An overall improvement in the treatment tolerance was observed with BVT, particularly intradialytic cardiovascular stability. Patients with the highest incidence of IDH during conventional HD and free from chronic pre-dialysis hypotension seem to respond better. Inter-dialysis symptoms also seem to improve with control of BV.

Patients undergoing long-term hemodialysis (HD) exhibit increased levels of oxidative stress, likely contributing to the increased rate of cardiovascular disease. The present study represents a critical evaluation of some of the most widely used oxidative indicators, as applied to the monitoring of hemodialysis-associated oxidative stress. Total plasma antioxidant capacity was determined by two independent procedures, the total antioxidant status (TAS) and the ferric reducing ability of plasma (FRAP) methods. Plasma lipid peroxidation was assessed by determining the peroxidation products malonaldehyde and 4-hydroxynonenal (MDA-4HNE) as well as lipid hydroperoxides ("Fox-2" and "d-ROMs" methods). Total plasma thiols and plasma alpha-tocopherol were also determined. MDA-4HNE levels were higher in HD patients and decreased following HD, possibly due to passive diffusion across dialysis filters. d-ROMs were also higher in HD patients but exhibited a further increase following the dialysis procedure. Serum alpha-tocopherol did not show any significant differences. Plasma thiols were lower in HD patients and were restored following HD. Plasma total antioxidant capacity determined with either method was unexpectedly higher in HD patients compared to controls, and decreased following HD. These data indicate that, of the biomarkers studied, d-ROMs level is the one more accurately reflecting the oxidative alterations taking place in HD patients, while determination of MDA-4HNE fails to detect oxidation occurring during the HD sessions. In addition, our findings point out that the determination of total antioxidant capacity in HD patients is severely affected by the concomitant fluctuations in plasma urate levels and therefore needs careful interpretation.

No abstract

To verify whether or not an increased secretion of ADH may cause the water retention commonly observed in nephrotic syndrome, 16 nephrotic patients and 13 normal control subjects were studied in basal conditions and following a water load or an iso-osmotic blood volume expansion by 20% albumin infusion. In the basal condition there were no differences in plasma ADH, urine output, urinary osmolality (UOsm), and plasma renin activity between nephrotic patients and control subjects; POsm, PNa+, UNaV, and blood volume (BV) instead, were significantly lower in nephrotic patients than in control subjects. Following the water load control subjects reached a minimal UOsm of 82 +/- 12 mOsm/kg at 60 min and excreted completely the ingested water in 150 min; nephrotic patients reached a minimal UOsm of 160 +/- 111 mOsm/kg at 120 min, and the water was eliminated completely in 240 min. Plasma ADH decreased significantly in the first hour following water load only in control subjects. A significant direct correlation was observed between plasma ADH and POsm in control subjects (ADH = -85 + 0.30 POsm, P less than 0.001) but not in nephrotic patients. Plasma ADH was inversely correlated with BV in nephrotic patients (ADH = 15.47 -0.17 BV, P less than 0.001) but not in normal control subjects. In nephrotic patients with reduced BV the expansion of BV with 20% albumin was effective in reducing the plasma levels of ADH and promoting a water diuresis. Our results demonstrate a sustained volume mediated secretion of ADH in the nephrotic syndrome, which is responsible for the impairment in water excretion.

Background/Aim: Oxidative damage has been suggested to play a key role in accelerated atherosclerosis and to be involved in cardiovascular disease (CVD) of dialyzed patients who are at risk of increased oxidative stress. The purpose of the present study was to examine the relationship between the severity of CVD and some markers of oxidative stress and antioxidant activity in our hemodialyzed (HD) and peritoneal dialysis (PD) patients. Methods: Plasma reactive oxygen metabolites, malondialdehyde and 4-hydroxynonenal (MDA-4HNE), thiols, α-tocopherol, and total antioxidant status (TAS) were measured in 55 HD and in 16 PD patients. CVD was considered as the result of variably combined cardiac, cerebral, and vascular pathologies which were scored and grouped in a single CVD index and analyzed with respect to the markers of the oxidative status. 16 normal subjects served as controls. Results: All patients showed evidence of increased oxidative stress which was more severe in HD than in PD patients and which was exacerbated by HD. When cardiac, cerebral, and vascular diseases were analyzed separately, plasma MDA-4HNE and TAS were significantly higher in more severely affected HD patients, but not in PD patients. In HD patients the CVD index was directly correlated with both MDA-4HNE and TAS (r = 0.42, p < 0.01; r = 0.39, p < 0.01) and inversely correlated with α-tocopherol (r = –0.32, p < 0.05). MDA-4HNE and TAS were directly correlated in HD patients and inversely correlated in control subjects. Conclusions: Our data show that, in spite of increased antioxidant defense, there is a relationship between the degree of lipid peroxidation and the severity of CVD in HD patients. Moreover, these data underscore the utility of MDA-4HNE, α-tocopherol, and TAS in the evaluation of cardiovascular disease.

To verify whether angiotensin II (ANG II) stimulates ADH release in humans and to evaluate whether endogenous prostaglandins influence the resulting renal effect of ADH, nonpressor and low pressor doses of ANG II were infused in nine normal volunteers under normal conditions (control study) and after prostaglandin synthesis inhibition with aspirin (ASA study). During ANG II infusion plasma ADH increased in both conditions. Plasma PGE2, urinary PGE2, and urinary 6-keto-PGF1 alpha increased only in the control study, whereas they were undetectable in the plasma and significantly reduced in the urine in the ASA study. ANG II caused a significant fall of glomerular filtration rate, renal plasma flow (with an increase in filtration fraction), fractional sodium excretion, and urine output in both studies. Despite the reduced urine output, urine osmolality decreased significantly in the control study, whereas it increased after aspirin administration. These results suggest that intravenous ANG II stimulates ADH release in humans but that the renal effects of the resulting increase in plasma ADH are different depending on the presence or absence of endogenous prostaglandins.

Renin-angiotensin-aldosterone system, plasma atrial natriuretic peptide (PANP), and blood volume (BV) have been investigated in 20 nephrotic patients with normal renal function and with (group 1; n = 12) or without (group 2; n = 8) sodium retention. Patients of group 1 had a plasma albumin (PALB) concentration < 1.7 g/dl, low BV and PANP levels, a reduced fractional excretion of lithium (FELi), and high plasma angiotensin II levels. Patients of group 2 had PALB > 1.7 g/dl, and the other parameters were normal. The spontaneous intake of dietary sodium was lower in group 1 than in group 2. In all patients the BV was directly correlated with PALB, and the plasma renin activity (PRA) was inversely correlated with both BV and PALB. A nonlinear inverse relationship was present between plasma aldosterone (PALD) levels and fractional excretion of sodium (FENa). The acute expansion of the BV in patients of group 1 normalized PRA, PALD, PAII, FENa, and FELi and increased PANP. The administration of spironolactone to the patients of both groups had variable effects on FENa, did not modify PRA and PALD, and reduced body weight, PANP, and FELi, thus suggesting that the reduction of BV induced by the drug increased the proximal reabsorption of sodium. Three additional patients who had sodium retention, PALB of 2.3-2.4 g/dl, normal PRA and PALD, elevated urinary excretion of aldosterone, and a slightly low PANP showed a spontaneous normalization of urinary aldosterone and PANP associated with natriuresis and weight loss, but thereafter urinary aldosterone increased, PANP decreased, and the sodium retention began again. Our data suggest that in nephrotic patients with severe hypoalbuminemia, contraction of BV plays a major role in promoting the sodium retention through the activation of compensatory hormonal mechanisms. On the other hand, when PALB is not severely reduced, the patients have normal BV, but they are very sensitive to small changes of BV which are better evidenced by modifications of the urinary excretion of aldosterone and PANP rather than by the profiles of PRA and PALD.

Using captopril (C), an angiotensin (ANG) I converting-enzyme inhibitor, to increase endogenous prostaglandins (PGs) and to decrease endogenous ANG II synthesis, we studied the relationship between endogenous ANG II, PG, and antidiuretic hormone (ADH) release in seven normal volunteers before (control study) and after inhibition of PG synthesis by a single dose of aspirin (ASA study). In the control study, following the administration of 100 mg of C, there was a significant increase of plasma PGE2, plasma-renin activity (PRA), and urinary PGE2 and 6-keto-PGF1 alpha and a decrease of plasma ADH. Glomerular filtration rate (GFR) and renal plasma flow (RPF) were unaffected by C; urine output, fractional sodium excretion (FENa), and osmolal clearance (Cosmol) increased; and urinary osmolality (Uosmol) decreased significantly after C. In the ASA study PG were undetectable in plasma and significantly reduced in urine 1 h after aspirin and did not increase when C was added. Plasma ADH decreased and PRA increased, as in the control study, after C, whereas GFR, RPF, urine output, FENa, Cosmol, and Uosmol were unchanged. These results suggest that the effect of C on ADH release may be mediated, to a large extent, by a fall in endogenous circulating ANG II, since ADH decreased in the presence of both high or undetectable levels of PGE2. The results also suggest that the increase in PGE2 induced by C may precipitate the diuretic and natriuretic effects of acute C administration.