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Plasma B-type natriuretic peptide (BNP) concentration was evaluated in end-stage renal disease patients to verify if measurements before or after the session could furnish different information. BNP levels in plasma from 52 hemodialysis (HD) patients were measured both before and after the first session of the week. Echocardiographic studies were also performed and patients were followed over a period of 28 months. BNP removal from plasma was influenced by equilibrated Kt/V and patient characteristics. Initial plasma BNP concentration was correlated both with cardiac systolic function (LVEF) and mortality rate, independent of blood sample timing (before or after HD). A relative risk of death of 2.67 was found for plasma BNP levels above 335 pg/mL or 232 pg/mL, before and after HD, respectively. Higher BNP levels were observed in patients with higher burden of comorbidity, as measured by the Charlson Comorbidity Index; however, statistical significance was obtained only for BNP measured before HD. In conclusion, measurement of plasma BNP could give a valuable risk stratification of HD patients while cutting costs, by confining echocardiographic studies only to cases with BNP levels above the established cutoff values.

Hyperhomocysteinemia is an independent risk factor for cardiovascular morbidity and mortality in end-stage renal disease (ESRD) with an increased relative risk (RR) of 1% per micromol/L in total homocysteine concentration. In ESRD patients who undergo hemodialysis (HD), the antioxidant system is largely inadequate in correcting the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of several cellulosic (CMs) and noncellulosic of synthetic membranes (NCMs) upon hyperhomocysteinemia and the oxidative stress, we measured plasma (P) homocysteine (t-HCY), plasma lipid peroxidation (LPO), and erythrocyte (E) concentration of several antioxidant enzymes in 20 normal subjects, in 35 HD patients treated with CMs, and in 29 patients treated with NCMs. Before, during, and after the first session of the week (at times 0', 120', end, 30' after HD end), blood samples were drawn. Plasma (P) homocysteine (t-HCY), cysteine (CYS), malondialdehyde (MDA), erythrocyte (E)-glutathione (GSH), glucose-6-phosphodehydrogenase (G6PD), glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), and superoxide-dismutase (SOD) were determined. The dialytic procedure significantly decreased the three plasma parameters, but none normalized (as a mean). The E-enzymes scavenging ROS (lower than normal before session) increased throughout the session, but the normal range of activity was never reached. Different membranes have shown different effects. When these effects on P and E spaces were pooled, we were able to classify the membranes as follows. In a general sense, cellulosic membranes are less effective than synthetic membranes both on lipoperoxides (LPO) and antioxidant activity (AOA). Among synthetic membranes, PMMA is the best membrane both for plasma values and lesser enzymatic derangement during the session. A practical system for classifying the anti-atherosclerotic action and antioxidant activity of dialytic membranes is proposed.

Today's patient population is increasingly older. Patients with chronic renal failure therefore start extracorporeal substitutive treatment having congestive heart failure, chronic liver disease, diabetes and so forth. In these patients, however, long-term haemodialytic treatment may add further aggravation on their pre-existing pathological conditions. Oxidative stress and alterations in lipid metabolism are caused by haemodialysis mainly due to (1) bioincompatibility type of reactions such as production of reactive oxygen species by inflammatory cells due to complement-mediated or -independent pathways, and (2) the imbalance between oxidants and antioxidants due to the diffusive loss of hydrophilic vitamins such as ascorbic acid. The events related to the oxidant stress may sustain a state of chronic inflammation. Recent advances suggest that atherosclerosis and proliferation of the smooth muscle are initiated and sustained by inflammatory mechanisms. Therefore, attempts to counterbalance the prooxidant effect of haemodialysis and to reduce the chronic inflammatory state will be presented.

In patients with chronic renal failure who undergo hemodialysis (HD), the antioxidant system is inadequate to correct the imbalance between the generation and scavenging of reactive oxygen species. To clarify the role of six different membranes on oxidative stress, the authors measured plasma lipid peroxidation and erythrocyte (E) concentrations of several antioxidant enzymes in 30 HD patients: 20 on bicarbonate HD, 4 on paired filtration dialysis, 3 on acetate free biofiltration, and 3 on hemodiafiltration. Before, during, and after the first session of the week (at times 0, 30, 60, and 120 min, end, and 30 min after end of HD), several blood samples were drawn. Plasma (P) homocysteine (HCY), cysteine (CYS), malondialdehyde (MDA), E-glutathione (GSH), glucose-6-phosphodehydrogenase, glutathione reductase (GR), glutathione peroxidase (GP), catalase (CAT), and superoxide dismutase (SOD) were determined. All six membranes (Hemophan [HEMO]; cellulose diacetate [DIAC]; acrylonitrile-69 [AN69]; polymethylmethacrylate [PMMA]; cuprammonium rayon [CURAY]; polysulfone plus hemophan [PS + HEMO]) induced a significant decrease in plasma lipid peroxidation (p < 0.001) and an increase in E-GSH, GR, GR + flavinadenine dinucleotide, GP, and SOD (p < 0.001). Some membranes, however, showed some peculiar effects on reactive oxygen species: HEMO is better than DIAC, as far as P-MDA and P-HCY are concerned; PMMA induces higher changes in E-GR and P-CYS than does HEMO; and patients chronically using PMMA and PS + HEMO membranes show the lowest P-HCY levels both before and after dialytic sessions. Based on these changes, implications as to the effects on vascular disorders could be derived.

Patients with end-stage renal disease (ESRD) who undergo hemodialysis manifest pronounced oxidative stress (OS), for the antioxidant system is inadequate to correct the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of two different membranes on the OS, we measured plasma lipid peroxidation (LPO) and erythrocyte concentration of several antioxidant enzymes on 20 controls and 6 patients on bicarbonate dialysis (BHD). At 7 days intervals, 2 BHD sessions were done on the same 6 hemodialysis patients: the two BHD sessions were similar, except for the membrane used (cuprophan, first study; regenerated cellulose = Bioflux, second study, 7 days later). Before, during, and after each session (0', 30', 60', 120', end, 30' after BHD end), several blood samples were drawn. Lipid peroxidation and erythrocyte glutathione (GSH), superoxide dismutase (SOD), and catalase were spectrophotometrically determined (Bioxytech, France), but for erythrocyte glutathione peroxidase (Gpx) and G-6-PD, Gunzler's and Beutler's methods were used, respectively. Both membranes induce a significant decrease in LPO (p < 0.01) and an increase in erythrocyte SOD (p < 0.05). Bioflux shows some peculiar effects: a significant increase in erythrocyte GSH (p < 0.05) and erythrocyte catalase (p < 0.01) with a gradual increase of erythrocyte SOD and catalase/SOD ratio. Cuprophan, on the contrary, causes a sudden increase in erythrocyte SOD, while erythrocyte catalase decreases. These data support the view that Bioflux induces an OS lower than cuprophan because with the former, increased H2O2 production leads (thanks to catalase and GPx action) to water generation. With cuprophan, instead the reduced SOD/catalase ratio causes a greater H2O2 generation and a lower conversion to water.

The defenses against the production of free radicals and reactive oxygen species (ROS) are to be found in plasma (ascorbate, urate, alpha tocopherol) and in erythrocytes (superoxide dismutase or SOD; catalase or CAT; glutathione peroxidase or GPx). In chronic renal failure, an increased lipid peroxidation and a reduced antioxidant activity seem to be present, but previous reports are conflicting. To clarify the peroxidative status and the defense mechanisms taking place in patients on dialysis, in 30 patients on dialysis (15 men, 15 women) and in 20 control subjects (10 men, 10 women), the following parameters were measured: plasma 4-hydroxinonenal (4-HNE) and erythrocyte reduced glutathione (GSH), SOD, GPx, and glucose-6-phosphate dehydrogenase (G-6-PD). Patients on dialysis, in comparison with control subjects, had 1) increased levels of 4-HNE (p < 0.001); 2) a significant increase in erythrocyte-GSH (p < 0.05); and 3) significant decreases in erythrocyte-SOD (p < 0.001), erythrocyte-G-6-PD (p < 0.005), and the erythrocyte-SOD/GPx ratio (p < 0.001). The dialysis procedure induced a certain reduction in plasma 4-HNE, an increase in erythrocyte-SOD activity, and an important consumption of erythrocyte-GSH, while the erythrocyte-SOD/GPx ratio changed. The current study supports the view that 1) erythrocytes act as small detoxifying packets; 2) in chronic renal failure, the antioxidant system is largely inadequate; and 3) in patients on dialysis, the antioxidant mechanism of erythrocytes in scavenging ROS is effectively exerted during dialysis but remains largely inadequate, as signs of lipid peroxidation persist with time.

The kidney is probably the major site of production of the plasma enzyme glutathione peroxidase (GSHPx-P). For this study, GSHPx-P activity was determined in 40 healthy people, in 34 patients with differing degrees of renal impairment, and in hemodialysis patients from whom blood samples were withdrawn either before or after each session (18 patients) or throughout the dialysis session (27 patients). Hemodialysis patients were treated by means of different techniques (bicarbonate hemodialysis, hemodiafiltration, and acetate free biofiltration), and different membranes (cuprophane, polyacrylonitrite, and polymethylmethacrylate). The following results were obtained: 1) GSHPx-P activity was significantly decreased in renal impairment patients; 2) GSHPx-P activity negatively correlated with serum creatinine values in renal impairment patients (r = -0.55; p < 0.001); and 3) the enzyme activity slightly increased after the session in hemodialysis patients. The following conclusions can be drawn: GSHPx-P activity could be new index of renal function, because it was decreased in patients with renal failure; the decrease in GSHPx-P activity paralleled the severity of renal impairment, and was maximal in hemodialysis patients; GSHPx-P activity was slightly raised at the end of the hemodialysis session, concomitant with other enzyme activities (aspartate transaminase, alanine transaminase, and alkaline phosphatase) and total protein concentration. This seems to be attributable to the process of water loss rather than other hypothetical mechanisms, such as A) enzyme activation by either peroxide generation during blood-membrane contact, or by the removal of a hypothetical inhibitor; and B) de novo synthesis in the residual renal mass or in other sites of production.

In view of multiple interactions of acetate with intermediary metabolism, we studied the effects of the exogenous acetate load during dialysis on glucose and energy metabolism. IV glucose tolerance test (glucose 0.33 g/kg BW) and platelet ATP content were evaluated in 16 patients before and after a single hemodialysis session with acetate 38 mEq/l in the dialysate. IV glucose tolerance was greatly impaired in all patients after hemodialysis (K: 1.08 +/- 0.30 vs predialysis value of 2.05 +/- 0.85, p less than 0.001). Platelet ATP content was unchanged by dialysis (3.74 +/- 1.02 mumol/10(11) PLTs before and 3.55 +/- 0.69 mumol/10(11) PLTs after), however, individual variations in platelet ATP content ranged from +32 to -31% of the initial values. Postdialysis plasma acetate levels ranged from 1.5 to 9.2 mmol/l and were inversely correlated with postdialysis glucose tolerance test (r: -0.61, p less than 0.01) and platelet ATP content variations (r: -0.51, p less than 0.05). Our study demonstrates that glucose utilization is acutely impaired by acetate dialysis and suggests that the reduced glycolytic activity may be due to a negative feed-back mechanism in the presence of exogenous fuel. It also demonstrates a great variability in platelet ATP content following hemodialysis, which probably depends on the different patients' ability to oxidize acetate.