Acompanhamento farmacoterapêutico do paciente com doença renal crônica

Texto que compõe o módulo 10 "Farmacologia em Nefrologia" do curso de especialização em Nefrologia Multidisciplinar, produzido pela UNA-SUS/UFMA. Aborda as principais reações adversas relacionadas aos medicamentos frequentemente utilizados por pacientes com doença renal crônica (DRC), a importância da adesão medicamentosa para êxito das medidas terapêuticas e os aspectos relacionados à conservação, armazenamento e uso dos medicamentos no tratamento da DRC.Ministério da Saúd

Monitoring renal function : measured and estimated glomerular filtration rates : a review

Chronic kidney disease (CKD) is a world-wide public health problem, with adverse outcomes of kidney failure, cardiovascular disease, and premature death. This finding has led to the hypothesis that earlier recognition of kidney disease and successful intervention may improve outcome. The National Kidney Foundation, through its Kidney Disease Outcomes Quality Initiative (K/DOQI), and other National institutions recommend glomerular filtration rate (GFR) for the definition, classification, screening, and monitoring of CKD. Blood creatinine clearance, the most widely used clinical marker of kidney function, is now recognized as an unreliable measure of GFR because serum creatinine is affected by age, weight, muscle mass, race, various medications, and extra-glomerular elimination. Cystatin C concentration is a new and promising marker for kidney dysfunction in both native and transplanted kidneys. Because of its low molecular weight, cystatin C is freely filtered at the glomerulus and is almost completely reabsorbed and catabolized, but not secreted, by tubular cells. Given these characteristics, cystatin C concentration may be superior to creatinine concentration in detecting chronic kidney disease. This review aims to evaluate from recent literature the clinical efficiency and relevance of these GFR markers in terms of screening CKD

Cistatina C e marcadores inflamatórios em receptores de transplante renal

OBJETIVO: O transplante renal é a melhor opção para pacientes renais crônicos em estágio terminal. Este estudo avaliou o perfil da cistatina C (CysC), interleucina 2 (IL-2), IL-6, e fator de necrose tumoral-α (TNF-α) como marcadores inflamatórios em 23 transplantados renais de doador vivo. MÉTODOS: Estudo descritivo, analítico e prospectivo conduzido entre 1o de janeiro (2007) e 30 de junho (2008) em 23 transplantados renais de doador vivo. Os biomarcadores foram avaliados no pré, com 30 e 180 dias do pós-transplante. RESULTADOS: A média de idade foi de 34,3 anos (± 11,7), 52% do sexo feminino e 61% de negros. Foi encontrada diferença significativa na CysC e creatinina antes do transplante e 30 dias após o procedimento (p < 0,0001) e antes do transplante e 180 dias após o procedimento (p < 0,0001). Houve uma diferença significativa na IL-2, entre 30 and 180 dias do pós-transplante (p = 0,0418) e no TNF-α antes do transplante e 30 dias após o procedimento (p = 0,0001). Foi observada uma correlação negativa entre CysC e TNF-α no pré-transplante, e entre CysC e IL-6 com 180 dias do pós-transplante. Em pacientes biopsiados houve uma diferença significante na creatinina e na CysC com 30 e 180 dias do pós-transplante. CONCLUSÃO: Em seguimento a curto prazo, não houve correlação relevante entre os níveis de CysC, IL-2, IL-6 e TNF-α em transplantados renais. Em pacientes biopsiados e não biopsiados, os níveis de CysC foram muito similares aos da creatinina, ao contrário de outros marcadores inflamatórios. Demais estudos são importantes para avaliar o perfil destes marcadores a longo prazo.OBJECTIVE: Kidney transplantation is the best option for patients with end-stage renal disease. This study evaluated the profile of cystatin C (CysC), interleukin 2 (IL-2), IL-6, and tumor necrosis factor-α (TNF-α) as inflammatory markers in 23 living donor kidney transplant recipients. METHODS: A descriptive, analytical and prospective study was conducted between January 1st, 2007 and June 30th, 2008 on 23 living donor kidney transplant recipients. The biomarkers were evaluated before and 30 and 180 days after transplantation. RESULTS: The mean age of the patients was 34.3 years (± 11.7), females (52%) and non-whites (61%). Significant difference was found in cystatin C and creatinine before and 30 days after transplantation (p < 0.0001) and before and 180 days after transplantation (p < 0.0001). There was a significant difference in IL-2 between 30 and 180 days post-transplant (p = 0.0418) and in TNF-α between pre-transplant and 30 days post-transplant (p = 0.0001). A negative correlation was observed between cystatin C and TNF-α at pre-transplant and between cystatin C and IL-6 at 180 days post-transplant. Comparison of biopsied and non-biopsied patients showed a significant difference in creatinine and cystatin C at 30 and 180 days post-transplant in biopsied patients. CONCLUSION: Our results showed no significant correlations between CysC, IL-2, IL-6 and TNF-α levels in kidney transplant recipients at short-term follow-up. Moreover, CysC levels were very similar to creatinine levels in contrast to other inflammatory markers studied in biopsied and non-biopsied patients. Further studies are important to evaluate the long-term profile of these markers

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Avaliação da cistatina C como marcador de função renal de pacientes com hipertensão arterial primária

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Ciências da Saúde, 2009.A hipertensão arterial sistêmica essencial é um importante fator de risco para o desenvolvimento da doença renal crônica. A monitorização acurada da função renal, que se traduz pela estimativa da taxa de filtração glomerular e pela determinação da microalbuminúria, é fundamental para garantir uma avaliação adequada dos pacientes hipertensos. A cistatina C tem sido proposta com um marcador alternativo da filtração em relação à creatinina. O presente estudo foi conduzido com o objetivo de avaliar o uso da cistatina C na identificação do comprometimento renal precoce em pacientes com hipertensão primária e avaliar a associação entre as equações baseadas na cistatina C com outros marcadores conhecidos da taxa de filtração glomerular (TFG). Para tanto, foi desenvolvido um estudo transversal com 199 pacientes não-diabéticos com hipertensão arterial. Para avaliação da função renal, foram medidosa creatinina sérica, a microalbuminúria de 24h e os níveis de cistatina C sérica. A TFG foi estimada de acordo com o clearance de creatinina (CrCl), com equações baseadas na cistatina C (fórmulas de Larsson e Levey), com as equações Cockcroft-Gault (C-G) e MDRD (Modification of Diet in Renal Disease) abreviada. A MDRD foi utilizada como método de referência, de acordo com as recomendações da KDIGO e da NKF-K/DOQI. As médias dos parâmetros séricos encontradas foram estatisticamente menores em normoalbuminúricos em comparação aos microalbuminúricos. A cistatina C sérica foi significantemente maior nos microalbuminúricos (1,070,48 mg/L) que nos normoalbuminúricos (0,860,17; p 0,95 mg/L estavam fortemente associados com a presença de microalbuminúria (OR=3,2; 95% CI, 1,40-7,42; p=0,006). Dentre as estimativas da TFG, diferenças significativas entre normoalbuminúricos e microalbuminúricos foram encontradas nas fórmulas de C-G, Larsson e Levey. Os melhores coeficientes de correlação foram observados entre MDRD com as fórmulas C-G (r=0,66) e Levey (r=0,88)(p0,95 mg/L were significantly associated to the presence of microalbuminuria (OR=3,2; 95% CI, 1,40-7,42; p=0,006). Of the estimations of GFR, significant differences among normoalbuminurics and microalbuminurics were found on CG, Larsson and Levey formulas. The best correlation coefficients were observed between MDRD with the C-G (r=0,66) and Levey formula (r=0,88)(p<0,001). The mean difference, calculated according to Bland-Altman plot analysis, between MDRD equation and Levey formula, was -1,3 mL/min/1,73m2 and the 95% limits of agreement attained -24,1 and 21,4 mL/min/1.73 m2. Our results indicate that serum cysC level is of clinical value for detecting mild reductions and early damages in patients with essential hypertension. Although MDRD equation showed no difference between normoalbuminurics and microalbuminurics, cystatin C-based equations, mainly Levey formula, compared to other traditional markers, can also provide the clinicians an available and reliable GFR measurement in hypertensive patients, specially when the kidney disease is suspected

The role of the fibroblast growth factor 21 in bone metabolism and marrow adiposity of chronic kidney disease patients under conservative treatment

Objetivo: Investigar a relação entre o FGF21 sérico e a adiposidade medular com parâmetros laboratoriais e histomorfométricos ósseos em pacientes com DRC não dialíticos. Métodos: Esta é uma análise post hoc de dois estudos transversais. O estudo A incluiu 89 pacientes com DRC estágio 2-5 ND para avaliar os fatores associados aos níveis de FGF21. O estudo B incluiu 37 pacientes submetidos à biópsia óssea para avaliação histomorfométrica dos adipócitos da medula. Os níveis séricos de FGF21, esclerostina e osteocalcina descarboxilada foram quantificados por ELISA. Foram realizadas análises histomorfométricas do tecido ósseo e medular. A histomorfometria óssea foi categorizada de acordo com o sistema TMV (remodelação, mineralização, volume). Resultados: Os níveis de FGF21 aumentaram entre os estágios da DRC e foram independentemente associados com a taxa de filtração glomerular estimada, triglicérides, fosfatase alcalina total e tratamento com estatinas (estudo A). Nos pacientes do estudo B, os níveis de FGF21 se correlacionaram diretamente com os níveis de osteoprotegerina (OPG) e com o intervalo de tempo para mineralização e, inversamente, com a taxa de formação óssea. Quanto à adiposidade medular, o FGF21 se relacionou diretamente com área e espessura dos adipócitos. A adiposidade medular esteve independentemente associada com idade, esclerostina e OPG. A área e o número de adipócitos estiveram associados com volume e microarquitetura óssea. Considerando-se a classificação TMV, a área adiposa foi maior em pacientes com baixa remodelação óssea e o número de adipócitos foi maior naqueles com volume trabecular ósseo diminuído. Conclusão: Em pacientes com DRC não dialíticos, os níveis séricos do FGF21 foram associados à função renal e alterações lipídicas (estudo A). No estudo B, o FGF21 se associou a alterações da homeostase óssea e à adiposidade medular. Por sua vez, a gordura medular se associou à microarquitetura óssea, à baixa remodelação e volume ósseos e a marcadores séricos ósseos.Aim: To investigate the relationship between serum FGF21 and marrow adiposity with laboratory and bone histomorphometric parameters in non-dialysis CKD patients. Methods: This was a post hoc analysis of two cross-sectional studies. The study A included 89 CKD patients stage 2-5ND to evaluate the factors associated with FGF21 levels. The study B included 37 patients who underwent transiliac bone biopsy for histomorphometric assessment of marrow adipocytes. Serum levels of FGF21, sclerostin and undercarboxylated osteocalcin were quantified by ELISA. Histomorphometric analysis of bone and marrow tissues was performed. Bone histomorphometry was categorized according to the TMV System. Results: FGF21 levels increased among CKD stages and were independently associated with estimated glomerular filtration rate, triglycerides, total alkaline phosphatase and statins therapy (study A). In study B patients, FGF21 levels correlated directly with osteoprotegerin levels (OPG) and mineralization lag time and inversely with bone formation rate. On marrow adiposity, FGF21 was directly related to adipocyte width and area. Marrow adiposity was independently associated with age, sclerostin and OPG. Adipocyte area and number were associated with bone volume and microarchitecture. Regarding the TMV classification, the adipose area was greater in patients with low bone turnover and the adipocyte number was higher in those with decreased trabecular bone volume. Conclusion: In non-dialyzed CKD patients, serum FGF21 levels were associated with renal function and lipid alterations (study A). In the study B, FGF21 was correlated with abnormal bone homeostasis and marrow adiposity. In its turn, marrow adiposity was associated with bone microarchitecture, low bone turnover and volume, and serum bone markers.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)00

Nefrotoxicidade e ajustes medicamentosos em pacientes em doença renal crônica

Texto que compõe o módulo 10 "Farmacologia em Nefrologia" do curso de especialização em Nefrologia Multidisciplinar, produzido pela UNA-SUS/UFMA. Enfatiza os principais mecanismos e diagnósticos de nefrotoxicidades, apontando as principais drogas nefrotóxicas utilizadas na práticas clínicas, assim como os mecanismos de toxicidade renal e medidas nefroprotetoras.Ministério da Saúd