Dietary intake of non-dialysis chronic kidney disease patients: the PROGREDIR study. A cross-sectional study.

BACKGROUND: Despite evidence that diet is very important in relation to chronic kidney disease (CKD) progression, studies in this field are scarce and have focused only on some specific nutrients. We evaluated the energy, macronutrient and micronutrient intakes and dietary patterns of non-dialysis CKD participants in the PROGREDIR study. DESIGN AND SETTING: Cross-sectional study; CKD cohort, São Paulo, Brazil. METHODS: Baseline data on 454 participants in the PROGREDIR study were analyzed. Dietary intake was evaluated through a food frequency questionnaire. Dietary patterns were derived through principal component analysis. Energy and protein intakes were compared with National Kidney Foundation recommendations. Linear regression analysis was performed between energy and nutrient intakes and estimated glomerular filtration rate (eGFR), and between sociodemographic and clinical variables and dietary patterns. RESULTS: Median energy and protein intakes were 25.0 kcal/kg and 1.1 g/kg, respectively. In linear regression, protein intake (ß = -3.67; P = 0.07) was related to eGFR. Three dietary patterns (snack, mixed and traditional) were retained. The snack pattern was directly associated with male gender (ß = 0.27; P = 0.006) and inversely with diabetes (ß = -0.23; P = 0.02). The traditional pattern was directly associated with male gender (ß = 0.27; P = 0.007) and schooling (ß = 0.40; P < 0.001) and inversely with age (ß = -0.01; P = 0.001) and hypertension (ß = -0.34; P = 0.05). CONCLUSIONS: We identified low energy and high protein intake in this population. Protein intake was inversely related to eGFR. Dietary patterns were associated with age, gender, schooling level, hypertension and diabetes.

Association between Dietary Intake and Coronary Artery Calcification in Non-Dialysis Chronic Kidney Disease: The PROGREDIR Study.

Coronary artery calcification (CAC) is a widespread condition in chronic kidney disease (CKD). Diet may play an important role in CAC, but this role is not clear. This study evaluated the association between macro-and micronutrient intakes and CAC in non-dialysis CKD patients. We analyzed the baseline data from 454 participants of the PROGREDIR study. Dietary intake was evaluated by a food frequency questionnaire. CAC was measured by computed tomography. After exclusion of participants with a coronary stent, 373 people remained for the analyses. The highest tertile of CAC was directly associated with the intake of phosphorus, calcium and magnesium. There was a higher intake of pantothenic acid and potassium in the second tertile. After adjustments for confounding variables, the intake of pantothenic acid, phosphorus, calcium and potassium remained associated with CAC in the generalized linear mixed models. In order to handle the collinearity between these nutrients, we used the LASSO (least absolute shrinkage and selection operator) regression to evaluate the nutrients associated with CAC variability. In this approach, the nutrients that most explained the variance of CAC were phosphorus, calcium and potassium. Prospective studies are needed to confirm these findings and assess the role of interventions regarding these micronutrients on CAC prevention and progression.

Serum RBP4 and CKD: Association with insulin resistance and lipids.

OBJECTIVE: Serum RBP4 is new adipokine and it has been related to insulin resistance and diabetes risk in animal and clinical studies. However, there is controversy on this relationship among CKD patients. In this study, we evaluated the association of serum RBP4 with insulin resistance and cardiovascular risk factors in CKD. METHODS: Baseline data from the PROGREDIR Study (Sao Paulo, Brazil) comprising 454 participants (mainly stages 3 and 4) was analyzed. RESULTS: In univariable analysis, RBP4 was inversely related to renal function, age and HDL, and positively related to other lipids, insulinemia, HOMA, glycemia, albumin, phosphorus and right hepatic lobe diameter. After adjustment for sex, age and eGFR, HOMA and lipids remained associated to RBP4. In multivariable analysis, eGFR and triglyceride remained significantly associated with RBP4, while HOMA showed no longer a significant positive association. An interaction term between RBP4 and eGFR was significantly related to HOMA. CONCLUSIONS: Renal function is inversely related to serum RBP4. As GFR decreases, the relationship between RBP4 and HOMA is attenuated. On the other hand, triglycerides remained strongly related to RBP4 and this was not affected by eGFR, suggesting that in the CKD population triglycerides may be a better marker of RBP4-associated metabolic effects.

Chronic kidney disease - determinants of progression and cardiovascular risk. PROGREDIR cohort study: design and methods.

CONTEXT AND OBJECTIVE:: Chronic kidney disease (CKD) has become an important public health issue. The socioeconomic burden of renal replacement therapy (RRT) is very high, as is CKD-related cardiovascular mortality and morbidity. Preventive and therapeutic measures only have modest impact and more research is needed. Few cohort studies have been conducted on populations with CKD. Our aim was to establish a cohort that would include more advanced forms of CKD (stages 3 and 4). Data collection was focused on renal and cardiovascular parameters. DESIGN AND SETTING:: Prospective cohort study; São Paulo, Brazil. METHODS:: Recruitment took place in Hospital das Clínicas, São Paulo, from March 2012 to December 2013. Data relating to medical history, food-frequency questionnaire, anthropometry, laboratory work-up, calcium score, echocardiography, carotid intimal-medial thickness, pulse-wave velocity, retinography and heart rate variability were collected. A biobank including serum, plasma, post-oral glucose tolerance test serum and plasma, urine (morning and 24-hour urine) and DNA was established. RESULTS:: 454 participants (60% men and 50% diabetics) of mean age 68 years were enrolled. Their mean estimated glomerular filtration rate-CKD Epidemiology Collaboration was 38 ml/min/1.73 m2. Follow-up is ongoing and the main outcomes are the start of RRT, cardiovascular events and death. CONCLUSIONS:: The PROGREDIR cohort is a promising prospective study that will allow better understanding of CKD determinants and validation of candidate biomarkers for the risks of CKD progression and mortality.

Proteome analysis of acute kidney injury - Discovery of new predominantly renal candidates for biomarker of kidney disease.

The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are organ and process specific. Here, we have used different tissues from a controlled porcine renal ischemia/reperfusion (I/R) model to identify new, predominantly renal biomarker candidates for kidney disease. Urine and serum samples were analyzed in pre-ischemia, ischemia (60min) and 4, 11 and 16h post-reperfusion, and renal cortex samples after 24h of reperfusion. Peptides were analyzed on the Q-Exactive™. In renal cortex proteome, we observed an increase in the synthesis of proteins in the ischemic kidney compared to the contralateral, highlighted by transcription factors and epithelial adherens junction proteins. Intersecting the set of proteins up- or down-regulated in the ischemic tissue with both serum and urine proteomes, we identified 6 proteins in the serum that may provide a set of targets for kidney injury. Additionally, we identified 49, being 4 predominantly renal, proteins in urine. As prove of concept, we validated one of the identified biomarkers, dipeptidyl peptidase IV, in a set of patients with diabetic nephropathy. In conclusion, we identified 55 systemic proteins, some of them predominantly renal, candidates for biomarkers of renal disease. BIOLOGICAL SIGNIFICANCE: The main bottleneck in studies aiming to identify novel biomarkers in acute kidney injury (AKI) has been the identification of markers that are predominantly renal. In fact, putative biomarkers for this condition have also been identified in a number of other clinical scenarios, such as cardiovascular diseases, chronic kidney failure or in patients being treated in intensive care units from a number of conditions. Here we propose a comprehensive, sequential screening procedure able to identify and validate potential biomarkers for kidney disease, using kidney ischemia/reperfusion as a paradigm for a kidney pathological event.

MYH9 and APOL1 gene polymorphisms and the risk of CKD in patients with lupus nephritis from an admixture population.

MYH9 polymorphisms have been described to be associated with the risk of CKD in non-diabetic nephropathy, HIV nephropathy and FSGS. Predominating in black descendants, MHY9 genetic variants could partially explain the excess risk of CKD associated with African ancestry. However, recent data suggests that APOL1 gene co-segregate with MYH9, and could be the gene truly associated with CKD risk. In this study, we evaluated the role of MYH9 and APOL1 gene polymorphisms in the risk of CKD in Brazilian patients with lupus nephritis (LN). A retrospective analysis of 196 LN patients was done. MYH9 rs4821480, rs2032487, rs4821481 and rs3752462, APOL 1rs73885319, rs16996616, rs60910145, rs71785313, and APOL3 rs11089781 gene polymorphisms were determined. Genetic ancestry was ascertained both by autossomal ancestry and mitochondrial haplogroup. Primary outcome was defined as doubling of serum creatinine (DC) or end stage renal disease (ESRD). Sixty-two patients presented the PO. In our population, MYH9 and APOL1 were not in LD. None APOL polymorphism was associated with the PO, whereas rs3752462 MYH9 polymorphism showed a positive association (HR3.72, 95%CI 1.47-9.38, p = 0.005). When we analyzed the MYH9 E1 haplotype, the GCCT carriers (1 or 2 alelles present in 29.7% in the PO group vs. 18.5% in controls) showed a significant association to the risk of PO, even after adjustments for baseline estimated creatinine clearance and autossomal ancestry (HR 2.0, 95%CI 1.2-3.4, p = 0.01). Our results show that in our population MYH9, but not APOL1, gene polymorphisms confer an increased risk of CKD in LN patients, independently of race.

Chronic kidney disease - determinants of progression and cardiovascular risk. PROGREDIR cohort study: design and methods / Doença renal crônica - determinantes de progressão e risco cardiovascular. Coorte PROGREDIR: desenho de estudo e métodos

ABSTRACT CONTEXT AND OBJECTIVE: Chronic kidney disease (CKD) has become an important public health issue. The socioeconomic burden of renal replacement therapy (RRT) is very high, as is CKD-related cardiovascular mortality and morbidity. Preventive and therapeutic measures only have modest impact and more research is needed. Few cohort studies have been conducted on populations with CKD. Our aim was to establish a cohort that would include more advanced forms of CKD (stages 3 and 4). Data collection was focused on renal and cardiovascular parameters. DESIGN AND SETTING: Prospective cohort study; São Paulo, Brazil. METHODS: Recruitment took place in Hospital das Clínicas, São Paulo, from March 2012 to December 2013. Data relating to medical history, food-frequency questionnaire, anthropometry, laboratory work-up, calcium score, echocardiography, carotid intimal-medial thickness, pulse-wave velocity, retinography and heart rate variability were collected. A biobank including serum, plasma, post-oral glucose tolerance test serum and plasma, urine (morning and 24-hour urine) and DNA was established. RESULTS: 454 participants (60% men and 50% diabetics) of mean age 68 years were enrolled. Their mean estimated glomerular filtration rate-CKD Epidemiology Collaboration was 38 ml/min/1.73 m2. Follow-up is ongoing and the main outcomes are the start of RRT, cardiovascular events and death. CONCLUSIONS: The PROGREDIR cohort is a promising prospective study that will allow better understanding of CKD determinants and validation of candidate biomarkers for the risks of CKD progression and mortality.

RESUMO CONTEXTO E OBJETIVO: A doença renal crônica (DRC) tornou-se um problema de saúde pública. A carga socioeconômica da terapia renal substitutiva é muito elevada, assim como a morbimortalidade cardiovascular associada à DRC. Medidas terapêuticas e preventivas têm impacto parcial e novos estudos são necessários. Há poucos estudos de coorte em populações com DRC. Nosso objetivo foi criar uma coorte que contemplasse formas mais avançadas de DRC (estágios 3 e 4). A coleta de dados foi centrada em parâmetros renais e cardiovasculares. TIPO DE ESTUDO E LOCAL: Estudo de coorte prospectivo; São Paulo, Brasil. MÉTODOS: O recrutamento ocorreu entre março de 2012 e dezembro de 2013, no Hospital das Clínicas, em São Paulo. Foram coletados dados de história médica, questionário de frequência alimentar, antropometria, exames laboratoriais, escore de cálcio, ecocardiografia, espessura de camada médio-intimal de carótidas, velocidade de onda de pulso, retinografia e variabilidade de frequência cardíaca. Um biobanco incluindo soro, plasma, soro e plasma pós-teste oral de tolerância à glicose, urina (manhã e 24 horas) e DNA foi estabelecido. RESULTADOS: 454 participantes (60% homens e 50% diabéticos) com idade média de 68 anos foram recrutados. A taxa média de filtração glomerular estimada-Colaboração da Epidemiologia para DRC foi de 38,4 ml/min/1,73 m2. O seguimento está em andamento e os desfechos principais são: início de terapia renal substitutiva, eventos cardiovasculares e óbito. CONCLUSÃO: A coorte PROGREDIR é um estudo prospectivo promissor que permitirá melhor compreensão dos determinantes de DRC e a validação de biomarcadores candidatos para o risco de progressão de DRC e de mortalidade.

Efeito da associação de enalapril e losartan sobre proteinúria e marcadores inflamatórios na nefropatia diabética: ensaio clínico em DM tipo 2 / The effect of enalapril and losartan association therapy on proteinuria and inflammatory biomarkers in diabetic nephropathy: clinical trial on type 2 DM

O tratamento combinado com IECA e BRA foi proposto como alternativa para o tratamento da ND. Nosso objetivo foi avaliar se o tratamento IECA+BRA era superior ao tratamento com IECA em termos de proteinúria e excreção urinária de marcadores inflamatórios. Cinqüenta e seis pacientes com ND iniciaram o uso de enalapril. Após 4 meses, os pacientes passaram a receber losartan (Grupo E+L) ou placebo (Grupo E). As incidências de hipercalemia (HK) e deterioração aguda da função renal (DAFR) foram avaliadas. A análise de ANOVA de medidas repetidas não revelou diferença entre os grupos, mas, após ajustes, a progressão da proteinúria foi pior no Grupo E+L. A proteinúria final mostrou-se significativamente maior no Grupo E+L (proteinúria final estimada de 1,2 vs 2,6 g/d/1.73m2, p= 0.03). Os resultados foram confirmados nos modelos de regressão logística. Ocorreram 7 eventos de HK (12,6%) e 9 de DAFR (16,1%). Nossos dados sugerem que, em ND avançada, o tratamento combinado IECA+BRA não seja superior ao tratamento com IECA isoladamente em relação à proteinúria e marcadores inflamatórios.

Combined treatment with an ACE inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) has been proposed for diabetic nephropathy (DN) treatment. In this study we compared the effect of association therapy versus ACEI on proteinuria progression and on urinary inflammatory biomarkers in DN. Fifty-six patients with DN were started on enalapril. After 4 months, losartan (Group E+L) or placebo (Group E) treatment was started. Incidences of hyperkalemia (HK) and acute kidney function deterioration (AKFD) were monitored. Unadjusted repeated measures ANOVA revealed no difference between groups. After adjustment, proteinuria progression was significantly higher in the E+L Group. In addition, final proteinuria was significantly higher in the E+L Group (predicted adjusted final proteinuria 1,2 vs 2,6 g/d/1,73m2, p=0,03). Finally, logistic regression models showed the same results. We observed 7 HK events (12,6%) and 9 AKFD events (16,1%). These results suggest that, at least in advanced DN, association therapy is not superior to ACEI monotherapy in terms of proteinuria and inflammatory biomarkers.

Validacao de questionario para diagnostico de cefaleia em ambulatorio de complexidade terciaria / Validation of a questionnaire to the headache diagnosis in ambulatory setting

A cefaleia e um sintoma de alta prevalencia na populacao, sendo queixa frequente na pratica clinica. Cursa geralmente com exame fisico e neurologico normais. A triagem de pacientes com cefaleia facilitaria o atendimento em grandes centros medicos. O objetivo deste trabalho e verificar a validade do questionario como metodo de triagem de cefaleias primarias. Aplicou-se o questionario a 204 pacientes do Ambulatorio Geral e Didatico do HCFMUSP, sendo a metade submetida a consulta medica...