Nefrotoxicidade e alterações de exames laboratoriais por fármacos: revisão da literatura

Use of nephrotoxic substances, arterial hypertension, diabetes mellitus, among others, may lead to renal injury and compromise their functioning. The presence of kidney damage and kidney function can be assessed by several biochemical markers, such as serum creatinine, serum urea, serum cystatin C, proteinuria, glomerular filtration rate and electrolytes. Several drugs can alter the results of laboratory tests to evaluate the kidney by in vivo or in vitro mechanisms, and it is important to know which drugs cause this type of interference. This review of the literature aimed to present the main drugs that can generate such interferences in the kidney assessment tests and the main mechanisms. Several nephrotoxic drugs can promote increased serum creatinine and urea levels, decreased glomerular filtration rate or proteinuria, and it is important to monitor the renal function of patients who use them. In addition, patients who have chronic kidney disease should avoid the use of some of these drugs or an appropriate dose adjustment should be made if the use of these drugs is essential. Some drugs can inhibit the renal secretion of creatinine, increasing its serum levels, in the absence of changes in renal function. Others may alter the serum electrolyte levels or urinary density, or interfere with the dosage of markers for assessment of renal tubule function. Knowledge of drugs that interfere with the kidney assessment tests by health professionals is essential so that they can correctly interpret laboratory tests, resulting in adequate diagnosis and therapy.O uso de substâncias nefrotóxicas, hipertensão arterial, diabetes mellitus, dentre outros, podem lesionar os rins e comprometer o seu funcionamento. A presença de lesão nos rins e a função renal podem ser avaliadas por meio de diversos marcadores bioquímicos, tais como creatinina sérica, ureia sérica, cistatina C sérica, proteinúria, taxa de filtração glomerular e eletrólitos. Diversos fármacos podem alterar os resultados dos exames laboratoriais de avaliação dos rins por mecanismos in vivo ou in vitro, sendo importante o conhecimento de quais medicamentos causam este tipo de interferência. Esta revisão da literatura teve como objetivo apresentar os principais fármacos que podem gerar tais interferências nos exames de avaliação dos rins e seus principais mecanismos. Vários fármacos considerados nefrotóxicos podem promover aumento dos níveis séricos de creatinina e ureia, diminuição da taxa de filtração glomerular ou proteinúria, sendo importante o monitoramento da função renal dos pacientes que os utilizam. Além disso, o uso de alguns destes fármacos deve ser evitado por pacientes que possuem doença renal crônica ou deve ser feito o ajuste adequado da dose caso oseu uso seja imprescindível. Alguns fármacos podem inibir asecreção renal da creatinina, aumentando seus níveis séricos, naausência de alteração da função renal. Outros podem alterar osníveis séricos de eletrólitos ou a densidade urinária, ou ainda interferir na dosagem de outros marcadores de avaliação da função dos túbulos renais. É fundamental o conhecimento dos fármacos que interferem nos exames de avaliação dos rins pelos profissionais da área da saúde para que estes possam interpretar corretamente os exames laboratoriais, resultando em diagnóstico e terapia adequada

Association between the occurence of iron-deficiency anemia with socioeconomic variables and school performance

Study design: Cross-sectional observational. Objective: Evaluate the association between the occurence of iron-deficiency anemia with socioeconomic variables and school performance. Method: They were included in the study 124 children aged between six and eight years old, municipal elementary school students, which were divided in two groups according to the presence (n=32) or absence of anemia (n=92). Hemoglobin and serum iron levels were determined by colorimetric method, red blood cells count was performed using Neubauer chamber, hematocrit was evaluated using microhematocrit centrifuge, and mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration hematimetric indexes were calculated. The school performance of children was provided by participating schools and socioeconomic variables were obtained by filling out the clinic file and the socioeconomic questionnaire of Brazilian Association of Research Companies by parents or guardians. Results: The prevalence of iron-deficiency anemia in school children was 25.8%, which is considered to be moderate. The proportion of better school grades was higher in children without anemia and in those belonging to the upper socioeconomic levels. However, it was not observed statistically differences between groups regarding school performance and socioeconomic variables. Conclusion: A moderate prevalence of iron-deficiency anemia was found in children aged between six and eight years old, however, it was not observed a significant association between irondeficiency anemia with socioeconomic variables and school performance.Modelo do estudo: Observacional transversal. Objetivo: Avaliar a associação entre a presença de anemia ferropriva com variáveis socioeconômicas e rendimento escolar. Método: Foram incluídas no estudo 124 crianças com idade entre seis e oito anos, estudantes do ensino fundamental de escolas municipais, as quais foram divididas em dois grupos de acordo com a presença (n=32) ou ausência de anemia (n=92). Os níveis de hemoglobina e ferro sérico foram determinados por método colorimétrico, a contagem de hemácias foi realizada utilizando a câmara de Neubauer, o hematócrito foi avaliado utilizando centrífuga de microhematócrito, e foram calculados os índices hematimétricos volume corpuscular médio, hemoglobina corpuscular média e concentração de hemoglobina corpuscular média. O desempenho escolar das crianças foi fornecido pelas escolas participantes e as variáveis socioeconômicas foram obtidas através de preenchimento de ficha clínica e do questionário socioeconômico da Associação Brasileira das Empresas de Pesquisa pelos pais ou responsáveis. Resultados: A prevalência de anemia ferropriva nos escolares foi de 25,8% que é considerada pelos parâmetros da OMS uma prevalência moderada. Foi observada uma maior proporção de crianças sem anemia que apresentaram melhores conceitos escolares e que pertencem aos níveis socioeconômicos mais altos do que de crianças com anemia. Contudo, não foram observadas diferenças estatisticamente significativas entre os grupos com relação ao rendimento escolar e as variáveis socioeconômicas. Conclusão: Uma prevalência moderada de anemia ferropriva foi encontrada nas crianças com idade entre seis e oitos anos, entretanto, não foi observada uma associação significativa entre a anemia ferropriva com variáveis socioeconômicas e o rendimento escolar

Analíse do papel do fator sigma C na resposta de Corynebacterium pseudotuberculosis a diferentes condições de estresse ambiental

Exportado OPUSMade available in DSpace on 2019-08-14T08:16:23Z (GMT). No. of bitstreams: 1 disserta_ao_carol8.pdf: 1677378 bytes, checksum: 19a2d74853f9b2b31ada27c3cee081f2 (MD5) Previous issue date: 3Corynebacterium pseudotuberculosis é uma bactéria Gram-positiva, causadora da linfadenite caseosa em ovinos e caprinos. Para causar uma infecção bem sucedida, este patógeno intracelular facultativo precisa responder de modo eficiente às alterações do ambiente extracelular, sendo capaz de sobreviver às condições adversas encontradas no organismo hospedeiro. Um dos principais mecanismos utilizados por bactérias patogênicas para alcançar este objetivo consiste na ativação transitória de genes específicos de resposta aos estresses ambientais extracelulares por fatores sigma alternativos da RNA polimerase. Com o seqüenciamento do genoma de C. pseudotuberculosis pela Rede Genoma de Minas Gerais e Rede Paraense de Genômica e Proteômica, foi possível identificar sete fatores sigma alternativos nesta bactéria: os fatores sigma B, C, D, E, H, K e M. Dentre estes, destaca-se o fator sigma C, o qual tem sido associado à virulência em Mycobacterium tuberculosis, e cujo gene se encontra em uma ilha de patogenicidade em C. pseudotuberculosis. Neste contexto, nosso grupo de pesquisa tem se dedicado ao estudo do papel dos fatores sigma alternativos de C. pseudotuberculosis na resposta a diferentes condições de estresse in vitro e na virulência da bactéria. Neste trabalho, foi construída uma linhagem de C. pseudotuberculosis deficiente para o fator sigma C, utilizando um plasmídeo suicida, e foi avaliada a resistência desta linhagem aos estresses oxidativo, ácido, osmótico e térmico in vitro, através da comparação das diferenças no crescimento relativo e na viabilidade relativa das bactérias expostas às condições de estresse em relação às bactérias crescidas sob condições normais, entre os tempos sucessivos de exposição das linhagens 1002 selvagem e mutante para o fator sigma C a cada agente gerador de estresse. Não foi observada uma diferença significativa na susceptibilidade da linhagem mutante para o fator sigma C ao estresse ácido em relação à linhagem 1002 selvagem. Contudo, foi verificado que esta linhagem é significativamente mais susceptível aos estresses oxidativo, osmótico e térmico do que a linhagem 1002 selvagem, indicando que o fator sigma C deve desempenhar um papel importante para a resposta da bactéria a estas condições de estresse, e possivelmente, para a sua sobrevivência no meio ambiente e no interior do hospedeiro e para a sua virulência.Corynebacterium pseudotuberculosis is a Gram-positive bacterium, which causes caseous lymphadenitis in sheep and goats. To cause a successful infection, this facultative intracellular pathogen needs to respond efficiently to the changes in the extracellular environment, being able to survive faced with the harsh conditions found in the host organism. One of the main mechanisms used by pathogenic bacteria to achieve this goal is the transient activation of specific genes in response to extracellular environmental stresses by alternative sigma factors of RNA polimerase. After the sequencing of the genome of C. pseudotuberculosis by Rede Genoma de Minas Gerais e Rede Paraense de Gen?ica e Prote?ica, it was identified seven alternative sigma factors in this bacterium, the sigma factors B, C, D, E, H, K and M. Between these, the sigma factor C stands out, which has been linked to virulence in Mycobacterium tuberculosis, and whose gene is located in a pathogenicity island in C. pseudotuberculosis. In this context, our research group has been studying the role of the alternative sigma factors of C. pseudotuberculosis in response to different stress conditions in vitro and in virulence of the bacterium. In this work, we constructed a strain of C. pseudotuberculosis deficient for the sigma factor C, using a suicide plasmid, and evaluated the resistance of this strain to oxidative, acid, osmotic and heat stresses in vitro, by comparing the differences in relative growth and relative viability of bacteria exposed to stress conditions in relation to bacteria grown under normal conditions, between the successive times of exposure of 1002 wild strain and the strain mutant for the sigma factor C for each stress generator agent. There was no significant difference in the susceptibility of the strain mutant for the sigma factor C for the acid stress in relation to the 1002 wild strain. However, it was found that this strain is significantly more susceptible to oxidative, osmotic and heat stresses than the 1002 wild strain, showing that the sigma factor C should play an important role for the bacteriums response to this stress conditions, and possibly, for its survival in the environment and in the host and for its virulence

Association Between Increased Levels of Cystatin C and the Development of Cardiovascular Events or Mortality: A Systematic Review and Meta-Analysis

Abstract Background: Cystatin C seems promising for evaluating the risk of cardiovascular events and mortality. Objective: To evaluate the association between high levels of cystatin C and the development of cardiovascular events or mortality. Methods: The articles were selected in the Medline/PubMed, Web of Science, and Scielo databases. The eligibility criteria were prospective cohort observational trials that assessed the association of high serum levels of cystatin C with the development of cardiovascular events or mortality in individuals with normal renal function. Only studies that evaluated the mortality outcome compared the fourth with the first quartile of cystatin C and performed multivariate Cox’s proportional hazard regression analysis were included in the meta-analysis. A p value < 0,05 was considered significant. Results: Among the 647 articles found, 12 were included in the systematic review and two in the meta-analysis. The risk of development of adverse outcomes was assessed by eight studies using the hazard ratio. Among them, six studies found an increased risk of cardiovascular events or mortality. The multivariate regression analysis was performed by six studies, and the risk of developing adverse outcomes remained significant after the analysis in four of these studies. The result of the meta-analysis [HR = 2.28 (1.70-3.05), p < 0.001] indicated that there is a significant association between high levels of cystatin C and the risk of mortality in individuals with normal renal function. Conclusion: There is a significant association between high levels of cystatin C and the development of cardiovascular events or mortality in individuals with normal renal function

The role of C-peptide in the attenuation of outcomes of diabetic kidney disease: a systematic review and meta-analysis

ABSTRACT Introduction: Preclinical trials have shown that C-peptide may contribute to the treatment of diabetic kidney disease (DKD). This systematic review and meta-analysis aimed to assess the use of C-peptide in attenuating the outcomes of DKD. Methods: Searches were made on databases PubMed, Web of Science, and Scielo for in vivo clinical and preclinical trials written in English, Portuguese or Spanish that looked into the use of C-peptide in the attenuation of the outcomes of DKD. Results: Twelve papers were included in this review, one clinical and eleven preclinical trials. In the clinical trial, DKD patients given C-peptide had lower levels of albuminuria than the subjects in the control group, but glomerular filtration rates were not significantly different. The main parameters assessed in the preclinical trials were glomerular filtration rate (six trials) and albuminuria (five trials); three trials described less hyperfiltration and three reported lower levels of albuminuria in the groups offered C-peptide. The meta-analysis revealed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels than the groups not given C-peptide. Conclusion: The results of the studies included in the systematic review diverged. However, the meta-analysis showed that the animals given C-peptide had lower glomerular volumes and lower urine potassium levels

MicroRNAs: new biomarkers and promising therapeutic targets for diabetic kidney disease

Abstract Diabetic kidney disease (DKD) is a chronic complication of diabetes mellitus associated with significant morbidity and mortality regarded as a global health issue. MicroRNAs - small RNA molecules responsible for the post-transcriptional regulation of gene expression by degradation of messenger RNA or translational repression of protein synthesis - rank among the factors linked to the development and progression of DKD. This study aimed to offer a narrative review on investigations around the use of microRNAs in the diagnosis, monitoring, and treatment of DKD. Various microRNAs are involved in the pathogenesis of DKD, while others have a role in nephroprotection and thus serve as promising therapeutic targets for DKD. Serum and urine microRNAs levels have also been considered in the early diagnosis and monitoring of individuals with DKD, since increases in albuminuria, decreases in the glomerular filtration rate, and progression of DKD have been linked to changes in the levels of some microRNAs

Clinical Usefulness of Cystatin C to Assess the Prognosis of Acute Coronary Syndromes: A Systematic Review and Meta-Analysis

<div><p>Abstract Cystatin C is used as a marker of renal function and has been shown to be promising for evaluating the prognosis of acute coronary syndromes (ACSs). To evaluate the prognostic value of cystatin C in patients with ACSs. The articles were searched using PubMed, Web of Science and Scielo databases. Observational cohort studies that evaluated the association between increased cystatin C and the development of cardiovascular events and mortality in patients with ACSs were included. Only studies that evaluated similar outcomes, studies that compared the highest with the lowest quartiles of cystatin C, and studies that performed multivariate analysis that included glomerular filtration rate or serum creatinine, were included in the meta-analysis. Methodological quality of the articles was assessed using the Newcastle-Ottawa Scale questionnaire for cohort studies. After applying the eligibility criteria, 17 studies were included in the systematic review. All included studies reported a significant association between higher levels of cystatin C and outcomes. The meta-analysis demonstrated that elevated levels of cystatin C are associated with increased risk of cardiovascular mortality or non-fatal myocardial infarction in patients with ACSs, and such association is independent of renal function [OR = 1.65 (1.464 - 1.861), p < 0.001]. Among the studies included, 4 have good quality and 13 have excellent methodological quality.The systematic review and meta-analysis demonstrated that there is a significant association between increased cystatin C levels and the development of cardiovascular events and mortality in patients with ACSs.</p></div

Von Willebrand Factor, Adamts13 And D-dimer Are Correlated With Different Levels Of Nephropathy In Type 1 Diabetes Mellitus

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)We have investigated whether von Willebrand factor, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13), and D-Dimer were associated with different levels of renal function in patients with type 1 diabetes. Patients were classified according to level of renal function through estimated glomerular filtration rate: >= 90 and = 60 and <90mL/min/1,73m(2), n=29 (mild renal dysfunction group), <60mL/min/1,73m(2), n=28 (severe renal dysfunction group); and through urinary albumin excretion: normoalbuminuria, microalbuminuria and macroalbuminuria. Von Willebrand factor, ADAMTS13, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay. ADAMTS13 activity was determined by fluorescence resonance energy transfer assay. Von Willebrand factor levels were increased in patients with mild (P=0.001) and severe (P<0.001) renal dysfunction as compared to the control group. ADAMTS13 levels were also increased in mild (P=0.029) and severe (P=0.002) renal dysfunction groups in comparison to the control group, while ADAMTS13 activity was increased only in the severe renal dysfunction group as compared to the control group (P=0.006). No significant differences were observed among the groups regarding vonWillebrand factor/ADAMTS13 ratio. ADAMTS13 activity/ADAMTS13 levels ratio was reduced in patients with mild (P=0.013) and severe (P=0.015) renal dysfunction as compared to the control group. D-Dimer levels were increased in patients with mild (P=0.006) and severe (P<0.001) renal dysfunction as compared to the control group; it was also higher in patients with severe renal dysfunction as compared to the mild renal dysfunction group (P=0.019). Similar results were found for albuminuria classification. Increased von Willebrand factor, ADAMTS13, and D-Dimer levels and decreased ADAMTS13 activity/ADAMTS13 levels ratio are associated with renal dysfunction in patients with type 1 diabetes, suggesting that endothelial dysfunction and hypercoagulability are associated with nephropathy in type 1 diabetes.107Fundação de Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

Association of different biomarkers of renal function with D-dimer levels in patients with type 1 diabetes mellitus (renal biomarkers and D-dimer in diabetes)

ABSTRACT Objective This study aimed to evaluate the association between different renal biomarkers with D-Dimer levels in diabetes mellitus (DM1) patients group classified as: low D-Dimer levels (< 318 ng/mL), which included first and second D-Dimer tertiles, and high D-Dimer levels (≥ 318 ng/mL), which included third D-Dimer tertile. Materials and methods D-Dimer and cystatin C were measured by ELISA. Creatinine and urea were determined by enzymatic method. Estimated glomerular filtration rate (eGFR) was calculated using CKD-EPI equation. Albuminuria was assessed by immunoturbidimetry. Presence of renal disease was evaluated using each renal biomarker: creatinine, urea, cystatin C, eGFR and albuminuria. Bivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels and odds ratio was calculated. After, multivariate logistic regression analysis was performed to assess which renal biomarkers are associated with high D-Dimer levels (after adjusting for sex and age) and odds ratio was calculated. Results Cystatin C presented a better association [OR of 9.8 (3.8–25.5)] with high D-Dimer levels than albuminuria, creatinine, eGFR and urea [OR of 5.3 (2.2–12.9), 8.4 (2.5–25.4), 9.1 (2.6–31.4) and 3.5 (1.4–8.4), respectively] after adjusting for sex and age. All biomarkers showed a good association with D-Dimer levels, and consequently, with hypercoagulability status, and cystatin C showed the best association among them. Conclusion Therefore, cystatin C might be useful to detect patients with incipient diabetic kidney disease that present an increased risk of cardiovascular disease, contributing to an early adoption of reno and cardioprotective therapies

Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus

This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m2), n=65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m2), n=60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P=0.001, P<0.001, P<0.001, P<0.001, and P<0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy