Could serum zonulin be an intestinal permeability marker in diabetes kidney disease?

Zonulin is a protein associated with the tight junction complex opening at the intestinal epithelium, previously linked to obesity, cardiovascular diseases, type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, its role in CKD has not been totally elucidated. This study aimed to evaluate zonulin levels in subjects with diabetic kidney disease (DKD). This case-control study included two cases groups: 1) Advanced DKD cases: T2DM patients with estimated glomerular filtration rate (eGFR) 30mg/g creatinine, but with eGFR>60ml/min/1.73m2 . Two control groups were also included: 1) T2DM controls: patients with T2DM without impaired kidney function; 2) Non-T2DM controls: subjects without T2DM and normal renal function. Serum levels of zonulin were measured by ELISA. Eighty-six individuals were included. Zonulin levels was different among study groups (P = 0.003). T2DM controls presented higher zonulin levels than non-T2DM controls [(131.35 (83.0–170.5) vs. 87.25 (54.7–111.8), P = 0.018] and advanced DKD cases [63.72 (45.03–106.0); P = 0.007]. Zonulin showed a positive correlation with eGFR (r = 0.222; P = 0.040), total cholesterol (r = 0.299; P = 0.034), LDL (r = 0.258; P = 0.021), and negative with albuminuria (r = -0.243; P = 0.024) and body fat (r = -0.271; P = 0.014). In the multivariate logistic regression analyses, zonulin levels were independently associated to renal outcomes [OR 0.99 (0.98–0.99, P = 0.012)] after 5-year inclusion. In conclusion, increased zonulin levels in patients with TD2M without renal disease suggest an impaired intestinal permeability. Moreover, its association with renal outcomes could indicate its use as a disease monitoring marker. However, the mechanisms behind this association should be better understood

Effect of an intensive nutrition intervention of a high protein and low glycemic-index diet on weight of kidney transplant recipients : study protocol for a randomized clinical trial

Background: Excessive weight gain is commonly observed within the first year after kidney transplantation and is associated with negative outcomes, such as graft loss and cardiovascular events. The purpose of this study is to evaluate the effect of a high protein and low glycemic-index diet on preventing weight gain after kidney transplantation. Methods: We designed a prospective, single-center, open-label, randomized controlled study to compare the efficacy of a high protein (1.3–1.4 g/kg/day) and low-glycemic index diet versus a conventional diet (0.8–1.0 g/kg/day of protein) on preventing weight gain after kidney transplantation. A total of 120 eligible patients 2 months after transplantation will be recruited. Patients with an estimated glomerular filtration rate through the modification of diet of renal disease (MDRD) formula 300 mg/24 h will be excluded. Patients’ diets will be allocated through simple sequential randomization. Patients will be followed-up for 12 months with nine clinic appointments with a dietitian and the evaluations will include nutritional assessment (anthropometrics, body composition, and resting metabolic rate) and laboratory tests. The primary outcome is weight maintenance or body weight gain under 5% after 12 months. Secondary outcomes include body composition, resting metabolic rate, satiety sensation, kidney function, and other metabolic parameters Discussion: Diets with higher protein content and lower glycemic index may lead to weight loss because of higher satiety sensation. However, there is a concern about the association of high protein intake and kidney damage. Nevertheless, there is little evidence on the impact of high protein intake on long-term kidney function outcome. Therefore, we designed a study to test if a high protein diet with low-glycemic index will be an effective and safe nutritional intervention to prevent weight gain in kidney transplant patients

Consumo alimentar e perfil inflamatório de pacientes transplantados renais : um estudo longitudinal

Introdução: O transplante renal é considerado a melhor escolha de tratamento para pacientes com doença renal crônica em estágio avançado. Embora possua uma série de benefícios quando comparado à diálise, apresenta ainda algumas complicações metabólicas. Esses pacientes possuem um aumento dos parâmetros inflamatórios, que pode estar relacionado com o aumento do tecido adiposo. Sabe-se ainda que, após o transplante, os pacientes possuem menores restrições alimentares e adequação do apetite, o que pode modificar o consumo alimentar. Objetivos: Avaliar o consumo alimentar nos momentos pré-transplante renal, três e doze meses pós-transplante renal. Além disso, avaliar a associação de dados do consumo alimentar com parâmetros inflamatórios, medidas antropométricas e com os demais exames laboratoriais de função renal, perfil lipídico e glicemia de jejum. Metodologia: Estudo longitudinal, onde foram incluídos 40 pacientes que realizaram transplante renal entre dezembro de 2014 e agosto de 2015. Os momentos de avaliação foram no pré-transplante, três e doze meses pós-transplante. Em todos os momentos foram coletados dados antropométricos, de composição corporal (bioimpedância elétrica e densitometria óssea) e bioquímicos, além do consumo alimentar pelo Questionário de Frequência Alimentar (QFA). Resultados: Houve redução do consumo energético ao longo do tempo (p overtime <0,001), com menor consumo de carboidrato e proteína. Além de redução do consumo de minerais como sódio, potássio, ferro e magnésio. No pós-transplante tardio (12 meses), obteve-se aumento do índice de massa corporal (IMC) (p = 0,002) e circunferência de cintura (CC) (p = 0,016). Perfil inflamatório não obteve diferença significativa entre os momentos. Ocorreu aumento da glicemia de jejum, colesterol total e colesterol HDL no pós-transplante imediato. Obteve-se correlação positiva entre carboidrato e colesterol HDL e glicemia de jejum com colesterol dietético. Houve correlação negativa entre carboidrato e IMC e CC, fibra e LDL e CT e consumo proteico e PCR. Conclusão: Embora não seja possível estimar o consumo alimentar em sua totalidade, é importante a realização do inquérito alimentar em transplantados renais. O estudo avaliou mudanças alimentares no primeiro ano pós-transplante renal. Foi encontrada uma redução da ingestão total em três meses, com seu respectivo o aumento no momento tardio pós-transplante. O perfil inflamatório não obteve alterações, porém os pacientes obtiveram piora do perfil lipídico, glicêmico e ganho ponderal. É necessário realizar uma observação contínua dessa população para melhor manejo terapêutico.Introduction: Kidney transplantation is considered the best choice of treatment for patients with chronic kidney disease in end stage. Although there is a series of benefits when compared with dialysis, it shows some metabolic outcomes. These patients have an increase of inflammatory parameters, which may be linked with an adipose tissue increase. It is known that, after transplant, patients have less food restrictions and appetite restoration, which may modify dietary intake. Objectives: To evaluate food intake before transplant, three and twelve months after kidney transplant. Evaluate association of food intake data with inflammatory parameters, anthropometric measures and further kidney function laboratory tests, lipid profile and fasting glucose. Methods: Longitudinal study that enrolled forty patients who made kidney transplantation between December 2014 and August 2015. In every moment were collected anthropometric and biochemical data, aside from the food intake by Food Frequency Questionnaire (FFQ). Results: We found a reduction on energy intake over time (p over time < 0,001), with less carbohydrate and protein intake. Besides, there was a reduction on minerals intake, like sodium, potassium, iron and magnesium. At twelve months post-transplant, body mass index (BMI) (p = 0,002) and waist circumference (WC) (p = 0,016) have had an increase. Inflammatory profile had no significant difference between intervals. There was an increase on fasting glucose, total cholesterol and HDL-cholesterol at immediate post-transplant. Also, the study got a positive correlation between carbohydrate and HDL-cholesterol, and fasting glucose and cholesterol intake. There was a negative correlation between carbohydrate and BMI and WC. Another negative correlation was found between fiber with LDLcholesterol and total cholesterol, even, protein intake and C-reactive protein. Conclusion: Although it isn’t possible to estimate food intake in its totality, is important to do a dietary evaluation. The study evaluated food changes in the first year of kidney transplantation. There was found a decrease in total intake at three months after transplantation, with a respective increase at twelve months post-transplant. Inflammatory profile had no changes, but patients had a worse lipid and glycemic profile, with weight gain. It is necessary to make a continuous observation in this population, in behalf of better treatment

Permeabilidade intestinal em indivíduos com doença renal do diabetes

Introdução: A permeabilidade intestinal é uma característica da barreira intestinal que realiza o controle de substâncias do meio externo para o meio interno do organismo. Estudos mostram sua associação com diversas doenças crônicas, como obesidade, doenças cardiovasculares, diabetes mellitus (DM) e doença renal crônica (DRC). Diversos marcadores têm sido estudados para avaliar a permeabilidade intestinal em diferentes patologias entre eles, a zonulina, uma proteína responsável por realizar a abertura das junções firmes ou tight junctions (do inglês), encontradas entre os enterócitos da barreira intestinal. Objetivos: Avaliar a permeabilidade intestinal, através da zonulina sérica, em indivíduos com doença renal do diabetes (DRD), e associá-los com parâmetros renais, glicêmicos, lipídicos, inflamatórios e antropométricos. Metodologia: Este é um estudo caso-controle, que incluiu quatro grupos de indivíduos: 1) controle não-DM2: sem DM2 ou DRC; 2) controle DM2: pacientes diabéticos sem função renal prejudicada; 3) DRD albuminúricos: pacientes diabéticos com albuminúria (EUA) > 30 mg/g de creatinina, mas taxa de filtração glomerular estimada (TFGe) > 60 ml/min/1,73 m3; 4) DRD avançada: pacientes diabéticos com EUA > 30 mg/g de creatinina e TFGe 30 mg/g creatinin, but estimated Glomerular Function Rate (eGFR) > 60 ml/min/1,73 m2; 4) Advanced DKD cases: diabetic patients with albuminuria (UAE) > 30 mg/g creatinin and eGFR < 60 ml/min/1,73 m2. Intestinal permeability was estimated by serum zonulin levels by ELISA. Other clinical parameters were evaluated, such as fasting glucose, glycated hemoglobin, total cholesterol, LDL-cholesterol (LDL), HDLcholesterol, triglycerides, interleukin-6, high sensitivity C-reactive protein, creatinine, albuminuria, proteinuria, body fat and handgrip strength (HGS). Results: Eighty-six patients were included in the study (18 non-DM control, 26 DM control, 20 albuminuric DKD, 22 advanced DKD). Most subjects were female and Caucasian. Diabetic patients had similar diabetes duration. In addition, most diabetic patient were hypertensive (P < 0,001), unlike the non-DM subjects. Serum zonulin was increased in control DM patients when compared to advanced DKD cases [131,3 (83,0-170,5) vs. 63,7 (45,0-106,0) μg/mL; P = 0,004]. After logarithmic transformation and adjustments for LDL, HGS and body fat, control DM group showed higher zonulin levels showing statistical difference between control DM group compared to non-DM control, albuminuric and advanced DKD (P = 0,003), indicating an impaired intestinal permeability in control DM subjects. There was a positive correlation between serum zonulin and total cholesterol (r = 0,29; P = 0,034), LDL (r = 0,26; P = 0,021), eGFR (r = 0,22; P = 0,040) e HGS (0,28; P = 0,011) and, negative correlation between zonulin and DM duration (r = -0,24; P = 0,049), body fat (r = -0,27; P = 0,014), proteinuria (r = -0,21; P = 0,048) and albuminuria (r = -0,24; P = 0,024) were observed. No correlation between zonulin and inflammatory parameters was found. Lowest zonulin levels were found in patients who presented renal function loss or started hemodialysis after 5 years of study inclusion (P = 0,007). Conclusion: Elevated serum zonulin levels suggests DM control group have an impaired intestinal permeability compared to non-DM controls. After evaluating different renal functions in diverse diabetic patients, we could observe that decreased zonulin levels seems to be related to worse renal outcomes

Progranulin serum levels in human kidney transplant recipients : a longitudinal study

Background: The adipokine progranulin has metabolic proprieties, playing a role in obesity and insulin resistance. Its levels seems to be dependent of renal function, since higher progranulin concentration is observed in patients with end-stage kidney disease. However, the effect of kidney transplantation on progranulin remains unknown. Objective To assess the serum progranulin levels in kidney transplant recipients before and after kidney transplantation. Methods: Forty-six prospective kidney transplant recipients were included in this longitudinal study. They were evaluated before transplantation and at three and twelve months after transplantation. Clinical, anthropometric and laboratorial measurements were assessed. Progranulin was determined with enzyme-linked immunosorbent assays. Results: Serum progranulin significantly decreased in the early period after transplantation (from 72.78 ± 2.86 ng/mL before transplantation to 40.65 ± 1.49 ng/mL at three months; p<0.01) and increased at one year (53.15 ± 2.55 ng/mL; p<0.01 vs. three months), remaining significantly lower than before transplantation (p<0.01) (pover time<0.01). At one year after transplantation, there was a significant increase in body mass index, trunk fat and waist circumference compared to immediate period after transplantation. Progranulin was associated with waist circumference and fasting plasma glucose after adjusted for age, gender, study period, glomerular filtration rate, interleukin-6, high sensitivity C reactive protein and adiponectin. Conclusion: Progranulin serum levels are increased before transplantation and a reduction is observed in the early period after transplantation, possibly attributed to an improvement in renal function. At one year after transplantation, an increment in progranulin is observed, seems to be independent of glomerular filtration, and remained significantly lower than before transplantation