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.

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.

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.

Reversal of uremic tumoral calcinosis by optimization of clinical treatment of bone and mineral metabolism disorder / Reversão da calcinose tumoral urêmica pela otimização do tratamento clínico da desordem do metabolismo ósseo e mineral

Abstract Tumoral calcinosis is an uncommon type of extraosseous calcification characterized by large rubbery or cystic masses containing calcium-phosphate deposits. The condition prevails in the periarticular tissue with preservation of osteoarticular structures. Elevated calcium-phosphorus products and severe secondary hyperparathyroidism are present in most patients with uremic tumoral calcionosis (UTC). Case report of an obese secondary to chronic glomerulonephritis, undergoing continuous ambulatory peritoneal dialysis (CAPD) reported the appearance of painless tumors in the medial surface of fifth finger and left arm. Tumoral calcinosis was confirmed by left biceps biopsy. Poor adherence to CAPD. The patient was transferred to the "tidal" modality of peritoneal dialysis and after was treated by hemodialysis, despite the persistence of severe hyperparathyroidism progressive reduction of UTC until near to its complete disappearance. Nowadays, one year after patient received deceased-donor kidney transplantation, he presents with an improvement in secondary hyperparathyroidism. UTC should be included in the elucidation of periarticular calcification of every patient on dialysis. Relevant laboratory findings such as secondary hyperparathyroidism and elevated calcium- phosphorus products in the presence of periarticular calcification should draw attention to the diagnosis of UTC.

Resumo A calcinose tumoral é um tipo raro de calcificação extraóssea caracterizada por grandes massas císticas e elásticas contendo depósitos de fosfato de cálcio. A condição é mais prevalente no tecido periarticular e preserva estruturas osteoarticulares. A elevação do produtos cálcio-fósforo e o hiperparatireoidismo secundário grave estão presentes na maioria dos pacientes com calcinose tumoral urêmica (UTC). O relato de caso em questão refere-se a um homem de 22 anos, branco, obeso, com doença renal crônica secundária à glomerulonefrite crônica, em diálise peritoneal ambulatorial contínua (CAPD), que apresentou aparecimento de tumores indolores na face medial do quinto quirodáctilio e braço esquerdo. A calcinose tumoral foi confirmada por biópsia do bíceps esquerdo. O paciente apresentava baixa adesão à CAPD. Foi transferido para a modalidade de diálise peritoneal e depois iniciou tratamento por hemodiálise. Apesar da persistência do hiperparatireoidismo grave, houve redução progressiva da UTC, com resolução próxima do seu desaparecimento completo. Há 1 ano o paciente foi submetido a transplante renal, doador falecido, e apresentou melhora do hiperparatiroidismo secundário. A UTC deve ser incluída na elucidação de calcificação periarticular de pacientes em diálise. Os achados laboratoriais relevantes, tais como hiperparatiroidismo secundário e elevação dos produtos cálcio-fósforo na presença de calcificação periarticular, devem chamar a atenção para o diagnóstico da UTC.

The quest for a better understanding of chronic kidney disease complications: an update on uremic toxins / Em busca de uma melhor compreensão da doença renal crônica: uma atualização em toxinas urêmicas

Chronic kidney disease is characterized by a progressive reduction of glomerular filtration rate and/or the appearance of proteinuria, and subsequently the progressive retention of organic waste compounds called uremic toxins (UT). Over the last decades, a large number of such compounds have been identified and their effects on organs and tissues, especially the cardiovascular system, has been demonstrated. In this review, we present the current classification of UT, as proposed by the EUTox Group, and the effects of some of the probably most important UTs, such as phosphate, FGF-23, PTH, AGEs, indoxyl sulfate and para-cresyl sulfate. We provide an overview on therapeutic approaches aimed to increase their extracorporeal removal via convective and/or adsorptive strategies and to lower their intestinal production/ absorption via dietetic and pharmacological interventions. The recognition that multiple toxins contribute to the uremia supports the need for new therapeutic targets, with a potentially positive impact on CKD progression and survival.

A doença renal crônica (DRC) caracteriza-se pela redução progressiva da filtração glomerular e/ou presença de proteinúria, e subsequente retenção progressiva de compostos orgânicos, denominados toxinas urêmicas. Nas últimas décadas, um grande número destes compostos foi identificado, assim como seus efeitos adversos no organismo, sobretudo no sistema cardiovascular. Nesta revisão, apresentamos a classificação das toxinas urêmicas, proposta pelo grupo europeu de estudo em toxinas urêmicas (EUTox), e discutiremos os efeitos de algumas das principais toxinas, como ADMA, fosfato, FGF-23, PTH, AGEs, indoxil sulfato e para-cresil sulfato. Além disso, abordaremos as principais estratégias terapêuticas para aumentar a remoção das toxinas urêmicas por métodos convectivos e/ou adsortivos; e para diminuir a produção e absorção intestinal dessas toxinas por meio de intervenções dietéticas e farmacológicas, respectivamente. A compreensão de que múltiplas toxinas contribuem para a uremia expõe a necessidade de novos alvos-terapêuticos, com potencial impacto positivo na progressão da DRC e na sobrevida dos pacientes.

Uremic pruritus in hemodialysis patients: treatment with desloratidine versus gabapentin / Prurido urêmico em pacientes em hemodiálise: tratamento com desloratidina versus gabapentina

INTRODUCTION: Uremic pruritus is common among dialysis patients. Effective treatments are not readily available. Early evidence with antihistamines and gabapentin indicate variable effects. OBJECTIVE: To compare the efficacy and side effects of gabapentin and desloratadine in patients with dialysis pruritus. METHODS: Prospective, open-label, cross-over clinical trial in 22 patients on chronic hemodialysis with sustained pruritus over a period of at least 60 days. After a one-week run-in period, we assigned patients to three weeks of either gabapentin 300 mg thrice weekly or desloratadine 5 mg thrice weekly. After a one-week washout period, each patient crossed-over to the alternate regimen for three more weeks. The primary endpoint of the study was the change in the visual analogue pruritus score (VAS). RESULTS: Nineteen subjects completed the two treatment blocks and were available for analysis. VAS scores decreased with both treatments (5.95 to 4.6 with gabapentin, p = 0.07; 5.89 to 3.4 with desloratadine, p = 0.004), but only desloratadine reached statistical significance. There were no differences when comparing the final pruritus score with gabapentin and desloratadine (4.6 versus 3.4, p = 0.16) Excessive sedation was common with gabapentin. Desloratadine was well tolerated. CONCLUSION: Desloratadine provides significant relief of uremic pruritus compared with no therapy. gabapentin has marginal efficacy. Desloratadine is better tolerated than gabapentin.

INTRODUÇÃO: Prurido urêmico é comum entre pacientes em diálise. Tratamentos eficazes não estão disponíveis até o momento. Provas recentes com anti-histamínicos e gabapentina indicam vários efeitos. OBJETIVO: Comparar a eficiência e os efeitos colaterais da gabapentina e da desloratadina em pacientes com prurido na diálise. MÉTODOS: Estudo prospectivo, aberto e comparativo com 22 pacientes em hemodiálise crônica com prurido constante durante um período de pelo menos 60 dias. Após uma semana, submetemos os pacientes a três semanas de gabapentina 300 mg, três vezes por semana, ou desloratadina 5 mg três vezes por semana. Após um período de eliminação de uma semana, os pacientes trocaram de regime por mais três semanas. O objetivo primário do estudo foi a mudança na escala visual analógica (EVA) de prurido. RESULTADOS: Dezenove indivíduos completaram os dois tratamentos e foram submetidos à análise. Os escores da EVA caíram com ambos os tratamentos (5,95 para 4,6 com gabapentina, p = 0,07; 5,89 para 3,4 com desloratadina, p = 0,004), mas somente a desloratadina teve significância estatística. Nenhuma diferença foi observada ao comparar o escore final do prurido com gabapentina e desloratadina (4,6 versus 3,4, p = 0,16). Excesso de sedação foi comum com gabapentina. A desloratadina teve alto nível de tolerância. CONCLUSÃO: A desloratadina dá alívio significante do prurido urêmico quando comparada a nenhum tratamento. A gabapentina tem eficiência marginal. A desloratadina tem maior nível de tolerância em relação à gabapentina.

Uremic Encephalopathy with Atypical Magnetic Resonance Features on Diffusion-Weighted Images

Uremic encephalopathy is a well-known disease with typical MR findings including bilateral vasogenic or cytotoxic edema at the cerebral cortex or basal ganglia. Involvement of the basal ganglia has been very rarely reported, typically occurring in uremic-diabetic patients. We recently treated a patient who had non-diabetic uremic encephalopathy with an atypical lesion distribution involving the supratentorial white matter, without cortical or basal ganglia involvement. To the best of our knowledge, this is only the second reported case of non-diabetic uremic encephalopathy with atypical MR findings.

Indução de resposta inflamatória sistêmica e espessamento de artérias subepicárdicas em um modelo animal de uremia / Induction of systemic inflammation and thickening of subepicardiac arteries in an animal model of uremia

A disfunção renal é um fator de risco para doença cardiovascular (DCV). Estudos experimentais controlados que possam analisar o impacto da disfunção renal no sistema cardiovascular, isolando esses fatores relacionados à uremia dos fatores de risco tradicionais, que são altamente prevalentes na população com doença renal crônica (DRC), ainda são escassos. OBJETIVO: Analisar o impacto cardiovascular em ratos com disfunção renal, analisando biomarcadores de risco cardiovascular e a histologia das artérias subepicárdicas desses animais. MÉTODOS: Estudo experimental envolvendo trinta ratos machos Wistar, divididos em dois grupos. Um grupo foi submetido à ablação renal e o outro grupo SHAM (grupo controle) à manipulação do pedículo renal. Ambos os grupos foram acompanhados por oito semanas, período em que foram feitas dosagens de ureia, fósforo e do fator de necrose tumoral alfa (TNF-α). Lâminas obtidas de cortes do miocárdio foram confeccionadas para análise das características das arteríolas subepicárdicas. RESULTADOS: O grupo DRC apresentou níveis elevados de uréia e fósforo em relação ao grupo SHAM. Já os níveis de TNF-α, em todas as análises, foram indetectáveis nos animais do grupo SHAM, em contraste com o grupo DRC, onde se observaram elevados níveis de TNF-α (p < 0,05). A espessura da camada média dos vasos subepicárdicos do grupo DRC foi significativamente maior do que em relação ao grupo SHAM (p = 0,011). CONCLUSÃO: A indução de disfunção renal determinou alterações em biomarcadores de risco cardiovascular e um aumento na espessura dos vasos subepicárdicos estudados em comparação aos animais com função renal normal.

Although renal dysfunction is a known risk factor for cardiovascular disease (CVD), there are few experimental studies investigating the cardiovascular consequences of this condition. OBJECTIVE: To analyze the impact of the induction of renal dysfunction on biomarkers of cardiovascular risk and on the histology of subepicardial vessels. METHODS: This experimental study involved thirty Wistar male rats, which were divided into two groups. One (chronic kidney disease - CKD group) underwent renal ablation, and the other (SHAM group) was submitted to kidney manipulation only. Both groups were followed up for eight weeks. During follow-up, serum levels of urea, phosphorus and TNF-α were measured. Heart tissue was processed for histological analysis. RESULTS: The CKD group had increased levels of urea and phosphorus, in comparison with the SHAM group. The levels of TNF-α were increased in the CKD group and undetectable in the SHAM group (p < 0.05). Thickness of the middle layer of the subepicardial vessels of the CKD group was significantly higher than that of the SHAM group (p = 0.011). CONCLUSION: Induction of renal dysfunction in rats increased the biomarkers of cardiovascular risk and led to a thickening of the subepicardial vessels when compared with normal controls,.

Avaliação e manejo da doença cardiovascular em pacientes com doença renal crônica / Assessment and management of cardiovascular disease in patients with chronic renal disease

Doenças cardiovasculares são as principais complicações fatais da doença renal crônica, tanto para pacientes em terapia renal substitutiva quanto para aqueles em tratamento conservador. A análise de seus fatores de risco, abordagem diagnóstica e adequado tratamento são fundamentais para a redução de mortalidade associada a essas complicações. Neste artigo de revisão são discutidos aspectos de fisiopatologia, métodos de investigação e abordagem terapêutica da doença cardiovascular na doença renal crônica.

Cardiovascular diseases are the major fatal complications of chronic kidney disease, both for patients in renal replacement therapy and for those on dialysis. The analysis of their risk factors, diagnosis and appropriate treatment are key to reducing mortality associated with these complications. In this review we discuss aspects of pathophysiology, research methods and therapeutic approach to cardiovascular disease in chronic kidney disease.

Prevalência da síndrome das pernas inquietas em pacientes em terapias de hemodiálise em um centro na região sul de Santa Catarina – Brasil / Restless legs syndrome prevalence in patients in haemodialysis therapy in a reference service in south Santa Catarina – Brazil

Introdução: A síndrome das pernas inquietas (SPI) tem sido relacionada a diversas doenças, entre elas doença renal e anemia. Objetivo: Descrever a prevalência da síndrome das pernas inquietas (SPI) nos pacientes em terapia de hemodiálise na região da Associação dos Municípios da Região de Laguna, Santa Catarina, Sul do Brasil (AMUREL). Métodos: 117 indivíduos submetidos à terapia de hemodiálise na região da AMUREL foram entrevistados para se avaliar a presença, o tipo (primária ou secundária) e a gravidade da SPI, creatinina, ureia, ferro e ferritina séricos. Resultados: A prevalência de SPI foi de 30,8% (n=36). Dos portadores, 33,3% tiveram o diagnóstico de SPI primária e 66,7% (n=24) o de SPI secundária .Quanto à gravidade, 58,3% foram classificados como intermitente, 16,7% em persistente leve, 8,3% em persistente moderada e 16,7% em ersistente grave. A maior parte dos casos de SPI não tinha sido diagnosticada anteriormente. Não foi encontrada correlação com os parâmetros bioquímicos nem diferenças significativas entre os sexos. Conclusão: A síndrome das pernas inquietas é comum e pouco diagnosticada. Sua prevalência é considerável e aumenta substancialmente em indivíduos urêmicos. Não encontramos nenhuma evidência de que anemia por deficiência de ferro e ferritina, nem índices altos de ureia e creatinina séricos possam desempenhar um importante papel patogênico.

Introduction: Restless legs syndrome (RLS) has been related to several diseases, including renal disease and anaemia. Aim: To determine the prevalence of restless legs syndrome in patients under haemodialysis therapy in the region of the Association of Municipalities of the Region of Laguna (AMUREL), in the state of Santa Catarina, South Brazil. Methods: 117 patients undergoing haemodialysis in the AMUREL region were interviewed in order to evaluate the presence, type (primary or secondary), and severity of RLS, as well as their serum creatinine, urea, iron, and ferritin levels. Results: The prevalence of RLS was 30.8% (n=36). Among the affected individuals, 33.3% were diagnosed with primary RLS and 66.7% (n=24) with secondary RLS. Concerning severity, 58.3% were rated as intermittent, 16.7% as mildly persistent, 8.3% as moderately persistent, and 16.7% as severely persistent. Most of the cases of RLS had not been diagnosed before. No correlation of RLS was detected with the biochemical measures, nor differences between the sexes. Conclusion: Restless legs syndrome is common and underdiagnosed. Its prevalence is considerable and increases significantly in uraemic individuals. We failed to find any evidence that iron and ferritin deficiency anaemia, or high serum urea and creatinine, can play an important pathogenic role.

Evaluation of the effect of narrow band UVB in the treatment of uremic pruritis and its relation to divalent ion: calcium and phosphorus

Pruritis occurs in about 35% of chronic renal failure patients, and up to 85% of those undergoing dialysis. Our study demonstrates the efficacy of narrow band 310-315, a relatively novel UVB machine in the treatment of uremic patients, since the difference in the number of patients who improved after narrow band UVB and those improved without narrow band UVB therapy was highly significant [P<0.001]. The study also shows that serum and skin phosphorus plays the major role in the pathogenesis of uremic patients and that narrow band UVB reduces serum phosphate level and possibly skin phosphate content thus preventing precipitation of phosphate molecules as magnesium phosphate in skin cells. The latter is responsible for pruritis through irritation of free nerve endings

Evaluation of some platelet functions and platelet membrane glycoproteins in uremic, hemodialysis and renal transplant patients

The hemostatic defect of chronic renal failure [CRF] is well recognized. Increased bleeding has been attributed to platelet dysfunction. However, the available reports are controversial. To study platelet aggregation and glycoprotein receptors' [GP] expression in a well identified population with CRF. 25 patients with advanced CRF on conservative treatment [CRF group], 25 patients on regular hemodialysis [HD group], 25 renal transplant patients [Tx group], and 20 age-, race- and sex-matched healthy controls [control group] were subjected to complete physical examination, complete blood count, bleeding time [BT], renal functional parameters and other necessary laboratory tests, in addition to estimation of platelet aggregation in response to adenosine 5-diphosphate [ADP] and ristocetin as well as GPIb, GPIIb, and GPIIIa receptors' expression using fluorescein isothiocyanate-conjugated monoclonal antibodies CD42b, CD41 and CD62, respectively and a flow cytometer. BT was prolonged in both CRF and HD groups [P<0.001], and was not attributed to a decrease in platelet count. Both CRF and HD patients had similar, but significantly decreased maximum percentage of platelet aggregation induced by either ADP or ristocetin compared with Tx and healthy control groups [P<0.001]. GPIb expression was significantly decreased in the CRF group than the Tx and healthy control groups [P<0.05], while HD group showed non significant difference when compared with CRF, Tx or control groups. GPIIb and GPIIIa showed a highly significant decreased expression in both CRF and HD groups compared with Tx and healthy control groups [P<0.001], with no significant difference in between both uremic groups. An inverse correlation was observed between serum creatinine and GPIIb [r=-0.641, P=0.023] and GPIIIa [r=-0.545, P=0.031] receptors' expression in CRF patients versus no correlation in HD patients. The results of the studied parameters in Tx group were comparable to healthy controls. Uremic patients have decreased platelet aggregability and decreased GP receptors' expression [mainly GPIIb and GPIIIa], denoting that platelet dysfunction is at least partially contributing to their hemorrhagic problem. The observed defects were not corrected by regular HD. Renal transplantation seemed to be a better choice

Doença renal crônica, inflamação e aterosclerose: novos conceitos de um velho problema / Chronic renal disease, inflammation and atherosclerosis: new concepts about an old problem

A doença renal crônica (DRC) atinge hoje proporções epidêmicas e constitui um problema emergente de saúde pública. Fatores de risco comuns entre a uremia e a doença cardiovascular (DCV) são reconhecidos e resultam na elevada prevalência de eventos cardiovasculares que são a principal causa de morte em pacientes com DRC. O desenvolvimento de aterosclerose acelerada está relacionado a fatores de risco tradicionais, como diabetes mellitus, hipertensão arterial, dislipidemia e tabagismo, mas recentemente tem sido verificado que outros fatores não tradicionais também estão fortemente associados, entre os quais inflamação, estresse oxidativo, disfunção endotelial e a uremia per se, mesmo em estágios mais precoces da DRC. Marcadores do estado inflamatório, como proteína C-reativa, interleucina 6 e fibrinogênio, correlacionam-se com mortalidade cardiovascular. A associação entre inflamação, desnutrição e aterosclerose acelerada compõe a síndrome MIA (malnutrition, inflammation and atherosclerosis), comumente detectada em urêmicos, e que está diretamente relacionada com a gênese da DCV. Outros fatores importantes são o estresse oxidativo exacerbado, medido pela oxidação lipídica, protéica e de carboidratos (AGES) e que ocasiona dano tecidual, e a disfunção endotelial, agravada pelo ambiente urêmico e por outros fatores. Estas alterações, em conjunto, constituem a base do processo patogênico de aterosclerose e da DCV em pacientes com DRC, contribuindo para a sua elevada morbi-mortalidade. Este artigo é uma revisão atualizada dos mecanismos de inflamação e estresse oxidativo e sua relação com aterosclerose na doença renal crônica.

Chronic kidney disease (CKD) has reached epidemic proportions in the last few years, generating an emergent public health problem. Common risk factors for CKD and cardiovascular disease (CVD) are now well known resulting in a high prevalence rate of cardiovascular events which are the main cause of death in CKD patients. Development of accelerated atherosclerosis is related to traditional risk factors such as diabetes mellitus, arterial hypertension, dislipidemia and smoking, but recently other non traditional factors were found to be significantly associated with cardiovascular mortality, including inflammation, oxidative stress, endothelial dysfunction and uremia, even at early stages of CKD. Inflammatory markers such as C-reactive protein, interleukin 6 and fibrinogen are all correlated with cardiovascular death. The MIA syndrome is characterized by the association between inflammation, malnutrition and accelerated atherosclerosis, a condition commonly found in uremic patients, which is related to the genesis of CVD. Other important factors are the high level of oxidative stress, expressed by oxidized lipids, proteins and carbohydrates (AGES) (Advanced Glycation End Products), which cause tissue damage and endothelial dysfunction, that is aggraveted by the uremic environment and other factors. These alterations are the basis for the pathogenic process of atherosclerosis and CVD in CKD patients, contributing to their high morbidity/ mortality. This article is an updated review of the mechanisms of inflammation and oxidative stress and their relation to atherosclerosis in CKD.

Lentidão cognitiva e psicomotora em hemodialisados crônicos / Cognitive and psychomotor slowing in chronic hemodialysis patients

FUNDAMENTOS: A encefalopatia urêmica subclínica pode levar a comprometimento ocupacional de difícil diagnóstico por requerer o emprego de medidas sensíveis. PROPOSITO: Testar as hipóteses de que (1) pacientes em hemodiálise crônica (HDC) se saem pior do que controles normais em uma bateria de desempenho, (2) um dia extra de uremia comprometeria ainda mais o comprometimento neuropsicológico desses pacientes, e (3) a uremia dificultaria a melhora do desempenho em uma segunda sessão de testes. MÉTODO: A agilidade cognitiva e motora de 28 pacientes em HDC foi avaliada com os testes de Trilhas (A e B), Algarismos e Símbolos, e Stroop. RESULTADOS: (1a) o desempenho cognitivo e motor se encontravam mais lento nos pacientes, (2a) um dia a mais de uremia comprometeu o desempenho na Parte B do Teste de Trilhas, e (3a) pacientes em HDC apresentaram redução da capacidade de aprender novos procedimentos. CONCLUSÃO: Pacientes em HDC podem apresentar uma "encefalopatia subclínica" cuja detecção pode requerer a aplicação de testes sensíveis. A agilidade mental e motora, e a capacidade de aprender novas rotinas estão comprometidas em, pelo menos, alguns pacientes em HDC com cognição global normal.

BACKGROUND: The diagnosis of "subclinical uremic encephalopathy" may need the administration of sensitive tests. PURPOSE: To test the hypotheses that (1) patients on chronic hemodialysis (CHD) fare worse than normal controls on a brief performance battery, (2) one extra-day of uremia further jeopardizes the neuropsychological performance of CHD patients, and (3) uremia impairs improvement on a second testing session. METHOD: The cognitive and motor agility of 28 patients on CHD were assessed with the Trails A and B, Digit Symbol, and Stroop tests. RESULTS: (1a) cognitive and psychomotor performance were slowed in patients, (2a) one extra-day of uremia impaired performance further on Trail Making B, and (3a) CHD patients had a decreased ability to learn novel procedures even in the short-term. CONCLUSION: CHD patients may present with a "subclinical encephalopathy" whose detection may require the administration of sensible tests. Mental and motor agility, and the ability to learn new routines are impaired in at least some CHD patients with a normal global cognitive state.

Effect of oral granisetron in uremic pruritus.

BACKGROUND: Renal itch is a relatively common and distressing problem for patients with chronic renal failure. Granisetron, is a potent and selective inhibitor of 5-HT3 receptors. There have been some studies about the effect of ondansetron in uremic pruritus and one case report has recently described relief of renal itch with granisetron. AIMS: To evaluate the effect of Granisetron on uremic pruritus in Continuous Ambulatory Peritoneal Dialysis (CAPD) and Hemodialysis (HD) patients. METHODS: To study the prevalence of uremic pruritus, patients on CAPD and HD were asked to complete a pruritus questionnaire. Their replies were scored based on numerical scales. Pruritus was graded, according to the total points for each patient, as mild, moderate or severe. Fourteen patients with moderate to severe pruritus were enrolled in the trial. During treatment, patients received granisetron (1 mg tablet twice a day P.O), for a period of 1 month. They were asked to score the severity of pruritus twice a day. RESULTS: Seventy seven percent of the patients responded to the treatment and at 1 st, 2 nd and 4 th week the mean values of the pruritus scores were 23, 16 and 8 points respectively. Before starting treatment the score was 31 points (P =0.03). Weekly clinical and laboratory examination showed no important side effects. CONCLUSION: Granisetron might be an effective, safe and well tolerated drug for the treatment of uremic pruritus.

Practical ways to deal with the high burden of cardiovascular disease in hemodialysis patients

CONTEXTO: A doença cardiovascular é a principal causa de morte em pacientes tratados por hemodiálise crônica. Embora a uremia por si só possa ser considerada um fator de risco cardiovascular, uma proporção significativa de pacientes tratados por diálise morre devido a problemas cardiovasculares não diretamente atribuíveis à uremia. De fato, muitas das alterações cardiovasculares e fatores de risco cardiovascular observados em pacientes renais crônicos são comuns aos que ocorrem na população geral e podem ser controlados por medidas de comprovada eficácia em indivíduos não-doentes renais. A falta de cuidados médicos apropriados durante as fases iniciais da insuficiência renal e os atuais métodos e rotinas empregadas na diálise, por não conseguirem garantir o controle adequado da hipertensão, hipervolemia e da hipertrofia ventricular, em muitos pacientes, contribuem para o aumento da pletora de problemas cardiovasculares. O autor sugere que, em adição à instituição de tratamento adequado e envio precoce aos especialistas, doentes renais crônicos devam ser submetidos a avaliação cardiovascular minuciosa visando o tratamento das alterações cardiovasculares e correção dos fatores de risco baseados nas diretivas estabelecidas para a população geral.

HD is beneficial for enzymatic conversion of some amino-acids in the elderly

Many different causes of abnormal amino acid profile in uremic patients including: inadequate nutritional intake, uremic disturbances in amino acid metabolism, loss or fibrosis of renal tissues, metabolic acidosis and hormonal derangement. Some of these factors; such as metabolic acidosis are particularly corrected with dialytic therapy; but others such as decreased intake or hormonal disturbances may persist or worsen after initiation of dialysis. This study was done to investigate the plasma amino acids profile in uremic elderly patients. The present study was carried out on three matched groups: [G1] on HD, [G2] CRF and a control. A significant uniform decrease of Threonine, Valine and Leucine in both HD and CRF. However, a peculiar situation of significant increase in phenylalanine in HD in comparison to CRF and to control. This is similar to the significant increase of Arginine in HD group in comparison to the others. In contrast, phenylalanine was significantly decreased in CRF in comparison to both HD group and the control. The latter was similar to the decrease of Leucine in CRF in comparison to the other two groups. Hence, Phenylalanine was the only AA that was found to be significantly increased in HD and significantly decreased in CRF in comparison to control. Moreover, only Phenylalanine and Arginine were significantly increased in HD group in contrast to the rest of the essential amino-acids, which showed either decrease or no change. Tyrosine and lysine were significantly lower in pre -dialysis CRF group in comparison to patients on HD and the control. This may imply that HD can correct the deficiency of tyrosine and lysine in uremic patients probably due to less inhibition of phenylalanine hydrorxylase. Inter-conversion of phenylalanine to tyrosine was reported to be impaired in CRF; whereas tyrosine metabolism per se does not seem to be grossly affected by uremia. However; Serine was significantly lower in both groups of uremic patients in the current study compared with the control group, with no significant difference in-between pre -dialysis patients and patients on HD. In conclusion, our study showed that HD may be beneficial in restoring the enzymatic turnover of certain amino-acids including: Phenylalanine hydroxylase to normalize tyrosine plasma level, Arginine synthetase to convert citrulline to Arginine. On the other hand, HD may be injurious to the production of other amino-acids like serine due to complete lost of the renal tissue that is responsible of its production from glycine