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 μg/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 μg/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 μg/L (p < 0.01). The amount of Al increment (ΔAl) in DFO test was not changed (29.1 ± 12.0 vs. 28.9 ± 15.9 μg/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 ΔAl. The data presented indicate that in the interpretation of serum aluminum levels the iron status should be taken into account.     

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.     

Serum soluble transferrin receptor reflects erythropoiesis but not iron availability in erythropoietin-treated chronic hemodialysis patients

BACKGROUND: The diagnosis of iron deficiency using the current commonly used tests is usually difficult in hemodialysis patients. Soluble transferrin receptor (sTfR) has caught the attention of physicians recently as regards its use as a parameter for the evaluation of iron status. This study was conducted in order to evaluate the correlation of serum soluble transferrin receptor (sTfR) concentration with hematological parameters and iron profiles, in the role of identifying iron deficiency among dialysis patients. METHODS: Seventy-three patients having received chronic hemodialysis and stable maintenance recombinant human erythropoietin (rHuEPO) therapy were included. Iron, total iron-binding capacity, ferritin and sTfR were measured in the first week. Following this, these patients began to receive intravenous iron dextran (2 mg/kg/week) for 4 weeks. The hematocrit (Hct), hemoglobin (Hb) levels and reticulocyte counts were evaluated weekly. At the beginning of fifth week, the sTfR level was measured again. Patients were classified as belonging to one of the following groups: serum ferritin < 100 microg/L - absolute iron-deficient group; initial ferritin level > or = 100 microg/L with an increase in hemoglobin of greater than 1 g/dL at the end of the study occult iron deficiency group; others - non iron-deficient group. RESULTS: Seventy-one patients completed the study. The concentration of sTfR was positively correlated with Hct, Hb and reticulocyte index at the beginning (r = 0.236, p = 0.047; r = 0.257, p = 0.04; r = 0.401, p < 0.01, respectively) and at the end of the study (r = 0.384, p < 0.01; r = 0.338, p < 0.01; r = 0.427, p < 0.001, respectively). After 4 weeks of iron and rHuEPO therapy, the sTfR concentration increased, rather than declined, from 21.85 +/- 8.06 nM to 23.76 +/- 7.42 nM (p = 0.04) and the change was positively correlated with the changes in Hct, Hb and reticulocyte index. The administered rHuEPO doses did not differbetween the iron deficiency group (absolute deficiency, n = 3; occult deficiency, n = 10) and non-iron deficiency group (n = 58). The sTfR levels failed to identify the occult iron deficiency group because there was no difference between occult iron-deficient and non-iron-deficient patients (24.73 +/- 9.09 nM versus 21.60 +/- 7.89 nM, p = 0.34). Instead, transferrin saturation (TS) could be a differential marker between the 2 groups (19.0 +/- 10.9% versus 30.1 +/- 12.7%, p = 0.012). CONCLUSION: The serum sTfR concentration is indeed an appropriate marker for erythropoiesis. The erythropoitic effect of administered rHuEPO could mask the effect of iron status on the sTfR concentration. This might make the sTfR concentration no longer an appropriate index to identify the presence of occult iron deficiency. Thus, TS and ferritin currently remain better methods for the evaluation of iron status in rHuEPO-treated chronic hemodialysis 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.     

Synergistic effect of desferrioxamine and recombinant erythropoietin on erythroid precursor proliferation in chronic renal failure.

BACKGROUND: Desferrioxamine (DFO) has been suggested to improve erythropoiesis in end-stage renal failure independently of its aluminium (Al)-chelating effect. A possible synergistic effect of DFO and recombinant human erythropoietin (r-HuEpo) could be very useful in treating anaemia of chronic renal failure. METHODS: In order to verify whether a synergistic action of DFO and r-HuEpo exists, we enrolled 11 patients undergoing chronic haemodialysis and r-HuEpo treatment. All had a negative DFO test, very low serum Al levels (< 20 microg/l), ferritin > 100 ng% and iPTH < 200 pg/l. Samples were drawn for a basal erythroid precursor (burst-forming unit-Erythroid, BFU-E) evaluation. After isolation by Ficoll Hypaque, a 14 day incubation was carried out with: (i) r-HuEpo 3 U/ml; (ii) r-HuEpo 30 U/ml; and (iii) r-HuEpo 30 U/ml + DFO 167 microg/ml. Patients then received 5 mg/kg DFO infused during the last hour of each dialysis session for 12 weeks. New BFU-E evaluations were performed after 2, 6 and 12 weeks of treatment. BFU-E colonies were counted in duplicate with an inverted microscope after 14 days. Haemoglobin (Hb), ferritin, transferrin, reticulocytes, hypochromic erythrocytes, soluble transferrin receptor and serum erythropoietin were also evaluated at the same time. RESULTS: High dose r-HuEpo achieved greater proliferation than low dose r-HuEpo cultures during all phases of the study. At baseline, r-HuEpo and DFO culture had a greater number of colony units than high dose r-HuEpo culture ( 103.7 +/- 50.2 vs 95.1 +/- 50.5, NS). This increase became significant after 2 weeks (145 +/- 59.3 vs 122.9 +/- 59.6, P < 0.02), and remained so at 6 (167.4 +/- 60.3 vs 149 +/- 55.6, P < 0.01) and 12 weeks (191 +/- 64.5 vs 155.1 +/- 56.3, P < 0.01). An increased proliferation was observed after DFO therapy in all culture studies: low dose r-HuEpo culture increased from 69.4 +/- 38.2 to 86.6 +/- 48.5, 115 +/- 39 and 123 +/- 46; high dose r-HuEpo culture increased from 95.1 +/- 50.5 to 122.9 +/- 59, 149 +/- 55.6 and 155.1 +/- 56.3 and r-HuEpo plus DFO culture from 103.7 +/- 50.2 to 145 +/- 59.3, 167 +/- 60.3 and 191 +/- 64.5 at 2, 6 and 12 weeks, respectively (all P < 0.01 by ANOVA). Haemoglobin, reticulocytes and soluble transferrin receptor were slightly increased, while ferritin decreased. Hypochromic erytrocytes were variable. CONCLUSIONS: DFO increases erythroid precursor proliferation and has a synergistic in vivo effect with r-HuEpo in patients with chronic renal failure. Further investigations are needed to evaluate whether such an effect may have clinical application.     

Comparison of intravenous ascorbic acid versus intravenous iron for functional iron deficiency in hemodialysis patients

The effect of intravenous ascorbic acid was compared with that of intravenous iron in the treatment of functional iron deficiency, as defined as serum ferritin levels over 300 ng/ml and serum iron levels below 50 microg/dl, in patients on chronic hemodialysis. Thirteen patients on chronic hemodialysis with functional iron deficiency received intravenous injections of ascorbic acid, 100 mg, three times a week, after hemodialysis. The therapy was continued until serum ferritin decreased to below 300 ng/ml (3 months at the maximum). The iron and control group were composed of patients who had serum iron levels below 50 microg/dl within 3 months after serum ferritin rose to over 300 ng/ml. Seven patients with the iron group received more than a total of 10 intravenous injections of saccharated ferric oxide (40 mg/dose) after hemodialysis, and seven patients with the control group received no iron preparation during the 3 months. In the ascorbic acid group, while hemoglobin did not change from 10.9 +/- 0.5 g/dl (mean +/- SE) during the three-month period, serum iron increased significantly from 37 +/- 4 microg/dl to 49 +/- 4 microg/dl after one month (p<0.01), and remained elevated until the end of the three-month period. Serum ferritin decreased significantly from 607 +/- 118 ng/ml to 354 +/- 30 ng/ml after 3 months (p<0.01). In the iron group, hemoglobin and serum iron increased significantly from the respective pre-treatment levels during the 2-month period, and serum ferritin rose significantly after 3 months. In the control group, hemoglobin, serum iron and ferritin levels decreased significantly from the respective pre-treatment levels during the 3 months. The recombinant erythropoietin dose remained stable for three months in the ascorbic acid, iron, and control groups, respectively. These results suggest that in hemodialysis patients with a functional iron deficiency, treatment with intravenous ascorbic acid can prevent iron overload due to treatment with intravenous iron, and provide a useful adjuvant means of maintaining hemoglobin and serum iron levels.     

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).     

Continuous intravenous sodium ferric gluconate improves efficacy in the maintenance phase of EPOrHu administration in hemodialysis patients

Although intravenous iron has proved to optimize the efficacy of EPOrHu in hemodialysis patients, hitherto no consensus exists with respect to the best regimen of intravenous iron administration. We started a prospective randomized study in 26 patients undergoing chronic hemodialysis who had adequate iron metabolism indices (serum ferritin >100 microg/l; %TSAT >20%; %HypoE <10% and CHr >26 pg) and were in the maintenance phase of EPOrHu administration (target hemoglobin obtained >10 g/dl). All patients were receiving sodium ferric gluconate (Ferrlecit) intermittently prior to the study and after a 1-month wash-out period where iron was not administered patients were randomized to receive the same previous dose of intravenous iron either in a continuous (6.25-21.3 mg in every hemodialysis session) or an intermittent regimen (62.5 mg every 1-4 weeks, not modifying the previous schedule of administration). At 16 weeks, the continuous group showed a significant increment in serum Hb (11.83 +/- 1.12 g/dl) with respect to baseline (10.96 +/- 1.31 g/dl) (p < 0.05), whereas no differences were obtained in intermittent group (baseline: 11.16 +/- 1.03 g/dl; 16 weeks: 11.14 +/- 0.90 g/dl, NS). In contrast with the intermittent group, serum ferritin increased significantly in the continuous group (16 weeks: 508 +/- 157 microg/l; baseline: 368 +/- 56 microg/l; p < 0.05), whereas %TSAT and CHr did not modified during the study in both groups. %HypoE increased significantly with respect to baseline values in the continuous group (p < 0.05) and close to significantly different in the intermittent group (p = 0.06). Our study suggests that hemodialysis patients in the maintenance phase of EPOrHu administration would obtain further benefit in terms of serum hemoglobin level with a continuous intravenous serum ferric gluconate regimen, at least in the short term.     

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.     

Elevation of blood thioredoxin in hemodialysis patients with hepatitis C virus infection

BACKGROUND: Thioredoxin (TRX) is a stress-inducible thiol-containing protein, which has been shown to be an indicator of oxidative stress in a variety of diseases. The association between oxidative stress and hepatitis C virus (HCV) infection, however, remains unknown in hemodialysis patients. METHODS: We measured serum TRX levels in 85 hemodialysis patients positive for anti-HCV antibodies (age, 60 +/- 1 years old; hemodialysis duration, 17 +/- 1 years; M/F = 57/28) by enzyme-linked immunosorbent assay (ELISA), and examined whether blood TRX may be associated with HCV-related hepatic injury. RESULTS: Serum TRX was significantly higher in hemodialysis patients with HCV infection (112.3 +/- 3.7 ng/mL, N = 85) than in those without HCV infection (69.7 +/- 3.3 ng/mL, N = 59) (age, 69 +/- 2 years old; hemodialysis duration, 6 +/- 1 years; M/F = 32/27, P < 0.01) or normal subjects (28.0 +/- 5.4 ng/mL, N = 9). TRX was significantly correlated with time on hemodialysis (r = 0.27, P = 0.01) in HCV-positive patients, while it was associated with the patient's age in HCV-negative patients (r = 0.42, P < 0.01). Blood TRX was significantly correlated with asparate aminotransferase in patients with HCV infection (r = 0.34, P < 0.01) and without HCV infection (r = 0.46, P < 0.01). However, serum TRX was not associated with blood alanine aminotransferase, a relatively specific marker of hepatic cellular damage, in HCV-infected hemodialysis patients. A significant relationship was found between serum ferritin and TRX (r = 0.25, P = 0.02) and malondialdehyde (MDA) values (r = 0.25, P = 002) in HCV-positive patients. Serum TRX was also higher in the patients receiving weekly iron supplement with HCV infection (135.3 +/- 10.2 ng/mL vs. 110.2 +/- 3.9 ng/mL, P = 0.06) and without HCV infection (91.8 +/- 12.1 ng/mL vs. 65.2 +/- 2.7 ng/mL, P < 0.01). CONCLUSION: There was a greater increase in serum TRX in hemodialysis patients with HCV viremia than without HCV viremia. However, there may not be an association between serum TRX and HCV-related hepatic injury. TRX increased with serum ferritin in HCV-infected patients and further increased by iron infusion. These findings indicate that HCV infection and iron loading may aggravate oxidative stress in dialysis patients.     

Determinants of soluble CD23 antigen levels in hemodialysis patients: effect of 1.25 dihydroxyvitamin D3 and recombinant human erythropoietin treatment.

BACKGROUND: The immunodeficiency of end-stage renal disease (ESRD) paradoxically coexists with T cell and monocyte activation. In spite of well known defective antibody responses in ESRD, the functional status of B cells in the immune system dysregulation of uremia is still controversial. Soluble CD23 (sCD23) antigen is a recently identified B cell activation marker and is also involved in T cell activation process. Effects of parathyroid hormone (PTH), red blood cells and ferritin on T and B cell functions have been shown both in vivo and in vitro. PATIENTS AND METHODS: In this study, serum levels of sCD23 in hemodialysis patients were determined to evaluate the functional status of B cells and possible linkages between this cytokine and PTH levels, ferritin levels, red blood cell counts were investigated. RESULTS: Serum sCD23 levels were significantly elevated in hemodialysis patients relative to healthy controls (12.5+/-8.4 micro/l vs. 2.4+/-1.1 micro/l, p<0.001). Serum sCD23 levels were negatively correlated with red blood cell count (r = -0.61, p = 0.009) and serum PTH levels (r = -0.62, p = 0.008), while positively correlated with serum ferritin levels (r = 0.63, p = 0.007) in hemodialysis patients. We also investigated the immunumodulator effects of 1.25 dihydroxyvitamin D3 (1.25OHD3) and recombinant human erythropoietin (rHu-Epo) treatment in hemodialysis patients. 1.25OHD3 treatment for eight weeks did not change serum sCD23 levels in hemodialysis patients (n = 8). On the other side, rHu-Epo administration for 16 weeks led to a decrease in serum sCD23 levels (17.7+/-8.6 microg/l vs. 9.8+/-3.5 microg/l, p = 0.007) in these patients (n = 9). CONCLUSION: These results suggests that similar to T cells, B cells are activated in uremia and the degree of this activation is correlated with red blood cell count, serum parathyroid hormone levels and iron status of the hemodialysis patients. Moreover, B cell activation could be altered by recombinant human erythropoietin therapy in hemodialysis patients.     

Significance of parenteral iron administration for HCV-positive hemodialysis patients

BACKGROUND: It is well recognized that parenteral iron administration is recommended for hemodialysis (HD) patients treated with rHuEPO. On the other hand, hepatic iron concentration increases in chronic hepatitis C, and iron reduction improves serum transaminase levels in these patients. METHODS: We compared the rHuEPO doses with hematological parameters in HCV-positive (n = 7) and HCV-negative (n = 32) HD patients when parenteral low-dose iron was administered for one year (target ferritin level: 200-300 ng/ml, target hematocrit level: 30-33%). RESULTS: None of the parameters was significantly different between the groups at the start of the study. One year later, levels of hematocrit and serum ferritin significantly increased compared with those at the start in each group (HCV-positive group: 28.0 +/- 2.7-->31.3 +/- 1.5%, p < 0.01, 119.3 +/- 171.9-->303.3 +/- 77.7 ng/ml, p < 0.05, respectively, HCV-negative group: 26.8 +/- 2.2-->30.0 +/- 3.5%, p < 0.01, 69.8 +/- 100.5-->278.4 +/- 66.4 ng/ml, p < 0.01, respectively). Serum transaminase levels were not significantly different between the start and end points in the HCV-positive group, but 2 patients showed an increase in these levels. In the HCV-negative group, the rHuEPO dose at the end point was significantly reduced compared with that at the start (4,875 +/- 2,089-->4,031 +/- 2,203 IU/W, p < 0.05). In the HCV-positive group, however, it was difficult to reduce the rHuEPO dose in order to maintain the target hematocrit level (4,071 +/- 1,134-->3,857 +/- 1,464 IU/W, NS). CONCLUSION: We suggested that rHuEPO should be used together with parenteral iron administration, even in HCV-positive HD patients, because it is safe at low doses under careful observation.     

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)     

Effect of a low calcium dialysate on parathyroid hormone secretion in diabetic patients on maintenance hemodialysis.

Diabetic patients on maintenance dialysis often are characterized by a relative parathyroid hormone (PTH) deficiency and a form of renal osteodystrophy with low bone turnover known as adynamic bone. The goal of the present study was to determine whether a reduction in the dialysate calcium concentration would increase the predialysis (basal) PTH and maximal PTH level. Thirty-three diabetic maintenance hemodialysis patients with basal PTH values less than 300 pg/ml were randomized to be dialyzed with either a regular (3.0 mEq/liter or 3.5 mEq/liter, group I) or low (2.25 mEq/liter or 2.5 mEq/liter, group II) calcium dialysate for 1 year. At baseline and after 6 months and 12 months of study, low (1 mEq/liter) and high (4 mEq/liter) calcium dialysis studies were performed to determine parathyroid function. At baseline, basal (I, 126+/-20 vs. II, 108+/-19 pg/ml) and maximal (I, 269 pg/ml+/-40 pg/ml vs. II, 342 pg/ml+/-65 pg/ml) PTH levels were not different. By 6 months, basal (I, 98+/-18 vs. II, 200+/-34 pg/ml, p = 0.02) and maximal (I, 276 pg/ml+/-37 pg/ml vs. II, 529 pg/ml+/-115 pg/ml; p = 0.05) PTH levels were greater in group II. Repeated measures analysis of variance (ANOVA) of the 20 patients who completed the entire 12-month study showed that only in group II patients were basal PTH (p = 0.01), maximal PTH (p = 0.01), and the basal/maximal PTH ratio (p = 0.03) different; by post hoc test, each was greater (p < 0.05) at 6 months and 12 months than at baseline. When study values at 0, 6, and 12 months in all patients were combined, an inverse correlation was present between basal calcium and both the basal/maximal PTH ratio (r = -0.59; p < 0.001) and the basal PTH (r = -0.60; p < 0.001). In conclusion, in diabetic hemodialysis patients with a relative PTH deficiency (1) the use of a low calcium dialysate increases basal and maximal PTH levels, (2) the increased secretory capacity (maximal PTH) during treatment with a low calcium dialysate suggests the possibility of enhanced parathyroid gland growth, and (3) the inverse correlation between basal calcium and both the basal/maximal PTH ratio and the basal PTH suggests that the steady-state PTH level is largely determined by the prevailing serum calcium concentration.     

Significance of serum neuron-specific enolase in patients with acute traumatic brain injury

OBJECTIVE: To study the association between serum neuron-specific enolase (NSE) and the extent of brain damage and the outcome after acute traumatic brain injury (TBI). METHODS: The release patterns of serum NSE in 78 patients after acute TBI were analyzed by using the enzyme linked immunosorbent assay. The levels of NSE were compared with Glasgow coma scale, the category of brain injury and the outcome after 6 months of injury. RESULTS: There were different NSE values in patients with minor (12.96 microg/L+/-2.39 microg/L), moderate (23.44 microg/L+/-5.33 microg/L) and severe brain injury (42.68 microg/L+/-4.57 microg/L). After severe TBI, the concentration of NSE in patients with epidural hematomas was 13.38 microg/L+/-4.01 microg/L, 24.03 microg/L+/-2.85 microg/L in brain contusion without surgical intervention group, 55.20 microg/L+/-6.35 microg/L in brain contusion with surgical intervention group, and 83.85 microg/L+/-15.82 microg/L in diffuse brain swelling group. There were close correlations between NSE values and Glasgow coma scale (r=-0.608, P<0.01) and the extent of brain injury (r=0.75, P<0.01). Patients with poor outcome had significantly higher initial and peak NSE values than those with good outcome (66.40 microg/L+/-9.46 microg/L, 94.24 microg/L+/-13.75 microg/L vs 32.16 microg/L+/-4.21 microg/L, 34.08 microg/L+/-4.40 microg/L, P<0.01, respectively). Initial NSE values were negatively related to the outcome (r=-0.501, P<0.01). Most patients with poor outcomes had persisting or secondary elevated NSE values. CONCLUSIONS: Serum NSE is one of the valuable neurobiochemical markers for assessment of the severity of brain injury and outcome prediction.     

Deferoxamine test and bone disease in dialysis patients with mild aluminum accumulation

Aluminum bone disease is a frequent complication of dialysis patients. The deferoxamine (DFO) test has been advocated as a noninvasive procedure for the diagnosis of AI bone lesion. However most of these studies have been performed in symptomatic patients with significant AI bone disease. Whether this test may provide similar data at an earlier stage of AI toxicity is not known. The present study evaluates prospectively 28 patients with mild AI load. Patients studied ranged in age from 21 to 65 years; duration of dialysis was 5.6 +/- 3.2 years; deferoxamine, 40 mg/kg body weight, was infused at the end of dialysis. Serum AI was measured before DFO administration and before the next dialysis treatment. Bone biopsies were performed in all patients. Cortical bone AI was determined biochemically; trabecular and cortical bone AI were also determined histochemically. Mean basal serum AI (43.2 +/- 30.8 micrograms/L) and cortical bone AI (25.7 +/- 35.2 micrograms/g) were moderately increased. Basal serum AI correlated (r = 0.77) with the increment in serum AI after DFO infusion. After DFO, stainable trabecular and cortical bone AI correlated in a similar manner with both basal serum AI and increment in serum AI. Only biochemically determined cortical bone AI was not significantly related to basal serum AI. Nineteen of the 28 patients had evidence of osteitis fibrosa on bone biopsy. Stained AI surfaces but not trabecular AI were different in patients with low and patients with high bone formation rates. The bone findings, assessed as bone formation rates and resorption surfaces, did not correlate with biochemically or histochemically determined bone AI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute aluminum encephalopathy in a dialysis center caused by a cement mortar water distribution pipe

BACKGROUND: In Cura?ao, distilled seawater from the water plant was used without further purification for hemodialysis for several decades. A new distribution pipe supplying water to a dialysis center on the island was installed in May 1996. To protect it from corrosion, this pipe was lined on the inside with a cement mortar. Because of the aggressiveness of the distilled water, calcium and aluminum (Al) leached from the cement mortar into the water used to prepare dialysate. This caused a possible hard water syndrome and definite acute Al intoxication. METHODS: We reviewed clinical details and outcome at follow-up, and arranged laboratory and toxicological studies of serum and hemodialysis water. RESULTS: Of the 27 patients who had a similar exposure ( approximately 60 hours) to the contaminated dialysate, 10 died from acute Al encephalopathy, whereas 17 patients had no or only minor symptoms and survived. The nonsurvivors were older (64 +/- 3 years vs. 52 +/- 2 years, P < 0.01) and had a lower body weight (57.5 +/- 5.9 kg vs. 86.5 +/- 4.1 kg, P < 0.01) and lower serum albumin concentrations (33 +/- 1 vs. 36 +/- 1 g/L, P < 0.01). Anuria tended to be more common in the nonsurvivors (8 out of 10 vs. 8 out of 17, P> 0.05). Serum Al concentrations, available in seven nonsurvivors, were significantly higher than in the survivors (808 +/- 127 vs. 255 +/- 25 microg/L, P < 0.01). CONCLUSIONS: The water distribution pipe was lined with a cement mortar that was probably inappropriate for transporting drinking water. Water distribution facilities as well as the dialysis community should be aware of the possibility of Al leaching from cemented water distribution pipes. Similar Al loads appear to induce a more severe intoxication in malnourished, older patients with smaller Al distribution volumes and anuria.