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BACKGROUND: In contrast to guidelines related to lipid therapy in other areas, 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend conducting a lipid profile upon diagnosis of chronic kidney disease (CKD) and treating all patients older than 50 years without defining a target for lipid levels. We evaluated multinational practice patterns for lipid management in patients with advanced CKD under nephrology care. METHODS: We analyzed lipid-lowering therapy (LLT), LDL- cholesterol (LDL-C) levels, and nephrologist-specified LDL-C goal upper limits in adult patients with eGFR < 60 ml/min from nephrology clinics in Brazil, France, Germany, and the United States (2014-2019). Models were adjusted for CKD stage, country, cardiovascular risk indicators, sex, and age. RESULTS: LLT treatment differed significantly by country, from 51% in Germany to 61% in the US and France (p = 0.002) for statin monotherapy. For ezetimibe with or without statins, the prevalence was 0.3% in Brazil to 9% in France (< 0.001). Compared with patients not taking lipid-lowering therapy, LDL-C was lower among treated patients (p < 0.0001) and differed significantly by country (p < 0.0001). At the patient level, the LDL-C levels and statin prescription did not vary significantly by CKD stage (p = 0.09 LDL-C and p = 0.24 statin use). Between 7-23% of untreated patients in each country had LDL-C ≥ 160 mg/dL. Only 7-17% of nephrologists believed that LDL-C should be < 70 mg/dL. CONCLUSION: There is substantial variation in practice patterns regarding LLT across countries but not across CKD stages. Treated patients appear to benefit from LDL-C lowering, yet a significant proportion of hyperlipidemia patients under nephrologist care are not receiving treatment.

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BACKGROUND: Approximately 30%-45% of patients with nondialysis CKD have iron deficiency. Iron therapy in CKD has focused primarily on supporting erythropoiesis. In patients with or without anemia, there has not been a comprehensive approach to estimating the association between serum biomarkers of iron stores, and mortality and cardiovascular event risks. METHODS: The study included 5145 patients from Brazil, France, the United States, and Germany enrolled in the Chronic Kidney Disease Outcomes and Practice Patterns Study, with first available transferrin saturation (TSAT) and ferritin levels as exposure variables. We used Cox models to estimate hazard ratios (HRs) for all-cause mortality and major adverse cardiovascular events (MACE), with progressive adjustment for potentially confounding variables. We also used linear spline models to further evaluate functional forms of the exposure-outcome associations. RESULTS: Compared with patients with a TSAT of 26%-35%, those with a TSAT ≤15% had the highest adjusted risks for all-cause mortality and MACE. Spline analysis found the lowest risk at TSAT 40% for all-cause mortality and MACE. Risk of all-cause mortality, but not MACE, was also elevated at TSAT ≥46%. Effect estimates were similar after adjustment for hemoglobin. For ferritin, no directional associations were apparent, except for elevated all-cause mortality at ferritin ≥300 ng/ml. CONCLUSIONS: Iron deficiency, as captured by TSAT, is associated with higher risk of all-cause mortality and MACE in patients with nondialysis CKD, with or without anemia. Interventional studies evaluating the effect on clinical outcomes of iron supplementation and therapies for alternative targets are needed to better inform strategies for administering exogenous iron.

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Vitamin K is a key cofactor for the activation of proteins involved in blood coagulation, apoptosis, bone mineralization regulation, and vessel health. Scientific evidence shows an important role of activated osteocalcin and matrix-Gla protein in bone and vessels, markedly affected along the course of chronic kidney disease (CKD). In fact, CKD corresponds to an unique condition of vitamin K deficiency caused by dietary restriction, intestinal dysfunction, and impaired vitamin K recycling. Clinical data suggest that vitamin K status can be modulated and this prompts us to speculate whether patients with CKD might benefit from vitamin K supplementation. However, as important as whether the improvement in vitamin K status would be able to result in better bone quality, less vascular calcification, and lower mortality rates, several issues need to be clarified. These include better standardized methods for measuring vitamin K levels, and definition of the optimal concentration range for supplementation in different subgroups. Here, we review the literature data concerning the impact of vitamin K deficiency and supplementation on CKD-associated mineral and bone disorders (CKD-MBD). We present and discuss the available evidence from basic science and clinical studies, and highlight perspectives for further research.

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Hyperphosphatemia is a common complication in patients with chronic kidney disease (CKD), particularly in those requiring renal replacement therapy. The importance of controlling serum phosphate has long been recognized based on observational epidemiological studies that linked increased phosphate levels to adverse outcomes and higher mortality risk. Experimental data further supported the role of phosphate in the development of bone and cardiovascular diseases. Recent advances in our understanding of the mechanisms involved in phosphate homeostasis have made it clear that the serum phosphate concentration depends on a complex interplay among the kidneys, intestinal tract, and bone, and is tightly regulated by a complex endocrine system. Moreover, the source of dietary phosphate and the use of phosphate-based additives in industrialized foods are additional factors that are of particular importance in CKD. Not surprisingly, the management of hyperphosphatemia is difficult, and, despite a multifaceted approach, it remains unsuccessful in many patients. An additional issue is the fact that the supposedly beneficial effect of phosphate lowering on hard clinical outcomes in interventional trials is a matter of ongoing debate. In this review, we discuss currently available treatment approaches for controlling hyperphosphatemia, including dietary phosphate restriction, reduction of intestinal phosphate absorption, phosphate removal by dialysis, and management of renal osteodystrophy, with particular focus on practical challenges and limitations, and on potential benefits and harms.

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Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic conditions their levels increase, and they assume a pro-inflammatory and pro-coagulant role via interactions with monocytes; these effects are related to the development of atherosclerosis. Chronic kidney dysfunction (CKD) characterizes this dysfunctional scenario through the accumulation of uremic solutes in the circulating plasma, whose toxicity is related to the development of cardiovascular diseases. Therefore, this review aims to discuss the formation of EMPs and their biological effects in the uremic environment. Data from previous research demonstrate that uremic toxins are closely associated with the activation of inflammatory biomarkers, cardiovascular dysfunction processes, and the release of EMPs. The impact of a decrease in circulating EMPs in clinical studies has not yet been evaluated. Thus, whether MPs are biochemical markers and/or therapeutic targets has yet to be established.

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Endothelial dysfunction in uremia can result in cell-to-cell junction loss and increased permeability, contributing to cardiovascular diseases (CVD) development. This study evaluated the impact of the uremic milieu on endothelial morphology and cell junction's proteins. We evaluated (i) serum levels of inflammatory biomarkers in a cohort of chronic kidney disease (CKD) patients and the expression of VE-cadherin and Zonula Occludens-1 (ZO-1) junction proteins on endothelial cells (ECs) of arteries removed from CKD patients during renal transplant; (ii) ECs morphology in vitro under different uremic conditions, and (iii) the impact of uremic toxins p-cresyl sulfate (PCS), indoxyl sulfate (IS), and inorganic phosphate (Pi) as well as of total uremic serum on VE-cadherin and ZO-1 gene and protein expression in cultured ECs. We found that the uremic arteries had lost their intact and continuous endothelial morphology, with a reduction in VE-cadherin and ZO-1 expression. In cultured ECs, both VE-cadherin and ZO-1 protein expression decreased, mainly after exposure to Pi and uremic serum groups. VE-cadherin mRNA expression was reduced while ZO-1 was increased after exposure to PCS, IS, Pi, and uremic serum. Our findings show that uremia alters cell-to-cell junctions leading to an increased endothelial damage. This gives a new perspective regarding the pathophysiological role of uremia in intercellular junctions and opens new avenues to improve cardiovascular outcomes in CKD patients.

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[ABSTRACT]. Objective. To compare the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in Latin America and Europe, as well as to study differences in macroeconomic indicators, demographic and clinical patient characteristics, mortality rates, and causes of death between these two populations. Methods. We used data from 20 Latin American and 49 European national and subnational renal registries that had provided data to the Latin American Dialysis and Renal Transplant Registry (RLADTR) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, respectively. The incidence and prevalence of RRT in 2013 were calculated per million population (pmp), overall and by subcategories of age, sex, primary renal disease, and treatment modality. The correlation between gross domestic product and the prevalence of RRT was analyzed using linear regression. Trends in the prevalence of RRT between 2004 and 2013 were assessed using Joinpoint regression analysis. Results. In 2013, the overall incidence at day 91 after the onset of RRT was 181 pmp for Latin American countries and 130 pmp for European countries. The overall prevalence was 660 pmp for Latin America and 782 pmp for Europe. In the Latin American countries, the annual increase in the prevalence averaged 4.0% (95% confidence interval (CI): 2.5%-5.6%) from 2004 to 2013, while the European countries showed an average annual increase of 2.2% (95% CI: 2.0%-2.4%) for the same time period. The crude mortality rate was higher in Latin America than in Europe (112 versus 100 deaths per 1 000 patient-years), and cardiovascular disease was the main cause of death in both of those regions. Conclusions. There are considerable differences between Latin America and Europe in the epidemiology of RRT for ESRD. Further research is needed to explore the reasons for these differences.

[RESUMEN]. Objetivo. Comparar los datos epidemiológicos del tratamiento sustitutivo de la función renal (TSFR) para la nefropatía terminal en América Latina y Europa, así como estudiar las diferencias en cuanto a indicadores macroeconómicos, características demográficas y clínicas de los pacientes, tasas de mortalidad y causas de defunción entre estas dos poblaciones. Métodos. Utilizamos los datos de 20 registros renales latinoamericanos y 49 europeos, a nivel nacional y subnacional, que le habían proporcionado datos al Registro Latinoamericano de Diálisis y Trasplante Renal (RLADTR) y al Registro de la Asociación Europea Renal–Asociación Europea de Diálisis y Trasplantes (ERA-EDTA, por su sigla en inglés), respectivamente. Se calculó la incidencia y la prevalencia del TSFR en el 2013 por millón de habitantes, en total y por subcategoría (edad, sexo, nefropatía primaria y modalidad de tratamiento). Se analizó la correlación entre el producto interno bruto y la prevalencia de TSFR mediante regresión lineal. Se evaluaron las tendencias en la prevalencia de TSFR entre el 2004 y el 2013 mediante un análisis de regresiones lineales segmentadas. Resultados. En el 2013, la incidencia general al día 91 después de iniciar el tratamiento sustitutivo de la función renal era de 181 por millón de habitantes en los países latinoamericanos y de 130 en los países europeos. La prevalencia general era de 660 por millón de habitantes para América Latina y de 782 para Europa. En los países latinoamericanos, el aumento anual promedio de la prevalencia fue de 4,0% (intervalo de confianza de 95% [IC]: 2,5%-5,6%) entre el 2004 y el 2013, mientras que los países europeos registraron un aumento anual promedio de 2,2% (IC de 95%: 2,0%-2,4%) durante el mismo período. La tasa bruta de mortalidad fue mayor en América Latina que en Europa (112 defunciones por 1 000 años-paciente, en comparación con 100 defunciones), y las enfermedades cardiovasculares fueron la principal causa de muerte en ambas regiones. Conclusiones. Hay considerables diferencias entre América Latina y Europa en cuanto a los datos epidemiológicos del tratamiento sustitutivo de la función renal para la nefropatía terminal. Es necesario hacer más investigaciones para explorar las razones de tales diferencias.

[RESUMO]. Objetivo. Comparar o perfil epidemiológico de pacientes com doença renal em estágio final (DREF) em terapia renal substitutiva (TRS) na América Latina e na Europa e examinar as diferenças nos indicadores macroeconômicos, características demográficas e clínicas, taxas de mortalidade e causas de morte entre as duas populações de pacientes. Métodos. O estudo foi baseado em informação de 20 registros latino-americanos e 49 registros nacionais e subnacionais europeus que haviam fornecido dados ao Registro Latino-Americano de Diálise e Transplante Renal (RLADTR) e Registro da Associação Europeia de Nefrologia e Associação Europeia de Diálise e Transplante (ERA-EDTA), respectivamente. A incidência e a prevalência de TRS em 2013 foram calculadas por milhão de habitantes (pmh), geral e por subcategorias de idade, sexo, doença renal primária e modalidade de tratamento. A correlação entre o produto interno bruto (PIB) e a prevalência de TRS foi analisada com o uso de regressão linear. Tendências na prevalência de TRS entre 2004 e 2013 foram analisadas com o uso de regressão linear segmentada. Resultados. Em 2013, a incidência geral ao dia 91 do início de TRS foi 181 pmh nos países latino-americanos e 130 pmh nos países europeus. Observou-se uma prevalencia geral de TRS de 660 pmh na América Latina e 782 pmh na Europa. No período 2004–2013, o aumento médio anual da prevalência foi de 4,0% (intervalo de confiança de 95% [IC 95%] 2,5%–5,6%) nos países latino-americanos, enquanto que houve um aumento médio anual de 2,2% (IC 95% 2,0%–2,4%) nos países europeus. A taxa de mortalidade bruta foi maior na América Latina que na Europa (112 versus 100 óbitos por 1.000 pacientes-anos) e doença cardiovascular foi a principal causa de morte em ambas as regiões. Conclusões. Existem diferenças consideráveis entre a América Latina e a Europa no perfil epidemiológico dos pacientes com DREF em TRS. Outras pesquisas devem ser realizadas para investigar mais a fundo estas diferenças.

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Background: Patients starting renal replacement therapy (RRT) for end-stage renal disease often present with one or more co-morbidities. This study explored the prevalence of co-morbidities in patients who started RRT in Europe during the period from 2005 to 2014. Methods: Using data from patients aged 20 years or older from all 11 national or regional registries providing co-morbidity data to the European Renal Association - European Dialysis and Transplant Association Registry, we examined the prevalence of the following co-morbidities: diabetes mellitus (DM) (primary renal disease and/or co-morbidity), ischaemic heart disease (IHD), congestive heart failure (CHF), peripheral vascular disease (PVD), cerebrovascular disease (CVD) and malignancy. Results: Overall, 70% of 7578 patients who initiated RRT in 2014 presented with at least one co-morbidity: 39.0% presented with DM, 25.0% with IHD, 22.3% with CHF, 17.7% with PVD, 16.4% with malignancy and 15.5% with CVD. These percentages differed substantially between countries. Co-morbidities were more common in men than in women, in older patients than in younger patients, and in patients on haemodialysis at Day 91 when compared with patients on peritoneal dialysis. Between 2005 and 2014 the prevalence of DM and malignancy increased over time, whereas the prevalence of IHD and PVD declined. Conclusions: More than two-thirds of patients initiating RRT in Europe have at least one co-morbidity. With the rising age at the start of RRT over the last decade, there have been changes in the co-morbidity pattern: the prevalence of cardiovascular co-morbidities decreased, while the prevalence of DM and malignancy increased.

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OBJECTIVE: To compare the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in Latin America and Europe, as well as to study differences in macroeconomic indicators, demographic and clinical patient characteristics, mortality rates, and causes of death between these two populations. METHODS: We used data from 20 Latin American and 49 European national and subnational renal registries that had provided data to the Latin American Dialysis and Renal Transplant Registry (RLADTR) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, respectively. The incidence and prevalence of RRT in 2013 were calculated per million population (pmp), overall and by subcategories of age, sex, primary renal disease, and treatment modality. The correlation between gross domestic product and the prevalence of RRT was analyzed using linear regression. Trends in the prevalence of RRT between 2004 and 2013 were assessed using Joinpoint regression analysis. RESULTS: In 2013, the overall incidence at day 91 after the onset of RRT was 181 pmp for Latin American countries and 130 pmp for European countries. The overall prevalence was 660 pmp for Latin America and 782 pmp for Europe. In the Latin American countries, the annual increase in the prevalence averaged 4.0% (95% confidence interval (CI): 2.5%-5.6%) from 2004 to 2013, while the European countries showed an average annual increase of 2.2% (95% CI: 2.0%-2.4%) for the same time period. The crude mortality rate was higher in Latin America than in Europe (112 versus 100 deaths per 1 000 patient-years), and cardiovascular disease was the main cause of death in both of those regions. CONCLUSIONS: There are considerable differences between Latin America and Europe in the epidemiology of RRT for ESRD. Further research is needed to explore the reasons for these differences.

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ABSTRACT Objective To compare the epidemiology of renal replacement therapy (RRT) for end-stage renal disease (ESRD) in Latin America and Europe, as well as to study differences in macroeconomic indicators, demographic and clinical patient characteristics, mortality rates, and causes of death between these two populations. Methods We used data from 20 Latin American and 49 European national and subnational renal registries that had provided data to the Latin American Dialysis and Renal Transplant Registry (RLADTR) and the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Registry, respectively. The incidence and prevalence of RRT in 2013 were calculated per million population (pmp), overall and by subcategories of age, sex, primary renal disease, and treatment modality. The correlation between gross domestic product and the prevalence of RRT was analyzed using linear regression. Trends in the prevalence of RRT between 2004 and 2013 were assessed using Joinpoint regression analysis. Results In 2013, the overall incidence at day 91 after the onset of RRT was 181 pmp for Latin American countries and 130 pmp for European countries. The overall prevalence was 660 pmp for Latin America and 782 pmp for Europe. In the Latin American countries, the annual increase in the prevalence averaged 4.0% (95% confidence interval (CI): 2.5%-5.6%) from 2004 to 2013, while the European countries showed an average annual increase of 2.2% (95% CI: 2.0%-2.4%) for the same time period. The crude mortality rate was higher in Latin America than in Europe (112 versus 100 deaths per 1 000 patient-years), and cardiovascular disease was the main cause of death in both of those regions. Conclusions There are considerable differences between Latin America and Europe in the epidemiology of RRT for ESRD. Further research is needed to explore the reasons for these differences.

RESUMEN Objetivo Comparar los datos epidemiológicos del tratamiento sustitutivo de la función renal (TSFR) para la nefropatía terminal en América Latina y Europa, así como estudiar las diferencias en cuanto a indicadores macroeconómicos, características demográficas y clínicas de los pacientes, tasas de mortalidad y causas de defunción entre estas dos poblaciones. Métodos Utilizamos los datos de 20 registros renales latinoamericanos y 49 europeos, a nivel nacional y subnacional, que le habían proporcionado datos al Registro Latinoamericano de Diálisis y Trasplante Renal (RLADTR) y al Registro de la Asociación Europea Renal-Asociación Europea de Diálisis y Trasplantes (ERA-EDTA, por su sigla en inglés), respectivamente. Se calculó la incidencia y la prevalencia del TSFR en el 2013 por millón de habitantes, en total y por subcategoría (edad, sexo, nefropatía primaria y modalidad de tratamiento). Se analizó la correlación entre el producto interno bruto y la prevalencia de TSFR mediante regresión lineal. Se evaluaron las tendencias en la prevalencia de TSFR entre el 2004 y el 2013 mediante un análisis de regresiones lineales segmentadas. Resultados En el 2013, la incidencia general al día 91 después de iniciar el tratamiento sustitutivo de la función renal era de 181 por millón de habitantes en los países latinoamericanos y de 130 en los países europeos. La prevalencia general era de 660 por millón de habitantes para América Latina y de 782 para Europa. En los países latinoamericanos, el aumento anual promedio de la prevalencia fue de 4,0% (intervalo de confianza de 95% [IC]: 2,5%-5,6%) entre el 2004 y el 2013, mientras que los países europeos registraron un aumento anual promedio de 2,2% (IC de 95%: 2,0%-2,4%) durante el mismo período. La tasa bruta de mortalidad fue mayor en América Latina que en Europa (112 defunciones por 1 000 años-paciente, en comparación con 100 defunciones), y las enfermedades cardiovasculares fueron la principal causa de muerte en ambas regiones. Conclusiones Hay considerables diferencias entre América Latina y Europa en cuanto a los datos epidemiológicos del tratamiento sustitutivo de la función renal para la nefropatía terminal. Es necesario hacer más investigaciones para explorar las razones de tales diferencias.

RESUMO Objetivo Comparar o perfil epidemiológico de pacientes com doença renal em estágio final (DREF) em terapia renal substitutiva (TRS) na América Latina e na Europa e examinar as diferenças nos indicadores macroeconômicos, características demográficas e clínicas, taxas de mortalidade e causas de morte entre as duas populações de pacientes. Métodos O estudo foi baseado em informação de 20 registros latino-americanos e 49 registros nacionais e subnacionais europeus que haviam fornecido dados ao Registro Latino-Americano de Diálise e Transplante Renal (RLADTR) e Registro da Associação Europeia de Nefrologia e Associação Europeia de Diálise e Transplante (ERA-EDTA), respectivamente. A incidência e a prevalência de TRS em 2013 foram calculadas por milhão de habitantes (pmh), geral e por subcategorias de idade, sexo, doença renal primária e modalidade de tratamento. A correlação entre o produto interno bruto (PIB) e a prevalência de TRS foi analisada com o uso de regressão linear. Tendências na prevalência de TRS entre 2004 e 2013 foram analisadas com o uso de regressão linear segmentada. Resultados Em 2013, a incidência geral ao dia 91 do início de TRS foi 181 pmh nos países latino-americanos e 130 pmh nos países europeus. Observou-se uma prevalência geral de TRS de 660 pmh na América Latina e 782 pmh na Europa. No período 2004-2013, o aumento médio anual da prevalência foi de 4,0% (intervalo de confiança de 95% [IC 95%] 2,5%-5,6%) nos países latino-americanos, enquanto que houve um aumento médio anual de 2,2% (IC 95% 2,0%-2,4%) nos países europeus. A taxa de mortalidade bruta foi maior na América Latina que na Europa (112 versus 100 óbitos por 1.000 pacientes-anos) e doença cardiovascular foi a principal causa de morte em ambas as regiões. Conclusões Existem diferenças consideráveis entre a América Latina e a Europa no perfil epidemiológico dos pacientes com DREF em TRS. Outras pesquisas devem ser realizadas para investigar mais a fundo estas diferenças.

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Recently, the clinical and experimental evidences that support the toxic effects of indoxyl sulfate, a protein-bound uremic toxin in chronic kidney disease (CKD) patients, has been discussed. In this panorama, the authors described several in vitro and in vivo studies, suggesting that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease. However, the discussion claims the need for relevant clinical studies in CKD patients whose bone turnover biomarkers and bone histomorphometry were assessed in order to demonstrate the association between serum levels of indoxyl sulfate and bone turnover. We would like to underline the availability of this clinical data to support the concept that indoxyl sulfate may play a part in the pathogenesis of low turnover bone disease in CKD patients.

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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.

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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.

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Vascular calcification (VC), an independent and strong predictor of cardiovascular risk, is often found in CKD patients. The degree of VC is providing incremental prognostic value over traditional risk markers. There is interest in improving our understanding of mechanisms, establishing diagnostic methods and effective prevention and treatment modalities. The abnormal mineral metabolism of CKD is known to facilitate the progression of VC, in concert with altered activities of VC inhibitors. Possible measures to prevent VC include the control of serum calcium and phosphate as well as other factors involved in its progression, including vitamin D sterols, parathyroid hormone, fibroblast growth factor-23, klotho, and VC inhibitors. In addition, we discuss new possible therapeutic approaches to halt VC or reverse its progression. The principal aim of this review is to provide an updated overview of VC in patients with CKD, with particular focus on pathophysiology, diagnosis, prevention and treatment.

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