Effect of High Sodium Intake on Gut Tight Junctions' Structure and Permeability to Bacterial Toxins in a Rat Model of Chronic Kidney Disease.

INTRODUCTION: Uremic toxicity changes the gut structure and permeability, allowing bacterial toxins to translocate from the lumen to the blood during chronic kidney failure (CKD). Clinical fluid overload and tissue edema without uremia have similar effects but have not been adequately demonstrated and analyzed in CKD. AIMS: To investigate the effect of sodium intake on the plasma concentration of gut-derived uremic toxins, indoxyl sulfate (IS), and p-cresyl sulfate (pCS) and the expression of genes and proteins of epithelial gut tight junctions in a rat model of CKD. METHODS: Sham-operated (control group, CG) and five-sixths nephrectomized (5/6Nx) Sprague-Dawley rats were randomly assigned to low (LNa), normal (NNa), or high sodium (HNa) diets., Animals were then sacrificed at 8 and 12 weeks and analyzed for IS and pCS plasma concentrations, as well as for gene and protein expression of thigh junction proteins, and transmission electron microscopy (TEM) in colon fragments. RESULTS: The HNa 5/6Nx groups had higher concentrations of IS and pCS than CG, NNa, and LNa at eight and twelve weeks. Furthermore, HNa 5/6Nx groups had reduced expression of the claudin-4 gene and protein than CG, NNa, and LNa. HNa had reduced occludin gene expression compared to CG. Occludin protein expression was more reduced in HNa than in CG, NNa, and LNa. The gut epithelial tight junctions appear dilated in HNa compared to NNa and LNa in TEM. CONCLUSION: Dietary sodium intake and fluid overload have a significant role in gut epithelial permeability in the CKD model.

Sex Modulates Cardiovascular Effects of Icodextrin-Based Peritoneal Dialysis Solutions.

Background/Aims: Some previous observations have noted that after six months of peritoneal dialysis (PD) treatment with icodextrin solutions, blood pressure (BP) and NT-proBNP tend to return to baseline values. This may be due to accumulation of icodextrin products that exert a colloid osmotic effect, which drives water into the bloodstream, causing the rise in blood pressure. Since icodextrin is metabolized by α-Amylase and its gene copies are lower in females than in males, we hypothesized icodextrin metabolites reach higher concentrations in females and that cardiovascular effects of icodextrin are influenced by sex. Methods: Secondary analysis of a RCT comparing factors influencing fluid balance control in diabetic PD patients with high or high average peritoneal transport receiving icodextrin (n = 30) or glucose (n = 29) PD solutions. Serum icodextrin metabolites, osmolality, body composition and Inferior Vena Cava (IVC) diameter were measured at baseline, and at 6 and 12 months of follow-up. Results: After six months of treatment, icodextrin metabolites showed higher levels in females than in males, particularly G5-7 and >G7, serum osmolality was lower in females. In spite of reduction in total and extracellular body water, ultrafiltration (UF) was lower and IVC diameter and BP increased in females, suggesting increment of blood volume. Conclusion: Females undergoing PD present with higher levels of icodextrin metabolites in serum that may exert an increased colloid-osmotic pressure followed by less UF volumes and increment in blood volume and blood pressure. Whether this could be due to the lesser number of α-Amylase gene copies described in diabetic females deserves further investigation.

La disminución de triyodotironina se asocia con la elevación del péptido natriurético cerebral N-terminal y con la mortalidad en pacientes en diálisis / Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients

Antecedentes: La disminución de hormonas tiroideas (HT) y el daño miocárdico son frecuentes en pacientes en diálisis y están asociados con la mortalidad. Sin embargo, poco se conoce de la importancia de las HT como factor de daño miocárdico, como se ha descrito en las enfermedades tiroideas primarias. El objetivo de este estudio fue explorar si existe interacción entre la disminución de triyodotironina total (tT3) y los marcadores de daño miocárdico y la relación de esta interacción entre ambos con la mortalidad, para establecer si el daño cardiovascular es el vínculo entre la disminución de HT y el riesgo de muerte en pacientes con ERC en diálisis. Material y métodos: Se estudiaron los niveles plasmáticos de HT, de marcadores de nutrición, inflamación y de daño al miocardio en 296 pacientes en diálisis peritoneal o en hemodiálisis, a los que se vigiló por 16 meses para conocer la asociación de las variables bioquímicas con la mortalidad. Resultados: En el 45% de los pacientes se encontró tT3 disminuida, lo cual tuvo correlación inversa con la proteína C reactiva (PCR) y con el NT-proBNP y directa con la albúmina y la transferrina. La diabetes, la PCR y la tT3 fueron factores de riesgo para la mortalidad por cualquier causa y la PCR, el NT-proBNP y la tT3 para mortalidad cardiovascular. Conclusiones: Los niveles bajos de tT3 son frecuentes en pacientes en diálisis, se asocian con inflamación, desnutrición y daño miocárdico: este último puede ser el vínculo entre la disminución de HT y la mortalidad por cualquier causa y la mortalidad cardiovascular (AU)

Background: Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. Material and methods: TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. Results: Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. Conclusions: Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality (AU)

Low triiodothyronine is associated with elevation of N-terminal pro-brain natriuretic peptide (NT-proBNP) and mortality in dialysis patients. / La disminución de triyodotironina se asocia con la elevación del péptido natriurético cerebral N-terminal y con la mortalidad en pacientes en diálisis.

BACKGROUND: Low thyroid hormone (TH) levels and myocardial damage are common in dialysis patients and are associated with mortality. However, little is known about the role of THs on myocardial damage as has been described in primary thyroid diseases. The aim of this study was to explore the potential relationship between low total triiodothyronine (total T3) and biomarkers of myocardial damage and the effect of their interaction on mortality, to ascertain if cardiovascular damage is the link between low THs and the risk of death in dialysis patients with CKD. MATERIAL AND METHODS: TH plasma levels, nutritional markers, inflammation and myocardial damage were studied in 296 patients undergoing peritoneal dialysis or haemodialysis, who were followed up for 16 months to ascertain the association between biochemical variables and mortality. RESULTS: Low total T3 levels were found in 45% of patients, which was inversely correlated with C-reactive protein (CRP) and NT-proBNP, and directly correlated with albumin and transferrin. Diabetes, CRP and total T3 were risk factors for all-cause mortality, and CRP, NT-proBNP and total T3 for cardiovascular mortality. CONCLUSIONS: Low total T3 levels are common in dialysis patients and are associated with inflammation, malnutrition and myocardial damage. The latter may be the link between low THs and all-cause and cardiovascular mortality.

Role of thyroid hormones and mir-208 in myocardial remodeling in 5/6 nephrectomized rats.

BACKGROUND AND AIMS: Thyroid hormones exert important effects on heart remodeling through mir-208. The process may have a role in myocardial changes in chronic kidney disease where thyroid abnormalities are common. In this study the effect of T4 supplementation on left ventricle (LV) remodeling in 5/6 nephrectomized rats (5/6Nx) was analyzed. METHODS: 5/6Nx rats and 5/6Nx under T4 supplementation (5/6Nx + T4) were compared with control (C) and thyroidectomized (Tx) rats. After 8 weeks of follow-up, LV was analyzed for α-MHC, ß-MHC, TGF-ß, and mir-208 expression, hydroxyproline content, and myocardial fibrosis. Serum collagenase activity was also analyzed. RESULTS: Heart weight increased in 5/6Nx rats compared to C, which was prevented with T4 supplementation (C, 1.5 ± 0.04; 5/6Nx, 1.8 ± 0.09; 5/6Nx + T4, 1.6 ± 0.07 g, p <0.05). The same pattern was seen for LV wall thickness, hydroxyproline content, LV fibrosis, and mRNA TGF-ß expression (C, 0.47 ± 0.17; 5/6Nx, 10.55 ± 3.4; 5/6Nx + T4, 3.01 ± 0.52, p <0.01). Tx rats had reduction in heart weight, increased LV wall thickness, and fibrosis. Collagenase activity did not change in any group. mRNA expression of α-, ß-MHC, and TGF-ß increased in 5/6Nx in comparison to C and 5/6Nx + T4. Expression of mir-208 decreased in 5/6Nx groups, and levels were restored with T4 supplementation (4.21 ± 0.28, 3.39 ± 0.29, and 4.26 ± 0.37 RU, respectively, p <0.01). CONCLUSIONS: Decreased plasma level of thyroid hormones or sensitivity at tissue level observed in chronic kidney disease induced by 5/6Nx has an important effect in heart remodeling processes, some of it related or mediated by mir-208 and TGF-ß expression in the heart.

Elevated prevalence of hepatitis B in Mexican hemodialysis patients. A multicentric survey.

BACKGROUND AND AIMS: The prevalence of hepatitis B virus (HBV) infection in patients on renal replacement has been reduced in developed countries, but information from developing nations is currently scarce and high prevalence rates are suspected. We undertook this study to analyze the prevalence of HBV infection and identify risk factors associated with it in a sample of Mexican hemodialysis patients. METHODS: A cross-sectional study was performed in patients on hemodialysis in Mexico. Adult patients from 10 hemodialysis centers were randomly selected. Patients answered a questionnaire for risk factors for HB infection and a blood sample was taken for HBsAg determination. RESULTS: We included 368 patients, 197 (53.5%) male, with a median age of 52 years (range: 18-93 years). In 26 patients HBsAg was positive with a prevalence of 7.1% (95% CI 4.4-9.7). Hepatitis C (HCV) was also tested, and 31 patients were positive with a prevalence of 8.4% (95% CI 5.5-11.2). Two patients (0.5%) were co-infected. Patients infected with HBV had been on hemodialysis longer (median time 50.5 months in HB positive vs. 34 months in HB negative; p = 0.005) and had history of more transfusions (median number of transfusions 5.5 vs 2; p < 0.009) compared with patients without HBV infection. CONCLUSIONS: The prevalence of HBV infection in patients on maintenance hemodialysis in Mexico is about 7%, 35 times higher compared with the general population (0.2%).

Icodextrin improves metabolic and fluid management in high and high-average transport diabetic patients.

BACKGROUND: Icodextrin-based solutions (ICO) have clinical and theoretical advantages over glucose-based solutions (GLU) in fluid and metabolic management of diabetic peritoneal dialysis (PD) patients; however, these advantages have not yet been tested in a randomized fashion. OBJECTIVE: To analyze the effects of ICO on metabolic and fluid control in high and high-average transport diabetic patients on continuous ambulatory PD (CAPD). PATIENTS AND METHODS: A 12-month, multicenter, open-label, randomized controlled trial was conducted to compare ICO (n = 30) versus GLU (n = 29) in diabetic CAPD patients with high-average and high peritoneal transport characteristics. The basic daily schedule was 3 x 2 L GLU (1.5%) and either 1 x 2 L ICO (7.5%) or 1 x 2 L GLU (2.5%) for the long-dwell exchange, with substitution of 2.5% or 4.25% for 1.5% GLU being allowed when clinically necessary. Variables related to metabolic and fluid control were measured each month. RESULTS: Groups were similar at baseline in all measured variables. More than 66% of the patients using GLU, but only 9% using ICO, needed prescriptions of higher glucose concentration solutions. Ultrafiltration (UF) was higher (198 +/- 101 mL/day, p < 0.05) in the ICO group than in the GLU group over time. Changes from baseline were more pronounced in the ICO group than in the GLU group for extracellular fluid volume (0.23 +/- 1.38 vs -1.0 +/- 1.48 L, p < 0.01) and blood pressure (systolic 1.5 +/- 24.0 vs -10.4 +/- 30.0 mmHg, p < 0.01; diastolic 1.5 +/- 13.5 vs -6.2 +/- 14.2 mmHg, p < 0.01). Compared to baseline, patients in the ICO group had better metabolic control than those in the GLU group: glucose absorption was more reduced (-17 +/- 44 vs -64 +/- 35 g/day) as were insulin needs (3.6 +/- 3.4 vs - 9.1 +/- 4.7 U/day, p < 0.01), fasting serum glucose (8.3 +/- 36.5 vs -37 +/- 25.8 mg/dL, p < 0.01), triglycerides (54.5 +/- 31.9 vs -54.7 +/- 39.9 mg/dL, p < 0.01), and glycated hemoglobin (0.79% +/- 0.79% vs -0.98% +/- 0.51%, p < 0.01). Patients in the ICO group had fewer adverse events related to fluid and glucose control than patients in the GLU group. CONCLUSION: Icodextrin represents a significant advantage in the management of high transport diabetic patients on PD, improving peritoneal UF and fluid control and reducing the burden of glucose overexposure, thereby facilitating metabolic control.

Inflammation and extracellular volume expansion are related to sodium and water removal in patients on peritoneal dialysis.

BACKGROUND: Inflammation is an important risk for mortality in dialysis patients. Extracellular fluid volume (ECFv) expansion, a condition commonly seen in peritoneal dialysis (PD) patients, may be associated with inflammation. However, published support for this relationship is scarce. OBJECTIVES: To quantify the proportion of patients on PD with inflammation and to analyze the role of ECFv expansion and the factors related to these conditions. DESIGN: A prospective, multicenter cross-sectional study in six hospitals with a PD program. PATIENTS AND METHODS: Adult patients on PD were studied. Clinical data, body composition, and sodium and fluid intake were recorded. Biochemical analysis, C-reactive protein (CRP), and peritoneal and urinary fluid and sodium removal were also measured. RESULTS: CRP values positive (>or=3.0 mg/L) for inflammation were found in 147 (80.3%) and negative in 36 patients. Patients with positive CRP had higher ECFv/total body water (TBW) ratio (women 47.69 +/- 0.69 vs 47.36 +/- 0.65, men 43.15 +/- 1.14 vs 42.84 +/- 0.65; p < 0.05), higher serum glucose (125.09 +/- 81.90 vs 103.28 +/- 43.30 mg/dL, p < 0.03), and lower serum albumin (2.86 +/- 0.54 vs 3.17 +/- 0.38 g/dL, p < 0.001) levels. They also had lower ultrafiltration (1003 +/- 645 vs 1323 +/- 413 mL/day, p < 0.005) and total fluid removal (1260 +/- 648 vs 1648 +/- 496 mL/day, p < 0.001), and less peritoneal (15.59 +/- 162.14 vs 78.11 +/- 110.70 mEq/day, p < 0.01) and total sodium removal (42.06 +/- 142.49 vs 118.60 +/- 69.73 mEq/day, p < 0.001). In the multivariate analysis, only ECFv/TBW was significantly (p < 0.04) and independently associated with inflammation. ECFv/TBW was correlated with fluid removal (r = 0.16, p < 0.03) and renal sodium removal (r = 0.2, p < 0.01). CONCLUSION: The data suggest that ECFv expansion may have a significant role as an inflammatory stimulus. The results disclose a relationship between the two variables, ECFv expansion and inflammation, identified as independent risk factors for mortality in PD patients.