced CrC and higher levels of P, FeP, and ALP compared to controls. DRx confirmed the lower BD in uremic animals (0.57±0.07 vs. 0.68 ± 0.06 a.u.; p = 0.016) compared to controls at the end of week 7, when MBD was more prominent. A severe form of high-turnover bone disease accompanied these biochemical changes. BD measured on DRx correlated to P (r=-0.81; p = 0.002), ALP (r = -0.69, p = 0.01), PTH (r = -0.83, p = 0.01), OS/BS (r = -0.70; p = 0.02), and ObS/BS (r = -0.70; p = 0.02). Conclusion: BD quantified by DRx was associated with the typical complications of MBD in CKD and showed to be viable in the evaluation of bone alterations in CKD.

RESUMO Introdução: A radiografia digital (RxD) pode representar uma alternativa adequada para investigar o distúrbio mineral e ósseo (DMO) e a perda de densidade óssea (DO) em modelos de roedores da doença renal crônica (DRC). O objetivo deste estudo foi utilizar a RxD para avaliar a DO em ratos com DRC, e avaliar a correlação entre os achados da RxD e marcadores séricos de DMO e histomorfometria óssea. Métodos: A uremia foi induzida pela alimentação de ratos Wistar com dieta enriquecida com adenina (0,75% por 4 semanas/0,10% por 3 semanas); os resultados foram comparados com um grupo controle nas semanas experimentais 3, 4 e 7. Os seguintes marcadores bioquímicos foram medidos: clearance de creatinina (CCr), fosfato (P), cálcio (Ca), fração excretada de P (FeP), fosfatase alcalina (ALP), fator de crescimento de fibroblastos-23 (FGF-23) e paratormônio (PTH). A imagem da RxD foi obtida e a análise histomorfométrica foi realizada com o fêmur esquerdo. Resultados: como esperado, na semana 7, os ratos urêmicos apresentaram redução do CCr e níveis mais altos de P, FeP e ALP em comparação aos controles. A RxD confirmou a menor DO em animais urêmicos (0,57 ± 0,07 vs. 0,68 ± 0,06 u.a.; p = 0,016) em comparação aos controles no final da semana 7, quando a DMO foi mais proeminente. Uma forma grave de doença óssea de alta renovação celular acompanhou essas mudanças bioquímicas. A DO, medida na RxD foi correlacionada a P (r = -0,81; p = 0,002), ALP (r = -0,69, p = 0,01), PTH (r = -0,83, p = 0,01), OS/BS (r = -0,70 p = 0,02) e Ob.S/BS (r = -0,70; p = 0,02). Conclusão: A DO quantificada por RxD esteve associada às complicações típicas da DMO na DRC e mostrou-se viável na avaliação de alterações ósseas na DRC.

Effect of Dialysis on Aryl Hydrocarbon Receptor Transactivating Activity in Patients with Chronic Kidney Disease

Updates on the Diagnosis and Treatment of Restless Legs Syndrome / 신경정신의학

Restless legs syndrome (RLS) is a neurological sleep disorder characterized by an urge to move the legs or arms and is associated with discomfort and paresthesia in the legs. RLS is diagnosed based on the clinical symptoms, and polysomnography is performed to quantify the periodic limb movements during sleep or in patients who undergo the suggested immobilization test. Determining the cause of RLS is important for accurately diagnosing and evaluating this condition. The treatment of RLS varies according to the etiology, severity, and frequency of the patients' symptoms. Accurate identification and treatment of the cause of RLS are important in patients with secondary RLS. Iron supplementation could be useful in patients with uremia, iron deficiency, and for RLS during pregnancy. Dopamine agonists have been used as the first-line treatment for primary RLS. On the other hand, augmentation is a known adverse effect associated with the long-term use of dopamine agonists. Therefore, recent treatment guidelines recommend the administration of anticonvulsants, such as pregabalin and gabapentin, to treat RLS. Iron, opioids, or benzodiazepines may be useful in patients refractory to anticonvulsants or dopamine agonists. RLS is a chronic condition. Therefore, it is essential to establish a long-term treatment plan, considering both the efficacy and adverse effects of therapeutic agents used in patients.

Dystrophic mineralization in uremic dogs: an update / Mineralização distrófica em cães urêmicos: uma atualização

Pathological mineralization is the abnormal deposition of minerals in body tissues, previously injured or not. In these lesions, in addition to calcium, other minerals can be found at lower concentrations. Classically, mineralization is divided into two types: dystrophic and metastatic. However, currently, there is no consensus among researchers on the type of mineralization that occurs in uremic dogs. The objective of this study was to elucidate the type of pathological mineralization that occurs in dogs with uremic syndrome through the correlation of biochemical examinations with gross and histopathological changes, given the existence of controversial information on this theme in the specialized literature. The Shapiro-Wilk, D'Agostino and Pearson tests were used to evaluate data normality distribution, and analysis of variance (ANOVA) was applied to compare the data between more than two groups. Additionally, the Dunnett's multiple comparison test was used in the comparison between the Control Group (CG) and the Experimental Groups (G1, G2, and G3). Serum levels of urea, creatinine, total and ionized calcium, phosphorus, calcium-phosphorus product (CPP), parathyroid hormone (PTH), and albumin of 40 azotemic dogs with chronic kidney disease (CKD) were evaluated. Dogs were categorized by degree of azotemia (mild, moderate, and severe). Ionized hypocalcemia was observed in 97.5% (39/40) of the dogs, and no animals presented ionized hypercalcemia. Hyperphosphatemia was frequent (62.5%), especially in dogs with severe azotemia. PTH concentration increased with progression of azotemia, and high PTH levels were verified in 100% of the dogs with severe azotemia. CPP >60mg2/dl2 was observed in 75% (30/40) of the dogs. Of the 29 dogs that died during the study period, 16 were necropsied. Soft tissue mineralization was observed in 93.7% (15/16) of these dogs at gross and histopathological evaluation (HE and Von Kossa), regardless of the degree of azotemia, in nine organs/tissues: kidneys (75%), lungs (50%), stomach (31.2%), heart (25%), larynx (25%), intercostal muscles (25%), aorta (6.2%), intestines (6.2%), and tongue (6.2%). In one animal, the serosa of all segments of the small intestine showed whitish, rough, irregular, multifocal plaques of varying sizes, confirmed by histopathology as dystrophic mineralization of the longitudinal outer muscular layer, which presented necrosis of coagulation and of the intestinal serosa. This intestinal lesion has not been described in dogs with uremic syndrome to date. In conclusion, the laboratory and histopathologic data previously described, especially regarding tissue and vascular mineralization, which occur in association with previous degenerative/necrotic lesions in the absence of hypercalcemia in dogs with CKD, assist with clarifying inconsistencies found in the existing literature. Therefore, conceptually, mineralization that occurs in uremic dogs should be considered dystrophic.(AU)

Mineralização patológica é a deposição anormal de minerais em tecidos previamente lesados ou não. Nessas lesões, além do cálcio, outros minerais podem ser encontrados em concentrações inferiores. Classicamente, as mineralizações são divididas em dois tipos: distrófica e metastática. Contudo, atualmente, ainda não há consenso entre os pesquisadores sobre o tipo de mineralização que ocorre em cães urêmicos. Objetivou-se com esse estudo elucidar o tipo de mineralização patológica que ocorre em cães com síndrome urêmica através da correlação de exames bioquímicos com alterações macroscópicas e histopatológicas, visto a existência de informações controversas na literatura especializada. Os dados obtidos foram submetidos ao teste de Shapiro-Wilk e teste de D'Agostino e Pearson para avaliação da normalidade da distribuição e para comparação de dados em mais de dois grupos foi utilizado o teste ANOVA. Adicionalmente, o teste de comparações múltiplas de Dunnett permitiu a comparação entre o grupo controle (GC) com os demais grupos (G1, G2 e G3). Foram avaliados os níveis séricos de ureia, creatinina, cálcio total e ionizado, fósforo, produto cálcio-fósforo (PCF), PTH e albumina de 40 cães azotêmicos com doença renal crônica (DRC). Os cães foram classificados quanto ao grau de azotemia (leve, moderada e severa). Verificou-se hipocalcemia ionizada em 97,5% (39/40) dos cães e, em nenhum animal houve hipercalcemia ionizada. Hiperfosfatemia foi frequente (62,5%), principalmente em cães com azotemia severa. A concentração do PTH aumentou conforme a progressão da azotemia, encontrando-se elevada em 100% dos cães com azotemia severa. Em 75% (30/40) dos cães o PCF foi superior a 60mg2/dl2. Durante o estudo, 29 cães morreram, sendo 16 desses necropsiados. Em 93,7% (15/16) desses cães observou-se mineralização de tecidos moles, durante a avaliação macroscópica e histopatológica (HE e Von Kossa), independentemente do grau de azotemia, em nove órgãos/tecidos: rins (75%), pulmões (50%), estômago (31,2%), coração (25%), laringe (25%), músculos intercostais (25%), aorta (6,2%), intestino (6,2%) e língua (6,2%). Adicionalmente, em um animal verificou-se na serosa de todos os segmentos do intestino delgado placas multifocais brancacentas, rugosas, irregulares de tamanhos variados, cuja histopatologia confirmou tratar-se de mineralização distrófica da camada longitudinal muscular externa que apresentava necrose de coagulação e da serosa intestinal. Essa lesão intestinal nunca havia sido descrita em cães com síndrome urêmica. Em suma, os dados laboratoriais e histopatológicos aqui descritos, sobretudo, no que se refere à mineralização tecidual e vascular, que ocorrem relacionadas a lesões degenerativo-necróticas prévias, na ausência de hipercalcemia, em cães com DRC, ajudam a esclarecer as incongruências existentes na literatura. Por conseguinte, conceitualmente, as mineralizações que ocorrem em cães urêmicos devem ser consideradas distróficas.(AU)

The specific impact of uremic toxins upon cognitive domains: a review / O impacto específico de toxinas urêmicas em domínios cognitivos: uma revisão

ABSTRACT One of the mechanisms proposed for chronic kidney disease (CKD)-related cognitive impairment is the accumulation of uremic toxins due to the deterioration of the renal clearance function. Cognition can be categorized into five major domains according to its information processing functions: memory, attention, language, visual-spatial, and executive. We performed a review using the terms 'uric acid', 'indoxyl sulfate', 'p-cresyl sulfate', 'homocysteine', 'interleukins' and 'parathyroid hormone'. These are the compounds that were found to be strongly associated with cognitive impairment in CKD in the literature. The 26 selected articles point towards an association between higher levels of uric acid, homocysteine, and interleukin 6 with lower cognitive performance in executive, attentional, and memory domains. We also reviewed the hemodialysis effects on cognition. Hemodialysis seems to contribute to an amelioration of CKD-related encephalopathic dysfunction, although this improvement occurs more in some cognitive domains than in others.

RESUMO Um dos mecanismos propostos para explicar o comprometimento cognitivo relacionado à doença renal crônica (DRC) é o acúmulo de toxinas urêmicas devido à deterioração da função de depuração renal. A cognição pode ser categorizada em cinco domínios principais de acordo com suas funções de processamento de informações: memória, atenção, linguagem, visual-espacial e executiva. Realizamos uma revisão usando os termos "ácido úrico", "indoxil sulfato", "p-cresil sulfato", "homocisteína", "interleucinas" e "paratormônio". Estes são os compostos que se mostraram fortemente associados ao comprometimento cognitivo na DRC na literatura. Os 26 artigos selecionados apontam para uma associação entre níveis mais elevados de ácido úrico, homocisteína e interleucina-6 com menor desempenho cognitivo nos domínios executivo, atenção e de memória. Também revisamos os efeitos da hemodiálise na cognição. A hemodiálise parece contribuir para uma melhoria da disfunção encefalopática relacionada à DRC, embora essa melhora ocorra mais em alguns domínios cognitivos do que em outros.

Uremic neuropathy: an overview of the current literature

SUMMARY INTRODUCTION: Peripheral neuropathy is a disorder that affects the cell body, axon or myelin of motor or peripheral sensory neurons and occurs in 60-100% of patients who are submitted to dialysis due to chronic kidney disease. Uremic neuropathy is attributed to the accumulation of organic waste, evident in patients with reduced glomerular filtration rate. Objectives: This review aims to make clinical characteristics of uremic neuropathy evident enabling early diagnosis and treatment. Methods: This is a literature review of articles published on PubMed over the last 10 years using "Uremic Neuropathy" as "Title/Abstract". Results: A total of nine articles that met the inclusion criteria were included. UN is a distal symmetric sensorimotor polyneuropathy that occurs due to the accumulation of uremic toxins associated with an oxidative stress-related free radical activity. Hyperkalemia is thought to play an important role in its pathophysiology. Diagnosis depends on nerve conduction studies, and treatment includes dialysis or renal transplant. Conclusion: Clinical presentations of UN are broad and non-specific; nonetheless, it is important to detect early changes in order to avoid its progression. The earlier UN is diagnosed and treated, the more successful are the clinical outcomes.

RESUMO INTRODUÇÃO: A neuropatia periférica (NU) é um distúrbio que afeta o corpo celular, o axônio ou a mielina do motor ou neurônios sensoriais periféricos e ocorre em 60%-100% dos pacientes que são submetidos à diálise por doença renal crônica. A neuropatia urêmica é atribuída à acumulação de resíduos orgânicos, evidente em pacientes com taxa de filtração glomerular reduzida. Objetivo: O objetivo desta revisão é fazer com que as características clínicas da neuropatia urêmica sejam evidenciadas, permitindo o diagnóstico e tratamento precoce. Método: Esta é uma revisão da literatura de artigos publicados no PubMed nos últimos dez anos usando "Neuropatia Urêmica" como "Título/Resumo". Resultados: No total, foram incluídos nove artigos que atendem aos critérios de inclusão. A NU é uma polineuropatia sensório-motora simétrica distal que ocorre devido ao acúmulo de toxinas urêmicas associadas à atividade de radicais livres relacionados ao estresse oxidativo. A hipercalemia tem um papel importante na sua fisiopatologia. O diagnóstico depende de estudos de condução nervosa e o tratamento inclui diálise ou transplante renal. Conclusão: As apresentações clínicas das NU são amplas e não específicas; no entanto, é importante detectar mudanças iniciais para evitar sua progressão. Quanto mais precoce for a detecção e tratamento da NU, melhor será o resultado clínico.

The Colonoscopic Characteristics and Clinical Manifestations Associated with Lower Gastrointestinal Tract Bleeding in Patients with Chronic Kidney Disease / 대한내과학회지

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have a high risk of gastrointestinal tract bleeding because of platelet dysfunction attributable to uremia, a poor blood supply, and frequent use of anticoagulant agents. We describe the colonoscopic characteristics of lower gastrointestinal tract bleeding (LGIB) in patients with CKD. METHODS: A total of 230 hospitalized patients with CKD who underwent colonoscopy because of suspected LGIB between January 2003 and August 2016 were reviewed retrospectively. We categorized CKD into five stages according to the estimated glomerular filtration rate and compared the colonoscopic findings and clinical manifestations among these five subgroups. RESULTS: Of the 230 patients with CKD suspected of LGIB, 73 (31.7%, 103 cases) were colonoscopically confirmed to exhibit LGIB. Their mean age was 65.7 ± 12.8 years, and 52.1% were female (n = 38). The most common causes of LGIB were hemorrhoidal bleeding (32 cases, 43.8%), followed by bleeding of colorectal ulcers (21 cases, 28.8%), diverticular bleeding (12 cases, 16.4%), colitis-related bleeding (12 cases, 16.4%), and angiodysplastic bleeding (12 cases, 16.4%). As the CKD stage progressed, the incidence of LGIB increased (p = 0.043). On multivariate logistic regression analysis, LGIB was more common in CKD patients with hemorrhoids (odds ratio [OR]: 4.349, 95% confidence interval [CI]: 2.043–9.256, p < 0.001) or colorectal ulcers (OR: 20.001, 95% CI: 4.780–83.686, p ℃ 0.001) and in those on hemodialysis (OR: 6.863, 95% CI: 1.140–41.308, p = 0.035). CONCLUSIONS: In CKD patients, the risk of LGIB is significantly increased by hemorrhoids, colorectal ulcers, and a positive hemodialysis status.

Proportion of Aspiration Pneumonia Cases Among Patients With Community-Acquired Pneumonia: A Single-Center Study in Korea

OBJECTIVE: To investigate the proportion of aspiration pneumonia cases among patients with community-acquired pneumonia in Korea. METHODS: This retrospective study included patients with community-acquired pneumonia who had been admitted to the emergency department of a university-affiliated tertiary hospital in Gyeonggi Province, Korea between January 1, 2016 and December 31, 2016. Among these patients, those with aspiration pneumonia were identified using ICD-10 codes (J69.*). Patients with recurrent pneumonia were excluded, as were those who were immunocompromised. The proportion of cases of aspiration pneumonia was calculated, and the characteristics and clinical outcomes of patients with aspiration pneumonia and non-aspiration pneumonia were compared. RESULTS: The proportion of aspiration pneumonia cases among patients with community-acquired pneumonia was 14.2%. Patients with aspiration pneumonia were significantly more likely to be older (p<0.001) and male (p<0.001), and to have a higher confusion, uremia, respiratory rate, blood pressure, and age ≥65 years (CURB-65) score (p<0.001) as compared to patients with non-aspiration pneumonia. They were also more likely to require admission to the intensive care unit (p<0.001) and a longer hospital stay (p<0.001). CONCLUSION: Aspiration pneumonia accounts for 14.2% of all cases of community-acquired pneumonia in Korea. These data may contribute to the establishment of healthcare strategies for managing aspiration pneumonia among Korean adults.

Comportamento da variabilidade da frequência cardíaca e da capacidade funcional de acordo com o tempo de transplante renal / Behavior of variability of heart rate and functional capacity according to renal transplant time

Introdução: Desequilíbrio autonômico, com aumento da atividade simpática e redução da parassimpática, pode ocorrer no transplantado renal, representando forte indicador de risco cardíaco. Objetivo: Avaliar a variabilidade da frequência cardíaca (VFC) e a capacidade funcional dos transplantados renais de acordo com o tempo de transplante renal. Métodos: Série de casos envolvendo transplantados renais divididos em grupos de acordo com a mediana do tempo de transplante renal (158 meses). Foram avaliados a VFC através do Holter por 24 horas, o nível de atividade física (IPAQ) e o desempenho funcional (teste de caminhada de 6 minutos). Resultados: Os indivíduos comportaram-se diferentemente em relação à VFC e à capacidade funcional. No entanto, aqueles com maior tempo de transplante apresentaram maior VFC, eram menos ativos e variaram mais no desempenho funcional. Conclusão: O presente estudo constata a presença de diferenças individuais na VFC e no desempenho funcional entre os transplantados renais de acordo com o tempo de realização do TX.

Introduction: Autonomic imbalance, with increased sympathetic activity and reduction of parasympathetic activity, may occur in the renal transplantation patient, representing a strong indicator of cardiac risk. Objective: To assess heart rate variability (HRV) and functional capacity of kidney transplantation recipients according to the time of transplantation. Methods: A case series involving renal transplant recipients divided into groups according to the median of kidney transplantation time (158 months). HRV was evaluated through 24-hour Holter monitoring, physical activity level (IPAQ) and functional performance (6-minute walk test). Results: The individuals behaved differently in relation to HRV and functional capacity. Those with longer transplantation had higher HRV, were less active and presented more diverse functional performance. Conclusion: The present study notes the presence of individual differences in HRV and functional performance between renal transplants according to the time of TX.

Experiencia en hemodiálisis domiciliaria en España / Spanish home hemodialysis experience

Resumen Antecedentes: existe actualmente un interés creciente, a nivel mundial, por las posibilidades que ofrece la hemodiálisis domiciliaria, la cual se encuentra más extendida en países del norte de Europa, Canadá, Reino Unido, Estados Unidos, Australia y Nueva Zelanda. En España, ha crecido de manera muy lenta, excepto en determinadas regiones como la provincia de Castellón, donde hemos puesto especial interés en la expansión de las técnicas dialíticas domiciliarias. Objetivo: describir la experiencia en el programa de hemodiálisis domiciliaria del Hospital General de Castellón. Metodología: estudio descriptivo de los pacientes incluidos en el programa de hemodiálisis domiciliaria del Hospital General de Castellón, desde su inicio en enero del 2008 hasta diciembre del 2017. Resultados: en su conjunto, entrenamos a 41 pacientes, de los que 36 llegaron a hemodializarse en casa (régimen corto-diario). La edad de los pacientes era 58,3±13,4 años; y el índice de Charlson, 4,1±1,6. 62 % de los pacientes eran hombres, 25,6 % padecían diabetes mellitus; 15,4 % tenían diagnóstico de insuficiencia cardíaca y 32 % eran portadores de fístula de hemodiálisis. El 38,5 % de los pacientes en edad laboral estaba activo. Obtuvimos una supervivencia técnica considerando el evento muerte+fallo técnico, censurando el trasplante, del 79,4 % al año, 75,2 % a los 2 años y 42,1 % a los 5 años. En el análisis univariante, resultaron determinantes la edad, la presencia de diabetes mellitus y la presencia de insuficiencia cardíaca. En el análisis multivariante, solo se mantuvo la insuficiencia cardíaca. Las reducciones semanales de fósforo y beta-2-microglobulina fueron significativamente mayores con hemodiálisis corta diaria, en comparación con la hemodiafiltración on-line. La hemodiafiltración on-line fue superior en la reducción semanal a partir de los 17 800 daltons para la mioglobina. Conclusiones: la hemodiálisis domiciliaria es una técnica posible que ofrece al paciente una adecuada reinserción sociolaboral, buenos niveles de reducción semanal de toxinas urémicas y una aceptable supervivencia técnica en el tiempo.

Abstract Background: There is currently a growing interest, worldwide, for the possibilities offered by home hemodialysis, which is more widespread in northern European countries, Canada, the United Kingdom, the United States, Australia and New Zealand. In Spain, it has grown very slowly, except in certain regions such as the province of Castellón, where we have placed special interest in the expansion of home dialysis techniques. Objective: To describe the experience in the Home Hemodialysis program of the Hospital General de Castellón. Methodology: Descriptive study of the patients included in the home hemodialysis program of the Hospital General de Castellón, from its beginning in January 2008 to December 2017. Results: As a whole, we trained 41 patients, of whom 36 came to hemodialysis at home (short-day regimen). Age 58,3±13,4 years, Charlson index 4,1±1,6, 62 % men, 25,6 % with diabetes mellitus, 15,4 % with diagnosis of heart failure, 32 % with hemodialysis fistula, 38,5 % of working-age patients were active. We obtained a technical survival considering the event death+technical failure, censoring transplant of 79,4 % a year, 75,2 % at 2 years and 42,1 % at 5 years, resulting determinants of the event in the univariate analysis: age, presence of diabetes mellitus and presence of heart failure, and only heart failure in the multivariate. The weekly reductions of phosphorus and beta-2-microglobulin were significantly greater with daily short hemodialysis with respect to on-line haemodiafiltration. Being the on-line hemodiafiltration superior in the weekly reduction from the 17800 daltons of myoglobin. Conclusions: Home hemodialysis is a possible technique that offers the patient an adequate social-labor reintegration with good levels of weekly reduction of uraemic toxins and an acceptable technical survival over time.

In vitro effect of uremic serum on barrier function and inflammation in human colonocytes / Efeito in vitro do soro urêmico sobre a função de barreira e inflamação em colonócitos humanos

ABSTRACT Introduction: In chronic kidney disease (CKD), it has been suggested that alterations within the gut are associated with an inflammatory state and uremic toxicity. Studies suggest that uremia may impair the function of the intestinal barrier via the promotion of increased intestinal permeability. To understand the mechanisms that are involved in intestinal barrier damage in the setting of uremia, we evaluated the in vitro effect of uremic serum on transepithelial electrical resistance (TER), inflammation, and apoptosis in intestinal epithelial cells (T84). Methods: Pools of serum from healthy individuals, patients not on dialysis, and patients on hemodialysis (Pre-HD and Post-HD) were prepared. T84 cells were incubated for 24 h in medium, of which 10% consisted of the pooled serum from each group. After incubation, the TER was measured and the following parameters were determined by flow cytometry: expression of toll-like receptors (TLRs), production of reactive oxygen species (ROS), and apoptosis. The level of IL-6 in the culture supernatant was determined by ELISA. Results: No difference was observed among the groups with respect to TER, apoptosis, and ROS or the expression of TLR-2, TLR-4, and TLR-9. IL-6 secretion was higher (p < 0.001) in cells that were incubated with pre- and post-HD serum. Conclusion: The results that were obtained from this model suggest that uremic serum per se does not seem to impair the integrity of intestinal epithelial cells. The increased IL-6 secretion by cells that were incubated with HD serum suggests a potential effect of uremia in the intestinal inflammatory response.

RESUMO Introdução: Tem sido sugerido que na doença renal crônica (DRC) a uremia pode causar alterações intestinais, tais como modificações na microbiota e danos à barreira intestinal, e que estas possíveis alterações podem ter uma relação importante com o estado inflamatório e a toxicidade urêmica apresentadas por pacientes com DRC. Objetivos: Avaliar o efeito in vitro do soro urêmico sobre a permeabilidade da monocamada de células epiteliais do intestino, inflamação e apoptose. Métodos: Pools de soro foram preparados a partir de soros de indivíduos saudáveis, pacientes em tratamento conservador e em hemodiálise (Pré e Pós-HD). As células T84 foram incubadas por 24 horas com os diferentes pools. Em seguida a TER foi medida e as células foram submetidas às seguintes análises: apoptose, produção de espécies reativas de oxigênio (EROs) e expressão de receptores toll-like (TLR) por citometria de fluxo e detecção de IL-6 no sobrenadante da cultura por ELISA. Resultados: Não foram encontradas diferenças, entre os grupos, com relação a TER, apoptose, EROs e expressão de TLR-2, TLR-4 e TLR-9. Já a secreção de IL-6 foi maior (p < 0,001) pelas células incubadas com soro pré-HD e pós-HD. Conclusão: Os resultados obtidos a partir deste modelo sugerem que a uremia per se parece não comprometer a integridade das células epiteliais do intestino. O aumento da secreção de IL-6 pelas células incubadas com soro HD (pré e pós) sugere um potencial efeito da uremia sobre a resposta inflamatória intestinal.

Estomatitis Urémica como Complicación Oral de Insuficiencia Renal Crónica: Reporte de Caso y Revisión de la Literatura / Uremic Stomatitis as an Oral Complication of Chronic Renal Failure: Case Report and Literature Review

RESUMEN: La Estomatitis Urémica es una lesión oral poco frecuente que se presenta generalmente en pacientes con insuficiencia renal crónica avanzada o no tratada. A continuación, se reporta un caso clínico de un paciente masculino de 22 años de edad que acude a un servicio de urgencia con la presencia de placas blanquecinas indoloras en piso de boca, cara interna de mejilla, y lengua. Las probables causas, presentaciones clínicas, y manejo odontológico son discutidos.

ABSTRACT: Uremic stomatitis is a rare oral lesion that usually occurs in patients with advanced or untreated chronic renal failure. Here we report a case of a 22-year-old male patient who comes to an emergency department with the presence of painless whitish plaques on the floor of the mouth, internal cheek face, and tongue. Probable causes, clinical presentations, and dental management are discussed.

Biomarkers of cardio-renal syndrome in uremic myocardiopathy animal model / Biomarcadores de síndrome cardiorrenal em modelo animal de miocardiopatia urêmica

ABSTRACT Introduction: Cardio-renal syndrome subtype 4 (CRS4) is a condition of primary chronic kidney disease that leads to reduction of cardiac function, ventricular hypertrophy, and risk of cardiovascular events. Objective: Our aim was to understand the mechanisms involved on the onset of CRS4. Methods: We used the nephrectomy 5/6 (CKD) animal model and compared to control (SHAM). Serum biomarkers were analyzed at baseline, 4, and 8 weeks. After euthanasia, histology and immunohistochemistry were performed in the myocardium. Results: Troponin I (TnI) was increased at 4 weeks (W) and 8W, but nt-proBNP showed no difference. The greater diameter of cardiomyocytes indicated left ventricular hypertrophy and the highest levels of TNF-α were found at 4W declining in 8W while fibrosis was more intense in 8W. Angiotensin expression showed an increase at 8W. Conclusions: TnI seems to reflect cardiac injury as a consequence of the CKD however nt-proBNP did not change because it reflects stretching. TNF-α characterized an inflammatory peak and fibrosis increased over time in a process connecting heart and kidneys. The angiotensin showed increased activity of the renin-angiotensin axis and corroborates the hypothesis that the inflammatory process and its involvement with CRS4. Therefore, this animal study reinforces the need for renin-angiotensin blockade strategies and the control of CKD to avoid the development of CRS4.

RESUMO Introdução: A síndrome cardiorrenal (SCR) tipo 4 é uma afecção da doença renal crônica primária que leva a redução da função cardíaca, hipertrofia ventricular e risco de eventos cardiovasculares. Objetivo: O objetivo do presente estudo foi compreender os mecanismos envolvidos no surgimento da SCR tipo 4. Métodos: Um modelo animal de nefrectomia 5/6 (DRC) foi comparado a animais de controle (Placebo). Biomarcadores séricos foram analisados no início do estudo e com quatro e oito semanas de estudo. Após eutanásia, foram realizados exames histológicos e de imunoistoquímica no tecido miocárdico. Resultados: Troponina I (TnI) estava aumentada nas semanas quatro (S4) e oito (S8), mas o NT-proBNP não apresentou diferenças. O diâmetro maior dos cardiomiócitos indicava hipertrofia ventricular esquerda. Os níveis mais elevados de TNF-α foram identificados na S4 com redução na S8, enquanto fibrose foi mais intensa na S8. A expressão de angiotensina mostrou elevação na S8. Conclusões: TnI parece sugerir lesões cardíacas em consequência da DRC, porém o NT-proBNP não sofreu alterações por refletir alongamento. O TNF-α evidenciou um pico inflamatório e a fibrose aumentou ao longo do tempo devido ao processo de conexão entre rins e coração. A angiotensina mostrou aumento da atividade do eixo renina-angiotensina, corroborando a hipótese do processo inflamatório e seu envolvimento com SCR tipo 4. Portanto, o presente estudo em modelo animal reforça a necessidade de em adotar estratégias com bloqueadores de renina-angiotensina e controle da DRC para evitar o desenvolvimento de SCR tipo 4.

Understanding and Therapeutic Strategies of Chinese Medicine on Gut-Derived Uremic Toxins in Chronic Kidney Disease / 中国结合医学杂志

Chronic kidney disease (CKD) is a major disease that threatens human health. With the progression of CKD, the risk of cardiovascular death increases, which is associated with the elevated levels of uremic toxins (UTs). Representative toxins such as indoxyl sulfate and p-cresyl sulfate are involed in CKD progression and cardiovascular events inseparable from the key role of endothelial dysfunction. The therapeutic strategies of UTs are aimed at signaling pathways that target the levels and damage of toxins in modern medicine. There is a certain relevance between toxins and "turbid toxin" in the theory of Chinese medicine (CM). CM treatments have been demonstrated to reduce the damage of gut-derived toxins to the heart, kidney and blood vessels. Modern medicine still lacks evidence-based therapies, so it is necessary to explore the treatments of CM.

Posterior Reversible Encephalopathy Syndrome Combined with Uremia Encephalopathy

No abstract available.

Early diagnosis, prevention and treatment for calcific uremic arteriolopathy / 中南大学学报(医学版)

Calcific uremic arteriopathy (CUA), termed calciphylaxis, is a rare but highly fatal clinical syndrome. There is no clearly laboratory diagnostic criteria for CUA. The medium and small arterial calcification and microthrombosis discovered by skin biopsy, radiologic imaging，bone scan and the evidence of activation of the bone morphogenetic protein signal (BMPs) transduction pathway are useful for early diagnosis of this disease. The common therapies (including intravenous sodium thiosulfate (STS) and bisphosphonates, hyperbaric oxygen therapy and other symptomatic supports) are used for the management of wounds, pain, nutrition, dialysis and so on. Controlling the chronic kidney disease-mineral and bone disorder (CKD-MBD) and some complications of dialysis and drugs (such as warfarin, active vitamin D) can prevent CUA. However, CUA patients still have poor prognosis and high mortality. Since some patients progress rapidly, it is of great importance to make early diagnosis and provide effective treatments with multidisciplinary management.

Brain consequences of acute kidney injury: Focusing on the hippocampus

The high mortality rates associated with acute kidney injury are mainly due to extra-renal complications that occur following distant-organ involvement. Damage to these organs, which is commonly referred to as multiple organ dysfunction syndrome, has more severe and persistent effects. The brain and its sub-structures, such as the hippocampus, are vulnerable organs that can be adversely affected. Acute kidney injury may be associated with numerous brain and hippocampal complications, as it may alter the permeability of the blood-brain barrier. Although the pathogenesis of acute uremic encephalopathy is poorly understood, some of the underlying mechanisms that may contribute to hippocampal involvement include the release of multiple inflammatory mediators that coincide with hippocampus inflammation and cytotoxicity, neurotransmitter derangement, transcriptional dysregulation, and changes in the expression of apoptotic genes. Impairment of brain function, especially of a structure that has vital activity in learning and memory and is very sensitive to renal ischemic injury, can ultimately lead to cognitive and functional complications in patients with acute kidney injury. The objective of this review was to assess these complications in the brain following acute kidney injury, with a focus on the hippocampus as a critical region for learning and memory.

Effects of renal dysfunction on healing of colonic anastomosis: experimental study in wistar rats / Efeitos da disfunção renal na cicatrização de anastomoses colônicas: estudo experimental em ratos wistar

ABSTRACT Background: Chronic kidney disease affects more than 500 million people worldwide. In this context, the uremic toxins present are related to worsening in tissue healing. Aim: Evaluate on healing of colonic anastomosis in uremic rats, serum and anatomopathological indicators, which may be related to the change tissue repair process. Methods: Twenty Wistar rats, were randomly separated into two groups. In the sham group they were submitted to 5/6 nephrectomy simulation in left kidney, simulation right nephrectomy, median laparotomy, colotomy and colorraphy. In the uremia group, they were submitted to 5/6 nephrectomy of the left kidney, total nephrectomy of the right kidney and median laparotomy, colotomy and colorraphy. Were collected for serum urea, creatinine and CRP dosages and the colonic segments were studied for evaluation of granulation tissue, collagen maturation, microvascular and myofibroblasts density, and cell viability. Through histochemical processing, microvascular density was evaluated by anti-CD34 monoclonal antibody marking, cell viability by cell proliferation nuclear antigen screening and myofibroblasts density with monoclonal anti-α-actin antibody. Computerized histometry was used for evaluations of collagens type I and III by the coloration of picrosirius. Results: The group submitted to nephrectomy 5/6, compared to the sham group, show urea increase (p<0.0000) and higher C reactive protein (p=0.0142). Decrease of granulation tissue formation (border reepithelialization p=0,0196, angiofibroblast proliferation p=0.0379), mean collagen I (p=0,0009) and collagen III (p=0,016), microvascular density (p=0,0074), cell proliferation nuclear antigen (p<0,0000) and myofibroblasts (p<0,0001). Conclusion: The uremia induced by nephrectomy 5/6 model establishes negative impact in the colonic wound healing.

RESUMO Racional: A doença renal crônica atinge mais de 500 milhões de pessoas em todo o mundo. Neste contexto, as toxinas urêmicas estão relacionadas ao comprometimento da cicatrização tecidual. Objetivo: Avaliar, na cicatrização de anastomoses colônicas de ratos urêmicos indicadores séricos e anatomopatológicos que possam estar relacionados com alteração do processo de reparação tissular. Métodos: Utilizaram-se 20 ratos Wistar divididos aleatoriamente em dois grupos. No grupo simulação eles foram submetidos à simulação da nefrectomia 5/6 do rim esquerdo, simulação de nefrectomia total do rim direito, laparotomia mediana, colotomia e colorrafia. No grupo uremia, eles foram submetidos à nefrectomia 5/6 do rim esquerdo, nefrectomia total do rim direito, laparotomia mediana, colotomia e colorrafia. Coletaram-se amostras de sangue para dosagens séricas da ureia, creatinina e proteína C reativa, e do cólon para processamentos histológicos e histoquímicos na avaliação do tecido de granulação, maturação de colágeno, densidade microvascular e de miofibroblastos, viabilidade celular cicatricial. Empregou-se a histometria computadorizada para as avaliações de colágenos tipos I e III, densidade microvascular pela marcação com anticorpo monoclonal anti-CD34, viabilidade celular pela pesquisa do antígeno nuclear de proliferação celular e a densidade de miofibroblastos com anticorpo monoclonal anti-α-actina. Resultados: O grupo submetido à nefrectomia 5/6, em comparação ao grupo simulação, demonstraram aumentos da ureia sérica (p<0,0000) e proteína C reativa (p=0,0142), redução da formação de tecido de granulação (reepitelização de bordas p=0,0196, proliferação angiofibroblástica p=0,0379), porcentagens de colágeno I (p=0,0009) e colágeno III (p=0,016), densidade microvascular (p=0,0074) e miofibroblastos (p<0,0001) e antígeno nuclear de proliferação celular (p<0,0000). Conclusão: A uremia induzida pelo modelo de nefrectomia 5/6 determina impacto negativo no processo de cicatrização colônico.