Hyperhomocysteinemia in chronic renal failure

Homocysteine is a sulfur-containing amino acid derived from the metabolism of methionine, whose abnormal accumulation in plasma is a risk factor for vascular disease in the general population and in patients with chronic renal disease. In these patients, the prevalence of individuals with hyperhomocysteinemia is very high, even in the pre-dialysis stage of the disease. The main factor that seems to be implicated on the elevation of homocysteine levels in this population is the renal mass loss, considering that the kidney has an important role in the metabolism of such amino acid. The treatment of hyperhomocysteinemia consists on supplementation of the vitamins that are involved in the homocysteine metabolism (folate, B6 and B12.). However, for chronic renal disease patients, this treatment is not completely effective, because although it promotes reduction of homocysteine levels, the normalization is not reached in the majority of the patients. This study reviews the hyperhomocysteinemia etiology on chronic renal disease, its main determinants, its relationship with vascular diseases, and the modes of treatment.A homocisteína é um aminoácido sulfurado proveniente do metabolismo da metionina, cujo acúmulo anormal no plasma é um fator de risco para doenças vasculares, tanto na população em geral como nos pacientes com insuficiência renal crônica. Nestes, a prevalência de indivíduos com hiperhomocisteinemia é bastante elevada, mesmo na fase não dialítica da doença, em que a função renal está diminuída, mas ainda não é necessário tratamento dialítico. O principal fator que parece estar implicado na elevação dos níveis de homocisteína nestes pacientes com insuficiência renal crônica é a perda da massa renal, já que esta exerce uma importante função no metabolismo desse aminoácido. O tratamento da hiperhomocisteinemia na população em geral consiste na suplementação com as vitaminas envolvidas no seu metabolismo (folato, B6 e B12). Porém, em pacientes com insuficiência renal crônica, este tratamento não é completamente eficaz, pois apesar de promover a redução dos níveis de homocisteína, não alcança a normalização dos mesmos na maioria dos pacientes. Este estudo compreende uma revisão da etiologia da hiperhomocisteinemia na insuficiência renal crônica, sua relação com as doenças vasculares, seus principais determinantes e as formas de tratamento.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

Serum albumin as nutritional marker of hemodialysis patients

The prevalence of protein-energy malnutrition is high in patients with chronic renal failure on long-term hemodialysis therapy. Among several parameters available for the assessment of nutritional status, albumin has been the most commonly used given its strong association with morbidity and mortality in those patients. However, many factors such as age, comorbidities, hypervolemia and body losses, can affect the serum albumin concentration. Furthermore, the albumin metabolism can be altered in the presence of inflammation, a common condition in this group of patients. Thus, this communication aimed to address the general aspects of albumin and discuss its usefulness for assessing nutritional status in chronic renal failure patients undergoing hemodialysis.A prevalência de desnutrição protéico-energético em pacientes com insuficiência renal crônica submetidos à terapia de hemodiálise é elevada. Dentre os diversos parâmetros disponíveis para a avaliação do estado nutricional, a albumina tem sido o mais comumente utilizado para este fim visto a sua estreita associação com a morbidade e mortalidade nesta população. No entanto, vários fatores como idade, comorbidades, hipervolemia e perdas corpóreas podem influenciar as concentrações séricas de albumina. Além disso, na vigência de inflamação, condição comumente presente neste grupo de pacientes, o metabolismo da albumina pode encontrar-se alterado, influenciando os seus níveis plasmáticos. Sendo assim, esta comunicação tem como objetivo abordar os aspectos gerais da albumina e discutir a sua utilização na avaliação do estado nutricional de pacientes com insuficiência renal crônica submetidos à hemodiálise.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de MedicinaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPM, Depto. de MedicinaUNIFESP, EPMSciEL

Resting energy expenditure and its determinants in hemodialysis patients

Objective: Chronic kidney disease is associated with several metabolic disturbances that can affect energy metabolism. As resting energy expenditure (REE) is scarcely investigated in patients on hemodialysis (HD) therapy, we aimed to evaluate the REE and its determinants in HD patients.Design: Cross-sectional study.Setting: Dialysis Unit of the Nephrology Division, Federal University of São Paulo, Brazil.Subjects: the study included 55 patients ( 28 male, 41.4 +/- 12.6 years old) undergoing HD therapy thrice weekly for at least 2 months, and 55 healthy individuals pair matched for age and gender. Subjects underwent fasting blood tests, as well as nutritional assessment, and the REE was assessed by indirect calorimetry.Results: REE of HD patients was similar to that of pair-matched controls (1379 +/- 7272 and 1440 +/- 7259 kcal/day, respectively), even when adjusted for fat-free mass (P = 0.24). REE of HD patients correlated positively with fat-free mass (r = 0.74; P < 0.001) and body mass index (r = 0.37; P < 0.01), and negatively with dialysis adequacy (r = -0.46; P < 0.001). No significant univariate correlation was found between REE and age, dialysis vintage, serum creatinine, urea, albumin, bicarbonate, parathyroid hormone (PTH) or high-sensitivity C-reactive protein (CRP). in the multiple linear regression analysis, using REE as dependent variable, the final model showed that besides the well-recognized determinants of REE such as fat-free mass and age, PTH and CRP were the independent determinants of REE in HD patients (R-2 = 0.64).Conclusions: in this study, the REE of HD patients was similar to that of healthy individuals, even with the positive effect of secondary hyperparathyroidism and inflammation on REE of these patients.Universidade Federal de São Paulo, Div Nephrol, BR-04039000 São Paulo, BrazilUniversidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, BR-04039000 São Paulo, BrazilUniversidade Federal de São Paulo, Nutr Program, São Paulo, BrazilWeb of Scienc

Short-term effects of a very-low-protein diet supplemented with ketoacids in nondialyzed chronic kidney disease patients

Objective: To evaluate the effects on the nutritional and metabolic parameters of a very-low-protein diet supplemented with ketoacids (VLPD+KA) in comparison with a conventional low-protein diet (LPD) in chronic kidney disease (CKD) patients.Design: Prospective, randomized, controlled clinical study.Setting: Outpatient Clinic of the Nephrology Division of Federal University of São Paulo, Brazil.Subjects: the study involved 24 patients with advanced CKD ( creatinine clearance <25 ml/min) that were randomly assigned to either a VLPD+KA (VLPD+KA group, 12 patients) or to a conventional LPD with 0.6 g/kg/day ( LPD group, 12 patients). the patients were followed for 4 months.Results: Nutritional status was adequately maintained with both diets for the studied period. Protein intake and serum urea nitrogen decreased significantly only in the VLPD+KA group ( from 0.68 +/- 0.17 to 0.43 +/- 0.12 g/kg/day, P<0.05; from 61.4 +/- 12.8 to 43.6 +/- 14.9 mg/dl, P<0.001; respectively). Ionized calcium did not change in the VLPD+KA group but tended to decrease in the LPD group. Serum phosphorus tended to decrease in the VLPD+KA group probably as a result of a significant reduction in dietary phosphorus (529 +/- 109 to 373 +/- 125 mg/day, P<0.05) associated to the phosphorus-binding effect of the ketoacids. No change in these parameters was found in the LPD group. Serum parathormone increased significantly only in the LPD group (from 241 +/- 138 to 494 +/- 390 pg/ ml, P<0.01). the change in PTH concentration was negatively correlated with changes in ionized calcium concentration ( r = - 0.75, P = 0.02) and positively correlated with changes in serum phosphorus ( r = 0.71, P = 0.03) only in the LPD group.Conclusion: This study indicates that a VLPD+KA can maintain the nutritional status of the patients similarly to a conventional LPD. Besides, an improvement in calcium and phosphorus metabolism and a reduction in serum urea nitrogen were attained only with the VLPD+KA. Thus, VLPD+KA can constitute another efficient therapeutic alternative in the treatment of CKD patients.Sponsorship: This study was supported by CAPES, Oswaldo Ramos Foundation and Fresenius Kabi, Ltda.Universidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniversidade Federal de São Paulo, Nutr Program, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilWeb of Scienc

Fast Reading of the KDIGO 2012: Guidelines for evaluation and management of chronic kidney disease in clinical practice

The authors of this fast reading present the data they have considered as more relevant in the KDIGO 2012 as concerned to evaluation and management of chronic kidney disease. The text does not correspond to their opinion, it is a brief presentation of guidelines that could be useful in clinical practice.Os autores desta leitura rápida apresentam os dados que consideraram mais relevantes na versão 2012 do KDIGO referente à avaliação e manuseio da doença renal crônica. Não se trata da opinião dos autores, mas sim de uma apresentação mais concisa das diretrizes, que podem ser úteis na prática clínica.Universidade Federal de São Paulo (UNIFESP)Universidade Federal do MaranhaoUniversidade Federal de UberlandiaUniversidade Federal do Rio Grande do SulUniversidade do Estado do Rio de JaneiroUniversidade Federal do Rio de JaneiroUNIFESPSciEL

Left ventricular hypertrophy in patients with chronic kidney disease under conservative treatment

Cardiovascular disease (CVD) remains the major cause of death in patients with chronic kidney disease (CKD). Left ventricular hypertrophy (LVH) is present in 75% of patients starting dialysis, suggesting that LVH might be present from an early stage of CKD. Few studies have addressed the predialysis prevalence of LVH. This study evaluated 309 clinically stable patients under treatment for at least three months at five Brazilian centers. Biochemical profile and inflammatory markers were assessed. Data were shown as mean ± SD. Left ventricular hypertrophy was present in 53% of the patients, whose mean age was 60 ± 13years. The mean age of those without LVH was 55 ± 14 years. Diabetes mellitus was the underlying disease in 35% of the patients in both groups. Estimated glomerular filtration rate was 30 ± 11 and 32 ± 12 mL/min for patients with and without LVH, respectively (p = 0.19). The distribution of patients showed that 60% of those with LVH were in stage 4. Multivariate logistic regression analysis indicated the following independent determinants for LVH: age (p < 0.001); calcium (p < 0.001); hemoglobin (p < 0.048); and diastolic blood pressure (p < 0.001). Systolic blood pressure, lipids, and inflammatory markers showed no correlation with LVH. In conclusion, the incidence of LVH was high even among patients under conservative treatment, and, except for age, LVH correlated with reversible factors. The need for strictly diagnosing CKD and preventing LVH in the predialysis phase is emphasized to decrease mortality due to CVD in that population.A doença cardiovascular (DCV) permanece sendo uma das maiores causas de morte em pacientes com doença renal crônica (DRC). A hipertrofia ventricular esquerda (HVE) está presente em 75% dos pacientes ao iniciarem diálise, sugerindo que esta deve estar presente precocemente no curso da DRC. Poucos estudos avaliaram a prevalência de HVE na pré-diálise. Foram avaliados 309 pacientes clinicamente estáveis em acompanhamento por pelo menos três meses em cinco Centros no Brasil. Perfil bioquímico e marcadores inflamatórios foram avaliados. Dados são apresentados como media ± DP. Observamos que a HVE esteve presente em 53% dos pacientes, idade = 60 ± 13 anos, e 55 ± 14 anos para aqueles sem HVE. Diabetes mellitus como doença de base esteve presente em 35% dos pacientes em ambos os grupos. Filtração glomerular estimada foi 30 ± 11 e 32 ± 12 mL/min para pacientes com HVE e sem, respectivamente (p = 0,19). A distribuição de pacientes mostrou que 60% com HVE se encontravam no estágio 4. Análise logística multivariada mostrou que eram determinantes independentes para HVE: idade (p < 0,001), cálcio (p < 0,001), hemoglobina (p < 0,048) e pressão arterial diastólica (p < 0,001). Pressão arterial sistólica, lipídeos e marcadores inflamatórios não se correlacionaram com a HVE. Em conclusão, a incidência de HVE foi alta mesmo entre pacientes sob tratamento especializado e com exceção da idade, a HVE se correlacionou com fatores reversíveis. Alertamos para a necessidade do diagnóstico da DRC e prevenção da HVE na pré-diálise de forma rigorosa para diminuir a mortalidade decorrente de DCV nesta população.Universidade do Estado do Rio de JaneiroPontifícia Universidade Católica do Paraná Centro de Ciências Biológicas e da SaúdeUniversidade de São Paulo Facildade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP)Universidade Federal de Juiz de ForaUNIFESP, EPM, São PauloSciEL

Pericardial Fat Is Associated with Coronary Artery Calcification in Non-Dialysis Dependent Chronic Kidney Disease Patients

Pericardial fat (PF) a component of visceral adipose tissue has been consistently related to coronary atherosclerosis in the general population. This study evaluated the association between PF and coronary artery calcification (CAC) in non-dialysis dependent chronic kidney disease (CKD) patients. This is a post-hoc cross sectional analysis of the baseline of a prospective cohort of 117 outward CKD patients without manifest coronary artery disease (age, 56.9 +/- 11.0 years, 64.1% males, 95.1% hypertensives, 25.2% diabetics, 15.5% ever smokers, CKD stage 2 to 5 with estimated glomerular filtration rate 36.8 +/- 18.1 ml/min). CAC scores, PF volume and abdominal visceral fat (AVF) areas were measured by computed tomography. the association of PF as a continuous variable with the presence of CAC was analyzed by multivariate logistic regression. CAC (calcium score >0) was present in 59.2% patients. Those presenting CAC were on average 10 years older, had a higher proportion of male gender (78.7% vs. 42.9%, p<0.001), and had higher values of waist circumference (95.9 +/- 10.7 vs. 90.2 +/- 13.2 cm, p=0.02), PF volumes (224.8 +/- 107.6 vs. 139.1 +/- 85.0 cm(3), p<0.01) and AVF areas (109.2 +/- 81.5 vs. 70.2 +/- 62.9 cm(2), p=0.01). in the multivariate analysis, adjusting for age, gender, diabetes, smoking and, left ventricular concentric hypertrophy, PF was significantly associated with the presence of CAC (OR: 1.88 95% CI: 1.03-3.43 per standard deviation). PF remained associated with CAC even with additional adjustments for estimated glomerular filtration rate or serum phosphorus (OR: 1.85 95% CI: 1.00-3.42, p=0.05). PF is independently associated with CAC in non-dialysis dependent CKD patients.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ São Paulo, Sch Med, Lipid Clin Heart Inst InCor, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilUniv São Paulo, Sch Med, Cardiovasc Magnet Resonance & Computed Tomog Sect, Heart Inst InCor, São Paulo, BrazilUniversidade Federal de São Paulo, Div Nephrol, São Paulo, BrazilFAPESP: 2011/14201-2Web of Scienc

Serum soluble-Fas is a predictor of red blood cell transfusion in critically ill patients

OBJECTIVE: To investigate the relation between the need for red blood cell transfusion and serum levels of soluble-Fas, erythropoietin and inflammatory cytokines in critically ill patients with and without acute kidney injury. METHODS: We studied critically ill patients with acute kidney injury (n=30) and without acute kidney injury (n=13), end-stage renal disease patients on hemodialysis (n=25) and healthy subjects (n=21). Serum levels of soluble-Fas, erythropoietin, interleukin 6, interleukin 10, iron status, hemoglobin and hematocrit concentration were analyzed in all groups. The association between these variables in critically ill patients was investigated. RESULTS: Critically ill patients (acute kidney injury and non-acute kidney injury patients) had higher serum levels of erythropoietin than the other groups. Hemoglobin concentration was lower in the acute kidney injury patients than in other groups. Serum soluble-Fas levels were higher in acute kidney injury and end-stage renal disease patients. Critically ill patients requiring red blood cell transfusions had higher serum levels of soluble-Fas (5,906±2,047 and 1,920±1,060; p<0.001), interleukin 6 (518±537 and 255+502; p=0.02) and interleukin 10 (35.8±30.7 and 18.5±10.9; p=0.02), better iron status and higher mortality rates in the first 28 days in intensive care unit. Serum soluble-Fas levels were independently associated with the number of red blood cell units transfused (p=0.02). Serum soluble-Fas behaved as an independent predictor of the need for red blood cell transfusion in critically ill patients (p=0.01). CONCLUSIONS: Serum soluble-Fas level is an independent predictor of the need for red blood cell transfusion in critically ill patients with or without acute kidney injury. Further studies are warranted to reconfirm this finding.OBJETIVO: Investigar a relação entre a transfusão de hemácias e os níveis séricos de Fas solúvel, eritropoietina e citocinas inflamatórias em pacientes gravemente enfermos, com e sem insuficiência renal aguda. MÉTODOS: Os seguintes grupos foram estudados: pacientes gravemente enfermos com insuficiência renal aguda (n=30) e sem insuficiência renal aguda (n=13), pacientes portadores de doença renal crônica terminal em hemodiálise (n=25) e indivíduos saudáveis (n=21). Os níveis séricos de Fas solúvel, eritropoietina, interleucina 6, interleucina 10 e ferro, além da concentração de hemoglobina e de hematócrito, foram analisados em todos os grupos. A associação entre tais variáveis foram estudadas nos pacientes gravemente enfermos. RESULTADOS: Os níveis séricos de eritropoietina mostraram-se mais elevados nos pacientes gravemente enfermos do que nos dos demais grupos. Concentrações mais baixas de hemoglobina foram documentadas nos pacientes com insuficiência renal aguda em relação aos demais. Níveis séricos mais elevados de Fas solúvel foram observados nos pacientes com insuficiência renal aguda e doença renal crônica terminal. Pacientes gravemente enfermos transfundidos apresentaram níveis séricos mais elevados de Fas solúvel (5.906±2.047 e 1.920±1.060; p<0,001), interleucina 6 (518±537 e 255±502; p=0,02), interleucina 10 (35,8±30,7 e 18,5±10,9; p=0,02) e ferro, além de maior mortalidade em 28 dias. Os níveis séricos de Fas solúvel mostraram-se independentemente associados ao número de transfusões (p=0,02). O nível sérico de Fas solúvel foi um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos (p=0,01). CONCLUSÃO: O nível sérico de Fas solúvel é um preditor independente da necessidade de transfusão de hemácias em pacientes gravemente enfermos, com ou sem insuficiência renal aguda. Mais estudos clínicos e laboratoriais são necessários para confirmar tal resultado.Universidade Federal de São Paulo (UNIFESP)Hospital Israelita Albert EinsteinUNIFESPSciEL