Therapeutic mechanism of Shenbing Decoction Ⅲ for renal fibrosis in chronic kidney disease: a study with network pharmacology, molecular docking and validation in rats / 南方医科大学学报

OBJECTIVE@#To observe the effect of Shenbing Decoction Ⅲ for improving renal function and pathology in rats with 5/6 nephrectomy and analyze its therapeutic mechanism for renal fibrosis in chronic kidney disease using network pharmacology combined with molecular docking.@*METHODS@#Forty male SD rats were randomized into two groups to receive two-staged 5/6 nephrectomy (n=30) or sham operation (n=10), and 2 weeks after the final operation, serum creatinine level of the rats was measured. The rats with nephrectomy were further randomized into Shenbing Decoction Ⅲ group, losartan group and model group for daily treatment with the corresponding drugs via gavage starting at 1 week after 5/6 nephrectomy. After 16 weeks of treatment, serum creatinine and urea nitrogen levels of the rats were measured, and HE staining and Western blotting were used to examine the changes in renal pathology and fibrosis-related factors. Network pharmacology combined with molecular docking study was performed to explore the therapeutic mechanism Shenbing Decoction Ⅲ against renal fibrosis in chronic kidney disease, and Western blotting was used to verify the expressions of the core targets.@*RESULTS@#Compared with those in the model group, the rats receiving 5/6 nephrectomy and Shenbing Decoction Ⅲ treatment showed significantly reduced serum creatinine and urea nitrogen levels, lessened renal pathologies, and improvement of the changes in epithelial mesenchymal transition-related proteins. Network pharmacological analysis showed that the main active ingredients of Shenbing Decoction Ⅲ were acacetin, apigenin, eupatilin, quercetin, kaempferol and luteolin, and the key targets included STAT3, SRC, CTNNB1, PIK3R1 and AKT1. Molecular docking study revealed that the active ingredients of Shenbing Decoction Ⅲ had good binding activity to the key targets. Western blotting showed that in rats with 5/6 nephrectomy, treatment with Shenbing Decoction Ⅲ obviously restored the protein expression of STAT3, PI3K, and AKT in renal tissue.@*CONCLUSION@#Shenbing Decoction Ⅲ can reduce renal injury induced by 5/6 nephrectomy in rats, and its therapeutic effects are mediated possibly by its main pharmacologically active ingredients that alleviate renal fibrosis via modulating multiple targets including STAT3, PIK3R1, and AKT1.

Shen Qi Wan attenuates renal interstitial fibrosis through upregulating AQP1 / 中国天然药物

Renal interstitial fibrosis (RIF) is the crucial pathway in chronic kidney disease (CKD) leading to the end-stage renal failure. However, the underlying mechanism of Shen Qi Wan (SQW) on RIF is not fully understood. In the current study, we investigated the role of Aquaporin 1 (AQP1) in SQW on tubular epithelial-to-mesenchymal transition (EMT). A RIF mouse model induced by adenine and a TGF-β1-stimulated HK-2 cell model were etablished to explore the involvement of AQP 1 in the protective effect of SQW on EMT in vitro and in vivo. Subsequently, the molecular mechanism of SQW on EMT was explored in HK-2 cells with AQP1 knockdown. The results indicated that SQW alleviated kidney injury and renal collagen deposition in the kidneys of mice induced by adenine, increased the protein expression of E-cadherin and AQP1 expression, and decreased the expression of vimentin and α-smooth muscle actin (α-SMA). Similarly, treatmement with SQW-containing serum significantly halted EMT process in TGF-β1 stimulated HK-2 cells. The expression of snail and slug was significantly upregulated in HK-2 cells after knockdown of AQP1. AQP1 knockdown also increased the mRNA expression of vimentin and α-SMA, and decreased the expression of E-cadherin. The protein expression of vimentin increased, while the expression of E-cadherin and CK-18 significantly decreased after AQP1 knockdown in HK-2 cells. These results revealed that AQP1 knockdown promoted EMT. Furthermore, AQP1 knockdown abolished the protective effect of SQW-containing serum on EMT in HK-2 cells. In sum, SQW attentuates EMT process in RIF through upregulation of the expression of AQP1.

Effect of Uremic Clearance Granules on improvement of chronic kidney disease in rats based on microbiome-metabolomics and its mechanism / 中国中药杂志

This research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.

Effect of traditional Chinese medicine in attenuating chronic kidney disease and its complications by regulating gut microbiota-derived metabolite trimethylamine N-oxide: a review / 中国中药杂志

Trimethylamine N-oxide(TMAO), a metabolite of gut microbiota, is closely associated with chronic kidney disease(CKD). It can aggravate the kidney injury and promote the occurrence of complications of CKD mainly by inducing renal fibroblast activation, vascular endothelial inflammation, macrophage foaming, platelet hyperreactivity, and inhibition of reverse cholesterol transport. Thus it is of great significance for clinical treatment of CKD to regulate circulating TMAO and alleviate its induced body damage. Currently, therapeutic strategies for TMAO regulation include dietary structure adjustment, lifestyle intervention, intestinal microflora regulation, and inhibition of intestinal trimethylamine synthesis and liver trimethylamine oxidation. Chinese medicinal herbs have the clinical advantage of multi-component and multi-target effects, and application of traditional Chinese medicine(TCM) to synergistically regulating TMAO and improving CKD via multiple pathways has broad prospects. This study systematically reviewed the clinical relevance and mechanism of TMAO in aggravating CKD renal function deterioration and complication progression. In addition, the effect and mechanism of TCM in improving TMAO-induced kidney injury, cardiovascular disease, hyperlipidemia, thrombosis and osteoporosis were summarized. The results provided a theoretical basis for TCM in attenuating gut microbiota-derived metabolite TMAO and improving CKD, as well as a basis and direction for in-depth clinical development and mechanism research in the future.

Research progress on the cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease / 生理学报

Mineralocorticoid receptor antagonists not only are used as a diuretics to treat essential hypertension, but also protect the heart and kidney by inhibiting inflammation and fibrosis. Since the discovery of spironolactone, the first generation of mineralocorticoid receptor antagonist, two types of non-steroid mineralocorticoid receptor antagonists (finerenone and esaxerenone) approved for clinical use have been developed, which have the advantages of high affinity, high selectivity and balanced distribution in heart and kidney, and can be used in clinic as a cardiorenal protective drug. In this paper, the development history of mineralocorticoid receptor antagonists was reviewed, and the pathophysiological mechanism of inflammation and fibrosis caused by mineralocorticoid receptors and the similarities and differences of different generations of mineralocorticoid receptor antagonists were analyzed. In particular, the phase III clinical research evidence of finerenone and esaxerenone was discussed. This paper also reviews the research progress of cardiorenal protection of non-steroid mineralocorticoid receptor antagonists in patients with chronic kidney disease.

Clinical comprehensive evaluation of Huangkui Capsules in treatment of chronic kidney diseases / 中国中药杂志

Based on Guidelines for the Management of Clinical Comprehensive Evaluation of Drugs(trial version 2021), this study aims to sort out the clinical evidence of Huangkui Capsules(HC) in the treatment of chronic kidney diseases in aspects of safety, effectiveness, economy, innovation, suitability, accessibility, and characteristics of traditional Chinese medicine( "6+1" dimensions) from real-world data, secondary literature evaluations, questionnaires, and public data, with the methods in evidence-based medicine, epidemiology, pharmacoeconomics, and health technology. Furthermore, with multi-criteria decision analysis(MCDA) model and CSC v2.0, the clinical value of the medicine is comprehensively assessed. All the above are to highlight the advantages and characteristics of HC and lay a basis for scientific decision-making by the medical management department. The dimensions are graded A, B, C, or D. According to the conclusions from phase Ⅳ clinical trial, spontaneous reporting system(SRS), systematic review and Meta-analysis, acute toxicity and long-term toxicity tests, it mainly results in the adverse reactions of nausea, abdominal distension, vomiting, pruritus, rash, and good prognosis in patients. According to the available research, the safety evidence is sufficient and the risk is controllable, so the safety of this medicine is grade B. According to Meta-analysis, HC in combination with conventional drugs in the treatment of chronic kidney disease is superior to conventional drugs alone in reducing urinary protein, serum creatinine concentration, and blood urea nitrogen. In addition, HC combined angiotensin receptor blocker(ARB) or angiotensin converting enzyme inhibitor(ACEI) is outstanding in improving total clinical effective rate, reducing 24 h urinary protein quantity, urinary albumin excretion rate, serum creatinine concentration, triglyceride, and total cholesterol in the treatment of diabetic nephropathy as compared with ARB or ACEI alone. As for chronic nephritis, the application together with ARB or ACEI can raise the total effective rate, reduce 24 h urinary protein content, serum creatinine concentration, and blood urea nitrogen, and delay the progress of the disease. HC boasts high-quality evidence in treating chronic kidney disease, diabetic nephropathy, and chronic nephritis. It has obvious clinical significance in treating chronic kidney disease and thus its efficacy in this aspect is grade B. It has outstanding clinical significance for diabetic nephropathy and chronic nephritis and corresponding and the effectiveness is grade A. As for the pharmacoeconomic value, HC combined with ARB or ACEI is more economical in the treatment of chronic kidney disease than Bailing Capsules combined with ARB or ACEI, with high-quality evidence, and thus the economy of the formula is grade B. HC is a key solution to the high urinary protein in patients with hypotension and chronic kidney disease. The innovation is evidenced by the methods to ensuring drug supply, community-level supply, drug safety, effectiveness, and reasonable price, as wells as the aspects of enterprise philosophy, equipment management, research and development in process and technology, enterprise management and marketing. Thus, the prescription is grade A in innovation. The suitability, as evidenced in drug administration, technical management, drug storage, information service, and medication, is grade B. The course of the medicine is affordable, and it is accessible in a wide range of areas and hospitals. Thus, the accessibility is grade A. HC was developed from an in-hospital preparation, with application in numerous patients and thus large-scale real-world data. As a result, HC is grade B in terms of characteristics of traditional Chinese medicine. After comprehensive evaluation, the clinical value of HC in treating chronic kidney disease is class B, and that for diabetic nephropathy and chronic nephritis is class A. The result is of great reference value for the basic clinical medication management.

Gliflozinas: más que antidiabéticos orales: una breve revisión de la literatura / Gliflozins: more than oral antidiabetics: a brief review of the literature / Gliflozinas: mais do que antidiabéticos orais: uma breve revisão da literatura

La diabetes mellitus, la insuficiencia cardíaca y la enfermedad renal crónica tienen alta prevalencia en la población. Asimismo, estas patologías están comprendidas en un "círculo vicioso" porque comparten mecanismos fisiopatológicos que predisponen a su coexistencia en un mismo paciente, incrementando significativamente el riesgo de eventos cardiovasculares. Recientemente se han agregado al arsenal terapéutico las gliflozinas, un grupo de fármacos con beneficios en las tres enfermedades mencionadas. Saber cómo se desarrolló la investigación con estos fármacos y sus mecanismos de acción es fundamental para optimizar el tratamiento de los pacientes.

Diabetes mellitus, heart failure, and chronic kidney disease are highly prevalent in the population. Likewise, these pathologies are included in a "vicious circle" because they share pathophysiological mechanisms that predispose to their coexistence in the same patient, significantly increasing the risk of cardiovascular events. Gliflozins, a group of drugs with benefits in the three mentioned pathologies, have recently been added to the therapeutic arsenal. Knowing how research with these drugs and its mechanisms of action is essential to optimize the treatment of patients.

Diabetes mellitus, insuficiência cardíaca e doença renal crônica são altamente prevalentes na população. Estas patologias fazem parte de um "círculo vicioso", compartilhando mecanismos fisiopatológicos que predispõem à coexistência no mesmo paciente, e aumentando significativamente o risco de eventos cardiovasculares. As gliflozinas, são un grupo de drogas com benefícios das três patologias citadas, foram adicionadas recentemente ao arsenal terapêutico. Saber como foram desenvolvidas as pesquisas com esses medicamentos e seus mecanismos de ação é essencial para otimizar o tratamento dos pacientes.

Prototype of an educational technology about appropriate diet for patients with chronic kidney disease / Protótipo de uma tecnologia educacional sobre dieta apropriada para pacientes renais crônicos

Introduction: Chronic kidney disease is a worldwide public health problem. If consideration should be given to the effect that this disease has on individuals, families, society and the country's economy, the urgency of patient education as a form of health promotion will be clearly understood. Patient education is key to the management of such conditions and a proactive approach to dealing with renal disease should be engaged. Chronic kidney disease describes the gradual loss of kidney function which, once established, tends to progress to end-stage renal failure and imminent death. Nursing care for patients with this condition include a number of areas of which patient education is paramount. In Guyana, the Georgetown Public Hospital Corporation alone has established that there are over five hundred people with chronic renal disease. Approximately 70% of patients with chronic kidney disease at this Hospital are readmitted frequently and their disease condition degenerates rapidly. Objective: To construct a prototype of educational technology for adult patients with chronic kidney disease. Methods: This was a study that used a methodological approach in three phases: Analysis & Diagnosis; Instructional Planning with Content systematization; and Didactic Drawing with Choice of illustration and Writing content. After gaining approval from the ethical committee of the Georgetown Public Hospital Corporation, hospitalized patients with chronic kidney disease and their families who were willing to be participants of this research during the period October to November 2019, were invited with their consent, to complete a questionnaire for the researchers to gather biographic and socioeconomic data. The number of participants was thirty, twelve were patients and eighteen were relatives. The majority of patients and relatives were female (58.3% and 61.1%), most of them were married. This was complemented with interviews where the participants shared their health education needs relating to their disease condition. Interviews were recorded and transcribed verbatim. From the themes that arise out of the interviews, along with the review of relative scientific literature, a prototype of an educational material for patients with chronic kidney disease was constructed as well as engaging design and layout artists and advertising professionals. Results: A prototype of a booklet for patients with chronic kidney disease and their caregivers was developed. Its selected theme came from interviews with the patients and their relatives. At the end, the prototype contains eight pages on the appropriate diet for patients with chronic kidney diseases. The contents were subdivided into steps so that educational guidelines were organized and could be discussed with patients and relatives. Conclusion: It is supposed that this prototype of educational technology will serve as a stimulus to the improved health of patients with chronic kidney disease through knowledge construction followed by self-care. It is anticipated to be a teaching technology for nurses and students who work on the clinical area to encourage the target population to take responsibility for their health maintenance when not hospitalized. Future work will examine the effectiveness of the implementation of this educational booklet

IIntrodução: a doença renal crônica é um problema de saúde pública mundial. Se for levado em consideração o efeito que esta doença tem sobre os indivíduos, famílias, sociedade e economia do país, a urgência da educação do paciente como forma de promoção da saúde será claramente compreendida. A educação do paciente é fundamental para o manejo de tais condições e uma abordagem proativa para lidar com a doença renal deve ser adotada. A doença renal crônica é compreendida como a perda gradual da função renal que, uma vez estabelecida, tende a progredir para insuficiência renal em estágio terminal e morte iminente. Os cuidados de enfermagem para pacientes com essa condição incluem várias áreas nas quais a educação do paciente é fundamental. Na Guiana, apenas no Georgetown Public Hospital Corporation há mais de quinhentas pessoas com doença renal crônica em tratamento. Aproximadamente 70% dos pacientes com doença renal crônica neste hospital são readmitidos com frequência e sua doença avança rapidamente. Objetivo: construir um protótipo de tecnologia educacional para pacientes adultos com doença renal crônica. Métodos: trata-se de um estudo que utilizou uma abordagem metodológica em três fases: análise e diagnóstico; planejamento instrucional com sistematização de conteúdo; e desenho didático com escolha de ilustração e conteúdo de escrita. Após obter a aprovação do comitê de ética da Georgetown Public Hospital Corporation, os pacientes internados com doença renal crônica e seus familiares que se dispuseram a participar desta pesquisa no período de outubro a novembro 2019, assinaram o termo de consentimento livre e esclarecido, e responderam a um questionário sociodemográfico. O número de participantes foi de trinta, sendo doze pacientes e dezoito parentes. A maioria dos pacientes e familiares era do sexo feminino (58,3% e 61,1%), a maioria casada. Este foi complementado com entrevistas nas quais os participantes compartilharam suas necessidades de educação em saúde relacionadas à sua condição de adoecimento. As entrevistas foram gravadas e transcritas na íntegra. Em segundo lugar, a partir dos temas que surgiram das entrevistas, junto com a revisão da literatura científica relativa à temática selecionada, um protótipo de um material educacional para pacientes com doença renal crônica foi construído, envolvendo artistas de design e layout e profissionais de publicidade. Resultados: foi desenvolvido um protótipo de cartilha para pacientes com doença renal crônica e seus cuidadores. Ao final, o protótipo contém oito páginas sobre a dieta adequada para pacientes com doenças renais crônicas. Os conteúdos foram subdivididos em passos para que as diretrizes educacionais fossem organizadas e pudessem ser discutidas com pacientes e familiares. Conclusão: supõe-se que este protótipo de tecnologia educacional servirá de estímulo à melhoria da saúde do paciente com doença renal crônica por meio da construção do conhecimento seguido do autocuidado. Prevê-se que seja uma tecnologia de ensino para enfermeiros e alunos que atuam na área clínica para estimular a população-alvo a se responsabilizar pela manutenção da saúde quando não estiver internada. O trabalho futuro examinará a eficácia da implementação deste livreto educacional

Exercício aeróbico intradialítico e o efeito sobre a pressão arterial de pacientes em hemodiálise: uma revisão integrativa / Intradialitic aerobic exercise and the effect of blood pressure of hemodialysis patients: an integrative review

Objetivo: trata-se de uma revisão integrativa da literatura sobre o efeito do exercício físico aeróbico na redução dos níveis de pressão arterial entre os pacientes com diagnóstico de hipertensão arterial e insuficiência renal crônica em tratamento de hemodiálise. Método: a busca foi realizada no mês de maio de 2020 nas bases PUBMED, SCOPUS, LILACS, PEDro, PBi. Para a busca foram usados descritores e estratégias combinadas de buscas. Foi usado o recorte de 15 anos (janeiro/2005 a maio/2020). A partir dos critérios de exclusão e leitura dos artigos com potencial para inclusão foram encontrados um total de 876 documentos. Foram considerados os idiomas português, inglês, chinês, japonês, coreano devido a quantidade de trabalhos encontrados nos tais idiomas. Resultados: foram incluídos 13 artigos nesta pesquisa. Dentre os artigos incluídos, 6 artigos foram retirados da PUBMED, 3 artigos da Scopus, 2 artigos da plataforma PEDro e Lilacs cada, e apenas 1 artigo da PBi. Foram consideradas as profissões dos autores dos estudos, os conteúdos relacionados deveriam corresponder a DRC, HAS, HD e exercício físico aeróbico durante a HD. Conclusão: os resultados sintetizados neste estudo permitem reforçar que os exercícios físicos aeróbicos realizados durante a HD são essenciais para o tratamento e redução da PA e para a saúde em geral do paciente renal crônico

Objective: This is an integrative literature review on the effect of aerobic physical exercise in reducing blood pressure levels among patients diagnosed with hypertension and chronic renal failure undergoing hemodialysis treatment. Method: a search was performed in May 2020 in the PUBMED, SCOPUS, LILACS, PEDro, PBi databases. For the search, descriptors and combined search strategies were used. The 15-year cut-off was used (January / 2005 to May / 2020). From the exclusion criteria and reading of articles with potential for inclusion, a total of 876 documents were found. Portuguese, English, Chinese, Japanese, Korean were considered due to the amount of works found in these languages. Results: 13 articles were included in this research. Among the articles included, 6 articles were taken from PUBMED, 3 articles from Scopus, 2 articles from the PEDro and Lilacs platform each, and only 1 article from PBi. Were considered as professions of the authors studies, the contents related to CKD, SAH, HD and aerobic exercise during HD. Conclusion: the results summarized in this study allow us to reinforce that aerobic physical exercises performed during HD are essential for the treatment and reduction of BP and for the general health of chronic renal patients

Bayesian network Meta-analysis of Chinese medicine injections in treatment of chronic renal insufficiency / 中国中药杂志

In this study, Honghua Injection, Danshen Injection, Shenkang Injection, Shuxuetong Injection, Lulutong Injection, Shenxiong Glucose Injection and Chuanxiong Injection were compared for their clinical efficacy on chronic renal insufficiency by using the method of network Meta-analysis, with Western medicine as the common reference. The randomized controlled trial(RCT) of Hong-hua Injection, Danshen Injection, Shenkang Injection, Shuxuetong Injection, Lulutong Injection, Shenxiong Glucose Injection and Chuanxiong Injection for the treatment of chronic renal insufficiency were obtained by computer-based retrieval. The literature quality was evaluated by using the method in Cochrane Reviewer's Handbook 5.1 after independent screening of the included literature by two reviewers. The RJAGS package and GEMTC package of RevMan 5.3, GEMTC software, R software were used for statistical analysis to compare and sort the different injections in terms of efficacy. A total of 6 197 patients with chronic renal failure were included in 79 RCTs, involving 8 treatment measures. The effective rates of conventional treatment combined with Shenxiong Injection(OR=3.55, 95%CI[1.98, 6.37], P<0.000 1), Honghua Injection(OR=3.77, 95%CI[2.45, 5.81], P<0.000 01), Shuxuetong Injection(OR=6.71, 95%CI[3.30, 13.65], P<0.000 01) and Shenkang Injection(OR=4.14, 95%CI[3.42, 5.03], P<0.000 01) were all better than that in control group, and the effective rate of Honghua Injection combined with conventional treatment(OR=3.89, 95%CI[1.73, 8.74], P=0.001) was better than that in Danshen Injection combined with conventional treatment, all with statistically significant differences. By comprehensive comparison, Shuxuetong Injection, Honghua Injection and Shenkang Injection combined with Western medicine had good clinical effect on the effective rate, serum creatinine reduction and urea nitrogen reduction in patients with chronic renal insufficiency. However, due to the relatively low quality of the included literature, the conclusion has yet to be verified clinically.

Hipertensão na doença renal crônica em tratamento conservador / Hypertension in chronic kidney disease under conservative treatment

A hipertensão arterial sistêmica (HAS) afeta aproximadamente 30% da população geral no mundo industrializado e é uma das principais causas de doença renal crônica (DRC), caracterizada por função renal anormal ou danos estruturais renais com mais de 3 meses de duração. A sua presença classifica o paciente hipertenso como de alto risco cardiovascular (CV). O controle pressórico é fundamental para diminuir a sua progressão e reduzir o risco de morbidade e mortalidade CV. A meta pressórica recomendada deve ser menor que 130x80mmHg para a maioria dos pacientes com DRC. O tratamento não medicamentoso tem como base as mesmas recomendações dos demais pacientes hipertensos. A terapia medicamentosa combinada deve ser iniciada o mais breve possível. Além dos inibidores do sistema renina angiotensina aldosterona, conhecidos por sua eficácia na DRC, os diuréticos e os bloqueadores de canal de cálcio compõem o trio de ouro utilizado no tratamento da HAS, capazes de reduzir o risco cardiovascular e desacelerar a progressão da doença renal. Em conclusão, a DRC é um preditor de risco CV e a presença concomitante de HAS aumenta expressivamente esse risco. A utilização da estratégia terapêutica adequada para manter os níveis pressóricos dentro das metas é fundamental na atenuação da progressão da doença renal e do risco

Systemic arterial hypertension (SAH) affects approximately 30% of the general population in the industrialized world and is a major cause of chronic kidney disease (CKD), characterized by abnormal renal function or structural damage lasting more than 3 months. Its presence classifies the hypertensive as a high cardiovascular (CV) risk patient. Blood pressure (BP) control is essential for slowing the progression and for reducing the risk of CV morbidity and mortality in patients with CKD. BP target <130x80mmHg is recommended for most hypertensives with CKD. Non pharmacological treatment is based on the same recommendations for other hypertensive patients. Combination drug therapy should be started as soon as possible. In addition to the renin angiotensin aldosterone system blockers, known for their effectiveness in CKD, diuretics and calcium channel blockers compose the gold trio used in the treatment of SAH, able to reduce cardiovascular risk and to slow the progression of kidney disease. In conclusion, CKD is a predictor of CV risk and the concomitant presence of SAH significantly increases this risk. The use of an appropriate therapeutic strategy to maintain BP control is crucial to mitigate the progression of kidney disease and CV

Adaptação transcultural do instrumento PAIR: Pharmacotherapy Assessment in Chronic Renal Disease para aplicação no Brasil / Cross-cultural adaptation of the PAIR instrument: Pharmacotherapy Assessment in Chronic Renal Disease for application in Brazil

Resumo Indivíduos com doença renal crônica (DRC) frequentemente utilizam polifarmácia o que os expõe ao risco de problemas relacionados a medicamentos (PRMs). No Brasil, não existem instrumentos que possam sistematizar a avaliação da farmacoterapia e a gestão de PRMs nesta população. Portanto, o objetivo deste trabalho foi realizar a adaptação transcultural do instrumento PAIR (Pharmacotherapy Assessment in Chronic Renal Disease) para o português brasileiro. O PAIR consiste numa lista de 50 PRMs considerados clinicamente significativos para renais crônicos. O processo de adaptação transcultural envolveu as etapas de tradução, síntese, retrotradução, análise por um comitê de especialistas e pré-teste da versão preliminar. O comitê de 2 farmacêuticos e 2 nefrologistas analisou a equivalência semântica, idiomática, experiencial e conceitual entre as versões original e traduzida. Todos os itens que obtiveram acordo inferior a 80% foram revisados. Foram realizados ajustes de palavras, assim como a exclusão de 6 PRMs devido à não aplicabilidade ao contexto brasileiro. Assim, foi obtida a versão final do PAIR definida como "Avaliação da farmacoterapia na doença renal crônica", traduzida e adaptada na língua portuguesa do Brasil.

Abstract Individuals suffering from chronic kidney disease (CKD) are often on multiple medications, which exposes them to drug-related problems (DRP). There are no available tools in Brazil to assess the pharmacotherapy and management of DRPs systematically in this population. The scope of this study was to perform a cross-cultural adaptation of PAIR criteria (Pharmacotherapy Assessment in Chronic Renal Disease) to Brazilian Portuguese. PAIR criteria consist of 50 DRP clinically significant items for CKD. The process of cross-cultural adaptation involved translation, synthesis, back-translation, and an analysis by an expert committee as well as a pre-test of the first draft document. A review committee consisting of 2 pharmacists and 2 nephrologists analyzed the semantic, linguistic, experiential, and conceptual equivalence between the original and translated versions. All items that obtained a score below 80% were reviewed. Word adjustments were made, as well as the exclusion of 6 DRP due to non-applicability to the Brazilian context. Thus, the final version of PAIR defined as "Avaliação da farmacoterapia na doença renal crônica" was translated and adapted into the Brazilian Portuguese language.

Efectos del Factor de crecimiento epidérmico sobre las características histológicas del riñón en ratas con Insuficiencia renal crónica / Effects of Epidermal growth factor on histological features of the kidney in rats with Chronic kidney failure

Introducción: la Insuficiencia renal crónica es un problema de salud pública, por lo que surge la necesidad de incrementar las acciones dirigidas a su prevención, diagnóstico e intervenciones terapéuticas eficaces; estudios recientes emplean el Factor de crecimiento epidérmico para evaluar su efecto reno-protector en variables funcionales; sin embargo se carece de estudios relacionados con los efectos de este producto sobre las características histológicas de riñones insuficientes. Objetivo: determinar los posibles efectos protectores y/o reparadores del Factor de crecimiento epidérmico humano recombinante sobre las características histológicas de riñones con insuficiencia renal crónica. Material y métodos: se trabajó con tres series, formadas por un grupo control y uno experimental cada una, de cinco animales, a los grupos experimentales se les realizó ablación quirúrgica de 5/6 de la masa renal. La serie A se conformó por animales controles, la B por los tratados con Factor de crecimiento epidérmico 24 horas antes del procedimiento y la C por los tratados con el bioproducto 24 horas después. Pasados 56 días del acto operatorio a los animales se les practicó la eutanasia y se procedió al estudio histológico del riñón. Resultados: en los animales de la serie A se observaron alteraciones histológicas en los corpúsculos y túbulos renales, en la serie B se observó que la mayor parte del parénquima renal presentó características normales y los de la serie C mostraron un daño renal incrementado. Conclusiones: El Factor de crecimiento epidérmico humano recombinante posee efecto reno-protector, sin embargo, no ofrece efecto reno-reparador(AU)

Introduction: Chronic Kidney Failure is a public health problem; therefore, the need for actions aimed at its prevention, diagnosis and effective therapeutic interventions is a most. Recent studies use the Epidermal Growth Factor to evaluate its reno-protective effect on functional variables; however, there are no studies related to the effects of this product on histological features of kidney in chronic failure. Objective: To determine the possible protective and / or repair effects of recombinant human epidermal growth factor on the histological features of kidneys in chronic renal failure. Material and methods: We worked with three series, each consisting of a control group and an experimental group of five animals. The experimental groups underwent 5/6 surgical ablation of the renal mass. Series A consisted of control animals, series B included those animals treated with Epidermal Growth Factor 24 hours before the procedure and series C was made up of those animals treated with the bioproduct 24 hours after the procedure. Fifty-six days after surgical act, euthanasia was practiced on the animals and the kidneys were histologically studied. Results: Histological alterations were observed in the renal corpuscles and tubules in the animals included in series A; in series B it was observed that most of the renal parenchyma presented normal characteristics and those in series C showed increased kidney damage. Conclusions: Recombinant human epidermal growth factor has a reno-protective effect; however, it does not offer a repair effect of acute kidney(AU)

Recomendación rápida sobre el uso de antihipertensivos IECA/ARA II en pacientes con riesgo o documentación de COVID-19 / Rapid recommendation on the use of ACEI/ARA antihypertensives in patients at risk or with documented COVID-19

Ciertos hallazgos preclínicos generaron preocupación en la comunidad científica y en la población general sobre el uso de inhibidores de la enzima convertidora de angiotensina (IECA) y los antagonistas del receptor de la angiotensina II (ARAII), y los posibles desenlaces adversos asociados con relación a la infección por el nuevo Coronavirus (SARS-Cov-2).Por este motivo, nos planteamos como objetivo proveer de recomendaciones dinámicas (living recommendations) para el tratamiento con fármacos IECA o ARA II en pacientes con riesgo o documentación de infección por SARS-CoV-2 (en todo su espectro de gravedad). Se utilizó como metodología la adaptación/adopción de guías de práctica clínica bajo el enfoque GRADE, actualizando la evidencia al 7 de abril de 2020 mediante búsquedas en múltiples bases de datos y consultando a un panel multidisciplinario libre de conflictos de interés. Como resultado de este proceso se arribó a la siguiente afirmación: se recomienda, en contexto de la pandemia de COVID-19, en personas que se encuentran en tratamiento con IECA/ARAII, mantener el tratamiento sin cambios por sobre suspenderlo o reemplazarlo por otros fármacos (Recomendación fuerte a favor - calidad de evidencia baja). (AU)

Certain preclinical findings raised concerns in the scientific community and in the general population about the use ofangiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) and the possible adverse outcomes associated with the infection with the new Coronavirus (SARS-Cov-2). For this reason, our objective is to provide living recommendations for treatment with ACEI or ARA in patients with risk or documentation of SARS-CoV-2 infection (inall its severity spectrum). The adaptation/adoption of clinical practice guidelines under the GRADE approach was used as a methodology, updating the evidence as of April 7, 2020, by searching multiple databases and consulting a multidisciplinary panel free of conflicts of interest. As a result of this process, the following statement was reached: it is recommended, in the context of the COVID-19 pandemic, in people who are undergoing treatment with ACEI/ARA, to maintain the treatment unchanged instead of its suspension or replacement with other drugs (Strong recommendation in favor - low quality ofevidence). (AU)

Prescripción de fármacos bloqueadores del sistema renina angiotensina en pacientes con enfermedad renal crónica etapa 3 en atención primaria de salud / Prescription of renin-angiotensin-aldosterone system blockers in patients with stage 3 chronic kidney disease

Background: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. Aim: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. Material and Methods: Review of clinical records of patients with CKD in an urban primary care clinic. Results: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. Conclusions: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.

Furosemide-induced pseudoporphyria in a patient with chronic kidney disease: case report / Pseudoporfiria induzida por furosemida em paciente com doença renal crônica: relato de caso

ABSTRACT Introduction: Pseudoporphyria is a rare photodermatosis with characteristics similar to those of porphyria cutanea tarda, without, however, presenting abnormalities in porphyrin metabolism. Its etiology is related to chronic kidney disease, ultraviolet radiation and certain medications. The aim of the present study is to describe a case of furosemide-related pseudoporphyria in a patient with chronic kidney disease. Case description: A 76-year-old male patient with stage 4 chronic kidney disease and in continuous use of furosemide presented ulcerated lesions with peripheral erythema and central hematic crust in the legs. On a skin infection suspicion, treatment with quinolone and neomycin sulfate was initiated, without improvement. A biopsy of the lesion was performed, with histopathological examination demonstrating findings compatible with porphyria, although the patient did not present high porphyrin levels. The diagnosis of furosemide-induced pseudoporphyria was then established, with medication suspension, and there was a significant improvement of the lesions. Discussion: There are few cases of pseudoporphyria described, but it is believed that this condition is underdiagnosed, especially in patients with chronic kidney disease. Both clinical and histopathological findings closely resemble porphyria, differentiating it from normal levels of porphyrin in plasma, urine, or feces. Conclusions: Although the lesions are mostly benign, they may increase the morbidity and mortality of these patients, so a proper diagnosis and early treatment are extremely important.

RESUMO Introdução: A pseudoporfiria é uma fotodermatose rara com características semelhantes às da porfiria cutânea tardia, sem, no entanto, apresentar anormalidades no metabolismo da porfirina. Sua etiologia está relacionada a doença renal crônica, radiação ultravioleta e determinados medicamentos. O objetivo do presente trabalho é descrever um caso de pseudoporfiria relacionada a furosemida em paciente portador de doença renal crônica. Descrição do caso: Paciente masculino, 76 anos, com doença renal crônica estágio 4 e em uso contínuo de furosemida, apresentou lesões ulceradas com eritema periférico e crosta hemática central nas pernas. Por suspeita de infecção de pele, foi iniciado tratamento com quinolona e sulfato de neomicina, sem melhora. Foi realizada então biópsia da lesão, com exame histopatológico demonstrando achados compatíveis com porfiria, sem, no entanto, o paciente apresentar níveis elevados de porfirinas. Foi então estabelecido o diagnóstico de pseudoporfiria induzida por furosemida, com suspensão de medicação , e houve melhora significativa das lesões. Discussão: Há poucos casos de pseudoporfiria descritos, mas acredita-se que essa condição seja subdiagnosticada, principalmente em pacientes com doença renal crônica. Tanto achados clínicos quanto histopatológicos se assemelham muito à porfiria, diferenciando desta por níveis normais de porfirina no plasma, na urina ou nas fezes. Conclusões: Embora as lesões sejam majoritariamente benignas, podem aumentar a morbimortalidade desses pacientes, por isso um diagnóstico adequado e tratamento precoce são de extrema importância.

Metastatic castration-resistant prostate cancer and the challenge of a patient with chronic kidney disease in hemodialysis

At a time when the population shows increasing longevity, entities such as cancer and chronic kidney disease (CKD) are more frequently connected. In the United States, approximately 6% of the patients on hemodialysis have cancer. The challenge to manage oncologic patients with CKD in a hemodialytic program represents a great shortage of available information on the choice of the best drug, timing, dosage adjustments, dialysis method, and treatment safety. We present the case of a patient with prostate cancer and terminal CKD in hemodialysis, and the treatment sequence after the development of resistance to hormonal blockade therapy, which included docetaxel, enzalutamide, and radium-223.

Adesão de portadores de doença renal crônica em hemodiálise ao tratamento estabelecido / Adhesión de enfermos de insuficiencia renal crónica al tratamiento establecido / Treatment adherence of chronic kidney disease patients on hemodialysis

Resumo Objetivo: Identificar o comportamento de adesão do paciente renal crônico ao regime terapêutico nas suas quatro dimensões: hemodiálise uso de medicamentos, dieta e restrição hídrica. Métodos: Estudo descritivo, transversal com abordagem quantitativa, desenvolvido em dois centros de hemodiálise no Estado do Rio de Janeiro. Para coleta de dados, foi utilizado um questionário de avaliação sobre a adesão do portador de doença renal crônica em hemodiálise. Os dados foram analisados por meio de estatística descritiva simples. Resultados: O domínio que apresentou maior percentual de pacientes não aderentes foi a hemodiálise, com 32%. Já a medicação foi o domínio com maior percentual de pacientes aderentes, 93,6%. Conclusão: A adesão à terapêutica é um comportamento dinâmico e, como tal, merece monitorização constante.

Resumen Objetivo: Identificar el comportamiento de adhesión del paciente renal crónico al régimen terapéutico en sus cuatro dimensiones: hemodiálisis, uso de medicamentos, dieta y restricción hídrica. Métodos: Estudio descriptivo, transversal, con abordaje cualitativo, desarrollado en dos centros de hemodiálisis del Estado de Río de Janeiro. Datos recolectados mediante cuestionario de evaluación sobre la adhesión del enfermo de insuficiencia renal crónica en hemodiálisis. Estos datos fueron analizados por estadística descriptiva simple. Resultados: El dominio que presentó mayor porcentaje de pacientes no adherentes fue la hemodiálisis, con 32%. La medicación fue el dominio con mayor porcentaje de pacientes adherentes, con 93,6%. Conclusión: La adhesión a la terapéutica es un comportamiento dinámico. Siendo esa su condición, merece recibir monitoreo constante.

Abstract Objective: Identify the adherence behavior of chronic kidney patients to the four dimensions of the therapeutic regimen: hemodialysis, medication use, diet and fluid restriction. Methods: Descriptive and cross-sectional study with a quantitative approach, developed at two hemodialysis centers in the State of Rio de Janeiro. To collect the data, an evaluation questionnaire was used on the adherence of the chronic kidney patient on hemodialysis. The data were analyzed through simple descriptive statistics. Results: The domain with the highest percentage of non-adherent patients was hemodialysis with 32%. Medication was the domain with the highest percentage of adherent patients, 93.6%. Conclusion: Treatment adherence is a dynamics behavior and, therefore, needs constant monitoring.