Plasma Al Levels Research Articles

The association between blood lymphocyte NMDAR, group I mGluRs and cognitive function changes in occupationally aluminum-exposed workers and verification in rats

BackgroundMany studies have shown that occupational aluminum (Al) exposure could affect the cognitive functions of workers and cause mild cognitive impairment (MCI). Glutamate receptors (GluRs) play an important role in learning and memory functions. Methods352 workers in a large Al production enterprise were investigated in this research. MMSE, CDT, DST, VFT, FOM were used to evaluate the cognitive functions of workers. Plasma Al levels as exposure indices were measured by Graphite Furnace Atomic Absorption Method (GFAAS). The expression of GluRs was measured by ELISA. Cognitive function comprehensive scores were obtained through factor analysis. Then a rat model of chronic AlCl3 exposure was established. The detection method of Al levels and protein expression were the same as mentioned-above. ResultsCompared with the Q1 group, the DST, VFT, and comprehensive cognitive function scores of the Q4 group were lower(P < 0.05). For every 1μg/L increase in plasma Al concentration, the risk of cognitive impairment increases 1.051 times (95 %CI:1.031,1.072). Both NMDAR1 and NMDAR2A protein expression level of Q1 group were higher than those of Q2, Q3, Q4 group (all P < 0.05). The mediating effect ratio of NMDAR1 between plasma Al levels and cognitive function comprehensive scores was a1*b1/c=11.30 %, and the mediating effect ratio of NMDAR2A was |a2*b2/c|=21.77 %. Compared with control group, the escape latency of rats in the high Al dose group was longer day by day (P < 0.05). With the increase of Al dose, the relative expression of NMDAR1, NMDAR2A, NMDAR2B, GluR1 and mGluR5 in cerebral cortex and lymphocytes of rats were decreased (P < 0.05). The result of correlation analysis on NMDAR1 protein expression between brain cortex and lymphocyte showed that the correlation coefficient is r = 0.646(P < 0.05). ConclusionTaking together the results from both Al exposed workers and animal, there is a certain correlation between NMDAR1 protein contents of brain cortex and peripheral lymphocytes. We propose that lymphocyte NMDAR1 could be considered as a peripheral potential marker of cognitive impairment for further observation.

The Relationship between Plasma Al Levels and Multi-domain Cognitive Performance among In-service Aluminum-exposed Workers at the SH Aluminum Factory in China: A Cross-sectional Study

BackgroundAluminum (Al) exerts neurotoxic effects following overexposure. We previously reported worse cognitive performance in workers exposed to Al than non-exposed individuals. Cognition involves multiple domains. The effect of Al on multi-domain cognition has been studied for decades, but still remains controversial. ObjectiveTo explore the relationship between plasma Al levels and multi-domain cognitive performance among in-service aluminum-exposed workers at the SH Aluminum Factory in China and identify possible types of early cognitive damage caused by exposure to aluminum. MethodsEight hundred thirty-one in-service aluminum-exposed workers at the SH Aluminum Factory in China were investigated. The plasma Al concentrations were measured using inductively coupled plasma-mass spectrometry (ICP-MS) and served as an internal exposure indicator. The participants were divided into four subgroups based on the quartiles of plasma Al concentrations, namely, the Q1, Q2, Q3, and Q4 subgroups. Cognitive function was assessed using the Mini-mental State Examination (MMSE) and the clock-drawing test (CDT). Multi-domain cognition was evaluated using sub-tests of the MMSE and the CDT. ResultsThe average plasma Al concentration was 15.26 (8.28, 27.02) μg/L. The neurobehavioral tests showed negative correlations between plasma Al levels and total CDT scores and executive/visuospatial cognitive performance, and a positive correlation between plasma Al levels and CDT-position errors (all P<0.05). Additionally, dose-response relationships between higher plasma Al levels and lower total CDT scores, worse executive/visuospatial cognitive performance, and more error rates in the CDT-position were observed (all Ptrend<0.05). However, no significant correlations or trends were observed between plasma Al levels and other cognitive domains (all P>0.05). The results from the multivariate logistic regression model and restricted cubic spline models of dose-response relationships were consistent with the results obtained from the general linear model. All potential confounders, such as age, marital status, education, income, type of work, and smoking and drinking habits, were considered. ConclusionBased on the results, aluminum exposure may exert a substantial effect on impairing executive/visuospatial functions in multi-domain cognition at the early stage, particularly the identification of spatial positions.

Aluminium toxicokinetics after intramuscular, subcutaneous, and intravenous injection of Al citrate solution in rats.

Knowledge of dose linearity, plasma clearance, rate and extent of subcutaneous (SC) and intramuscular (IM) absorption of soluble aluminium (Al) citrate is considered a prerequisite for evaluation of toxicokinetic data obtained from SC or IM administration of Al adjuvants in medicinal products. Therefore, total Al plasma kinetics was investigated after SC, IM, and IV administration of single Al doses (36 and 360µg/kg IM or SC; 30 and 300µg/kg IV) given as citrate solution in rats. Control groups receiving vehicle (saline) were run in parallel to monitor background plasma Al levels over time resulting from dietary intake. Evaluation of Al plasma profiles was done by both non-compartmental analysis of baseline-corrected data and simultaneous model fitting to the raw data using a population kinetics approach. High anddose-independent total plasma clearance (6.6mL/min/kg) was observed after IV administration corresponding to 60-82% of normal rat GFR. This supports the previous assumptions that parenterally administered Al citrate is more rapidly cleared from plasma than other Al species (e.g., chloride or lactate). Furthermore, plasma exposure of Al (Cmax and AUC0-inf) increased dose-proportionally at all administration routes. Fast and complete absorption of Al was observed at each dose level after both SC and IM administration (bioavailability estimates: 88 and 110%). Estimates for the first-order absorption rate constant ka correspond to absorption half-lives of 36min (SC) and ≤ 13min (IM). There was no increase in tissue Al content (whole bone and brain) after 36µg/kg IM compared to control rats.

In vivo evaluation of the effects of hydraulic calcium silicate dental cements on plasma and liver aluminium levels in rats.

Our aim was to test whether the presence of three hydraulic calcium silicate dental cements--MTA Angelus, MTA Fillapex, and Theracal LC--in the dental extraction socket of an in vivo model, would affect the levels of aluminium (Al) in the plasma and liver. Following anesthesia, the right upper incisor of each male Wistar albino rat was extracted and polyethylene tubes filled with MTA Angelus, MTA Fillapex, or Theracal LC were inserted into the depth of the extraction socket and gingival tissue was sutured. The rats were killed 7, 30, or 60 d after the operation. Blood and liver samples were obtained from the rats before they were killed, and the levels of Al were measured by atomic absorption spectrometry. Plasma Al levels were higher in the rats in which the mineral trioxide aggregate (MTA) cements were implanted, especially MTA Angelus and MTA Fillapex, compared with control rats. In liver samples, however, the differences in Al level were not statistically significant. Our results show that Al might have been released into the circulation from the three dental cements tested, especially MTA Angelus and MTA Fillapex. Further research should be carried out on the possible biological effects of Al liberated from dental cements.

Abstract 2838: Intratumoral-regulated expression of IL-12 as a potential immunotherapeutic strategy for the treatment of breast cancer.

Abstract A major obstacle for the development of immunotherapeutics is the ability of tumors to escape the immune system coupled with toxicity associated with systemic administration of cytokines. To overcome these challenges we have developed an adenoviral vector with regulated expression of IL-12, Ad-RTS-mIL-12 (Ad), was administered intratumorally under the control of the RheoSwitch Therapeutic System® (RTS®) expression platform. Previously we have shown that a single intratumoral injection of Ad combined with oral administration of the activator ligand, INXN-1001 (AL), led to significant inhibition of tumor growth and increased survival. Herein, we show that localized delivery of IL-12 is well tolerated and its mechanism of action is through an increase in tumor infiltrating leukocytes concomitant with a reduction in tumor growth. In vitro studies using HT1080 human fibrosarcoma cells transduced with Ad and incubated with AL have shown a concentration-related increase in IL-12 mRNA concomitant with an increase in expression of IL-12 protein. Removal of AL from the media resulted in return of IL-12 expression to baseline within 48 hours. In the 4T1 BALB/c mouse model, oral administration of AL elicited a dose- related increase in plasma AL levels which correlated with increasing tumor levels of AL. The increase in tumoral AL in turn activated the RheoSwitch® portion of the adenoviral vector leading to a dose-related increase in tumor IL-12 production with virtually no increase in systemic IL-12. The maximal tumoral IL-12 protein level of ∼280 pg/mg protein was achieved on Day 4 of AL dosing with a concomitant serum IL-12 level of 0.5 pg/mg protein following a single intratumoral injection of Ad-RTS-mIL-12 (1x1010 vp) on Day 1 combined with once daily oral administration of AL at 150 mg/m2 on Days 1-7. This increase in tumoral IL-12 levels correlated with a dose-related increase in tumor-infiltrating CD4-positive and CD-8 positive lymphocytes in and adjacent to the tumor, coupled with an increase in apoptotic marker caspase 3 in the tumor when compared with vehicle. No increase in IL-12 protein expression in mice treated with Ad or AL alone was observed. Moreover, this therapeutic strategy appears to be well-tolerated as no change in clinical signs or body weight was observed in the treated animals when compared with vehicle alone. These results support our hypothesis that localized delivery of IL-12 is well tolerated and results in an increase in tumor infiltrating leukocytes concomitant with a reduction in tumor growth. These findings suggest the applicability of our immunotherapeutic strategy for the treatment of metastatic breast cancer. Citation Format: John A. Barrett, Lei Sun, Maria Grigoriadis, Christan Fulan-Freguia, Tim Chan, Bill Fogler, Laurent Humeau, Roya Khosravi-Far, Robert A. Morgan, Hagop Youssoufian. Intratumoral-regulated expression of IL-12 as a potential immunotherapeutic strategy for the treatment of breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2838. doi:10.1158/1538-7445.AM2013-2838

The relationship of plasma aluminum to oxidant–antioxidant and inflammation status in asthma patients

Aluminum (Al) is a non-essential mineral which human beings are exposed to on day-to-day life. The purpose of this study was to assess the concentrations of plasma Al and the relationship of those levels with risk factors for asthma. In total, 27 allergic asthmatics and 30 healthy volunteers were enrolled. Plasma Al and selected blood parameters were measured, and a pulmonary function test was performed. Higher Al concentrations were found in the asthmatics than the healthy controls. Increased immunoglobulin E, high-sensitivity C-reactive protein, lipid peroxidation products, and pro-inflammatory cytokines (tumor necrosis factor-α and interleukin [IL]-4) were observed, but IL-10 and overall antioxidant and enzyme activities were lower. Associations between oxidative-antioxidant status and inflammatory markers with plasma Al levels in asthmatics were noted. Al status was also linked to cytokine concentrations and pulmonary function. In conclusion, abnormal Al distribution may further precipitate oxidative stress and inflammation, alter Th1/Th2 lymphocyte balance, and therefore contribute to the development of asthma.

The addition of acetic acid or ethanol to orally taken aluminum salt solution enhanced its availability and then induced toxic effects

Background:Aluminum (Al) intoxication was initially reported in patients undergoing hemodialysis and then was linked to Alzheimer's disease. Man usually is exposed to Al containing antacids, vaccines or foods cooked in Al utensils. The assumption of ingesting sour juices as acetic acid or ethanol may affect favorably the degree of Al absorption is justified when taken in conjunction with the above mentioned appetizers.Materials and methods: Four groups of 10 mature male rats each were used. The drinking water (DW) containing 5mM of Al2(SO4)3 with 1% glacial acetic acid and/or 10% ethanol made available ad-libidum. Weekly body weight and each other day drinking water volume were measured. Brain and plasma analysis at and Ca were determined from blood obtained by cardiac puncture, in addition to automated complete blood count (CBC), after 10 wks of treatments.Results: The results of plasma Al levels indicated that, the addition of acetic acid or ethanol to Al containing drinking water enhanced significantly its absorption and even more when combined relative to control. This enhancement was evident as well in increased Al and Ca deposited in the brain while no change in plasma Ca. The CBC results showed highly significant thombocytopnia for the 1st time, in addition to microcytosis and hypochromia. Evidently, thrombocytopoietin synthesis, and/or action is blocked by Al from acting on the cellularity of bone marrow.Conclusion: The addition of acetic acid and/ or 10% ethanol to Al containing drinking solution enhanced Al absorption when acid is used and an addative effect when both are used. The toxic plasma level caused hypochromia, microcytosis and severe thrombocytopenia in addition to brain atrophy.

Trace Metals' abnormalities in hemodialysis patients: relationship with medications.

A multicenter collaborative study was performed to investigate the prevalence of abnormal blood contents of 6 trace metals, copper (Cu), zinc (Zn), aluminum (Al), lead (Pb), cadmium (Cd), and mercury (Hg), in hemodialysis (HD) patients and to analyze their relationship with the medications, such as CaCO3, Ca acetate, Al containing phosphate-binding agents, 1,25-dihydroxy vitD3, 1-hydroxy vitD3, and erythropoietin (EPO), as well as hematocrit level, by chi-square statistics. From 6 medical centers in Taiwan, we included 456 patients in maintenance HD for more than 4 months for this study, and they had continued the previously mentioned medications for at least 3 months. Blood samples were collected before initiating HD, and atomic absorption spectrophotometry was used to measure plasma levels of Cu, Zn, and Al as well as whole blood levels of Pb, Cd, and Hg. Three hundred seventy-five (78%) of the HD patients had low plasma Zn levels, that is, <800 microg/L, and the mean (+/-SD) concentration was 705.8 (+/-128.23) microg/L in all subjects. One hundred forty-one (31%) of the HD patients had high plasma Al, that is, >50 microg/L, and the mean (+/-SD) was 44.30 (+/-28.28) microg/L in all subjects. Three hundred thirty-three (73%) of the dialysis patients had high Cd levels, that is, >2.5 microg/L, and the mean (+/-SD) was 3.32 (+/-1.49) microg/L in all subjects. The majority of HD patients had normal blood levels of Cu, PB, and Hg. Only 21 (4. 6%), 5 (1.1%), and 3 (0.06%) patients had elevated blood levels of Cu, Pb, and Hg, respectively. Their mean (+/-SD) blood concentration of Cu, Pb, and Hg were 1,049.78 (+/-233.25) microg/L, 7.45 (+/-3.95) microg/dL, and 3.17 (+/-25.56) microg/L, respectively. Three patients had elevated plasma Hg concentrations, that is, 546, 12.6, and 24.0 microg/L, respectively. In the 152 normal healthy age and sex matched control group, the blood levels of Al, Cd, and Pb were all significantly lower than the HD patients. However, the levels of Cu and Zn were higher in the control group. The Hg level was not significantly different in both groups. There was no statistical difference between patients with normal and abnormal blood levels of trace metals in various medications except Al containing phosphate binder. The Al containing phosphate binder users had significantly higher plasma Al levels (54.71 +/- 26.70 versus 41.15 +/- 28.03 microg/L, p < 0.001) and hematocrit levels (29.61 +/- 4.61 versus 27. 81 +/- 3.91, p < 0.0005). There was no statistical correlation between erythropoietin (EPO) dose and hematocrit level in these patients. In conclusion, the blood level of trace metals of these HD patients except Al was not related to their medications. However, caution must be exercised in interpreting this result as dose and duration of medication; efficiency of HD and water treatment may play an important role. Otherwise, environmental factors, diet, and the aging process may contribute to the trace metal burden in uremia. Thus, Zn and Cu are abundant in seafood, and Cd is abundant in contaminated plants such as rice.

Biological levels of Aluminium After Use of Aluminium-containing Bone Cement in Post-Otoneurosurgery

Use aluminium-containing biomaterials in otoneurosurgery for reconstitution of bone in contact with cerebrospinal fluid (CSF) also led to cases of encephalopathy and death. We report aluminium (Al) concentrations in the biological fluids of six French patients following use of Al-containing bone cement in otoneurosurgery. In five patients, the mean plasma Al levels (microgram/L) were: 1.20 +/- 0.05 (case 2), 9.20 +/- 0.10 (case 3), 1.00 +/- 0.05 (case 4), 2.80 +/- 0.05 (case 5) and 2.00 +/- 0.05 (case 6). In case 1, Al concentrations were 176 micrograms/L in the postauricular CSF accumulation, 34 micrograms/L in the pontocerebellar angle and 4 and 6 micrograms/L in the lumbar shunt. As a precautionary measure, in the first three cases the biomaterial was removed soon after the intervention, and no increase in plasma or CSF Al was observed. In the other cases, absence of neurobiological symptoms and normal concentrations of Al in plasma led neurosurgeons not to extract this biomaterial. Al assay thus may be considered to be a complementary and at times a decision-generating factor. Care is needed at all stages from sampling through analysis because Al is ubiquitous and factually high results may be clinically misleading. Herein, such considerations are discussed in conjunction with the neurotoxicity of this metal in man. In addition, the authors call for in-depth preliminary trials of these biomaterials in animals prior to introduction on the market.

Status and future concerns of clinical and environmental aluminum toxicology.

A wide range of toxic effects of aluminum (Al) have been demonstrated in plants and aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical conditions in humans. Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of arable soils in the world. In fresh waters acidified by acid rain, Al toxicity has led to fish extinction. Aluminum is a very potent neurotoxicant. In humans with chronic renal failure on dialysis, Al causes encephalopathy, osteomalacia, and anemia. There are also reports of such effects in certain patient groups without renal failure. Subtle neurocognitive and psychomotor effects and electroencephalograph (EEG) abnormalities have been reported at plasma Al levels as low as 50 micrograms/L. Infants could be particularly susceptible to Al accumulation and toxicity, reduced renal function being one contributory cause. Recent reports clearly show that Al accumulation occurs in the tissues of workers with long-term occupational exposure to Al dusts or fumes, and also indicate that such exposure may cause subtle neurological effects. Increased efforts should be directed toward defining the full range of potentially harmful effects in humans. To this end, multidisciplinary collaborative research efforts are encouraged, involving scientists from many different specialties. Emphasis should be placed on increasing our understanding of the chemistry of Al in biological systems, and on determining the cellular and molecular mechanisms of Al toxicity.

Aluminium deposition in liver and kidney following acute intravenous administration of aluminium chloride or citrate in conscious rats

1. Plasma, urinary, liver and kidney cell aluminium (Al) levels were monitored in the rat, 1h after intravenous administration of 29630 nmol (800 micrograms) Al as either Al chloride or as Al citrate (Al chloride plus excess sodium citrate). Al levels were measured in plasma, urine and liver by atomic absorption spectroscopy (AAS). Liver and kidney Al content was measured at the cellular and subcellular level by electron probe X-ray microanalysis (EPXMA). 2. Urinary excretion of Al was significantly higher (P < 0.01), when Al was given as the citrate than as the chloride. After 1h, plasma Al levels were significantly lower in the Al citrate group than the Al chloride group (59 +/- 3.7 vs 877 +/- 214 nmol ml-1, respectively; P < 0.01). 3. Al concentrations were significantly higher in the livers of rats receiving Al chloride (818 +/- 252 nmol g-1 wet weight; P < 0.05), than in either control or Al citrate groups (122 +/- 41 and 107 +/- 26 nmol g-1 wet weight, respectively). Al concentrations derived from EPXMA measurements were in agreement with AAS values for the three groups, with significantly higher Al concentrations in the Al chloride group (1.7 +/- 0.4 nmol mg-1 dry weight; P < 0.05) than in the control or Al citrate groups, where Al was not detectable. EPXMA analysis showed that Al was distributed in all liver organelles analysed (cytoplasm, mitochondria, nucleus, ER) and was not preferentially taken up by any one organelle in Al chloride treated rats. 4. Significant amounts of Al were found in cytoplasm and mitochondria of proximal tubule cells of rats given Al citrate (0.64 +/- 0.15 and 0.80 +/- 0.11 nmol mg-1 dry weight, respectively), but not in nuclei or lysosomes of these cells. Al levels were not detectable in control kidneys, in proximal tubule cells after Al chloride administration or distal tubule cells after either Al treatment.

Plasma levels of aluminium after tea ingestion in healthy volunteers

12 healthy volunteers on a controlled aluminium (Al) diet each consumed a tea infusion (500 ml/70 kg body weight), with either milk or lemon juice as additives, or mineral water, following a three-way crossover design. The concentrations of Al were determined in the diet, mineral water and tea infusions, and in plasma samples collected before and up to 24 hr after consumption of tea or water, using graphite-furnace atomic absorption spectrophotometry or inductively coupled plasma emission spectrometry. Consumption of up to 1.60 mg Al from tea with milk or lemon juice did not increase plasma Al levels compared with consumption of approximately 0.001 mg Al from mineral water. The results suggest that, in the short-term, drinking tea does not contribute significantly to the total body burden of Al.

Site and mechanism of enhanced gastrointestinal absorption of aluminum by citrate

Clinical and experimental studies have shown that citrate markedly enhances the intestinal absorption of aluminum (Al), but the site and mechanism of enhanced absorption are unknown. To determine where in the gastrointestinal tract aluminum citrate (Alcitr) was absorbed. Alcitr was gavaged with D-[1-3H] glucose in male Sprague-Dawley rats. Plasma Al levels increased rapidly and simultaneously peaked with D-[1-3G] glucose, suggesting early proximal bowel absorption. In in vitro duodenal and jejunal everted gut preparations, Alcitr incubation resulted in increased tissue Al levels and markedly enhanced transmural transport of Al and citr. Unlike citr, the transmural movement of Al was independent of temperature (37 degrees C vs. 4 degrees C). On the other hand, Al lactate (al Lac) increased tissue associated Al levels but had no effect on transmural Al movement. To determine if this large flux of Al following Alcitr administration was due to paracellular movement, ruthenium red and Ussing chamber studies were used to evaluate the morphologic and functional integrity of cellular tight junctions. Alcitr, as opposed to AlCl3, markedly increased ruthenium red deposits in intercellular spaces, especially around goblet cells, and induced a prolonged significant reduction in transmural resistance. Alcitr also resulted in rapid and nearly complete (99.7%) chelation of free calcium, an event known to disrupt cellular tight junction integrity. Taken together, these data suggest that enhanced Al absorption following administration of Alcitr occurs in the proximal bowel via the paracellular pathway due to the opening of cellular tight junctions.

Aluminium Bone Deposits in Normal Renal Function Patients after Long-Term Treatment by Plasma Exchange

The accumulation of aluminium (Al) can cause Al bone deposits, osteomalacia and encephalopathy. As albumin solutions used as replacement fluid in plasma exchange (PE) are contaminated with Al, we studied Al overload in two symptomless patients with normal renal function, treated by long-term plasma exchange (PE). Total Al loading was calculated at 1750 mumol in patient 1 (178 PE sessions) and 2100 mumol in patient 2 (153 PE sessions). Bone biopsy showed Al deposits and low bone formation without osteomalacia in patient 1 and only osteoporosis in patient 2. Plasma Al levels were useless in detecting early Al overload, because the remained in the normal range, even after PE in both patients. Bone biopsy was the best means of recognizing Al intoxication, but cannot be recommended for frequent evaluations. However, the desferrioxamine mobilization test can be proposed as a repetitive non-invasive investigation method.

Short-term effects of parathyroidectomy on plasma biochemistry in chronic uremia

Parathyroidectomy (PTx) is indicated in hemodialysis (HD) patients who have severe osteitis fibrosa unresponsive to vitamin D therapy or in whom the latter treatment is contraindicated. Immediately after PTx, plasma immunoreactive parathyroid hormone, calcium and phosphorus concentrations decline abruptly. However, little is known in such patients about the short-term effects of PTx on plasma alkaline phosphatase (AP) activity and plasma aluminum (Al) levels. The present, preliminary study was performed to determine such parameters in 37 HD patients, and to correlate them with data of bone histology. Mean plasma AP activity started to increase after PTx from day 4 onwards. Thus, AP values significantly higher than pre-PTx values were observed at day 7 and 14 (415 +/- 54 vs. 619 +/- 77 and 749 +/- 83 IU/liter, means +/- SEM; N = 37; P less than 0.05 and 0.001, respectively). This increase, in the absence of changes in liver function, was mainly due to the bone-specific iso-AP. Moreover, the degree of increase in plasma AP activity was higher in the subgroup with negative (group I, 21 patients) than in that with positive bone Al staining (group II, 16 patients). However, plasma osteocalcin (BGP) did not change after PTx (N = 8). Basal plasma Al levels were significantly higher in group II both before and two weeks after surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid removal of DFO-chelated aluminum during hemodialysis using polysulfone dialyzers

Aluminum (Al) removal following deferoxamine (DFO) therapy in hemodialysis patients was evaluated in a paired-fashion comparing cuprophane (Travenol 12.11) and polysulfone (Fresenius F-80) dialyzers. QB and QD were held constant at 250 and 500 ml/min, respectively. The polysulfone dialyzer increased total plasma Al clearance from 20.0 +/- 2.8 to 80.5 +/- 7.6 ml/min (P less than 0.01), and reduced the t 1/2 of plasma Al during hemodialysis from 538 +/- 113 to 112 +/- 12 min (P less than 0.01). The polysulfone F-80 dialyzer increased Al removal during the first hour of hemodialysis from 518 +/- 191 to 1812 +/- 720 micrograms/hr (P less than 0.01). During a four hour hemodialysis the F-80 dialyzer returned plasma Al levels to pre-DFO values (103 +/- 36 vs. 93 +/- 23, P less than 0.05), suggesting complete removal of the DFO chelated Al complex. In one patient Al removal was evaluated using cuprophane, F-40, F-60 and F-80 dialyzers and the t 1/2 for Al removed decreased from 484.6 to 276.1 and 108 to 99 minutes, respectively. These data show the Fresenius F-80 polysulfone dialyzer effects the rapid removal of DFO-Al complexes. We propose use of the Fresenius F-80 dialyzer in conjunction with reduced DFO doses and i.m. administration of DFO the day prior to dialysis to limit DFO exposure as a method to decrease DFO-related side-effects in hemodialysis patients.