Giorgio Splendiani

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.

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

Abstract 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. Clin Chem Lab Med 2007;45:1211–8.

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.

Experience of apheresis in the intensive care unit

Introduction Sepsis is one of the main causes of death in critically ill patients worldwide, and in many cases it is associated with renal and/or other organ failure. However, we do not have an efficient therapy to reduce its extremely high mortality rate. In the last years the interest around the use of extracorporeal blood purification techniques has increased. One of the emerging treatments in patients with severe sepsis and septic shock is coupled plasma filtration adsorption (CPFA). CPFA is a novel extracorporeal blood purification therapy aimed at non-selectively reducing the circulating levels and activities of both pro and anti-inflammatory mediators. The aim of this study, conducted in septic patients, was to observe the effects of CPFA on mortality and several laboratory and hemodynamic parameters. Patients and Methods We treated 65 patients (50 males and 15 females) with CPFA. We then analysed the mean arterial pressure (MAP), the sequential organ failure assessment (SOFA) score, and the acute physiology and chronic health evaluation II (APACHE II) score. Serum levels of interleukin-6 and procalcitonin were also measured. Results After 28 days we observed a mortality of 36.9% (24 patients) and a significant reduction in IL-6, procalcitonin, SOFA and APACHE scores. Conclusion CPFA represents a promising new approach for blood purification in sepsis.

RHEOPHERESIS IN VASCULAR DISEASES

BACKGROUND Endothelial dysfunction is a common condition in many microvascular diseases, such as Age-related Macular Degeneration (AMD) and Peripheral Arterial Occlusive Disease (PAOD). Rheopheresis therapy improves ematic viscosity, shear stress and endothelial function while decreasing fibrinogen, LDL-cholesterol and alpha-2-macroglobulin levels. OBJECTIVE To evaluate the therapeutic efficacy of rheopheresis in patients with microcirculatory diseases. MATERIALS AND METHODS Eight patients (7 male and 1 female) were treated with rheopheresis: 3 males were affected by AMD, 4 male and 1 female by uremia and PAOD. We used Membrane Differential Filtration (MDF) with an ethinylvinyl alcohol copolymer membrane as plasmafiltrator. Patients with AMD were treated once a week for ten weeks. Patients affected with PAOD were treated twice weekly for 3 weeks and then were placed on a once-a-week program. RESULTS In all treated patients with AMD, visual acuity improved. In all patients affected with PAOD, we observed a complete resolution of pain; 3 out of 5 had a complete remission of ulcers. There was partial reduction of ulcers in the other patients and no adverse effects were observed. CONCLUSION Rheopheresis is a safe, effective form of hemorheotherapy.

SELECTIVE ADSORPTION OF HOMOCYSTEINE USING 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.