RESUMO
AIMS: Sulforaphane (SFN), a naturally occurring isothiocyanate found in cruciferous vegetables, has received extensive attention as a natural activator of the Nrf2/Keap1 cytoprotective pathway. In this review, a meta-analysis and systematic review of the renoprotective effects of SFN were performed in various preclinical models of kidney diseases. MAIN METHODS: The primary outcome was the impact of SFN on renal function biomarkers (uremia, creatininemia, proteinuria or creatinine clearance) and secondary outcomes were kidney lesion histological indices/kidney injury molecular biomarkers. The effects of SFN were evaluated according to the standardized mean differences (SMDs). A random-effects model was applied to estimate the overall summary effect. KEY FINDINGS: Twenty-five articles (out of 209 studies) were selected from the literature. SFN administration significantly increased creatinine clearance (SMD +1.88 95 % CI: [1.09; 2.68], P < 0.0001, I2 = 0 %) and decreased the plasma creatinine (SMD -1.24, [-1.59; -0.88], P < 0.0001, I2 = 36.0 %) and urea (SMD -3.22 [-4.42, -2.01], P < 0.0001, I2 = 72.4 %) levels. SFN administration (median dose: 2.5 mg/kg, median duration: 3 weeks) significantly decreased urinary protein excretion (SMD -2.20 [-2.68; -1.73], P < 0.0001, I2 = 34.1 %). It further improved two kidney lesion histological indices namely kidney fibrosis (SMD -3.08 [-4.53; -1.63], P < 0.0001, I2 = 73.7 %) and glomerulosclerosis (SMD -2.24 [-2.96; -1.53], P < 0.0001, I2 = 9.7 %) and decreased kidney injury molecular biomarkers (SMD -1.51 [-2.00; -1.02], P < 0.0001, I2 = 0 %). SIGNIFICANCE: These findings provide new insights concerning preclinical strategies for treating kidney disease or kidney failure with SFN supplements and should stimulate interest in clinical evaluations of SFN in patients with kidney disease.
Assuntos
Nefropatias , Fator 2 Relacionado a NF-E2 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Creatinina , Fator 2 Relacionado a NF-E2/metabolismo , Nefropatias/tratamento farmacológico , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Biomarcadores/metabolismoRESUMO
Objective: To better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined. Methods: We performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability. Results: Two studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified. Conclusion: By providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.
Assuntos
Prevalência , Insuficiência Renal Crônica , Ciências da Nutrição , Metabolismo , NefropatiasRESUMO
The stomach may play an important role in central feeding regulation because it produces two peptides, ghrelin and the recently identified obestatin. These peptide hormones exert opposite actions on weight regulation. Whereas ghrelin is orexigenic, obestatin seems to be anorexigenic. Studies on feeding regulation are of particular importance for patients with chronic kidney disease (CKD), because anorexia and weight loss are associated with wasting and increased morbidity and mortality. This review discusses recent information about ghrelin and obestatin and their potential role in CKD. In addition, it seems important to consider not only single values but also their ratios, because both compounds could be affected disharmoniously by CKD.
Assuntos
Regulação do Apetite/fisiologia , Grelina/fisiologia , Nefropatias/fisiopatologia , Estômago/fisiopatologia , Animais , Anorexia/fisiopatologia , Doença Crônica , Ingestão de Alimentos/fisiologia , Metabolismo Energético/fisiologia , Jejum/fisiologia , Humanos , Nefropatias/terapia , Células Parietais Gástricas/metabolismo , Diálise RenalRESUMO
OBJECTIVE: Compounds involved in the regulation of appetite and body composition appear to be of interest in chronic kidney disease. The purpose of this study was to analyze plasma obestatin and acyl and des-acyl ghrelin in patients on hemodialysis (HD). METHODS: Fifty patients on HD (56.0% women, mean age 62.2 ± 15.2 y) were studied. Blood samples were collected during fasting, before a regular HD session. Serum acyl and des-acyl ghrelin levels, leptin, and obestatin were measured using enzyme immunometric assay methods. Anthropometric parameters, appetite score, and food intake were recorded. RESULTS: Patients showed elevated serum leptin (34.1 ± 30 ng/mL), normal acyl ghrelin (137 ± 116.5 pg/mL), high des-acyl ghrelin (670 ± 479 pg/mL), and low obestatin (2.0 ± 1.4 ng/mL) levels compared with healthy volunteers. According to body mass index (BMI), patients with a BMI >23 kg/m(2) had significantly lower plasma obestatin. In contrast, leptin levels were increased and acyl ghrelin tended to be higher in these patients. There was a strong positive correlation between obestatin and des-acyl ghrelin (r = 0.56, P = 0.0001) and inverse correlations between obestatin and BMI (r = -0.40, P = 0.007), waist circumference (r = -0.38, P = 0.024), and C-reactive protein (r = -0.29, P = 0.048). By multivariate analysis, obestatin was independently and positively correlated with des-acyl ghrelin (P = 0.01), but not with C-reactive protein, BMI, or waist circumference. CONCLUSION: In summary, patients on HD exhibited increased plasma levels of des-acyl ghrelin, normal acyl ghrelin levels, and low obestatin levels. In lean patients, the obestatin and des-acyl ghrelin levels were increased, suggesting that these hormones may influence appetite and body composition in patients on HD.