Aluminum exposure in chronic renal failure in iberoamerica at the end of the 1990s: overview and perspectives.

Epidemic aluminum neurotoxicity has virtually disappeared in the dialysis population; however, sporadic toxic effects caused by contamination of water with aluminum are still reported. In this review, the current situation in Iberoamerica is analyzed. Exposure to aluminum through dialysate shows considerable geographical differences even within the same country, including seasonal variability. Sometimes the tap water showed very high aluminum content that does not permit the water treatment system to efficiently remove all the aluminum, forcing the use of water treatment systems with a double reverse-osmosis filter on line. The use of adequate water treatment systems and a correct control policy has improved the quality of the dialysate, minimizing the aluminum exposure. However, an additional problem in Iberoamerica is the difficulty to obtain aluminum-free concentrates for the preparation of the final dialysis solution. Aluminum still seems to be implicated in a great percentage of symptomatic low-bone remodeling lesions in South America compared with Europe, demonstrating that exposure to aluminum through dialysate is still a cause of concern in some areas of the world.

Ultrafiltrable aluminium after very low doses of desferrioxamine.

BACKGROUND: The recommended dose of desferrioxamine for the treatment of aluminium intoxication is 5 mg/kg/week. However, there are no data about the efficiency of lower doses. The objective of this study was to investigate the capacity of very low doses of desferrioxamine in the generation of ultrafiltrable aluminium. METHODS: Five patients undergoing haemodialysis with a similar biochemical profile and serum aluminium levels >40 microg/l were studied. The three different doses of desferrioxamine used (0.5, 2.5 and 5.0 mg/kg) were administered randomly to each patient at 1 week intervals. Total and ultrafiltrable serum aluminium was measured before and 44 h after the administration of desferrioxamine. RESULTS: All doses of desferrioxamine significantly increased the total serum aluminium; no differences were found between 2.5 and 5.0 mg/kg. The total serum aluminium levels doubled with the 2.5 and 5.0 mg/kg doses, while the increase with 0.5 mg/kg was lower (32.6%, P<0.05). Ultrafiltrable aluminium increased with the three doses; from 7.1+/-2.8, 3.9+/-0.6 and 7.5+/-4.1 to 25.7+/-7.3, 44.3+/-10.1 and 59.1+/-19.8 microg/l, respectively (P<0.05). The efficiency of each dose was calculated using the ratio between the increase in ultrafiltrable aluminium and the dose of desferrioxamine administered. The efficiency ranged from 10.3+/-3.9 for the higher dose (5 mg/kg) to 37.2+/-10.3 for the lower dose (0.5 mg/kg). CONCLUSIONS: Our results suggest that very low-dose desferrioxamine (>5 mg/kg) increases the ultrafiltrable (potentially dialysable) aluminium.

Aluminium removal with the double chamber technique: paired filtration-dialysis (PFD).

Several dialysis techniques have been used to improve aluminium removal. So far there are no data available using paired filtration-dialysis (PFD). In this study, we evaluated the aluminium removed by PFD in two phases. Bovine plasma with known concentrations of aluminium and desferrioxamine was used in both experiments. In phase I, the aluminium removal was investigated using the PFD system (single pass) in its usual configuration, modifying the order of the convective and diffusive processes, dialysis with high permeability membranes and dialysis with low permeability membranes. During the second phase, the experiment lasted longer using recirculation, and the PFD was compared with conventional dialysis using high permeability membranes. Changes in the PFD configuration did not alter the aluminium removal; the efficiency of PFD for aluminium removal was very close to that of dialysis with high permeability membranes and much greater than with low permeability membranes. The aluminium is removed mainly in the first part of the dialysis. Aluminium mobilization using the double chamber technique (PFD) was efficient and might be of value for those patients with aluminium overload who needs high depurative techniques and are unable to tolerate high-flux techniques.

Effect of desferrioxamine and deferiprone (L1) on the proliferation of MG-63 bone cells and on phosphatase alkaline activity.

In the present work, we studied: (i) the effect of different doses of desferrioxamine and deferiprone on the proliferation of osteoblasts and the possible role of iron in this; and (ii) the effect of both chelators on the metabolic activity of these cells, using the quantification of alkaline phosphatase as an enzymatic marker of cellular activity or differentiation. Cellular proliferation was investigated at different concentrations of deferiprone and desferrioxamine, and the effect of the addition of iron citrate on this proliferation was measured. The production of alkaline phosphatase after incubation with deferiprone (150 and 300 microM) and desferrioxamine (20 and 100 microM) was also studied. Cellular proliferation was completely inhibited with 100 microM of desferrioxamine and 300 microM of deferiprone. In both cases, this effect was corrected by means of co-incubation with iron citrate. In the second phase, using the same dose that inhibited the proliferation, it was observed that after 24 h, both chelators slightly decreased alkaline phosphatase activity, while at 48 and 96 h they increased alkaline phosphatase activity. These results demonstrate that both desferrioxamine and deferiprone inhibit the proliferation of the osteoblast-like cell line MG-63; the effect seems to be related to the chelation of some fraction of available iron. In spite of the effect on bone cell proliferation, the chelators do not impair cellular activity.

Prevention of aluminium exposure through dialysis fluids. Analysis of changes in the last 8 years.

Despite extensive measures to control aluminium exposure, chronic and acute episodes of aluminium intoxication still occur. The objective of this study was to analyse the changes in the aluminium content of dialysis fluid and the effect on serum aluminium in different dialysis centres in Spain in the last 8 years. For this purpose, the aluminium content in dialysis fluid and serum samples (N=5609) from 17 dialysis centres was analysed for >8 years (from the last quarter of 1988 to 1996). In that period of time, the percentage of dialysis fluid samples with acceptable concentrations of aluminium (<2 microg/l) increased from 0% in 1988 to 80% in 1996. The percentage of dialysis fluid samples with high aluminium levels (>6 microg/l) ranged between 37.5% in 1988 and 2.3% in 1996. The improvement in the quality of the dialysis fluid resulted in lower values of serum aluminium. The percentage of serum samples with low aluminium (<20 microg/l) increased from 16.5% in 1988 to 54.2% in 1966. The mean serum aluminium correlated with the mean dialysis fluid aluminium (r=0.55, P<0.001). A higher correlation was found when the aluminium in dialysis fluid ranged between 4 and 10 microg/l (r=0.802, P<0.001), and no correlation was found when the aluminium in dialysis fluid was <4 microg/l. Even taking into account that the dialysis fluid is not the only source of aluminium for dialysis patients, our study clearly demonstrated a close relationship with the serum aluminium content. Therefore, we must emphasize the necessity for controlling the aluminium content in dialysis fluid more often than is done at present.

Time course and functional correlates of post-transplant aluminium elimination.

Urinary excretion of aluminium after a successful transplant can reverse pre-transplant aluminium intoxication. We have evaluated the time course of urinary aluminium excretion and its correlation with several parameters of renal function and mineral metabolism in 49 patients (33 men and 16 women) with a wide range of pre-transplant serum aluminium concentrations, performing sequential determinations at pre-transplant time and at 7, 30, 60, and 90 post-transplant days. Mean serum aluminium at pre-transplant was 54.5+/-46.8 microg/l decreasing progressively to 28.7+/-24.4 microg/l at 90 days (P<0.0002), paralleling the decrease in serum creatinine. Urinary aluminium decreased from 63.0+/-77.9 to 52.4+/-55.9 microg/l at 90 days (P<0.0001). The maximum urinary aluminium/creatinine was 1.8+/-2.7 at 7 days and was associated with the greatest fractional excretion of sodium (4.7+/-5.1%), and the lowest tubular reabsorption of phosphate (55.7+/-25.1%). The fractional excretion of aluminium was also greatest at day 7 (1.1+/-0.9%) when serum creatinine was still elevated (3.6+/-2.3 mg/dl). At each period of time after transplantation fractional excretion of aluminium was similar in all patients despite disparate serum aluminium concentrations. Fractional excretion of aluminium was highest in those patients who developed post-Tx acute tubular necrosis (0.7+/-0.5 vs 1.5+/-1.0%, P=0.008). We found a direct positive correlation (r=0.43; P<0.002) between urinary aluminium and urinary phosphate. Basal levels and sequential changes in serum PTH, calcium, and phosphate did not correlated with fractional excretion of aluminium. These findings suggest: (i) urinary aluminium remains elevated during prolonged periods after transplant and is probably a marker of pre-transplant tissue aluminium accumulation; (ii) post-transplant fractional excretion of aluminium seems to correlated positively with other evidences of renal tubular dysfunction. Early post-transplant tubular malfunction could significantly enhance urinary aluminium elimination.

Staining of bone aluminium: comparison between aluminon and solochrome azurine and their correlation with bone aluminium content.

The aim of this study was to compare the sensitivity and specificity of the two histochemical stains most commonly used as indirect markers of the aluminium bone content. The clinical study was made in 28 biopsies from patients undergoing haemodialysis and the experimental study in 17 tibias from Wistar rats aluminium overloaded and with different deposits of iron. All samples were stained with aluminon, solochrome azurine and Perls and aluminium bone content was also measured. When the positive cases with Perls were excluded in the clinical study (without iron interference), the trabecular surface stained with solochrome azurine correlated with the aluminium bone content (r = 0.71, P < 0.001). With aluminon, on the other hand, no correlation was found. Solochrome azurine was always positive with aluminium contents greater than 8 micrograms/g. Aluminon was positive over 17 micrograms/g. In the experimental study, the iron concentration, in addition to other parameters, was also measured. As in the clinical study, the trabecular surface stained with solochrome azurine correlated with the aluminium content. If the positive Perls cases were excluded, the trabecular surface stained with solochrome azurine doubled the trabecular surface stained with aluminon (P < 0.001). No intratrabecular aluminon staining was observed while the intratrabecular solochrome staining correlated with the aluminium content (P < 0.001). Solochrome azurine was more sensitive than the aluminon and its lack of specificity can be easily corrected by employing Perls staining to exclude the iron interference.