Effect of body iron stores on serum aluminum level in hemodialysis patients.

To evaluate the influence of body iron stores on the serum aluminum (Al) level, we studied the correlation between iron status (the serum ferritin, serum iron and transferrin saturation) and serum Al levels in 68 severely anemic hemodialysis patients. Among them, 36 underwent the desferrioxamine (DFO) mobilization test. These 68 patients were divided into three groups according to their serum ferritin level. The basal Al level in the patient group was 41.4 +/- 37.4 micrograms/l (control, 4.1 +/- 2.4 micrograms/l). The serum Al level after DFO infusion of the patient group was 111.1 +/- 86.8 micrograms/l. A significantly higher basal Al and peak Al level after DFO infusion were found in group 1 patients (serum ferritin less than 300 micrograms/l) when compared to group 2 (serum ferritin 300-1,000 micrograms/l) and group 3 (serum ferritin greater than 1,000 micrograms/l) patients. A significant negative correlation between serum ferritin and basal serum Al (r = -0.544, p = 0.0001), as well as peak serum Al after DFO infusion (r = -0.556, p = 0.0001), was noted. Similarly, a negative relationship between serum Al (both basal and peak) and either serum iron or transferrin saturation was noted. However, there was no correlation between the serum Al level and the dosage of aluminum hydroxide. In conclusion, serum ferritin, serum iron and transferrin saturation were inversely correlated with serum Al in our hemodialysis patients. Iron deficiency may probably increase Al accumulation in these patients.     

High deposition rate of aluminum in tissues in diabetic hemodialysis patients

Aluminum (Al) accumulation in bone is a serious problem in patients on hemodialysis. We studied deferoxamine infusion test (DFO test) in 14 diabetic patients on hemodialysis (HDDM) and 23 hemodialysis patients originated from glomerulo nephritis (HDCGN) to determine whether Al accumulation is different between the two groups or not. There was no difference in hemodialysis duration and total oral intake of Al containing drugs between two groups. Serum C-terminal parathyroid hormone (C-PTH) in HDDM was lower than that in HDCGN group (1.82 +/- 1.30 vs. 3.80 +/- 1.82 ng/ml; P less than 0.01). However serum Al (s-Al) levels were comparable (61.9 +/- 53.0 vs, 45.0 +/- 32.3 micrograms/l). A significant correlation was observed between duration of dialysis period and s-Al in HDDM (r = 0.806, p less than 0.01), but in HDCGN, the relation was not significant. The patients in HDDM whose cumulative aluminum intake was less than 2.0 kg showed the higher serum A1 concentrations before DFO and greater increases in s-Al after DFO test, as compared with those in HDCGN with matched aluminum intake (93.8 +/- 67.6 vs. 35.9 +/- 23.6 micrograms/l; p less than 0.001 and 141.2 +/- 81.8 vs. 70.3 +/- 41.1 micrograms/l; p = 0.035). These results indicate that in uremic diabetic patients with lower intake of Al containing drugs, an early accumulation of Al in the whole body occurs possibly because of the enhanced absorption rate of Al at an intestine and/or the low PTH level.     

Aluminium interference in the treatment of haemodialysis patients with recombinant human erythropoietin

In nine chronic haemodialysis patients a desferrioxamine (DFO) load test (40 mg/kg body-weight) was performed 1 year after the beginning of treatment with recombinant human erythropoietin (rHuEpo). The patients were then divided into two groups. Group A comprised five patients with a greater mean aluminium (204 +/- 28 micrograms/l) than the four patients in group B. Group A was given a mean dose of 25.8 g (range 14-39 g) of DFO over 6 months. Group B (aluminium values 112 +/- 36 micrograms/l) was never treated with DFO. During the period of observation, plasma iron, serum ferritin and transferrin, as well as iron supplementation, did not differ between the groups. After DFO treatment a second DFO load test was performed. The mean predialysis aluminium value was significantly reduced in group A (204 +/- 28 vs 111 +/- 72 micrograms/l; P less than 0.05), while remaining unchanged in group B (112 +/- 36 vs 140 +/- 39 micrograms/l; P = ns). In both groups, the doses of rHuEpo necessary to maintain the same haemoglobin values decreased with time, but reduced significantly only in group A (298 +/- 105 vs 110 +/- 61 mu/kg per week; delta -63%; P less than 0.01). Thus, aluminium interferes with the response to rHuEpo in haemodialysis patients, and the correction of aluminium overload with DFO can allow a considerable sparing of rHuEpo.     

Deferoxamine test and PTH serum levels are useful not to recognize but to exclude aluminum-related bone disease.

The use of noninvasive diagnostic tools, like the deferoxamine (DFO) test and serum iPTH, to identify aluminum-related bone disease has proved to be inadequate due to false-negative cases; therefore, bone biopsy becomes a necessary diagnostic procedure. Our purpose was to verify whether these non-invasive parameters, appropriately used, may result valid in the identification of patients not at risk of Al toxicity, therefore restricting the need for histologic evaluation. We studied 68 hemodialyzed patients, aged 49.0 +/- 11.6 years, with a M/F ratio of 37/31 and a dialytic age of 85.0 +/- 47.0 months, by means of bone biopsy, DFO test and serum C-PTH. 19.1% of the cases had positive stainable Al and/or high bone Al content (greater than 60 mg/kg/dw) and could be intoxicated. To obtain the highest sensitivity, we selected the following limit values: the lower limit of increment so far proposed for DFO test positivity (greater than 150 micrograms/l) and a value capable of selecting patients with pathologic osteoclasia for C-PTH (greater than 15 ng/ml). With these limits, four different groups of patients were recognized: group A, DFO test positive and PTH high, n = 12; group B, DFO test positive and PTH low, n = 6; group C, DFO test negative and PTH high, n = 30; group D, DFO test negative and PTH low, n = 20. In group B, which could be anticipated as being at higher risk, we actually found the highest (p less than 0.05) bone Al content as compared to other groups, associated with a reduced bone formation rate.(ABSTRACT TRUNCATED AT 250 WORDS)     

Prevention and treatment of aluminum overload in uremic patients: long-term results

The authors evaluate the efficacy of a protocol of prevention and treatment of aluminum (Al) overload in RDT patients during a 7-year period (from 1981, 164 patients, to 1987, 161 patients). Al in dialysate solutions was always less than 25 micrograms/l. Baseline Al levels greater than 100 micrograms/l were found in 22% of patients in 1981 but in none in 1987, while the percentage of values less than 60 micrograms/l increased from 55 to 91%. DFO tests were positive in 54% and 7% of cases in 1981 and 1987, respectively. A clinical diagnosis of Al intoxication was performed in 6 patients in 1981, and no further cases were diagnosed later. DFO treatment (50 mg/kg once a week) was employed preventively in 31 patients owing to positive DFO-tests, and in the 6 Al-intoxicated patients therapeutically. In the former patients none developed clinical intoxication. In the latter group clinical improvement was only temporary in the three parathyroidectomized patients. Al hydroxide [Al(OH)3] as a phosphate binder was tapered off in 1981 and substituted by Al-free chelants. In 1987, 66% of patients were given CaCO3 or Mg (OH)2 alone or in association, while 34% still needed Al(OH)3, although at low dosages (less than 2 g/day). The conclusion is that such a protocol is able to prevent and to treat cases of Al intoxication, albeit only partially.     

Aluminum concentrations in serum, dialysate, urine and bone among patients undergoing continuous ambulatory peritoneal dialysis (CAPD)

Aluminum (Al) concentration in serum, urine, and dialysate was estimated in 21 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). In 12 of the patients bone Al concentration was measured as well. Mean serum Al level was 32.4 +/- 21.0 micrograms/l. The Al concentrations in the dialysate and urine were 9.1 +/- 4.1 micrograms/l and 52.5 +/- 47.3 micrograms/l, respectively. Bone Al concentration was 21.0 +/- 14.9 ppm and correlated significantly with concentrations of Al in serum (p less than 0.01) and dialysate (p less than 0.01). A mass transfer (MT) from the patients to the dialysate was observed in all patients (-44.0 +/- 28.8 micrograms/24 h). There was a highly significant correlation between peritoneal Al MT and serum Al (p less than 0.001), actual Al consumption (p less than 0.05) and bone Al concentration (p less than 0.005) supporting the existence of an overflow phenomenon. Despite very low Al levels in the dialysate, patients are at risk of elevated Al levels in the serum, dialysate, urine and bone because of consumption of Al-containing phosphate binders.     

Kinetics of aluminoxamine and feroxamine chelates in dialysis patients.

To achieve a rational basis for the use of deferoxamine (DFO) in aluminum (AL) -and iron (Fe)-overloaded uremic patients, important insights may be provided by the recently available micromethods to determine DFO and its metallochelates aluminoxamine (AlA) and feroxamine (FeA). With this procedure, AlA and FeA plasma kinetics were evaluated in a pilot study in 10 uremic patients during a whole week after a single DFO infusion performed during the first hour of the first standard bicarbonate hemodialysis (HD) of the week. Patients were divided into normal (n = 6) and high (n = 4) ferritin groups (1 and 2 respectively). Baseline Al concentrations were greater than 2 less than 6 in group 1 and less than 1.5 mumol/l in group 2. DFO was given at doses of 40, 20 and 10 mg/kg. AlA and FeA showed substantially different kinetics. AlA kinetics were similar in group 1 and 2: they reached their peak at the beginning of the 2nd HD, decreased during the 2nd and 3rd HD, and with the highest DFO dose still increased between the 2nd and 3rd HD. At similar pre-DFO Al values (greater than 2 less than 3.3 mumol/l), increased DFO doses produced increased AlA concentrations ranging from 95 to 40% of total plasma Al for all the week. At higher pre-DFO Al values (greater than 3.5 less than 6 mumol/l), even a DFO dose as low as 10 mg/kg was sufficient to form consistent AlA amounts (from 80 to 15% of total Al).(ABSTRACT TRUNCATED AT 250 WORDS)     

Deferoxamine and coated charcoal hemoperfusion to remove aluminum in dialysis patients

We studied the in vitro and in vivo characteristics of aluminum (Al) removal by coated charcoal hemoperfusion (HP) in combination with intravenous deferoxamine (DFO). DFO enhanced the clearance of Al by HP in vitro after 180 minutes of perfusion with a solution containing 403.3 +/- 14.0 ng/ml of Al at 150 ml/min. The Al clearance was 139 +/- 1.0 ml/min with DFO and 49 +/- 10.0 ml/min (P less than 0.001) without DFO. Addition of DFO enhanced in vitro Al removal from 5.5 +/- 0.9 mg to 10.0 +/- 1.2 mg (P less than 0.05). During our in vivo studies, an HP device was in series in the dialysis circuit after a Cuprophan hemodialyzer. Eight patients with Al toxicity were studied on twelve occasions. Patients received DFO (40 mg/kg) 40 hours before the study. The total Al clearance with the combined hemodialysis (HD) and HP devices was higher than that obtained by the dialyzer alone at 30 minutes (62 +/- 4.9 ml/min vs. 25 +/- 2.5 ml/min, P less than 0.02) and after 180 to 210 minutes (32 +/- 3.0 ml/min vs. 19 +/- 2.9 ml/min, P less than 0.02). After 120 minutes the Al clearance by the HP device alone was significantly lower than the initial Al clearance by HP. Combined HD plus HP removed 2.9 +/- 0.4 mg of Al, whereas the total removal of Al by HD alone was 1.5 +/- 0.3 mg (P less than 0.01).     

Concomitant iron and aluminum mass transfer following deferoxamine infusion during hemofiltration

Variable tissue overloading can alter the removal rate of iron and aluminum from uremics. Owing to its higher affinity to deferoxamine (DFO) and higher plasma concentrations, Fe could impair Al removal in cases of simultaneous body burden. Fe and Al plasma kinetics and mass transfer were therefore studied in 12 uremic patients with different Fe and Al status: six with normal ferritin levels (less than 400 micrograms/L [ng/mL]), and Al 1.4 to 4.7 mumol/L (40 to 131 micrograms/L) (group A); six with increased ferritin (greater than 2,000 micrograms/L), and Al 1.7 to 17 mumol/L (47 to 476 micrograms/L) (group B). DFO (40 and 80 mg/kg in a random sequence) was administered once a week during the first hour of the first hemofiltration (HF). The results show that in both groups and with both DFO doses, maximum Fe and Al mass transfer was achieved in the first and second HF, respectively. The 80-mg/kg dose of DFO significantly raised Al mass transfer in both groups, whereas Fe mass transfer was only slightly affected. Even though plasma Fe levels were almost always higher than Al, Al mass transfer eventually exceeded that of Fe, in both Fe-normal and Fe-overload patients. The bias towards Al in mass transfer was enhanced in both groups in the second HF, and at the higher DFO doses. Thus, DFO once a week reduced Fe loss to less than 30 mumol/wk in patients with normal ferritin levels. In both Fe and Al overloaded patients, Al can be removed, and Al mass transfer may often exceed Fe mass transfer, depending on the degree of tissue burden, the time from DFO infusion, and the DFO dose.     

Non-invasive prediction of aluminum bone disease in hemo- and peritoneal dialysis patients.

Between October 1987 and October of 1989, we conducted a prospective study to evaluate non-invasive test strategies for predicting aluminum bone disease (ABD) in a group of largely unselected dialysis patients based on their deferoxamine (DFO) test alone, or the combined results of their DFO test and intact 1-84 parathyroid hormone (PTH) levels. These test parameters were evaluated against the pathological diagnosis of ABD based on bone biopsy ("gold standard"). A total of 445 patients in three dialysis centers in Toronto were serially followed for their clinical, laboratory and risk parameters for renal osteodystrophy during the study, and 259 (142 PD and 117 HD) patients underwent a series of investigations which included the DFO test, measurement of intact 1-84 PTH levels, and an iliac crest bone biopsy. Serum aluminum ([Al]) level greater than or equal to 3700 nM (or 100 micrograms/liter) had a positive predictive value (PPV) of 75% for ABD in our PD and 88% in our HD patients, but its sensitivity was low (10 and 37%). Delta [Al] (that is, incremental rise of serum [Al] from baseline post-DFO) was useful in predicting ABD in our PD but not HD patients. Test combination based on delta [Al] greater than or equal to 5550 nM (or 150 microgram/liter) and PTH levels less than 20 pM (or 200 pg/ml) yielded the best PPV greater than or equal to 95% for ABD in both PD and HD patients. This test cut-off would remain highly predictive of ABD even if the prevalence of ABD decreases to as low as 5% for the PD patients and 10% for the HD patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of desferrioxamine on concentration and distribution of aluminum in bone

Aluminum (Al) loaded rats were injected chronically with either desferrioxamine (DFO) or saline. Six rats of each treatment group were sacrificed before and after one, three, and nine months of treatment for determination of tissue and serum Al, and for histological localization of bone Al. Urinary Al was measured during one week before sacrifice. Al loading caused significant elevations of bone (136.2 +/- 22.0 micrograms/g) and liver (114.4 +/- 41.9 micrograms/g) aluminum. Serum Al in DFO-treated animals was not different from their controls (216.4 +/- 80.5 and 226.9 +/- 42.9 micrograms/liter after one month; 151.0 +/- 20.8 and 138.0 +/- 63.9 micrograms/liter after three months; 72.1 +/- 40.7 and 61.6 +/- 14.2 micrograms/liter after nine months in control and DFO-treated animals respectively). Urinary Al excretion in the DFO-treated group was increased at all times as compared to the control rats. A decrease of muscle Al occurred after one month of DFO treatment, but no significant differences of liver and bone Al could be shown between DFO-treated rats and their controls. Al decreased to a comparable degree in all tissues of both DFO and control rats after nine months of treatment. Histomorphometric examination of the bones showed that after one and three months of treatment, significantly less Al was localized at the calcification front of DFO-treated rats compared to their controls (75.6 +/- 6.9% and 53.4 +/- 20.9% after one month; 52.3 +/- 10.2% and 34.8 +/- 10.6% after three months in control and DFO rats respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Removal of trace metals by continuous ambulatory peritoneal dialysis after desferrioxamine B chelation therapy.

We studied the removal of aluminum (Al), iron (Fe), copper (Cu), lead (Pb) and zinc (Zn) with continuous ambulatory peritoneal dialysis, before and after desferrioxamine B (DFO) administration (2 g intravenously) in two patients with chronic renal failure and Al-related osteopathy. Both patients had 4 peritoneal dialysis exchanges (2 liters each) per day. Blood concentrations of Al increased 413% (patient A) and 190% (patient B) after DFO. Patient B had a 15% increase in Fe; other metals remained unchanged. Dialysate efflux Al concentrations had peak post-DFO increments of 761% and 840% in patients 1 and 2, respectively. Peak post-DFO increments in Fe dialysate concentration were 342% and 89.5% in the respective patients. Dialysate/plasma (D/P) concentration ratios of Al increased from pre-DFO levels (mean +/- SEM) of 0.370 +/- 0.048 to 0.523 +/- 0.061 after DFO; similarly, Fe D/P ratios increased from 0.259 +/- 0.053 to 0.446 +/- 0.075 with DFO therapy. These results indicate an increase in the ultrafiltrable proportion of Al and Fe in plasma after DFO administration. During 3 days after DFO, patient 1 had a total removal of Al and Fe of 2.9 mg and 4.9 mg, respectively. Metal removal in patient 2 was 7.6 mg of Al and 2.7 mg of Fe. Peritoneal extraction of other trace metals was minor.     

Use of the low-dose desferrioxamine test to diagnose and differentiate between patients with aluminium-related bone disease, increased risk for aluminium toxicity, or aluminium overload

BACKGROUND.: Aiming at a safe method in the diagnosis of aluminium-relatedbone disease (ARBD)/aluminium overload the low-dose desferrioxamine(DFO) test was developed. In a multicentre study histologicaland histochemical data and aluminium bulk analysis of bone biopsiesof 77 dialysis patients were correlated with the results ofboth the 5 mg/kg and 10 mg/kg DFO tests. METHODS.: ARBD was considered to be present when > 15% of the bonesurface was positively stained for aluminium and the bone formationrate was below 220 µm²/mm²/day. Patients in which theAluminon® staining was positive (>0%) were consideredat an increased risk for aluminium toxicity independent of thetype of renal osteodystrophy. Patients were considered aluminiumoverloaded when the bone aluminium content was >15 µg/gwet weight and/or the Aluminon® staining was positive (>0%). RESULTS.: Using the proposed criteria 15 patients were found to have ARBD;13 of them presenting with a serum iPTH below 150 ng/l. In conjunctionwith an iPTH measurement the DFO test had a more than acceptablesensitivity and specificity in the diagnosis of ARBD. The testwas considered positive when a post-DFO serum aluminium increment(sAl) above 50 µg/l (5 mg/kg) or 70 µg/l (10 mg/kg)together with a serum iPTH below 150 ng/l was found. Using thesecut-off levels the 5 and 10 mg/kg tests in the diagnosis ofARBD had a sensitivity of 87% and a specificity of 95% and 92%respectively whereas the predictive value for a positive testfor the population under study was 80% (5 mg/kg). Not a singlepatient with a serum iPTH >650 ng/l had a positive staining(>0%) even when the bone aluminium level was elevated (>15 µg/g wet weight). In the detection of patients at riskfor aluminium toxicity sAl thresholds of 50 µg/l (5 mg/kg)and 70 µg/l (10 mg/kg) in combination with a serum iPTH<650 ng/l had a sensitivity of 92% and specificity of 86%and 84% respectively. In the clinical setting of aluminium overload,threshold sAl levels of 50 µg/l (5 mg/kg) and 70 µg/l(10 mg/kg) had a sensitivity of 91% and a specificity of 95%and 90% respectively. CONCLUSIONS.: The low-dose DFO test is a reliable test for the detection ofaluminium overload; however, it is not specific enough to differentiatebetween ARBD, increased risk of aluminium toxicity, and aluminiumoverload unless it is used in combination with a serum iPTHmeasurement. In conjunction with a serum iPTH measurement itis an important tool in the differential diagnosis and may avoidthe necessity of a bone biopsy in the majority of patients.Data obtained in the present study have allowed us to updatethe strategies for monitoring, diagnosis and patient follow-upproposed at the Consensus Conference on Diagnosis and Treatmentof Aluminium Overload in End-Stage Renal Failure; Paris, 1992.     

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.     

Low calcium dialysate and high-dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients

We treated nineteen haemodialysis patients with secondary hyperparathyroidism with increasing oral doses of 1,25 dihydroxycholecalciferol (calcitriol) over a 12-week period and used low calcium dialysate (1.0 mmol/l) to prevent hypercalcaemia. Nine patients received daily calcitriol and ten received calcitriol thrice weekly, and at the end of the study the mean doses were 2.0 micrograms daily and 2.6 micrograms thrice weekly respectively. The regimen was well tolerated with nine episodes of mild hypercalcaemia, none of which were symptomatic. Mean PTH and alkaline phosphatase concentrations decreased from 62.0 pmol/l (15-125) to 22.0 pmol/l(1-70) (P less than 0.01), and 144 IU/l (48-461) to 123 IU/l (61-346) (P less than 0.05) respectively. Mean serum calcium increased from 2.33 mmol/l (2.05-2.55) to 2.52 mmol/l (2.26-2.67) (P less than 0.01). There were no significant changes in serum phosphate, magnesium, or aluminium concentrations and there were no significant differences in outcome between patients receiving daily therapy compared to those receiving it thrice weekly. A combination of high-dose oral calcitriol and low calcium dialysate can reverse secondary hyperparathyroidism without causing hypercalcaemia and these results suggest a benefit over conventional low-dose calcitriol.     

Association between aluminum accumulation and cardiac hypertrophy in hemodialyzed patients

In order to investigate the possible role of aluminum accumulation on the myocardium, 50 stable asymptomatic hemodialysis patients were studied. Patient cardiac status was assessed by echocardiography. A deferroxamine (DFO) test, together with a bone biopsy, was performed to determine the magnitude of AI accumulation. Thus, an increase in serum AI after DFO (delta AI DFO) and stainable cortical bone aluminum (SCBA) were taken as parameters of AI load. Fourteen of 50 patients had no SCBA. They differed from the 36 patients with SCBA in that they had lower left ventricular mass (LVM) (P less than 0.001), increased velocity of circumferential fiber shortening (Vcf) (P less than 0.001), and higher mitral E-F slope (P less than 0.01). In the overall population there was a mild increment in serum AI and in delta AI DFO. The duration of dialysis treatment was correlated with SCBA and delta AI DFO (P less than 0.001). A correlation was observed between LVM and delta AI DFO (P less than 0.001) and between LVM and SCBA (P less than 0.001). Multivariate correlations analysis indicated that these relationships were independent of the duration of dialysis treatment. The present data suggest that, in hemodialysis patients aluminum accumulation may be associated with increased LVM.     

The effect of an iron supplement on serum aluminum level and desferrioxamine mobilization test in hemodialysis patients.

BACKGROUND: The serum aluminum (Al) measurement with desferrioxamine (DFO) mobilization is a screening test for uremic patients with an Al overload. In these patients, body iron status is one of the factors affecting the serum Al level. This study is designed to elucidate the effects of iron supplements on the serum Al and the DFO mobilization test. METHODS: Our study featured ten hemodialysis patients with iron deficiency anemia. The iron supplement was given intravenously with saccharated ferric oxide, 40 mg three times weekly, at the end of each hemodialysis. The total amount of iron supplement was 1,000 mg. All the patients underwent a DFO test at a dose of 5 mg/kg. The same test was repeated two weeks after completion of the iron supplement. RESULTS: After the iron supplement, patients' iron deficiency anemia improved with a serum ferritin elevation from 312.4 +/- 589.5 to 748.2 +/- 566.2 microg/L (p < 0.01), and iron saturation from 21.6 +/- 20.3 to 41.1 +/- 21.7% (p = 0.06). The basal serum Al level decreased from 34.3 +/- 13.8 to 21.8 +/- 8.5 microg/L (p = 0.01). In the DFO mobilization test, the peak serum Al level decreased from 63.4 +/- 19.3 to 50.7 +/- 20.5 microg/L (p < 0.01). The amount of Al increment (deltaAl) in DFO test was not changed (29.1 +/- 12.0 vs. 28.9 +/- 15.9 microg/L, p = 0.86). The change in basal Al level tended to negatively correlate with the percentage of increment in iron saturation (r = -0.628, p = 0.05). CONCLUSION: Results in this study suggest that iron supplements may significantly reduce the basal serum Al and peak Al in DFO mobilization test, without significant change of the mean deltaAl. The data presented indicate that in the interpretation of serum aluminum levels the iron status should be taken into account.     

Desferrioxamine enhances the haemopoietic response to erythropoietin, but adverse events are common.

To determine whether the chelation of aluminium enhances the haemopoietic response to recombinant human erythropoietin (r-HuEPO), desferrioxamine (DFO) at a dose of 20-30 mg/kg was given to 7 of 17 transfusion-dependent haemodialysis patients treated with r-HuEPO (40 units/kg/dialysis i.v.). The two randomly allocated groups did not differ in age, initial haemoglobin, plasma aluminium, plasma aluminium after DFO challenge, and ferritin, but, by chance, dialysis time was longer in the DFO group (69 vs. 32 months; p = 0.02). DFO was administered for 16 +/- 4 (SE) dialyses. During this period, Hb rose faster in the DFO group, in relation to time (0.61 vs. 0.29 g/l day; p less than 0.05) and r-HuEPO dose (3.35 vs. 1.88 g/l/100 units r-HuEPO/kg; p less than 0.05). However, in the DFO group, there was a high incidence of side effects, especially visual toxicity. It is concluded that DFO enhances the effectiveness of r-HuEPO in correcting the anaemia of chronic renal failure, but the combination of DFO and r-HuEPO is unsafe under the conditions described.     

Calcium carbonate is an effective phosphate binder when dialysate calcium concentration is adjusted to control hypercalcemia

The efficacy of calcium carbonate (CaCO3) as a phosphate binder has been limited by its tendency to cause hypercalcemia. Since standard dialysate calcium concentrations (3.0-3.5 mEq/l) increase the risk of developing hypercalcemia with large doses of CaCO3 by inducing positive calcium balance during hemodialysis (HD), we compared control of hyperphosphatemia in 41 HD patients during 4 months each of aluminum hydroxide (Al(OH)3) and CaCO3 when the dialysate calcium concentration was lowered, as required, to maintain the predialysis serum calcium concentration within the normal range. Mean predialysis serum phosphorus and calcium concentrations were 5.0 +/- 0.2 mg/dl and 9.3 +/- 0.1 mg/dl, respectively, during 4 months CaCO3 (9.2 +/- 0.3 g/day) and 4.9 +/- 0.2 g/dl and 9.1 +/- 0.1 mg/dl during the previous 4 months Al(OH)3 therapy (2.9 +/- 0.2 g/day). Reducing the dialysate calcium concentration to below 3.0 mEq/l (mean 2.1 +/- 0.04) in the 11 patients who developed hypercalcemia on CaCO3 decreased serum calcium (-1.1 +/- 0.15 mg/dl) and ionized calcium (-0.3 +/- 0.04 mEq/l) during HD, enabled CaCO3 (8.8 +/- 0.4 g/day) to be continued, and maintained predialysis serum calcium and phosphorus at 10.4 +/- 0.1 mg/dl and 5.2 +/- 0.3 mg/dl, respectively. No improvement in acidosis or biochemical hyperparathyroidism was observed during CaCO3 therapy but serum aluminum was significantly decreased after CaCO3 (p less than 0.005). We conclude that CaCO3 prevents interdialytic hyperphosphatemia as effectively as Al(OH)3 without increasing the predialysis serum calcium x phosphorus product, provided serum calcium is maintained within the normal range by adjusting the dialysate calcium concentration.     

Residual renal function in hemodialysis patients may protect against hyperaluminemia

We investigated 106 home hemodialysis patients whose mean [+/- SEM] serum aluminum (Al) concentration was 60.9 +/- 4.1 micrograms/liter. Serum Al concentration was inversely related to daily urine output (r = -0.52, P less than 0.001). Urine volume and measurements of Al exposure were included in a multivariate analysis of serum Al concentration in the 62 patients whose urine output was greater than 10 ml/day. The multiple correlation coefficient (r) was 0.70 (P less than 0.001) and the percentage contributions to r2 (indicating the relative importance of each factor) were: urine output 57%, oral Al intake 36%, total dialysis hours 7%. The additional contribution from cumulative water Al was negligible. In a subgroup of 26 patients with a urine output exceeding 10 ml/day, urinary Al excretion averaged 15.4 micrograms/day, and renal Al clearance and serum Al concentration were inversely related (r = -0.69, P less than 0.001). We conclude that Al-containing phosphate binders were a more important source of Al than was dialysate in these patients and that residual renal function can reduce the severity of hyperaluminemia in hemodialysis patients.