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Ciro Tetta

Publications and source records attributed to Ciro Tetta.

43 records · Page 3Linked to original sources

Convective and diffusive losses of vitamin C during haemodiafiltration session: a contributive factor to oxidative stress in haemodialysis patients.

BACKGROUND: Enhanced oxidative stress in haemodialysis (HD) patients may be considered as a risk factor for accelerated atherosclerosis. Reduced antioxidant defences include impairment in enzyme activities and decreased plasma levels of hydrophilic vitamin C (vit C), and cellular levels of lipophilic vitamin E (vit E). METHODS: We investigated plasma levels of vit C in 19 patients undergoing regular haemodiafiltration (HDF) (mean age 62+/-7 years) and in 1846 healthy elderly subjects (HS) (mean age 69+/-5 years). The contribution of convection and diffusion was determined using paired filtration dialysis (PFD), a modified HDF technique which physically separates convective from diffusive fluxes. Blood samples were collected before and after the HDF session; in addition at 60 min of HDF, samples were drawn from arterial lines (AL) and venous lines (VL), dialysate (D) and ultrafiltrate (UF). Blood levels of total vit C were determined using an HPLC fluorescence method. Markers of oxidative stress were also assessed in both populations as follows: levels of malondialdehyde (MDA) were determined by fluorometric assay, measurements of advanced oxidation protein products (AOPP) and glutathione peroxidase (GSH-Px) activity were performed by spectrophotometric assay, and plasma vit E content was obtained by an HPLC procedure. RESULTS: A significant reduction in plasma vit C level was observed in HDF patients when compared with HS (1.6+/-1.4 microg/ml in HDF vs 6.6+/-3.7 microg/ml in HS; P<0.01). The HDF session was associated with a dramatic reduction in vit C levels (1.87+/-1.57 microg/ml before HDF and 0.98+/-0.68 microg/ml after HDF); at 60 min of HDF, concentrations were as follows: AL=1.35+/-1.27 microg/ml; VL=0.37+/-0.31 microg/ml, D=0.40+/-0.34 microg/ml, UF=1.24+/-1.18 microg/ml; corresponding to a diffusive flux of 271 microg/min and a convective flux of 126 microg/min. Total loss of vit C could be assessed at 66 mg/session (8--230 mg/session). According to this loss of vit C, presence of an oxidative stress was demonstrated in HD population as shown by a significant increase in MDA (1.66+/-0.27 microM in HD vs 0.89+/-0.25 microM in HS; P<0.01) and AOPP (77.5+/-29.3 microM in HD vs 23.5+/-13.2 microM in HS; P<0.01) levels, and a decrease in GSH-Px activity (259.2+/-106.3 U/l in HD vs 661.2+/-92.2 U/l in HS; P<0.01). No change in plasma vit E between both populations (30.7+/-9.1 microM in HD vs 35.3+/-7.34 microM in HS) was observed. CONCLUSIONS: These results suggest that HDF with highly permeable membranes is associated with a significant loss of vit C. Diffusive transport is responsible for two-thirds whereas convective phenomenon accounts for only one-third of this loss.

Adult↗

A pilot study of coupled plasma filtration with adsorption in septic shock.

OBJECTIVE: To test the hypothesis that nonselective plasma adsorption by a hydrophobic resin (coupled plasmafiltration and adsorption) could improve hemodynamics and restore leukocyte responsiveness in patients with septic shock. DESIGN: Prospective, pilot, crossover clinical trial. SETTING: General intensive care unit in a teaching hospital. SUBJECTS: Ten patients with hyperdynamic septic shock. INTERVENTIONS: Patients were randomly allocated to 10 hrs of either coupled plasma filtration adsorption plus hemodialysis (treatment A) or continuous venovenous hemodiafiltration (treatment B) in random order. We measured the change in mean arterial pressure, norepinephrine requirements, and leukocyte tumor necrosis factor-alpha (TNF-alpha) production (both spontaneous and lipopolysaccharide-stimulated) after 10 hrs of each treatment. We also tested TNF-alpha production from normal human adherent monocytes incubated with patients' plasma obtained before and after the resin, both with or without incubation with an anti-interleukin-10 monoclonal antibody. RESULTS: Mean arterial pressure increased after 10 hr by 11.8 mm Hg with treatment A and by 5.5 mm Hg with treatment B (p =.001). There was an average decrease of norepinephrine requirement of 0.08 microg/kg/min with treatment A and 0.0049 microg/kg/min with treatment B (p =.003). All patients but one survived. Spontaneous and lipopolysaccharide-induced TNF-alpha production from patients' whole blood increased over time with treatment A. This increase was more marked in blood drawn after the device (plasmafiltrate-sorbent plus hemodialyzer) (p =.009). Preresin plasma suppressed lipopolysaccharide-stimulated production of TNF-alpha by 1 x 10(6)cultured adherent monocytes from healthy donors. This suppressive effect was significantly reduced after passage of plasma through the resin (p =.019) and after incubation with anti-interleukin-10 monoclonal antibodies (p =.028). CONCLUSIONS: In patients with septic shock, coupled plasmafiltration-adsorption combined with hemodialysis was associated with improved hemodynamics compared with continuous venovenous hemodiafiltration. This result might be related to its ability to restore leukocyte responsiveness to lipopolysaccharide. These findings suggest a potential role for blood purification in the treatment of septic shock.

APACHE↗

Physiologic endpoints (efficacy) for acute renal failure studies.

Acute renal failure research has been hampered by the lack of useful physiologic surrogate endpoints. Acute renal failure prevention and therapy studies using variables such as urine output and serum and urine chemistries have not yielded interventions proven to decrease the morbidity and mortality associated with acute renal dysfunction. Of those interventions that have been successful in smaller, phase II-level efficacy studies, none subsequently decreased the incidence of clinical (effectiveness) endpoints such as dialysis requirement or mortality in larger phase III trials. Suitable physiologic endpoints are needed to test the efficacy of new proposed therapies for the prevention and management of acute renal failure. Candidate endpoints for efficacy studies in acute renal failure prevention and management include glomerular filtration rate markers, renal blood flow, urine markers, and urine output. Possible endpoints for efficacy studies of renal replacement therapy in acute renal failure include serum markers of renal function and a variety of nonrenal markers. In this article, we present an approach to the choice of physiologic endpoints to determine the efficacy of interventions in acute renal failure.

Acute Kidney Injury↗

C-reactive protein and interleukin-6 levels are related to renal function in predialytic chronic renal failure.

BACKGROUND: Several studies have provided convincing evidence that in apparently healthy subjects elevated serum levels of plasma C-reactive protein (CRP) are associated with an increased risk of experiencing myocardial infarction and sudden cardiac death. It has been claimed that, in dialytic patients, the hepatic synthesis of this 'acute phase response' plasma protein is primarily induced by the macrophage-derived interleukin 6 (IL-6). Little information is available, however, regarding CRP and IL-6 plasma levels in pre-dialytic renal failure. METHODS: Plasma CRP by a modification of the laser nephelometry technique, IL-6 and serum albumin were determined in 103 chronic pre-dialytic patients (mean age 50 +/- 6.3 years; creatinine clearance (Cr.cl.) 36.3 +/- 23.1 ml/min). RESULTS: CRP was >5 mg/l (normal upper range) in 42% of the global population. CRP and IL-6 were significantly related (r = 0.35, p < 0.0004). CRP and IL-6 were related to renal function (CRP vs. Cr.cl., r = -0.56, p < 0.0001; IL-6 vs. Cr.cl., r = -0.55, p < 0.0001, Spearman correlation coefficient). When patients were divided in tertiles according to renal function, CRP median value resulted 7.9 mg/l (interquartile interval: 5-12) in the first tertile (Cr.cl. <18.5 ml/min), 4.0 mg/l (3-6) in the second tertile (Cr.cl. 18.5-45 ml/min) and 3.2 mg/l (2.7-4.0) in the last tertile (Cr.cl. >45 ml/min) (p < 0.0001). A negative correlation between CRP and S-albumin was also found (r = -0.52, p < 0.0001, Spearman correlation coefficient). CONCLUSIONS: IL-6 and CRP were increased and were inversely related to creatinine clearance in our population of 103 chronic predialytic patients. The possibility of a decreased renal clearance of CRP and/or cytokines as a cause of an activated acute-phase response is discussed. A negative correlation between CRP and S-albumin was found confirming the link between chronic inflammation and malnutrition in chronic renal patients.

Adult↗

Longitudinal study of apoptosis in chronic uremic patients.

Uremia is associated with a state of immune dysfunction, increasing infection and malignancy rates. Dysregulation of homeostasis may be directly related to abnormal apoptosis regulation, a process which is crucial for the maintenance of the biologic system. Abnormal apoptosis rates (ARs) have been reported in the literature. We performed a longitudinal study over a 10-week period in three groups of uremic subjects-hemodialysis (HD), peritoneal dialysis (PD), and predialysis chronic renal failure (CRF). Our results showed that ARs were consistent over the observed period. Monocytes extracted from HD and CRF subjects had higher ARs compared to PD and controls (HD: 26.06 +/- 8.82; CRF: 26.96 +/- 12.81; PD: 14.77 +/- 5.87; C: 11.42 +/- 4.60) when placed in culture medium. The plasma of HD and CRF subjects when incubated with U937 cells had a stronger apoptogenic potential compared with PD and controls (HD: 26.08 +/- 11.39; CRF: 24.87 +/- 9.07; PD: 12.13 +/- 4.51; C: 11.69 +/- 4.02). Inflammatory markers (C-reactive protein [CRP], procalcitonin) and cytokines (interleukin [IL]-1beta, IL-2, IL-10) had a generally poor correlation except for tumor necrosis factor (TNF)-alpha (p < 0.001). The phagocytic ability of U937 cells when incubated with the various plasma demonstrated impaired response in the HD and CRF subjects (HD: 27.56 +/- 6.67; CRF: 30.24 +/- 9.08; PD: 36.55 +/- 9.80; C: 40.04 +/- 6.98). These results suggest continuous renal purification, such as in continuous ambulatory peritoneal dialysis (CAPD), may have advantages over intermittent therapies in regulating apoptosis and maintaining biologic function and homeostasis.

Adult↗

Uremic toxins: a new focus on an old subject.

The uremic syndrome is characterized by an accumulation of uremic toxins due to inadequate kidney function. The European Uremic Toxin (EUTox) Work Group has listed 90 compounds considered to be uremic toxins. Sixty-eight have a molecular weight less than 500 Da, 12 exceed 12,000 Da, and 10 have a molecular weight between 500 and 12,000 Da. Twenty-five solutes (28%) are protein bound. The kinetics of urea removal is not representative of other molecules such as protein-bound solutes or the middle molecules, making Kt/V misleading. Clearances of urea, even in well-dialyzed patients, amount to only one-sixth of physiological clearance. In contrast to native kidney function, the removal of uremic toxins in dialysis is achieved by a one-step membrane-based process and is intermittent. The resulting sawtooth plasma concentrations of uremic toxins contrast with the continuous function of native kidneys, which provides constant solute clearances and mass removal rates. Our increasing knowledge of uremic toxins will help guide future treatment strategies to remove them.

Albumins↗