Anti-inflammatory effects of combined treatment with acetyl salicylic acid and atorvastatin in haemodialysis patients affected by Normal Weight Obese syndrome.

Low-grade inflammation is a common feature of chronic kidney disease (CKD) and persistent systemic inflammation is thought to be a strong predictor of cardiovascular events. Inflammation plays a role in determining the serum albumin levels in haemodialysis patients (HD) independently of the nutritional status. Increased cardiovascular mortality in CKD has been associated with the increased incidence of obesity in uremic patients. Ingenbleek suggested a prognostic inflammation and nutritional index (PINI), based on serum albumin, pre-albumin, C-reactive protein, and alpha1 acid glycoprotein, to identify and to follow up acutely ill patients at risk of major complications. The aims of the present study were: to verify the incidence of Normal Weight Obese (NWO) syndrome; to evaluate by PINI the effect of 8 weeks acetyl salicylic (100 mg/die) and atorvastatin (10 mg/die) combined treatment on chronic inflammation in 52 selected HD patients. Laboratory evaluation, anthropometric and body composition measurements were detected. At baseline the 56.25% of non-obese, the 84.21% of pre-obese-obese, and the 41.17% of NWO women showed PINI values >1 (normal status PINI<1). After the pharmacological treatment, high significant (P<0.001) reduction in lipid profile, an elevated increase of HDL levels, and a significant reduction of inflammatory markers were obtained. Firstly, our results showed that ASA and atorvastatin combined treatment was effective in reducing inflammatory status in HD patients independently of body composition: at the end of the study only 7.49% of the patients exhibited PINI>1. Further studies will be necessary to understand the causes of inflammation in non-responder patients.

Homocysteinemia correlates with plasma thiol redox status in patients with end-stage renal disease.

BACKGROUND/AIMS: In end-stage renal disease (ESRD), hyperhomocysteinemia is a common finding associated with increased cardiovascular risk. However, the pathogenic role of homocysteine is still unclear. In vitro studies show that thiol redox status affects endothelial cell functions. We therefore investigated the possible association between homocysteinemia and plasma thiol redox status in ESRD patients. METHODS: Total plasma homocysteine (Hcy), cysteine (Cys) and free thiols (SH) were measured both before and after a dialytic session in 54 ESRD patients receiving (n = 15) or not receiving (n = 39) folate supplementation, and 17 control subjects. RESULTS: High predialysis levels of both Hcy and Cys were found to be negatively correlated with low SH levels both in supplemented (r = -0.680, p < 0.01 and r = -0.624, p < 0.02, respectively) and unsupplemented (r = -0.698, p < 0.001 and r = -0.445, p < 0.01, respectively) patients. Following dialysis, SH values returned to normal and the above correlations were no longer appreciable. CONCLUSION: A strong, folate therapy-insensitive association between homocysteinemia and plasma free thiol levels was found in ESRD patients. These results support a role for oxidative stress in ESRD-related hyperhomocysteinemia and suggest the plasma thiol redox status alteration as a possible pathogenic mechanism underlying the cardiovascular toxicity of hyperhomocysteinemia in these patients.

Reliability of oxidative stress biomarkers in hemodialysis patients: a comparative study.

BACKGROUND: Oxidative stress (OS) is considered to play a major role in the development of end-stage renal disease (ESRD) complications. However, conflicting and inconsistent data have been reported on OS in ESRD patients. Our aim was to investigate the reliability of the most popular non-enzymatic plasma OS biomarkers in ESRD. METHODS: Vitamins A (VitA), E and C (VitC), uric acid, plasma antioxidant and ferric-reducing potential (PAP and PRP), thiols (SH), malondialdehyde (MDA) and lipid hydroperoxides (HPO) were determined before and after dialysis in plasma from 33 ESRD patients on hemodialysis, hemodiafiltration or peritoneal dialysis and 20 control subjects. RESULTS: In ESRD patients, high PRP and normal PAP values were positively correlated with VitC levels. After dialysis, PRP levels decreased, while unchanged PAP levels correlated positively with high VitA and transiently recovered SH values. All patients showed high levels of both MDA and cholesterol-normalized HPO. However, while the former significantly decreased after dialysis, the latter were unaffected by treatment. Paradoxical correlations of MDA with both VitA and HPO were found. CONCLUSIONS: Plasma PRP and MDA levels may be dramatically affected by both uremia and dialysis; their use in ESRD patients may therefore lead to OS misevaluation and should be avoided. More reliable results can be obtained using physiologically relevant OS functional tests, such as PAP, and early biomarkers of OS damage, such as SH and HPO.

Cardiac calcifications: Fetuin-A and other risk factors in hemodialysis patients.

Cardiac calcifications are a frequent finding in hemodialysis for chronic renal failure. Several factors may play a role in the intimal and medial calcification of coronary arteries such as age and some known atherogenetic factors. In addition, Fetuin-A has been proposed as a protective agent through solubilization of calcium phosphate salt. Fetuin-A is also a marker of inflammatory-nutritional state, and its changes could be an expression of this condition. The aim of this cross-sectional study is to evaluate the relative importance of risk factors of calcifications with special regard to Fetuin-A. The study was conducted with 132 hemodialysis patients. They were subjected to multislice computed tomography for evaluation of calcium deposits in the heart. In addition, the patients were sampled for evaluation of calcium-phosphate parameters, lipid profile, nutritional and inflammatory markers, and also Fetuin-A. There was a wide variability of the extent of calcium deposits expressed as Agatston score, with only 9.3% of patients without calcifications. Age, hemodialysis age, sex, calcium-phosphate parameters, and lipid profile were important risk factors, together with nutritional and inflammatory status of the patients. An inverse correlation between coronary calcium score and Fetuin-A emerged from a multiple regression analysis. However, there was no significant difference in serum Fetuin-A among different grades of calcium score. By dividing the patients in tertiles of serum Fetuin-A, an association between low levels of Fetuin-A and high calcification score was found. Fetuin-A as dependent variable was strictly linked to prealbumin serum levels. In addition, there was a clear link between cardiac calcification scores and inflammatory-nutritional markers. Serum calcium and treatment with calcitriol emerged as predictive variables of coronary score.Fetuin-A could be involved in the process of calcification both in the case of markedly low serum levels, due to decreased prevention of calcium phosphate precipitation, and also as a marker of inflammation, a well-known risk factor of atherogenesis. Treatment with intravenous calcitriol could marginally enhance cardiac calcifications, probably through its hypercalcemic effect.

Effects of folic acid before and after vitamin B12 on plasma homocysteine concentrations in hemodialysis patients with known MTHFR genotypes.

BACKGROUND: Treatment with folic acid and vitamin B12 appears to be effective in lowering total plasma homocysteine (tHcy) concentrations, but whether vitamin B12 alone lowers tHcy in patients with normal vitamin B12 status is unknown. The aims of the present study were to explore the effect of individual supplementation with folic acid or vitamin B12 on tHcy concentrations in hemodialysis (HD) patients and to compare changes in tHcy concentrations with MTHFR genotype. METHODS: We recruited 200 HD patients (119 men) from the "Umberto I" Hospital (Frosinone, Italy) and the Dialysis Unit of University Hospital "Tor Vergata". These patients were randomized blindly into 2 groups of 100 each. Unfortunately, during the study, 36 patients in the first group and 16 in the second group died. The first group was treated initially with vitamin B12 for 2 months and with folic acid for a following 2 months. The second group was treated initially with folic acid and then with vitamin B12. Samples were drawn before administration of either, after the first and second periods, and again 2 months after treatment. RESULTS: The concentrations of tHcy decreased in both groups after the consecutive vitamin therapies, and the decrease was genotype-dependent. The decrease was greater for the T/T genotype (P <0.05) and was more significant when the treatment was started with folic acid (P <0.01). CONCLUSION: The alternating vitamin treatment demonstrated for the first time the importance of folate therapy and the secondary contribution of vitamin B12 in lowering tHcy in HD patients.

Selective adsorption of homocysteine using an HFR-ON LINE technique.

HFR-ON LINE (double chamber HDF with reinfusion of ultrafiltrate regenerated through a charcoal-resin cartridge) is a novel method which combines the processes of diffusion, convection, and adsorbance. We have investigated the effect of such a treatment on the homocysteine (Hcy) levels in ten patients with a mean Hcy level of 57.6 micromol/L (range 24.1-119.7 micromol/L). We have measured the Hcy, folate, and vitamin B12 predialysis and postdialysis, and in the ultrafiltrate precartridge and postcartridge at 10, 120, and 240 min. The mean Hcy levels were 57.6 and 35.3 micromol/L (range 9.9-80.3 micromol/L) (P = 0.005) predialysis and postdialysis, respectively, while folate and vitamin B12 were unchanged. Precartridge and postcartridge Hcy levels were 11.6 vs. 2.5 micromol/L (P = 0.005), 9.3 vs. 3.9 micromol/L (P = 0.005), and 7.7 vs. 4.6 micro mol/L (P = 0.012) at the three time points considered, while folate and vitamin B12 were essentially undetectable. These preliminary data, which need confirmation in a long-term study, seem to indicate that HFR-ON LINE is able to reduce Hcy levels not only through a likely reduction of uremic toxins, but also through an actual removal of Hcy by adsorbance onto the charcoal-resin cartridge.