A Randomized Trial of Short-term Treatment with Folic Acid to Reduce the Oxidative Stress of Patients with Chronic Kidney Disease.

BACKGROUND: Increased generation of reactive oxygen and nitrogen species in chronic kidney disease (CKD) patients leads to increased oxidative stress. The antioxidant capacity of folic acid has been shown to scavenge radicals efficiently. OBJECTIVE: The current study was carried out to examine the effects of folic acid treatment on biochemical and oxidative stress biomarkers in patients in different stages of CKD. METHODS: This was a randomized, non-blinded, clinical trial that assessed the effects of 3 months of treatment with 5 mg of folic acid daily or no treatment in 113 outpatients within CKD stages 3a and 3b. At the end of the intervention, we analyzed the data of 66 patients treated with folic acid and 47 in the control group. Serum homocysteine levels and biochemical and oxidative/nitrosative stress biomarkers were analyzed in all patients. RESULTS: In most patients, folic acid treatment normalized homocysteine levels and increased antioxidant enzyme activity (paraoxonase 1) and decreased sulfhydryl (SH) groups. In addition, oxidative biomarkers (products of nitric oxide and lipid hydroperoxide) were significantly lower post-treatment compared to baseline in the active intervention group. In the no active intervention group, no statistically significant effects were found on the oxidative and biochemical biomarkers. CONCLUSION: Folic acid treatment in stages 3a-4 CKD patients effectively ameliorated their hyperhomocysteinemia and increased the activity of antioxidant enzymes, as well as decreased the levels of pro-oxidant biomarkers in stage G3a and G3b CKD patients. Folic acid treatment attenuated oxidative/nitrosative stress and may be considered as a possible strategy to improve redox status and diminish the damages associated with oxidative/nitrosative stress in CKD patients. Further studies are needed to confirm these findings. Clinical Trials Registration No.: This study is registered in the Brazilian Record of Clinical Trials (ReBEC), under reference RBR-2bfthr.

Vitamin D deficiency is not associated with increased oxidative stress in chronic kidney disease pre-dialysis patients / A deficiência de vitamina D não está associada ao aumento do estresse oxidativo em pacientes renais crônicos em pré-diálise

Abstract Introduction: The progressive decline in 25-hydroxyvitamin D [25(OH)D] in chronic kidney disease (CKD) limits the kidney ability of synthesizing the vitamin. Vitamin D deficiency as defined by KDIGO (25(OH)D <20 ng/mL) is prevalent in CKD patients and associated to oxidative stress (OS). We studied a possible association between vitamin D deficiency and OS in pre-dialysis patients. Methods: A cross-sectional study with 206 CKD patients was carried out. Laboratory tests for 25(OH)D, 1,25(OH)2D, inflammatory markers, and OS were added to routine tests including creatinine, albumin, calcium, phosphorus, alkaline phosphatase, iPTH, glucose, hemoglobin, uric acid, total cholesterol, LDL, HDL, and triglycerides. Results: Vitamin D deficiency was present in 55 CKD patients and normal vitamin D levels were seen in 149 patients. There was a significant association between vitamin D and estimated glomerular filtration rate (eGRF). Homocysteine levels were best predicted by eGRF, sex, and age; high sensitivity C-reactive protein (hsCRP) by staging and BMI; nitric oxide metabolites (NOx) were increased in late disease; leptin was influenced by BMI and higher in women than man; and adiponectin levels were higher in women. Conclusions: OS biomarkers were not correlated with vitamin D deficiency but increased NOx were seen in stages 4-5 CKD patients. Even though a relatively large number of CKD patients was included and a broad number of OS and inflammatory biomarkers were used in this studied we failed to find an association between vitamin D levels and eGRF. More studies are needed to evaluate the influence of vitamin D status in OS in pre-dialysis CKD patients.

Resumo Introdução: A queda da 25-hidroxivitamina D [25 (OH) D] na doença renal crônica (DRC) limita a capacidade renal de sintetizar a vitamina. A deficiência de vitamina D, (25(OH)D<20 ng/mL), é prevalente em pacientes com DRC e associada ao estresse oxidativo (EO). Avaliamos possível associação entre a deficiência de vitamina D e EO em pacientes pré-dialíticos. Métodos: estudo transversal com 206 pacientes com DRC. Exames para 25(OH)D, 1,25(OH)2D, marcadores inflamatórios e EO foram adicionados àqueles de rotina, incluindo creatinina, albumina, cálcio, fósforo, fosfatase alcalina, iPTH, glicose, hemoglobina, ácido úrico, colesterol total , LDL, HDL e triglicerídeos. Resultados: 55 pacientes com DRC tinham deficiência de vitamina D e os 149 tinham níveis normais da vitamina. Houve uma associação significativa entre a vitamina D e a taxa estimada de filtração glomerular (TFGe). Os níveis de homocisteína foram melhor previstos pela TFGe, gênero e idade; proteína C reativa de alta sensibilidade (hsCRP) por estadiamento e IMC; os metabólitos de óxido nítrico (NOx) aumentaram na doença tardia; a leptina foi influenciada pelo IMC, e mais alta em mulheres, assim como os níveis de adiponectina. Conclusões: biomarcadores do EO não correlacionaram com a deficiência de vitamina D, mas houve aumento de NOx nos estágios 4-5 da DRC. Apesar dos grandes números de pacientes com DRC, de biomarcadores inflamatórios e EO usados neste estudo, não houve associação entre os níveis de vitamina D e a TFGe. Mais estudos são necessários para avaliar a influência do status da vitamina D no EO em pacientes com DRC em pré-diálise.

Vitamin D deficiency is not associated with increased oxidative stress in chronic kidney disease pre-dialysis patients.

INTRODUCTION: The progressive decline in 25-hydroxyvitamin D [25(OH)D] in chronic kidney disease (CKD) limits the kidney ability of synthesizing the vitamin. Vitamin D deficiency as defined by KDIGO (25(OH)D <20 ng/mL) is prevalent in CKD patients and associated to oxidative stress (OS). We studied a possible association between vitamin D deficiency and OS in pre-dialysis patients. METHODS: A cross-sectional study with 206 CKD patients was carried out. Laboratory tests for 25(OH)D, 1,25(OH)2D, inflammatory markers, and OS were added to routine tests including creatinine, albumin, calcium, phosphorus, alkaline phosphatase, iPTH, glucose, hemoglobin, uric acid, total cholesterol, LDL, HDL, and triglycerides. RESULTS: Vitamin D deficiency was present in 55 CKD patients and normal vitamin D levels were seen in 149 patients. There was a significant association between vitamin D and estimated glomerular filtration rate (eGRF). Homocysteine levels were best predicted by eGRF, sex, and age; high sensitivity C-reactive protein (hsCRP) by staging and BMI; nitric oxide metabolites (NOx) were increased in late disease; leptin was influenced by BMI and higher in women than man; and adiponectin levels were higher in women. CONCLUSIONS: OS biomarkers were not correlated with vitamin D deficiency but increased NOx were seen in stages 4-5 CKD patients. Even though a relatively large number of CKD patients was included and a broad number of OS and inflammatory biomarkers were used in this studied we failed to find an association between vitamin D levels and eGRF. More studies are needed to evaluate the influence of vitamin D status in OS in pre-dialysis CKD patients.

Schizophrenia phenomenology comprises a bifactorial general severity and a single-group factor, which are differently associated with neurotoxic immune and immune-regulatory pathways.

In schizophrenia, a single latent trait underlies psychosis, hostility, excitation, mannerism, negative (PHEMN) symptoms, formal thought disorders (FTD) and psychomotor retardation (PMR). Schizophrenia is accompanied by a breakdown of gut and blood-brain-barrier (BBB) pathways, increased tryptophan catabolite (TRYCAT) levels, bacterial translocation, and lowered natural IgM and paraoxonase (PON)1 activity. The aim of this study was to examine the factor structure of schizophrenia symptom domains and the biomarker correlates of these factors. We recruited 80 patients with schizophrenia and 40 healthy subjects and assessed the IgA/IgM responses to paracellular/transcellular (PARA/TRANS) ratios, IgA responses to TRYCATs, natural IgM to malondialdehyde and Gram-negative bacteria, and PON1 enzymatic activity. Direct Hierarchical Exploratory Factor Analysis showed a bifactorial oblique model with a) a general factor which loaded highly on all symptom domains, named overall severity of schizophrenia ("OSOS"); and b) a single-group factor (SGF) loading on negative symptoms and PMR. We found that 40% of the variance in OSOS score was explained by IgA/IgM to PARA/TRANS ratio, male sex and education while 36.9% of the variance in SGF score was explained by IgA to PARA/TRANS, IgM to Gram-negative bacteria, female sex (positively associated) and IgM to MDA, and PON1 activity (negatively associated). Schizophrenia phenomenology comprises two biologically-validated dimensions, namely a general OSOS dimension and a single-group negative symptom dimension, which are associated with a breakdown of gut/BBB barriers, increased bacterial translocation and lowered protection against oxidation, inflammation and bacterial infections through lowered PON1 and natural IgM.