FGF21 and Chronic Kidney Disease.

The global nephrology community recognizes the increasing burden of kidney disease and its poor health outcomes in the general population. Given this, strategies to establish early diagnosis, improve understanding of the natural course and develop novel therapeutic interventions to slow progression and reduce complications are encouraged. Fibroblast growth factor 21 (FGF21), a member of the endocrine FGF subfamily, has emerged as a master homeostasis regulator of local and systemic lipid, glucose and energy metabolism. In addition, FGF21 should be considered an autonomic and endocrine regulator of stress responses in general. Promising results has been shown in both dysmetabolic animal models and metabolic disease patients after pharmacological administration of FGF21 analogs. The association of FGF21 with renal function has been studied for more than ten years. However, the functional role of FGF21 in the kidney is still poorly understood. This review summarizes the biological effects of FGF21 and discusses what is currently known about this hormone and chronic kidney disease, highlighting important gaps that warrant further research.

Increased Glycated Hemoglobin Levels in Patients With Helicobacter pylori Infection Are Associated With the Grading of Chronic Gastritis.

Background: Recent studies have found an association between Helicobacter pylori infection and prediabetes. Whether H. pylori per se or host factors are involved in the disturbance of glycated hemoglobin needs further investigation. The aim of this study was to determine the association of glycated hemoglobin levels with endoscopic diagnosis and the inflammatory response in H. pylori infection. Methods: A cross-sectional study was carried out in 88 dyspeptic non-diabetic adults who underwent esophagogastroduodenoscopy. The diagnosis of H. pylori infection was performed through urease test and histopathological exam. Cases were initially distributed into two groups: control (without H. pylori infection, n = 22) and HP (patients with H. pylori infection, n = 66). HbA1c was measured to determine prediabetes status according to the American Diabetes Association criteria, and then the groups were subdivided into non-prediabetic (n = 14), prediabetic (n = 8), non-prediabetic HP (n = 26) and prediabetic HP (n = 40) groups. Gastric mucosa was histologically evaluated to determine H. pylori density and inflammatory activity according to Sydney System. To investigate the balance of anti-inflammatory and pro-inflammatory cytokines we measured interleukin 10 (anti-inflammatory) and Tumor Necrosis Factor-a (pro-inflammatory) in the plasma or in the gastric mucosa. Results: Patients with H. pylori infection had higher mean HbA1c levels than those without H. pylori infection. However, increased HbA1c levels were not associated with H. pylori-related factors but with the bacterial density, the intensity of inflammation and the activity of the chronic gastritis. In addition, H. pylori infection per se did not alter IL-10 and TNF-α neither in the plasma nor in the gastric mucosa, but the bacterial density was negatively correlated with systemic and local IL-10 expression. Although no correlation was found between systemic cytokines and HbA1c levels, local anti-inflammatory cytokine was correlated with HbA1c levels. Conclusion: Long-term H. pylori infection is associated with prediabetes. This association is not related to the presence of H. pylori per se but depends on the extent of bacterial colonization and the degree of both local inflammation and activity of the chronic gastritis.

Usefulness of visceral adipose tissue estimation in the prevention of chronic kidney disease in hypertensive patients in primary health care.

BACKGROUND: studies have shown an association between obesity and a reduction in estimated glomerular filtration rate (eGFR). However, little is known regarding whether this association is related to total fat or, more specifically, to central or visceral fat. OBJECTIVE: this study evaluated the correlations among the nutritional indices that measure total, central and visceral obesity with eGFR. METHODS: a cross-sectional study, involving 288 hypertensive patients. Kidney function was estimated by GFR, using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Explanatory variables included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist stature ratio (WSR), estimated visceral adipose tissue (eVAT) and body fat percentage (BF%). RESULTS: the mean BMI was 27.8 ± 4.7 kg/m². Most of the patients (68.1%) were in the normal range of BF%, but regarding WC and eVAT, they were at very high risk (58.3% and 64.6%, respectively). In men, there were no correlations between nutritional indices and eGFR. In women, only eVAT remained negatively correlated with eGFR, estimated by MDRD and CKD-EPI equations, independent of BMI, smoking, physical inactivity, blood pressure, glycated hemoglobin, LDL and HDL cholesterol, uric acid and microalbuminuria. CONCLUSIONS: the majority of obesity indices were not associated with eGFR. Only eVAT was negatively associated with eGFR by MDRD and CKDEPI equations in hypertensive women. In primary health care, visceral adipose tissue estimation could support the identification of hypertensive women at increased risk for developing chronic kidney disease.

Usefulness of visceral adipose tissue estimation in the prevention of chronic kidney disease in hypertensive patients in primary health care / Utilidad de la estimación del tejido adiposo visceral en la prevención de la enfermedad renal crónica en pacientes hipertensos en Atención Primaria

Background: studies have shown an association between obesity and a reduction in estimated glomerular filtration rate (eGFR). However, little is known regarding whether this association is related to total fat or, more specifically, to central or visceral fat. Objective: this study evaluated the correlations among the nutritional indices that measure total, central and visceral obesity with eGFR. Methods: a cross-sectional study, involving 288 hypertensive patients. Kidney function was estimated by GFR, using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. Explanatory variables included body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist stature ratio (WSR), estimated visceral adipose tissue (eVAT) and body fat percentage (BF%).Results: the mean BMI was 27.8 ± 4.7 kg/m². Most of the patients (68.1%) were in the normal range of BF%, but regarding WC and eVAT, they were at very high risk (58.3% and 64.6%, respectively). In men, there were no correlations between nutritional indices and eGFR. In women, only eVAT remained negatively correlated with eGFR, estimated by MDRD and CKD-EPI equations, independent of BMI, smoking, physical inactivity, blood pressure, glycated hemoglobin, LDL and HDL cholesterol, uric acid and microalbuminuria. Conclusions: the majority of obesity indices were not associated with eGFR. Only eVAT was negatively associated with eGFR by MDRD and CKDEPI equations in hypertensive women. In primary health care, visceral adipose tissue estimation could support the identification of hypertensive women at increased risk for developing chronic kidney disease

Antecedentes: los estudios han demostrado una asociación entre la obesidad y una reducción en la tasa de filtración glomerular estimada (eGFR). Sin embargo, poco se sabe sobre si esta asociación está relacionada con la grasa total o, más específicamente, con la grasa central o visceral. Objetivo: este estudio evaluó las correlaciones entre los índices nutricionales que miden la obesidad total, central y visceral con eGFR. Métodos: estudio transversal con 288 pacientes hipertensos. La función renal se estimó mediante TFG, utilizando las ecuaciones de Modificación de la Dieta en la Enfermedad Renal (MDRD) y la Colaboración en Epidemiología de la Enfermedad Renal Crónica (CKD-EPI). Las variables explicativas incluyeron el índice de masa corporal (IMC), la circunferencia de cintura (WC), la relación cintura-cadera (WHR), la proporción cintura-estatura (WSR), el tejido adiposo visceral estimado (eVAT) y el porcentaje de grasa corporal (% BF). Resultados: el IMC medio fue de 27,8 ± 4,7 kg/m². La mayoría de los pacientes (68,1%) se encontraban en el rango normal de BF%, pero en cuanto a WC y eVAT, presentaban un riesgo muy alto (58,3% y 64,6%, respectivamente). En los hombres, no hubo correlaciones entre los índices nutricionales y eGFR. En las mujeres, solo el eVAT permaneció correlacionado negativamente con el eGFR, estimado por las ecuaciones MDRD y CKD-EPI, independiente del IMC, el tabaquismo, la inactividad física, la presión arterial, la hemoglobina glicosilada, el colesterol LDL y HDL, el ácido úrico y la microalbuminuria. Conclusiones: la mayoría de los índices de obesidad no se asociaron con el eGFR. Solo eVAT se asoció negativamente con eGFR por las ecuaciones MDRD y CKD-EPI en mujeres hipertensas. En la Atención Primaria, la estimación del tejido adiposo visceral podría apoyar la identificación de las mujeres hipertensas con mayor riesgo de desarrollar enfermedad renal crónica

Prevalence of chronic kidney disease and comorbidities in isolated African descent communities (PREVRENAL): methodological design of a cohort study.

BACKGROUND: Chronic kidney disease (CKD) is considered a serious public health problem, both in Brazil and worldwide, with an increasing number of cases observed inrecent years. Especially, CKD has been reported to be highly prevalent in those of African descent. However, Brazil lacks data from early-stage CKD population studies, and the prevalence of CKD is unknown for both the overall and African descent populations. Hence, the present study aimsto estimate the prevalence of early-stage CKD and its associated risk factors in African-Brazilians from isolated African-descent communities. Herein, the detailed methodology design of the study is described. METHODS: This population-based, prospective, longitudinal, cohort study (PREVRENAL) is performed in three stages: first, clinical, nutritional, and anthropometric evaluations; measurements of serum and urinary markers; and examinations of comorbiditieswere performed. Second, repeated examinations of individuals with CKD, systemic arterial hypertension, and/or diabetes mellitus; image screening; and cardiac risk assessment were performed. Third, long-term monitoring of all selected individuals will be conducted (ongoing). Using probability sampling, 1539 individuals from 32 communities were selected. CKD was defined asaglomerular filtration rate (GFR) ≤60 mL/min/1.73m2 and albuminuria > 30 mg/day. DISCUSSION: This study proposes to identify and monitor individuals with and without reduced GFR and high albuminuria in isolated populations of African descendants in Brazil. As there are currently no specific recommendations for detecting CKD in African descendants, four equations for estimating the GFR based on serum creatinine and cystatin C were used and will be retrospectively compared. The present report describes the characteristics of the target population, selection of individuals, and detection of a population at risk, along with the imaging, clinical, and laboratory methodologies used. The first and second stages have been concluded and the results will be published in the near future. The subsequent (third) stage is the long-term, continuous monitoring of individuals diagnosed with renal abnormalities or with CKD risk factors. The entire study population will be re-evaluated five years after the study initiation. The expectation is to obtain information about CKD evolution among this population, including the progression rate, complication development, and cardiovascular events.

Abordagem farmacêutica na Doença Renal Crônica

São abordados assuntos como: as indicações e contraindicações dos diferentes fármacos utilizados em pacientes com doença renal crônica e a legislação direcionada para a sua dispensação; as ações para o adequado acompanhamento farmacoterapêutico de acordo com o estágio da doença renal; as diferentes formas de apresentação clínica e recomendações quanto a exposição a nefroxicidade das drogas utilizadas no tratamento da DRC. Este recurso educacional integra o conjunto de objetos na área temática de Nefrologia, ofertados pela UNA-SUS/UFMA. Trata-se de um recurso autoinstrucional, com carga horária sugerida de 30 horas. O curso é composto por 3 unidades educacionais com o objetivo de capacitar os profissionais da saúde que atuam ou que pretendem atuar na Atenção Básica.

Acompanhamento farmacoterapêutico com DRC

E-book que visa promover a compreensão sobre o papel do farmacêutico junto ao paciente renal crônico quanto à orientação do tratamento medicamentoso. São explicados os aspectos relacionados à prescrição individualizada para pacientes em diferentes estágios da doença renal, bem como os métodos de armazenamento, conservação e administração correta dos medicamentos. Também aborda-se neste material o incentivo para a adesão do paciente ao tratamento. Além deste, há mais 31 e-books tratando sobre diversas questões relacionadas à Nefrologia, todos com conteúdos para a formação dos profissionais da saúde que atuam no SUS e dos acadêmicos da área. Este recurso educacional integra o conjunto de objetos autoinstrucionais ofertados pela UNA-SUS/UFMA na área temática de Nefrologia.

Nefrotoxidade e ajuste medicamentoso em pacientes com DRC

Este recurso educacional integra o conjunto de objetos autoinstrucionais ofertados pela UNA-SUS/UFMA na área temática de Nefrologia. Trata-se de um e-book que apresenta a nefrotoxicidade como um problema grave e frequente, que pode ser prevenido com medidas simples. No material, faz-se a identificação das principais drogas nefrotóxicas e mecanismos de nefrotoxicidade. Ademais, são abordadas as diferentes formas de apresentação clínica e recursos diagnósticos para nefrotoxicidade, bem como as principais recomendações para exposição a drogas nefrotóxicas na DRC. Além deste, há mais 31 e-books tratando sobre diversas questões relacionadas à Nefrologia. Todos eles fornecem conteúdos interessantes para a formação dos profissionais da saúde que atuam no SUS e dos acadêmicos da área.

Métodos diagnósticos em nefrologia

Aborda os principais métodos de diagnóstico da doença renal crônica. Este recurso educacional integra o conjunto de objetos ofertados pela UNA-SUS/UFMA na área temática de Nefrologia. Além deste, há mais 35 e-books tratando sobre diversas questões relacionadas à Nefrologia, com conteúdos que visam a formação dos profissionais da saúde que atuam no SUS e dos acadêmicos da área

Atendimento ao portador de Doença Renal

Curso autoinstrucional, composto por 3 unidades que abordam os métodos diagnósticos para a detecção da doença renal crônica e os principais aspectos clínicos e psicossociais relacionados ao cuidado do paciente. Este recurso educacional integra o conjunto de objetos na área temática de Nefrologia, ofertados pela UNA-SUS/UFMA

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.

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.

Is vitamin d deficiency a new risk factor for cardiovascular disease?

The role of vitamin D in the regulation of bone metabolism has been well established. However, in recent years, many studies have demonstrated that its role extends far beyond bone health. Growing evidence has shown a strong association between vitamin D deficiency and hypertension, metabolic syndrome, diabetes mellitus and atherosclerosis. The mechanisms by which vitamin D exerts its cardiovascular protective effects are still not completely understood, but there is evidence that it participates in the regulation of renin-angiotensin system and the mechanisms of insulin sensitivity and activity of inflammatory cytokines, besides its direct cardiovascular actions. In this review, several studies linking vitamin D deficiency with cardiometabolic risk as well as small randomized trials that have evaluated the cardiovascular effects of its supplementation are presented. However, large randomized placebo-controlled studies are still needed before we can definitively establish the role of vitamin D supplementation in the prevention and control of cardiovascular disease.

Occult hepatitis B among patients with chronic renal failure on hemodialysis from a capital city in northeast Brazil.

Occult hepatitis B (OHB) is characterized by the presence of HBV-DNA in the absence of HBsAg in the serum of patients. Hemodialysis patients are at high risk for hepatitis B virus and there are few data on the prevalence of OHB in this population, mainly in Brazil. Thus, the aim of this study was to determine the prevalence of OHB in patients undergoing hemodialysis. A cross-sectional study was performed, including 301 patients on chronic hemodialysis at two dialysis centers in São Luís (Maranhão), northeast Brazil. Serological tests were performed for HBsAg, anti-HBc, anti-HBs, and anti-HCV using enzyme immunoassays (ELISA); HBV-DNA and HCV-RNA were studied by real-time PCR. The mean age was 49 ± 15 years, and 128 (42%) were female. Serological tests confirmed that all samples were HBsAg negative. Anti-HBc was positive in 114 (38%) patients, anti-HBc and anti-HBs were simultaneously positive in 104 (35%), and anti-HBc alone was positive in 10 (3%). Tests were negative for anti-HBc and anti-HBs in 55 patients (18%). Anti-HBs was the only positive marker in 132 (44%) patients. Anti-HCV was positive in 15 (5%) patients with HCV-RNA present in 14 of them (93%). HBV-DNA was positive in seven cases (2.3%). There was no association of HBV-DNA with age, gender, time on dialysis, previous kidney transplant, or HBV serological pattern, but there was a positive correlation with the presence of anti-HCV (P < 0.001). OHB in chronic renal failure patients on hemodialysis appears to be a relevant finding, suggesting that studying HBV-DNA in this population using sensitive molecular tests should be a recommended course of action, especially in candidates for renal transplant.

Increased urinary cystatin C level is associated with interstitial fibrosis and tubular atrophy in kidney allograft recipients.

AIM: The objective of this study was to investigate the correlation between the urinary excretion of cystatin C (CysC) and the presence of interstitial fibrosis/tubular atrophy (IF/TA) in renal transplant (RT) recipients. METHODS: This prospective study included 21 adult patients who had undergone renal biopsy and RT ≥6 months prior. According to the renal biopsy reports, the patients were divided into groups with (n=12) or without (n=9) IF/TA. Analytical parameters included the following: serum and urinary levels of CysC, creatinine (Cr) and sodium (Na), total urinary protein, urinary CysC/creatinine ratio [u(CysC/Cr)], fractional excretion of sodium (FENa) and estimated glomerular filtration rate (eGFR) based on the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: The values of uCysC, u(CysC/Cr), proteinuria, and FENa were significantly higher in patients with IF/TA than in patients without IF/TA. The values of eGFR were statistically lower in patients with IF/TA (p=0.001). Values of uCysC significantly correlated with those of serum Cr, FENa, and eGFR (p<0.001). Among the patients with IF/TA, 67% presented with glomerulosclerosis (segmental/global). CONCLUSION: Elevated levels of urinary CysC are associated with interstitial fibrosis and tubular atrophy in RT recipients and may become a useful tool for monitoring kidney allografts.

Myeloradicular Form of Neuroschistosomiasis in a Six-Year-Old Boy Infected With Schistosoma mansoni.

Neuroschistosomiasis is a severe disease caused by the presence of Schistosoma eggs and/or adult worms in the central nervous system. Schistosomal transverse myelitis represents a rare clinical form with nonspecific clinical findings, and it is thus underdiagnosed, especially in children. In this report, we describe a 6-year-old patient with the myeloradicular form of neuroschistosomiasis.

Deficiência de vitamina D: um novo fator de risco cardiovascular? / Vitamin D deficiency: a new cardiovascular risk factor?

O papel da vitamina D na regulação do metabolismo ósseo já está bem estabelecido. Entretanto, nos últimosanos, vários estudos evidenciam que a função da vitamina D se estende muito além da saúde óssea, incluindo a regulação do sistema imunológico e efeitos antiproliferativos nas células, podendo ainda desempenhar papel importante na fisiologia do sistemacardiovascular. Evidências crescentes demonstram forte associação entre hipovitaminose D e hipertensão arterialsistêmica (HAS), síndrome metabólica (SM), diabetes mellitus (DM) e aterosclerose, podendo representar, pois,um fator de risco cardiovascular emergente. Os mecanismos pelos quais a vitamina D exerceria seus efeitos cardio e vasculoprotetores ainda não estão completamente esclarecidos, mas há inúmeras evidências de que ela possa exercer importantes papéis na regulaçãodo sistema renina-angiotensina (SRA), nos mecanismos de secreção e sensibilidade à insulina e na atuação dascitocinas inflamatórias, além de ações cardíacas e vasculares diretas. Nesta revisão, são apresentados vários estudos associando deficiência de vitamina D com marcadores de aterosclerose e risco cardiometabólico,assim como pequenos ensaios randomizados que avaliaram os efeitos cardiovasculares de sua suplementação. No entanto, embora seja plausívelconsiderar a suplementação dessa vitamina como um meio promissor de interferir favoravelmente no riscocardiovascular, grandes estudos randomizados e controlados com placebo, com poder estatísticoadequado para avaliação de desfechos pesados ainda são necessários para que se possa estabelecer definitivamente seu papel na prevenção e tratamento dadoença cardiovascular.(DCV)

The role of vitamin D in bone metabolism regulation is already well established. However, during the past fewyears, several studies have shown that the function of vitamin D extends well beyond bone health, including immune system regulation and antiproliferative effects in cells, while also playing an important role in cardiovascular system physiology. Growing evidence is demonstrating strong associations between hypovitaminosis D and hypertension, metabolic syndrome, diabetes and atherosclerosis, thus possibly indicating an emergent cardiovascular risk factor. Themechanisms through which vitamin D exerts its protective cardiovascular effects are not yet fully elucidated, but there is ample evidence that it may playimportant roles in renin-angiotensin system regulation, as well as insulin secretion and sensitivity mechanismsand the actions of inflammatory cytokines, in addition to direct cardiac and vascular actions. This reviewpresents several studies associating vitamin D deficiency with cardiometabolic risk and atherosclerosis markers,as well as some minor randomized clinical trials assessing the cardiovascular effects of vitamin Dsupplements. However, although it is plausible to consider vitamin D supplementation as a promisingway of intervening favorably in cardiovascular risk, major randomized placebo-controlled trials, with adequate statistical power for evaluating hardendpoints, are still needed in order to definitively confirm its role in the prevention and treatment ofcardiovascular diseases.

Estimated visceral adipose tissue, but not body mass index, is associated with reductions in glomerular filtration rate based on cystatin C in the early stages of chronic kidney disease.

Information on the association between obesity and initial phases of chronic kidney disease (CKD) is still limited, principally those regarding the influence of visceral adipose tissue. We investigated whether the visceral adipose tissue is more associated with reductions in glomerular filtration rate (GFR) than total and abdominal obesity in hypertensive individuals with stage 1-2 CKD. A cross-sectional study was implemented which involved 241 hypertensive patients undergoing treatment at a primary health care facility. GFR was estimated using equations based on creatinine and cystatin C levels. Explanatory variables included body mass index (BMI), waist circumference (WC), and estimated visceral adipose tissue (eVAT). The mean age was 59.6 ± 9.2 years old and 75.9% were female. According to BMI, 28.2% of subjects were obese. Prevalence of increased WC and eVAT was 63.9% and 58.5%, respectively. Results from the assessment of GFR by BMI, WC, and eVAT categories showed that only women with increased eVAT (≥150 cm(2)) had a lower mean GFR by Larsson (P = 0.016), Levey 2 (P = 0.005), and Levey 3 (P = 0.008) equations. The same result was not observed when the MDRD equation was employed. No association was found between BMI, WC, eVAT, and GFR using only serum creatinine. In the early stages of CKD, increased eVAT in hypertensive women was associated with decreased GFR based on cystatin C.

Association between oral DNA-HPV and genital DNA-HPV.

BACKGROUND: Human papillomavirus (HPV) infection is one of the most common sexually transmitted diseases worldwide and is observed in both men and women. The presence of the virus is often associated with benign and malignant neoplasms of the oral cavity. We wished to investigate whether HPV infection in the genitalia was associated with HPV infection in the oral mucosa. METHODS: The prevalence of HPV in the oral cavity and genitalia was evaluated by DNA extraction from genital and oral cavity samples of 105 women, followed by nested PCR. RESULTS AND CONCLUSIONS: The prevalence of HPV in the oral cavity was significantly higher in women who had genital HPV (P < 0.0001). Oral sex, alcohol, and tobacco consumption were not associated with the oral HPV infection.