José Carlos Carraro-Eduardo

Resveratrol: Why Is It a Promising Therapy for Chronic Kidney Disease Patients?

Resveratrol, a phenolic compound found in various plants, including grapes, berries, and peanuts, shows promise for the treatment of cancer, aging, type 2 diabetes, and cardiovascular diseases. Resveratrol can promote transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) activation, increase the expression level of SIRT-1, which is a sirtuin family protein, and reduce mTOR pathway signaling. This compound has anti-inflammatory properties in that it inhibits or antagonizes the nuclear factor-κB (NF-κB) activity, which is a redox-sensitive transcription factor that coordinates the inflammatory response. Inflammation and oxidative stress, which are common features in patients with chronic kidney disease (CKD), are interrelated and associated with cardiovascular disease and the progression of CKD itself. Because of the modulation of the mechanisms involved in the inflammatory-oxidative stress cycle, resveratrol could play an important role in controlling CKD-related metabolic derangements. Although resveratrol supplementation in theory is a promising therapy in this patient group, there are no studies evaluating its effects. Thus, the present review aims to describe the role of resveratrol in inflammation and oxidative stress modulation and its possible benefits to patients with CKD.

Is There Association between Uric Acid and Inflammation in Hemodialysis Patients

Background: Elevated serum uric acid has been associated with a variety of cardiovascular disease and with inflammation, but these have been little explored in chronic kidney disease (CKD). Elevated uric acid levels are common in CKD patients and could be involved in inflammatory milieu; our aim was to analyze the association between uric acid and inflammatory markers in hemodialysis (HD) patients. Design: This was a cross-sectional study. Setting: This study was conducted from private clinic, Rio de Janeiro, Brazil. Patients: This study included 50 HD patients and 21 healthy subjects. Methods and procedures: This study included 50 HD patients [62% men, 54.3 ± 12.6 years, 57.5 ± 50.1 months on dialysis, and body mass index (BMI), 24.4 ± 4.1 kg/m2] and 21 healthy individuals (45% men, 50.7 ± 15.7 years and BMI, 25.5 ± 4 kg/m2). Uric acid was measured using uricase-PAP method; inflammatory [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP)] and atherosclerosis markers [intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1), plasminogen activator inhibitor-1 (PAI-1)] were measured by a multiplexed assay. Results: Patients presented high levels of TNF-α, IL-6, CRP, VCAM-1, ICAM-1 (5.5 ± 2.1 pg/mL, 4.1 ± 1.6 pg/mL, 0.32 ± 0.30 mg/mL, 48.5 ± 8.5 ng/mL, 20.5 ± 15.9 ng/mL, respectively), compared with healthy individuals (2.4 ± 1.1 pg/mL, 2.7 ± 0.4 pg/mL, 0.11 ± 0.12 mg/mL, 23.8 ± 5.5 ng/mL, 7.2 ± 1.2 ng/mL, respectively) ( p < 0.04). Uric acid levels were also higher in HD patients (5.4 ± 1.3 mg/dL) than in healthy individuals (3.9 ± 0.9 mg/dL) ( p < 0.02). There was a positive correlation between uric acid and inflammatory markers, IL-6 (r = 0.30, p = 0.01), CRP (r = 0.37, p = 0.003), TNF-α (r = 0.40, p = 0.001), ICAM-1 (r = 0.53, p = 0.0001), and VCAM-1 (r = 0.45, p = 0.0001). Conclusion: These original data suggest that uric acid may have a role in inflammation and atherosclerosis in HD patients. However, further prospective studies involving intervention trials should be conducted in order to search for actual causality relationship between these markers.

Is there a relationship between tryptophan dietary intake and plasma levels of indoxyl sulfate in chronic kidney disease patients on hemodialysis

INTRODUCTION Gut microbiota is involved in generation of uremic toxins in chronic kidney disease (CKD) patients on hemodialysis (HD), like indoxyl sulfate (IS) that is originated from tryptophan amino acid fermentation. OBJECTIVE To evaluate the tryptophan intake by chronic renal failure patients on HD and its possible relationship with IS plasma levels. METHODS Participated of the study 46 patients with CKD on HD regular program (56.5% men; 52.7 ± 10.3 years; 63 (32.2-118.2) months on HD; BMI 25.6 ± 4.9 kg/m2). The tryptophan intake was evaluated by a 24-hours dietary recall (R-24h) performed on 3 different days. Routine biochemical tests and anthropometric measurements were evaluated. IS plasma levels were determined by High Performance Liquid Chromatography (HPLC) with fluorescent detection and the interleukin-6 (IL-6) plasma levels by immunoenzymatic method (ELISA, Enzyme Linked Immunosorbent Assay). RESULTS The average of tryptophan intake was according to recommendation, but IS plasma levels (35.0 ± 11.9 mg/L) were elevated, however according to the EUTox values for uremic individuals. There was no correlation between the tryptophan intake and IS plasma levels. However, there was positive correlation between protein intake and tryptophan and variables used to evaluate lean body mass, and moreover, IS levels were positively associated with IL-6 (r = 0.6: p = 0.01). CONCLUSION The present study suggests that tryptophan dietary intake may not be a determinant factor to IS levels. However, it suggests that gut microbiota may play an important role in systemic inflammation in patients with CKD.

Acyl-Ghrelin and Obestatin Plasma Levels in Different Stages of Chronic Kidney Disease

OBJECTIVE This study assessed acyl-ghrelin and obestatin plasma levels in nondialysis chronic kidney disease (CKD) and hemodialysis (HD) patients compared with healthy volunteers. DESIGN This was a cross-sectional study conducted at Renal Vida Clinic (Rio de Janeiro, Brazil) and Renal Nutrition Ambulatory (Niterói, Brazil). SUBJECTS Sixty-four subjects were studied: 29 HD patients (55.4 ± 10.5 years, body mass index [BMI], 24.4 ± 3.9 kg/m(2), 17 men); 19 nondialysis patients (59.8 ± 7.5 years, BMI, 26.3 ± 4.8 kg/m(2), glomerular filtration rate, 28.8 ± 10.5 mL/minute/1.73 m(2), 5 men), and 16 healthy volunteers (53.8 ± 5.4 years, BMI, 24.6 ± 2.7 kg/m(2), 7 men). MAIN OUTCOME MEASURE Acyl-ghrelin and obestatin were assessed using enzyme immunometric assays. Body weight, height, waist circumference (WC), and skinfold were measurement, and body fat percentage, arm muscle area, BMI, and conicity index were calculated. The average daily intake of calories and protein were estimated using a 3-day, 24-hour dietary recall, and the appetite was assessed by the first question of the Hemodialysis Study Appetite Questionnaire. RESULTS The highest serum acyl-ghrelin (34.1 ± 13.0 pg/mL) and acyl-ghrelin/obestatin ratio (34.0 [6.7-90.2]) were found in nondialysis CKD patients who also presented with the lowest obestatin levels (0.8 [0.30-2.7] ng/mL) when compared with HD patients and healthy volunteers. HD patients presented the highest obestatin plasma levels (3.0 [2.7-3.4] ng/mL) and the lowest acyl-ghrelin/obestatin ratio (P < .05). Obestatin levels inversely correlated with WC (r = -0.6, P < .04) and BMI (r = -0.56, P < .04) in healthy volunteers. CONCLUSION Although no correlation was found for appetite and food intake with acyl-ghrelin and obestatin in CKD patients, HD patients have the most important alteration of acyl-ghrelin and obestatin plasma levels and had a more impaired nutritional status than nondialysis CKD individuals.

Impact of gender in early structural changes of contrast induced nephropathy in rats

INTRODUCTION Contrast-induced nephropathy (CIN) is a major iatrogenic cause of acute kidney injury. Experimental studies have shown that intravascular injection causes intense vacuolization of the contrast agent in the proximal renal tubules cells, preceding the increase in serum creatinine, and that the female may be at a higher risk for CIN. OBJECTIVE To study the early kidney histomorphometric changes in contrast-induced nephropathy according to the gender. METHODS Twenty previously uninephrectomized Wistar rats were divided into 4 groups (n = 5): control males; control females; contrast exposed males; and contrast exposed females. The animals were sacrificed immediately after contrast administration and kidney tissue samples were collected for histomorphometric analysis. The research project was approved by the Research Ethics Committee of the School of Medicine of Universidade Federal Fluminense. RESULTS There was a more intense presence of microvacuoles in proximal tubules in the rats exposed to contrast than in the control groups. Such proximal tubular vacuolation was more intensive in the female rats (p = 0.001). CONCLUSION Proximal tubular vacuolation is a very early change in CIN and is more intensive in female than in male rats.

Urinary tract infection and indwelling urinary catheters: prospective study in gynecological surgery with antibiotic prophylaxis

CONTEXT AND OBJECTIVES Urinary tract infections are the most common cause of hospital-acquired infections, and the use of indwelling urinary catheters is a predisposing factor for their development. The aims of this study were to estimate the frequency of pre and postoperative bacteriuria, identify the microorganisms involved, count the colony-forming units, determine the antibiotic sensitivity profile and compare the results from pre and postoperative urinalyses among women undergoing gynecological surgery with implantation of a urinary catheter. DESIGN AND SETTING Non-controlled prospective observational single-cohort epidemiological study carried out at a university hospital. METHODS Urine samples were collected before and 24 hours after catheterization for urinalysis, culturing and antibiotic sensitivity testing. Pre and postoperative urinalyses were compared using Wilcoxon and McNemar non-parametric tests. RESULTS Fifty-one women participated in the study. Escherichia coligrew in six preoperative samples (11.8%) and Klebsiella pneumoniae in one (1.9%), but bacterial growth did not occur in any postoperative sample. Urinalysis showed lower number of pus cells in the postoperative urine samples (P < 0.05). There were no differences in red blood cell counts or in the nitrite and leukocyte esterase tests, between the samples. CONCLUSION Bacteriuria was found in 13.7% of the preoperative samples. Gram-negative bacteria sensitive to most antibiotics were identified. In the postoperative samples, no bacterial growth was observed. Urinalysis only showed significant reduction of leukocyturia in the postoperative period.

O uso de vacinas na profilaxia das infecções do trato urinário

The urinary tract is the most common site of bacterial infections. Urinary tract infections (UTIs) in women without urinary tract anatomic abnormalities require frequent and repeated use of antibiotics, increasing the prevalence of antimicrobial-resistant microorganisms. The possibility of an alternative approach, with the use of vaccines produced from inactivated bacteria or structural components of these microorganisms, is a reality. Confirming the results observed experimentally, controlled clinical studies of oral or vaginal immunotherapy have shown reductions in the number of episodes of recurrence, without significant side-effects. We reviewed the mechanisms of aggression and defense involved in the pathogenesis of UTIs in women with anatomically normal urinary tracts, the evolution of knowledge about the immunotherapy of UTIs, and the vaccines already available or under development for the treatment of this important clinical condition.The urinary tract is the most common site of bacterial infections. Urinary tract infections (UTIs) in women without urinary tract anatomic abnormalities require frequent and repeated use of antibiotics, increasing the prevalence of antimicrobial-resistant microorganisms. The possibility of an alternative approach, with the use of vaccines produced from inactivated bacteria or structural components of these microorganisms, is a reality. Confirming the results observed experimentally, controlled clinical studies of oral or vaginal immunotherapy have shown reductions in the number of episodes of recurrence, without significant side-effects. We reviewed the mechanisms of aggression and defense involved in the pathogenesis of UTIs in women with anatomically normal urinary tracts, the evolution of knowledge about the immunotherapy of UTIs, and the vaccines already available or under development for the treatment of this important clinical condition.