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.     

Trace elements and lipid peroxidation abnormalities in patients with chronic renal failure

Plasma selenium (Se), zinc (Zn) and copper (Cu) levels and antioxidant metalloenzymes, glutathione peroxidase (GPX) and superoxide dismutase (SOD), were studied in 17 patients on maintenance hemodialysis (HD) (group I), 14 uremic patients (group II) and 14 healthy subjects (group III). Plasma Se levels and erythrocyte GPX were significantly lower in the HD group (for Se: 0.69 +/- 0.12 vs. 1.05 +/- 0.13 mumol/l in controls; for erythrocyte GPX: 34.4 +/- 6.4 vs. 49.2 +/- 9 IU/g hemoglobin in controls) and a significant correlation was found between the two parameters (r = 0.66, p less than 0.005). There was also a correlation between decreased plasma Zn and erythrocyte SOD activity (r = 0.58, p less than 0.02) and between decreased plasma Cu and erythrocyte SOD (r = 0.60, p less than 0.02). Plasma malondialdehyde levels were augmented in HD patients (5.08 +/- 0.26 vs. 2.55 +/- 0.15 mumol/l in controls and 2.79 +/- 0.40 mumol/l in the uremic group). The catalase activity was increased in HD patients (202 +/- 24 vs. 140 +/- 40 IU/mg hemoglobin in group III). A defective antioxidant activity may thus contribute to increased peroxidative damage to cells in the course of dialysis.     

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.     

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.     

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.     

Vitamin D, desferrioxamine and aluminum-induced bone disease in uremic rats

The effect of 100 ng 1 alpha-OH vitamin D/week alone and in combination with desferrioxamine (DFO), 150 mg/week, was evaluated in aluminum loaded uremic rats. Vitamin D (Vit D) caused an increase of Al in muscle and a decrease in serum Al. Bone histology showed mineralization defect and an increase in bone mass, due to an increase in unmineralized bone, induced both by Al and Vit D administration. Treatment with DFO enhanced urinary Al excretion and lowered tissue Al, without inducing major changes of static bone histology. It is concluded that in Al-loaded uremic rats Vit D can redistribute body Al and that both Al and Vit D can cause a mineralization defect. A 6-week treatment with DFO lowers tissue Al without changing significantly static bone parameters.     

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.     

The effects of discontinuation of aluminum exposure on aluminum-induced osteomalacia

Studies in patients on dialysis have shown that aluminum (Al) accumulation in bone plays a major role in the pathogenesis of osteomalacia. It has been suggested that deferoxamine (DFO) may be beneficial in the treatment of aluminum-induced osteomalacia. The present studies were performed in four groups of uremic rats to determine if DFO and/or discontinuation of Al administration have an effect on bone histomorphometry and blood chemistries. The groups were: 1) uremic control 2) aluminum (0.75 to 1.0 mg/rat i.p., five times a week for twelve weeks): 3) aluminum + DFO, after twelve weeks Al was discontinued and the rats received DFO (75 mg/rat two times a week for nine weeks); 4) aluminum + time, after twelve weeks Al was discontinued and the rats were sacrificed after nine weeks. High levels of Al in serum and bone and low levels of PTH were seen in rats receiving Al. Bone histology revealed Al at the mineralization front, abnormal tetracycline uptake, and an increase in osteoid. DFO treatment did not significantly change the level of Al in bone, however both DFO treatment and discontinuation of Al reversed towards normal the above described lesions. In conclusion, these studies suggest that DFO and/or discontinuation of Al administration to rats with approximately 30% of renal function greatly improve aluminum-induced osteomalacia.     

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).     

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)     

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)     

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.     

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.     

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.     

Indirect clinical evidence that 1 alpha OH vitamin D3 increases the intestinal absorption of aluminum

In a previous study we showed that 1 alpha OH vitamin D3 [1 alpha (OH)3] given to 16 hemodialyzed patients taking Al(OH)3 at a constant dose increased their plasma concentrations of aluminum [Demontis et al. 1986]. In order to choose between 2 possible mechanisms explaining this increase (increased intestinal absorption or decreased tissue storage of aluminum), we gave, in the present study, 1 alpha (OH)3 the same dose (6 micrograms per week) for the same period (4 weeks) to 15 stable hemodialyzed patients after their Al(OH)3 had been discontinued for 6 weeks. Under Al(OH)3 treatment they had a mean plasma aluminum (2.33 +/- 2.36 mumol/l) which was not significantly different from that of the patients in our former study (1.23 +/- 0.25 mumol/l). After Al(OH)3 discontinuation, plasma aluminum (measured by inductively coupled plasma emission spectrometry) decreased significantly as early as the 2nd week of the control period (1.39 mumol/l). The decrease was maintained at a plateau throughout the 5 weeks of the control period (1.38 mumol/l), the 4 weeks of 1 alpha OH vitamin (vit) D3 administration (1.40 mumol/l) and the 8 weeks of the post 1 alpha (OH)3 period (1.22 mumol/l). Plasma calcium and phosphate concentrations increased significantly with 1 alpha (OH)3 and decreased thereafter whereas plasma PTH concentrations decreased during 1 alpha (OH)2 D3 and increased after its discontinuation suggesting biological activity of 1 alpha (OH)3. Since 1 alpha (OH)3 increases plasma aluminum in hemodialyzed patients only when they are simultaneously taking Al(OH)3, it is suggested that this increase is explained by an increase of intestinal absorption of aluminum and not by a tissue redistribution of aluminum.     

Comparative evaluation of bone aluminum content and bone histology in patients on chronic hemodialysis and hemofiltration

In order to compare hemofiltration (HF) and hemodialysis (HD) in connection with the risk of aluminum overload and renal osteodystrophy, double bone biopsies after double tetracycline labeling and a desferrioxamine test were performed in 12 patients on HF and 15 patients on HD. The aluminum concentration was low (less than 0.6 mumol/l) both in the dialysate and the substitution fluid. The duration of treatment (about 2 years) and the cumulative doses of Al(OH)3 and CaCO3 were comparable in the two groups. None of the patients was taking 1 alpha-OH-D. The aluminum balance during an HF run ranged from -22 to +1.8 mumol/l, the balance being positive only when the plasma aluminum was less than 0.5 mumol/l. Basal plasma aluminum and its increase induced by desferrioxamine were comparable in the two groups. Bone aluminum content was also comparable, but was about 10 times higher than in 7 nonuremic controls. Bone aluminum content and plasma aluminum increase after desferrioxamine were correlated to the Al(OH)3 cumulative dose. None of the patients had florid osteomalacia with increased osteoid thickness, and only 1 in each group had traces of stainable aluminum. The mineralization front was decreased in 8 of 12 HF and in 9 of 14 HD patients, so that no difference was observed between the means of the two groups. The predominant histological bone picture of the patients was osteitis fibrosa which was present in 10 of 12 HF and in 13 of 15 HD patients. Mean osteoclast count and active resorption surface were comparable in the two groups, but was increased (5-10 times the mean of the controls).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum-aluminum in nondialyzed chronic uremic patients before and during treatment with aluminum-containing phosphate-binding gels

Se-aluminum was measured in a study group and a control group of undialyzed chronic uremic patients having a similar reduction of kidney function (median GFR 7 [range 5-15] ml/min/1.73 m2). Se-aluminum values (0-11, median 3, micrograms/l) in the control group (31 patients) receiving no treatment with aluminum-containing phosphate-binding gels, were all below the upper normal range (17 micrograms/l). The study group (28 patients) was treated with oral Al(OH)3 for 0.5-18 (median 6) months. Se-aluminum in this group was 17-230 (median 35) micrograms/l. It is concluded that se-aluminum increases in undialyzed chronic uremic patients ingesting aluminum-containing antacids. The study suggests that se-aluminum varies with the daily dose of aluminum hydroxide, and that se-aluminum in particular increases when the daily doses are more than 3 g Al(OH)3.     

Implications of hypervitaminosis A on the calcium-phosphate metabolism and on blood lipids in hemodialysis

Serum levels of vitamin A (VA) were measured in 71 hemodialysis (HD) patients and in 30 normal controls. 65 of the 71 patients were taking multivitamin preparations (MP) containing VA. The HD patients had significantly greater values: 7.81 +/- 2.86 mumol/l (224 +/- 82 micrograms/dl) versus 3.97 +/- 0.97 mumol/l (114 +/- 28 micrograms/dl; p less than 0.0005); those taking MP with large doses of VA showed the highest levels. Patients were divided as having normal (group I, n = 21) or elevated (group II, n = 50) serum levels of VA. Patients of group II had higher levels of serum calcium (Ca) and lower of serum phosphate (P) and PTH than those of group I. Four months after the withdrawal of oral VA, the serum levels of VA and Ca fell significantly in group II, while the serum P increased. On the contrary, in group I serum levels of VA, Ca and P remained unchanged. Serum triglycerides (TG) were significantly higher in group II but did not change after the withdrawal of VA. No differences between both groups of patients were observed for age, time on HD, residual diuresis, residual renal function, serum levels of cholesterol (CL) or anemia. A retrospective study of 18 hepatic biopsies of HD patients disclosed hyperplasia of Ito cells (VA-storaging cells) in 7 of them. These 7 biopsies belonged to patients who had taken large amounts of oral VA. Our data indicate that prolonged VA intake in HD patients is followed by an increase of serum CA, a decrease of serum P and PTH and a hepatic accumulation of VA.(ABSTRACT TRUNCATED AT 250 WORDS)     

不同血液净化方式对尿毒症透析患者血中细胞因子清除的临床应用

目的 研究不同血液净化方式对尿毒症透析患者血中细胞因子的清除效果.方法 将2006年4月至2009年2月在我院血液净化中心透析的45例患者按随机数字表法分为(1)血液透析联合血液灌流组;(2)血液透析滤过组;(3)HD组,血液透析组,每组15例.血液透析联合血液灌流组、血液透析滤过组每周治疗1次,每组患者治疗3次,中间间隔1周,第1次及第3次治疗前、后各从动脉端采血5 ml,并留取正常健康对照组血液,整批送检.测定治疗前、后血清细胞因子的浓度.结果 血液灌流联合血液透析组、血液透析滤过组及血液透析组治疗前、后白细胞介素1β、白细胞介素6、肿瘤坏死因子α浓度与健康对照组比较差异有统计学意义(P＜0.01);血液透析组患者血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(3±10)ng/L、(4±9)ng/L、(4±9)ng/L,治疗前、后差值比较分别为176.0%、141.0%、187.0%,血液透析滤过组血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(39±15)ng/L、(36±14)ng/L、(45±16)ng/L,治疗前后差值比较分别为24.6%、22.1%、29.8%,血液灌流联合血液透析组血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平分别为(48±16)ng/L、(38±15)ng/L、(50±14)ng/L,治疗前差值比较分别为27.8%、23.9%、32.3%,3组患者血肿瘤坏死因子α、白细胞介素1β、白细胞介素6水平间比较差异有统计学意义(t分别=17.39、11.24、21.89,P均＜0.01).结论 不同的血液净化方式对各类细胞因子的清除效果不同,其中液灌流联合血液透析组及血液透析滤过组治疗埘细胞因子清除有效,血液透析组治疗对细胞因子清除基本无效,液灌流联合血液透析组及血液透析滤过组细胞因子清除效果与血液透析滤过组比较差异无统计学意义(P＞0.05).     

The effect of trimethoprim on serum creatinine

The influence of trimethoprim on renal function has been investigated in two groups of volunteers, both without a history of either acute or chronic urinary tract disease. All had normal serum creatinine. They were treated with trimethoprim 200 mg bd for 14 days. In group A (median age 78 years), serum creatinine increased significantly from median 89 to 134 mumol/l (P less than 0.01) during the first week and returned to normal 1 week after termination of treatment to median 90 mumol/l (P less than 0.02). After 1 week's treatment in group B (median age 29 years), serum creatinine had increased significantly from median 87 to 107 mumol/l (P less than 0.05), remained stable in the second week and returned to the pre-treatment level 1 week after cessation of treatment: 87 mumol/l (P less than 0.05). The glomerular filtration rate determined by 51Cr-EDTA clearance did not change. There was a significant decrease in the 24-h endogenous creatinine clearance after 14 days' treatment from 111 to 87 ml/min/1.73 m2 (P less than 0.05). Our results are consistent with an age-independent reversible trimethoprim-induced inhibition of the tubular secretion of creatinine.