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.     

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.     

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.     

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.     

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).     

Accelerated removal of deferoxamine mesylate-chelated aluminum by charcoal hemoperfusion in hemodialysis patients

Although deferoxamine mesylate (DFO) is effective in removing aluminum (Al) in hemodialysis patients, treatment with this drug is associated with a number of adverse effects. In order to limit the exposure of patients to DFO-Al complexes, the efficacy of colloidin-coated microencapsulated charcoal cartridges added in series to conventional dialyzers was investigated. The clearances of Al by the sorbent system were initially 116 +/- 4.7 mL/min, but decreased to 42.5 +/- 6.6 mL/min after 120 minutes of treatment. Thereafter, the Al clearances remained constant. In contrast, the Al clearances of the dialyzer were 29.5 +/- 1.8 mL/min initially and did not change during the treatment period. Both the percent and absolute decrease in Al levels after four hours of dialysis were greater with the dialyzers plus carbon cartridges than with the dialyzers alone. This resulted in an increase in the minimum net Al removal from 1,862 +/- 174 micrograms/treatment to 3,007 +/- 43 micrograms/treatment (P less than 0.05). Treatment with sorbent hemoperfusion should be considered in selected hemodialysis patients being treated with DFO for Al overload.     

The diagnostic critical value in DFO low dose loading test on patient with aluminum accumulation compared to each parameter of ROD

One hundred two hemodialyzed patients were examined to determine the standard level of delta Al value which is the difference of serum Al concentrations between pre and post DFO loading test. We applied low dose of DFO 15 mg/kg in this loading test. Some significant negative correlations were found between delta Al and MCI, sigma GS/D, osteocalcin, free-Hydroxyproline (dialysate) and free-gamma-Carboxyglutamic acid (dialysate). Each correlation rate was -0.58, -0.44, -0.76, -0.57 and -0.51 respectively. In addition tendencies of correlation were found between delta Al and ALP and between delta Al and %QCT (QCT/mean QCT in patient's age x 100). And statistical significant differences were found between (0 less than delta Al less than or equal to 150 micrograms/l) group and (150 micrograms/l less than delta Al) group in each osteobiochemical parameter. These results indicate that 150 micrograms/l is the lower diagnostic standard level of delta Al in 15 mg/kg DFO loading test.     

Hyperaluminemia in renal failure: the influence of age and citrate intake

Following the occurrence of aluminum encephalopathy in four patients with chronic renal failure, we studied 34 azotemic patients seen during the same year and five volunteers who took varying combinations of aluminum hydroxide and an alkalinizing citrate (Shohl's) solution. We found that the four encephalopathic cases were older than the 34 azotemic patients (68 years +/- 14 SD, vs 50 +/- 13, p less than 0.05), had a higher mean serum aluminum value (727 micrograms/l +/- 320 vs 92 +/- 73, p less than 0.005), had taken more aluminum hydroxide (5 g/day +/- 0.9 vs 1.6 +/- 1.8, p less than 0.01), and more Shohl's solution (64 ml/day +/- 19 vs 20 +/- 29, p less than 0.01). In all 38 patients the serum aluminum values correlated directly with age (p = 0.01), aluminum hydroxide (p = 0.001) and concomitant citrate intake (p = 0.004). In the five healthy volunteers the 24-hour urinary aluminum excretion increased from a baseline of 22 micrograms +/- 19 SD to 167 +/- 109 (p = 0.05) during aluminum hydroxide intake, rising to 580 +/- 267 (p = 0.01) during the simultaneous intake of citrate and aluminum hydroxide. Corresponding serum aluminum values were 11 micrograms/l +/- 2 SD, 44 +/- 34 (p = 0.1), and 98 +/- 58 (p less than 0.05). Thus citrate seems to enhance aluminum absorption and may cause encephalopathy in patients with chronic renal failure, especially the elderly.     

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.     

The role of aluminum in the pathogenesis of anemia in an outpatient hemodialysis population

Anemia is a well-defined complication of aluminum overload in chronic dialysis patients which may be present before other manifestations of aluminum toxicity are obvious. Causes of anemia in chronic renal failure are multiple, and at the present time there is no marker for aluminum-induced anemia. Deferoxamine (DFO) treatment can correct aluminum-related anemia and microcytosis, but may be associated with side effects. Because of the possible role of aluminum in red blood cells in causing the anemia associated with aluminum overload, we attempted to test red blood cell (RBC) aluminum as a marker for aluminum-associated anemia and to assess the prevalence of aluminum-associated anemia in an outpatient dialysis population. Both random plasma aluminum and RBC aluminum correlated well with the increase in plasma aluminum seen following DFO challenge. However, RBC aluminum was affected less by changes in oral aluminum intake than plasma aluminum. There were strong correlations of RBC and plasma aluminum to corpuscular volume (MCV) in our patients. Moreover, patients within the highest quartile of RBC aluminum had a lower mean MCV (82.1 +/- 1.7 vs 89.6 +/- 1.7, p less than .01) and hematocrit (HCT) (24.3 +/- 4 vs 28.2 +/- 1.5, p less than .05) than those within the lowest quartile. These data suggest that aluminum toxicity is an important cause of microcytic anemia in outpatient hemodialysis patients. Prospective long-term studies are needed to further define the usefulness of RBC aluminum in diagnosing and following hemodialysis patients with aluminum-induced anemia.     

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)     

Aluminium determination in the skin of patients with and without end-stage renal failure

Aluminium (Al) concentration in the skin was determined by inductively coupled plasma optical emission spectrometry to look for a correlation between Al exposure and skin content in patients with end-stage renal failure. Skin Al concentrations were higher in dialyzed patients than in the nondialyzed group (1.02 +/- 0.30 vs. 0.26 +/- 0.10 micrograms/g; p less than 0.001). Moreover, in the dialyzed group, the patients treated for more than 100 months had a higher concentration of Al in the skin than the others (1.20 +/- 0.26 vs. 0.80 +/- 0.18 micrograms/g; p less than 0.05). Al skin content correlated better with the deferoxamine infusion test (DIT) than with Al blood plasma concentration. In conclusion, our data confirm that the DIT is a valuable tool for the evaluation of body Al content.     

Correlation between serum aluminum concentration and signs of encephalopathy in a large population of patients dialyzed with aluminum-free fluids

The role of persistently high serum aluminum levels (sAl) in the pathogenesis of dialysis encephalopathy (DE) was evaluated in two groups selected from 170 patients dialyzed with low Al fluids. Group 1 (G1) consisted of 24 patients showing two or more sAl below 50 micrograms/l and group 2 (G2) consisted of 27 patients with sAl above 100 micrograms/l in at least 2 of 3 determinations. The two groups did not show any significant difference for age, sex, education or duration of the dialysis treatment. All G1 patients were treated by hemodialysis. In G2, 24 patients underwent hemodialysis and 3 were on continuous ambulatory peritoneal dialysis (CAPD). We evaluated body loads of Al in 25 of 27 G2 patients with the desferrioxamine (DFO) infusion test. All 51 patients underwent a neurological examination and a waking EEG. Intelligence was assessed by Raven's Progressive Matrices 47 test in 19 of the G1 patients and in 20 of the G2 patients; short-term memory was measured by digit span and by word span and long-term memory by a short story in 10 G1 patients and 17 G2 patients. We diagnosed DE only in the presence of the typical EEG changes, with or without manifest clinical symptoms. DE was diagnosed in none of the G1 patients and in 8 of the G2 patients (0 vs 29.6%, chi 2 = 6.34; p less than 0.025). Five of the patients with DE showed both clinical and EEG signs, while the remaining three showed only EEG signs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum hyaluronic acid and procollagen III amino terminal propeptide in chronic renal failure

Elevated serum concentrations of hyaluronic acid (HA) and procollagen III amino terminal propeptide (PIIINP) have been found in various diseases characterized by altered metabolism of collagen. In the present study, their serum levels were measured in 105 renal patients and 22 normal controls. Median HA concentrations were 23 micrograms/l in controls, 47 micrograms/l in patients with chronic renal failure (CRF, not on dialysis; p less than 0.001), 75 micrograms/l on CAPD (p less than 0.001) vs. controls, p = 0.045 vs. CRF), and 167 micrograms/l on hemodialysis (p less than 0.001 vs. controls, CRF, and CAPD), respectively. The values correlated positively with age but not with renal function or the type of renal disease. In hemodialysis patients, HA correlated with the duration of renal replacement therapy and serum beta 2-microglobulin but not with serum alkaline phosphatase or C-terminal parathormone. Serum HA did not change significantly during hemodialysis treatment and was independent of the type of dialyzer membrane material. Median PIIINP values were 2.7 micrograms/l in controls, 4.4 micrograms/l in patients with CRF (p less than 0.001), 6.9 micrograms/l on CAPD (p less than 0.001 vs. controls, p = 0.022 vs. CRF), and 8.6 micrograms/l on hemodialysis (p = 0.001 vs. controls, NS vs. CRF or CAPD). Values correlated with HA only in patients on CAPD but they did not correlate with age, renal function or duration of renal replacement therapy. It is concluded that renal failure, especially long-term dialysis treatment, is associated with elevated serum concentrations of HA and--to a minor degree--PIINP. Thus, they may be a sign of altered connective tissue metabolism in patients on long-term dialysis.     

Whole blood serotonin levels are markedly elevated in patients on dialytic therapy.

The normal range for whole blood serotonin levels in chronic renal failure patients has not been defined. As serotonin may be implicated in platelet abnormalities, hypo- and hypertension and itch in dialysis patients, serotonin whole blood levels were measured in a group of patients with chronic renal failure and/or who were dialysis dependent. The levels were elevated in 12 patients with moderate (mean serum creatinine 335 +/- 54 mumol/l) chronic renal failure (270 +/- 46 micrograms/l) compared to 11 normals (163 +/- 17 micrograms/l, p less than 0.05; quoted normal range less than 300 micrograms/l) but did not correlate with serum creatinine levels. There was a marked elevation in serotonin levels in dialyzed patients, including those on hemodialysis (polysulfone, n = 6, 747 +/- 234 micrograms/l; cuprophane membranes, n = 6, 708 +/- 198 micrograms/l), hemodiafiltration (n = 12, 695 +/- 130 micrograms/l) and especially peritoneal dialysis (n = 6, 1,148 +/- 162 micrograms/l). All results were significant (p less than 0.01) compared to normals and compared to the nondialyzed group (p less than 0.05). The level of serotonin decreased during hemodialysis regardless of the membrane used. There was no positive correlation of serotonin levels with pruritus or hypertension, although there was a negative correlation with systolic blood pressure. The reference range for serotonin whole blood levels needs to be broadened when considering dialyzed patients.     

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.     

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 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)     

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.     

Apoprotein A-I and high density lipoprotein subfractions in patients with chronic renal failure receiving hemodialysis

Serum concentration of apoprotein A-I (apo A-I) and cholesterol content in high density lipoprotein (HDL) subfractions have been studied in 19 men and 11 women at the end stage of chronic renal failure undergoing hemodialysis. HDL2 cholesterol concentration was decreased in males [0.33 +/- 0.12 (mean +/- SD) mmol/l, controls 0.45 +/- 0.09 mmol/l; p less than 0.001]; in females HDL2 cholesterol was also decreased although without statistical significance (0.45 +/- 0.15 vs. 0.55 +/- 0.10 mmol/l). HDL3 cholesterol was significantly decreased in men (0.65 +/- 0.11 vs. 0.77 +/- 0.04 mmol/l; p less than 0.001) and also in women (0.61 +/- 0.12 vs. 0.82 +/- 0.07 mmol/l; p less than 0.005). However, serum concentration of apo A-I was within the normal range (1.13 +/- 0.16 milligram in males and 1.25 +/- 0.17 milligram in females; controls 1.24 +/- 0.17 and 1.35 +/- 0.19 milligram, respectively). The raised apo A-I/HDL2 cholesterol ratio in both men and women suggests the existence of qualitative changes in HDL subfractions as has been proposed in previous studies measuring total apo A and total HDL cholesterol in patients with chronic renal failure receiving hemodialysis. These abnormalities in the relative composition of HDL subfractions could play an important role as a vascular risk factor in patients with chronic renal failure undergoing hemodialysis.