dinoprost and Renal-Insufficiency--Chronic

Dietary advanced glycation end-products (AGEs) form during heating and processing of food products and are widely prevalent in the modern Western diet. Recent systematic reviews indicate that consumption of dietary AGEs may promote inflammation, oxidative stress and insulin resistance. Experimental evidence indicates that dietary AGEs may also induce renal damage, however, this outcome has not been considered in previous systematic reviews. The purpose of this review was to examine the effect of consumption of a high AGE diet on biomarkers of chronic disease, including chronic kidney disease (CKD), in human randomized controlled trials (RCTs). Six databases (SCOPUS, CINHAL, EMBASE, Medline, Biological abstracts and Web of Science) were searched for randomised controlled dietary trials that compared high AGE intake to low AGE intake in adults with and without obesity, diabetes or CKD. Twelve dietary AGE interventions were identified with a total of 293 participants. A high AGE diet increased circulating tumour necrosis factor-alpha and AGEs in all populations. A high AGE diet increased 8-isoprostanes in healthy adults, and vascular cell adhesion molecule-1 (VCAM-1) in patients with diabetes. Markers of CKD were not widely assessed. The evidence presented indicates that a high AGE diet may contribute to risk factors associated with chronic disease, such as inflammation and oxidative stress, however, due to a lack of high quality randomised trials, more research is required.

Topics: Biomarkers; Diet; Dinoprost; Glycation End Products, Advanced; Humans; Inflammation; Inflammation Mediators; Oxidative Stress; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Cilazapril; Cross-Over Studies; Dinoprost; Drug Therapy, Combination; Female; Humans; Isoprostanes; Male; Oxidative Stress; Renal Insufficiency, Chronic; Renin-Angiotensin System; Telmisartan

Mechanisms of accelerated atherothrombosis in patients with chronic kidney disease (CKD) are only partly characterized. The aims of this study were to evaluate the extent of thromboxane (TX)-dependent platelet activation in patients with CKD, and to characterize the determinants of altered TX biosynthesis in this setting, with particular reference to enhanced lipid peroxidation, low grade inflammation and CKD-related anemia.. A cross sectional comparison between urinary 8-iso-PGF2α and 11-dehydro-TXB2, in vivo markers of oxidative stress and platelet activation, respectively, was performed in 115 patients with stage 1-4 CKD.. Levels of both urinary 11-dehydro-TXB2 and 8-iso-PGF2α increased sequentially across the four CKD stages (P<0.0001, Kruskal-Wallis test). Both urinary prostanoids were inversely associated with either estimated glomerular filtration rate (eGFR, P<0.0001) or hemoglobin levels (P<0.0001). A significant direct correlation was also observed between urinary 11-dehydro-TXB2 and 8-iso-PGF2α (Rho=0.620, P<0.0001). On multivariate analysis, urinary 8-iso-PGF2α (β=0.459, P<0.0001), hemoglobin levels (β=- 0.261, P=0.002) and eGFR (β=-0.172, P=0.032) were independent predictors of urinary 11-dehydro-TXB2 (adjusted R(2)=0.488).. This study provides biochemical evidence of persistent platelet activation in patients with CKD. This condition occurs early in the natural history of the disease and is related to kidney function and oxidative stress. Moreover, we found an independent inverse relationship between hemoglobin levels and TX-dependent platelet activation. This finding may provide a mechanistic link between CKD-related anemia and increased cardiovascular risk.

Topics: Aged; Biomarkers; Cardiovascular Diseases; Cross-Sectional Studies; Dinoprost; Erythropoietin; Female; Glomerular Filtration Rate; Hemoglobins; Humans; Italy; Linear Models; Male; Middle Aged; Multivariate Analysis; Oxidative Stress; Platelet Activation; Prostaglandins; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Thromboxane B2

Accumulation of protein-bound uraemic toxins (PBUTs) is one of the reasons for the development of uraemia-related complications including cardiovascular disease; however, conventional haemodialysis is limited in its ability to remove PBUTs. We aimed to examine whether the oral charcoal adsorbent AST-120 has an additive effect on PBUT removal in haemodialysis patients. During the 4-week study, anuric patients undergoing haemodialysis received AST-120 (6 g/day) in the last 2 weeks (n = 10) or the first 2 weeks (n = 10). Serum levels of total and free PBUTs such as indoxyl sulfate, p-cresyl sulfate, and phenyl sulfate at the pre- and postdialysis sessions were measured before and after AST-120 use and after discontinuation. Levels of the oxidative stress markers oxidized albumin and 8-isoprostane were also measured. AST-120 use induced dramatic reduction of indoxyl sulfate (total, 45.7% [33.2-50.5%]; free, 70.4% [44.8-79.8%]), p-cresyl sulfate (total, 31.1% [25.0-48.0%]; free, 63.5% [49.3-70.9%]), and phenyl sulfate (free, 50.6% [32.3-71.2%]) levels; however, this effect disappeared after the discontinuation of AST-120. AST-120 use also induced substantial reduction of the oxidized albumin and 8-isoprostane levels. In conclusion, oral administration of AST-120 had additive effects on the continuous reduction of some PBUTs in anuric patients undergoing haemodialysis.

Topics: Aged; Biomarkers; Carbon; Cresols; Dinoprost; Female; Humans; Indican; Male; Middle Aged; Oxidative Stress; Oxides; Renal Dialysis; Renal Insufficiency, Chronic; Serum Albumin; Sulfuric Acid Esters; Toxins, Biological; Uremia

The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear.. Seventy-four older adults with type 2 diabetes and chronic kidney disease (stage G3b-G4) were enrolled in the study. During the 4-wk baseline period (T0), all patients were asked to follow a normal protein diet regimen, providing 1.1 g/kg daily. Successively, all patients were asked to follow an MPD, for 36 mo, providing 0.7 g/kg daily, for only 6 d/wk. Patients who refused to follow an MPD treatment were included in the control (NPD [normal protein diet] group). During the 36 mo of the study, creatinine clearance, blood urea nitrogen, proteinuria, blood pressure, glycated hemoglobin (Hb)A1c, fat-free mass, low-grade inflammation (interleukin-6 and C-reactive protein) were evaluated monthly and oxidative stress (urinary 8-epiprostaglandin [Epi-PG]F2α) was evaluated every 3 mo.. During T0, mean creatinine clearance, proteinuria, blood urea nitrogen, blood pressure, HbA1c, fat free mass, low-grade inflammation, and oxidative stress were similar in both groups. After 36 mo, a significant reduction in decline of renal function was observed in the MPD group but not in controls (2.4 ± 0.2 versus 5.7 ± 0.5 mL·min·y, respectively; P < 0.05 versus control). Similarly, a significant reduction in proteinuria, serum interleukin-6, serum C-reactive protein, and urinary 8-Epi-PGF2α excretion, was observed in the MPD group (P < 0.05 versus NPD).. In older adults with type 2 diabetes, long-term effects of an MPD regimen are associated with a significant decline of renal function, proteinuria, low-grade inflammation, and oxidative stress without a change in fat-free mass.

Topics: Aged; C-Reactive Protein; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diet; Diet, Protein-Restricted; Dietary Proteins; Dinoprost; Female; Humans; Inflammation; Interleukin-6; Kidney; Male; Oxidative Stress; Patient Compliance; Proteinuria; Renal Insufficiency, Chronic; Time Factors

Hypertension and additional non-traditional risk factors can damage the kidney directly and by promoting atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate a large part of the effects of risk factors on the kidney. We hypothesized that in hypertensive patients (HT), oxidative stress, measured as 8-ISO-prostaglandin F2alpha (8-ISO-PGF2alpha), should raise paralleling decreasing renal function and should correlate with estimated glomerular filtration rate (eGFR).. In 626 HT with renal function ranging from stages 1 to 5 and 100 healthy controls, plasma levels of 8-ISO-PGF2alpha, high-sensitivity C-reactive protein (CRP), transforming growth factor-beta (TGF-beta) and endothelin-1 (ET-1) were measured. GFR was estimated by the Modification of Diet in Renal Disease study equation.. When HT were stratified according to renal function stages, 8-ISO-PGF2alpha, CRP, TGF-beta and ET-1 increased progressively and significantly with decreasing eGFR. The multiple regression analysis, considering eGFR as a dependent variable, showed that 8-ISO-PGF2alpha (beta = -0.361, P < 0.000001), ET-1 (beta = -0.197, P < 0.0001) and TGF-beta (beta = -0.170, P < 0.0004) correlated independently with eGFR. All biomarkers were good predictors of eGFR <60 ml/min/1.73 m(2) [receiver-operator-curve (ROC) areas]. ET-1 was shown to be the best predictor with a ROC area = 0.938; with a threshold of 4 pg/ml, 91% sensitivity and 85% specificity were observed, whereas 8-ISO had a ROC area = 0.931, and for a threshold of 329 pg/ml, sensitivity and specificity were 89%, respectively. In contrast, CRP showed the lower predictive value with a ROC area = 0.917; with a threshold of 2.52 mg/l, an 87% sensitivity and an 83% specificity were obtained.. Our findings are a clear-cut demonstration of a strong and negative correlation of both oxidative stress and ET-1 with renal function stages in HT. ET-1 and 8-isoprostane are predictive of eGFR.

Topics: Adult; Aged; Atherosclerosis; C-Reactive Protein; Case-Control Studies; Dinoprost; Endothelin-1; Female; Glomerular Filtration Rate; Humans; Hypertension; Kidney; Male; Middle Aged; Oxidative Stress; Renal Insufficiency, Chronic; Risk Factors; Transforming Growth Factor beta

Oxidative stress appears to have a central role in the pathophysiological process of uremia and its complications, including cardiovascular disease. However, there is little evidence to suggest how early oxidative stress starts developing during the progression of chronic kidney disease (CKD). The aim of this study is to assess oxidative stress activity in a cross-sectional study of patients with CKD stages 1 to 4.. Eighty-seven steady patients (47 men, 40 women) with a median age of 62 years (range, 28 to 84 years) and mean estimated glomerular filtration rate (eGFR) of 57 mL/min (0.95 mL/s) were studied. Levels of plasma 8-isoprostanes (8-epiPGF2a) and serum total antioxidant status (TAS) were used as markers of oxidative stress. 8-epiPGF2a levels were determined by using an enzyme-linked immunosorbent assay method, whereas a chromatometric method was used to determine TAS.. Plasma 8-epiPGF2a levels increased significantly as CKD stages advanced (P < 0.001). There was a highly significant inverse correlation between 8-epiPGF2a level and GFR (P < 0.01). Serum TAS levels also increased in a similar fashion (P < 0.009) and showed a significant inverse correlation with GFR (P < 0.01). 8-epiPGF2a and TAS levels showed a positive correlation (P < 0.05). Multiple regression analysis showed that the most significant predictor variable for 8-epiPGF2a level was eGFR, whereas the association between eGFR and TAS was affected strongly by confounding variables, mainly uric acid level.. Oxidative stress appears to increase as CKD progresses and correlates significantly with level of renal function. Increased TAS seems to be dependent on several confounding variables, including increased uric acid levels, and therefore does not seem to be a reliable method for assessing the antioxidant capacity of patients with CKD. These results suggest that larger studies using the correct markers to assess the timing and complex interplay of oxidative stress and other risk factors during the progression of CKD should be carried out.

Topics: Adult; Aged; Aged, 80 and over; Cross-Sectional Studies; Dinoprost; Disease Progression; Female; Glomerular Filtration Rate; Humans; Male; Middle Aged; Oxidative Stress; Regression Analysis; Renal Insufficiency, Chronic; Uric Acid