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.

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.

Five nephrotic patients, who did not present sodium retention when on sodium balance, have been studied. All had membranous nephropathy, were normotensive and renal function was normal in 2 and slightly reduced in 3. The following parameters were measured: 24-hour excretion of aldosterone, the response of plasma renin activity (PRA) and of plasma aldosterone to upright posture, postural changes of the fractional excretion of sodium and lithium, and natriuretic response to spironolactone. The resting values of plasma aldosterone were low in all patients, and after stimulation by upright posture they increased hardly to the low-normal limit only in 1 patient. Resting PRA was normal in all patients and increased slightly, after stimulation. The 24-hour urinary excretion of aldosterone was low in 4 patients and borderline in 1. No natriuretic response to spironolactone was observed in any patients. After upright posture the fractional excretions of sodium and lithium decreased significantly and to the same extent in all patients. Four nephrotic patients with fluctuating, spontaneous episodes of sodium retention and of sodium excretion have been studied as controls. These patients had normal values of urinary aldosterone and of resting PRA and aldosterone. After upright posture the changes of PRA and of aldosterone were clearly evident in 2, and exaggerated in the other 2 patients. In these patients, a significant increase of sodium excretion occurred after treatment with spironolactone. These results suggest that a not negligible number of patients with nephrotic syndrome have hyporeninemic hypoaldosteronism. This diagnosis should be taken into account when investigating the role of aldosterone in sodium retention in nephrotic syndrome.

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Torasemide, a new loop diuretic, was administered in 9 hospitalized patients with chronic renal failure to treat both arterial hypertension and peripheral edema. The urine of 5 patients was collected over 12-hour periods to assess the long-lasting diuretic activity of torasemide. Torasemide induced a significant decrease in blood pressure and reversion of peripheral edema in all patients without adverse effects. Torasemide is a high-ceiling loop diuretic, useful in correcting extracellular fluid volume expansion in patients with chronic renal failure.