Vitamin E-coated filter decreases levels of free 4-hydroxyl-2-nonenal during haemodialysis sessions.

Uraemic subjects undergoing chronic haemodialysis show increased oxidative stress. The use of non-biocompatible filters and reduced antioxidative defences are important sources of reactive oxygen species (ROS) release. The highly oxidative environment accelerates the onset and progression of tissue damage and atherosclerotic cardiovascular disease. The aldehyde 4-hydroxyl-2-nonenal (HNE) is probably the best marker of oxidative stress. In this study, the concentration of plasma HNE was evaluated in eight uremic subjects during two sessions of haemodialysis: the first using a standard biocompatible filter and the second using a filter coated with vitamin E. Baseline plasma levels of HNE were elevated, and dropped during haemodialysis. At the end of the session, however, low levels were maintained only when the vitamin E-modified filter was used. By contrast, a marked increase in HNE was recorded at the end of the session in all subjects who underwent haemodialysis with the conventional filter. This study provides evidence that the vitamin E-coated filter plays a role in counteracting oxidative stress. The chronic use of vitamin E-modified filters in haemodialysed subjects might help to counterbalance oxidative attack and, consequently, contribute to preventing cardiovascular disease.

Kidney protein dynamics and ammoniagenesis in humans with chronic metabolic acidosis.

To evaluate the effects of chronic metabolic acidosis on protein dynamics and amino acid oxidation in the human kidney, a combination of organ isotopic ((14)C-leucine) and mass-balance techniques in 11 subjects with normal renal function undergoing venous catheterizations was used. Five of 11 studies were performed in the presence of metabolic acidosis. In subjects with normal acid-base balance, kidney protein degradation was 35% to 130% higher than protein synthesis, so net protein leucine balance was markedly negative. In acidemic subjects, kidney protein degradation was no different from protein synthesis and was significantly lower (P < 0.05) than in controls. Kidney leucine oxidation was similar in both groups. Urinary ammonia excretion and total ammonia production were 186% and 110% higher, respectively, and more of the ammonia that was produced was shifted into urine (82% versus 65% in acidemic subjects versus controls). In all studies, protein degradation and net protein balance across the kidney were inversely related to urinary ammonia excretion and to the partition of ammonia into urine, but not to total ammonia production, arterial pH, [HCO(-)(3)], urinary flow, the uptake of glutamine by the kidney, or the ammonia released into the renal veins. The data show that response of the human kidney to metabolic acidosis includes both changes in amino acid uptake and suppression of protein degradation. The latter effect, which is likely induced by the increase in ammonia excretion and partition into the urine, is potentially responsible for kidney hypertrophy.

Role of blood cells in leucine kinetics across the human kidney.

To evaluate the role of blood cells in interorgan amino acid transport and in the estimates of regional protein turnover, we studied the effects of plasma vs. whole blood sampling on regional leucine kinetics in postabsorptive humans. Studies were carried out by combining the arteriovenous difference technique with the measurement of [14C]- and [15N]leucine isotope exchange across the human kidney, the splanchnic area, and the leg. In the kidney, whole blood-derived rates of leucine-carbon appearance, disappearance, and net balance (NB) were greater (by 3-15 times; P < 0.035) than those calculated in plasma. In addition, the net leucine-carbon (i.e., protein) balance across the kidney was negative in whole blood (-5.6 +/- 1.3 micromol/min x 1.73 m2, P < 0.01 vs. 0) but neutral in plasma [-0.24 +/- 1.33, P = not significant from 0; P < 0.01 vs. whole blood]. A net leucine transport out of renal cells was shown in blood but not in plasma. In contrast, rates of leucine-carbon appearance, disappearance, NB, and net transport, in both the splanchnic area and the leg, were similar in whole blood and plasma. These data suggest that blood cells play a key role in leucine transport out of the kidney and, consequently, in the leucine-derived estimates of renal protein degradation and NB, which is at variance with what is observed across the splanchnic organs or the leg. These data also emphasize the need for complete whole blood arteriovenous measurements to accurately estimate protein turnover across the kidney.