Removal of aluminoxamine and ferrioxamine by charcoal hemoperfusion and hemodialysis.

We studied the removal of aluminoxamine (AlO) and ferrioxamine (FO) by (i) hemoperfusion/hemodialysis using an AluKart in combination with either a Cuprophan F-120 or a Hemophan FH-160 membrane, or (ii) hemodialysis with a high-flux F-60 polysulfone membrane. The same six dialysis patients underwent in a random order dialysis by the three set-ups after i.v. infusion of 30 mg/kg of desferrioxamine (DFO) during the last half an hour of the preceding dialysis session. The mean +/- SD plasma AlO and FO clearances of the AluKart combined with either a F-120 or FH-160 membrane were 194.3 +/- 25.8 ml/min (AlO) and 164.2 +/- 41.3 ml (FO) at the start of dialysis declining to respectively 76.6 +/- 27.3 and 68.5 +/- 42.6 ml/min at the end of dialysis. With a high-flux dialysis membrane the intra-dialytic plasma clearance remained constant at 81.5 +/- 6.8 ml/min for AlO and 60.0 +/- 2.8 ml/min for FO. In the presence of an AluKart combined with a FH-160 up to 84 +/- 27% and 84 +/- 19% of the available AlO and FO could be removed during a four-hour hemoperfusion/hemodialysis session. During the first hour of dialysis, respectively 59 and 58% of the total amount of AlO and FO extracted by the AluKart was removed compared to only 9 and 16% during the last hour.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of dry body-weight in haemodialysis patients by the biochemical marker cGMP

We investigated whether cGMP might be a suitable marker of ideal weight in chronic haemodialysis patients. In 20 patients on chronic haemodialysis (10 males, 10 females, mean age 55.5 +/- 7.4 years; mean interdialytic weight gain 2.4 +/- 1.1 kg) we determined plasma ANP and cGMP values before and after several haemodialysis treatments. ANP and cGMP before haemodialysis were markedly elevated (ANP 255 +/- 190 pg/ml; cGMP 28.6 +/- 16.2 pmol/ml). A significant decrease was found after haemodialysis (ANP 169 +/- 88 pg/ml; cGMP 13.5 +/- 7.4 pmol/ml). These values were still well above normal. There was a significant positive correlation between excessive body-weight delta P (difference between actual weight and estimated ideal weight), indicating fluid overload and ANP before (r = 0.57; P less than 0.001) and after haemodialysis (r = 0.47; P less than 0.001) as well as cGMP before (r = 0.42; P less than 0.01) and after haemodialysis (r = 0.85; P less than 0.0001). With cGMP and delta P after haemodialysis, the correlation appeared to be close enough for clinical application. All patients with a cGMP value of 18 pmol/ml or more after haemodialysis had an excessive body-weight of at least 0.5 kg. We conclude from these data that the plasma cGMP value determined immediately after haemodialysis is a sensitive marker for hyperhydration in patients with end-stage renal disease.     

Diagnosis and treatment of iron overload in paediatric patients on chronic haemodialysis

In this study the incidence and contributing factors of iron overload in paediatric patients treated with intermittent haemodialysis were evaluated. Particular attention was given to the diagnostic value of serum ferritin in the assessment of body iron stores in patients with hepatocellular damage. The results of treatment of secondary haemosiderosis with desferrioxamine (DFO) are reported. Serum ferritin levels were measured in 18 children and adolescents undergoing long-term haemodialysis; 8 of these had biochemical evidence of hepatocellular damage. In all patients a good correlation was found between serum ferritin levels and the amount of iron stored in the reticuloendothelial system. Six patients developed iron overload. Patients with secondary haemosiderosis were younger at the start of haemodialysis and received significantly more blood. Although not significant, more patients with haemochromatosis-associated alleles and bilateral nephrectomy had iron overload, and the duration of dialysis was obviously longer for overloaded patients (40 months versus 26 months). The patients with iron overload were treated with DFO. The data from all patients showed that DFO was ineffective when administered at a dose of 25 mg/kg during dialysis and that in individual patients changes in serum ferritin correlated with changes in the amount of blood transfusions administered.     

Daily nutrient intake represents a modifiable determinant of nutritional status in chronic haemodialysis patients.

BACKGROUND: In maintenance haemodialysis patients, daily food intake is changeable; however, its relationship with nutritional status is unexplored. This study aimed to evaluate the isolated, long-term effect of daily nutrient intake on nutritional status in haemodialysis patients. METHODS: We performed a prospective 1-year controlled study in 27 chronic haemodialysis patients, without recognized risk factors for malnutrition. Each day for 1 week, four times in the year, we measured protein nitrogen appearance, and assessed dietary protein (DPI) and energy (DEI) intake from dietary diaries. We compared the nutritional outcome of patients spontaneously reducing nutrient intake below the threshold of 0.8 g/kg body weight/day for DPI and 25 kcal/kg body weight/day for DEI during the week (LOW, n = 8), with controls at adequate nutrient intake (CON, n = 19). An interventional 6-month study was then carried out in LOW to verify the cause-effect relationship. RESULTS: All patients showed a day-by-day reduction of whole nutrient intake during interdialytic period, which was mostly relevant in the third interdialytic day (L3). During the 1-year study, even in the presence of adequate dialysis dose and normal inflammatory indexes, body weight (68.0 +/- 5.5 to 65.8 +/- 5.9 kg), serum albumin (3.96 +/- 0.07 to 3.66 +/- 0.06 g/dl) and creatinine (9.2 +/- 1.1 to 8.1 +/- 0.7 mg/dl) significantly decreased in LOW but not in CON. Diaries evidenced in LOW a reduced number of meals at L3 that was explained by the fear of excessive interdialytic weight gain. During the interventional study, daily DPI and DEI increased at L3; this was associated with a significant increment of body weight, and serum albumin and creatinine levels. CONCLUSIONS: In maintenance haemodialysis patients the persistent, marked reduction of daily nutrient intake, even if limited to a single day of the week, is an independent determinant of reversible impairment of nutritional status.     

Low sodium haemodialysis reduces interdialytic fluid consumption but paradoxically increases post-dialysis thirst.

BACKGROUND: Interdialytic weight gain (IDWG) can be reduced by lowering the dialysate sodium concentration ([Na]) in haemodialysis patients. It has been assumed that this is because thirst is reduced, although this has been difficult to prove. We compared thirst patterns in stable haemodialysis patients with high and low IDWG using a novel technique and compared the effect of low sodium dialysis (LSD) with normal sodium dialysis (NSD). METHODS: Eight patients with initial high IDWG and seven with low IDWG completed hourly visual analogue ratings of thirst using a modified palmtop computer during the dialysis day and the interdialytic day. The dialysate [Na] was progressively reduced by up to 5 mmol/l over five treatments. Dialysis continued at the lowest attained [Na] for 2 weeks and the measurements were repeated. The dialysate [Na] then returned to baseline and the process was repeated. RESULTS: Baseline interdialytic day mean thirst was higher than the dialysis day mean for the high IDWG group (49.9+/-14.0 vs 36.2+/-16.6) and higher than the low weight gain group (49.9+/-14.0 vs 34.1+/-14.6). This trend persisted on LSD, but there was a pronounced increase in post-dialysis thirst scores for both groups (high IDWG: 46+/-13 vs 30+/-21; low IDWG: 48+/-24 vs 33+/-18). The high IDWG group demonstrated lower IDWG during LSD than NSD (2.23+/-0.98 vs 2.86+/-0.38 kg; P<0.05). CONCLUSIONS: Our results indicate that patients with high IDWG experience more intense feelings of thirst on the interdialytic day. LSD reduces their IDWG, but paradoxically increases thirst in the immediate post-dialysis period.     

Recombinant erythropoietin reverses polymorphonuclear granulocyte dysfunction in iron-overloaded dialysis patients

Iron overload increases the risk of bacterial infection in dialysis patients, partly by impairing functions of the polymorphonuclear granulocytes (PMNs). PMN defence was studied sequentially in haemodialysis patients with transfusional haemosiderosis, treated for 6 +/- 1.5 months (n = 8) to 13 +/- 1.7 months (n = 4) with recombinant human erythropoietin (rHuEpo). Over this period, signs of iron overload (increased serum ferritin and serum iron) improved, and stainable iron disappeared in PMNs. Simultaneously, phagocytosis of Yersinia enterocolitica by PMNs improved. The decrease in serum ferritin was significantly related to the improved phagocytosis. Killing of Y. enterocolitica by PMNs also improved. It is anticipated that rHuEpo therapy in iron-overloaded dialysis patients could decrease the incidence of bacterial infection by improving PMN functions in these 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.     

Nutritional status in type 2 diabetic patients requiring haemodialysis.

BACKGROUND: Type 2 diabetic patients with end-stage renal disease are often overweight (BMI > 24) at the start of dialysis therapy. However, there are very few reports in the literature concerning the nutritional status of these patients after prolonged haemodialysis treatment. Therefore, we compared nutritional parameters in type 2 diabetic patients and age-matched non-diabetic patients after at least 18 months of renal replacement therapy with haemodialysis. METHODS: In a cross-sectional study, we measured BMI, serum albumin, total protein, serum cholesterol and interdialytic weight gain (IWG), and performed a subjective global assessment (SGA) in 14 patients with type 2 diabetes and 16 non-diabetic patients (aged > or = 50 years, haemodialysis therapy > or = 18 months). Protein intake was estimated using the protein catabolic rate (PCR) and Kt/V was calculated to compare the dose of dialysis. RESULTS: BMI was significantly higher in patients with type 2 diabetes (30+/-7 vs 24+/-3, P<0.01). In contrast, the concentration of serum albumin was significantly lower (3180+/-499 mg/dl vs 3576+/-431 mg/dl, P<0.05), but six of the diabetic patients had signs of chronic inflammation. All other nutritional parameters did not differ between the two groups. In addition, there were no significant differences in the intake of protein (PCR 0.93+/-0.19 vs 0.92+/-0.22) and the dose of dialysis (Kt/V 1.13+/-0.19 vs 1.2+/-0.2). CONCLUSION: After > or = 18 months of haemodialysis therapy, the majority of type 2 diabetic patients (9/14) were still overweight (BMI > 24). The nutritional status of diabetic patients was similar to that of age-matched non-diabetic patients on prolonged haemodialysis, but serum albumin levels were significantly lower in diabetics. The lower albumin levels in the diabetic patients may be explained by a state of subclinical chronic inflammation.     

Desferrioxamine infusion can modify EEG tracing in haemodialysed patients

Neurological derangement has been reported in haemodialysed patients receiving intravenous desferrioxamine (DFO) for aluminium-related disorders. The possible direct effects of desferrioxamine on EEG recordings were investigated in ten haemodialysed patients who underwent a DFO test 2 h after the end of dialysis. According to a commonly accepted protocol, 40 mg/kg body-weight of desferrioxamine was infused in 60 min. EEG recording was continuously performed, starting 30 min before and stopping 30 min after the desferrioxamine infusion. Besides visual inspection, EEG records were digitised, tapered, and spectrally analysed with Digital PDP 11/73 microcomputer. Basal EEG recording was normal in all patients. In three patients a progressive EEG slowing was detected by visual inspection during desferrioxamine infusion; in these cases automatic analysis revealed a 50% increase in power of slower frequencies 30 min after starting the infusion, when no changes in plasma aluminium concentrations are detected; a complete recovery was observed 30 min after desferrioxamine withdrawal. In one patient bilateral paroxysms of slow waves appeared, so we stopped desferrioxamine infusion. Two of the three patients who developed EEG abnormalities also had an increased aluminium body burden (positive DFO test). Results indicated that desferrioxamine per se can modify EEG in haemodialysis patients and that its effect is not mediated by acute increases of plasma aluminium concentrations. The finding of a positive DFO test in two of three patients with EEG changes may suggest that an aluminium-induced blood-brain barrier derangement could have played a role. However, prompt recovery after ceasing desferrioxamine infusion strongly suggests a direct role of desferrioxamine in the induction of EEG changes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of body fluid distribution between chronic haemodialysis and peritoneal dialysis patients as assessed by biophysical and biochemical methods.

BACKGROUND: The control of extracellular volume is a key parameter for reducing hypertension and the incidence of cardiovascular mortality in dialysis patients. In recent years bioimpedance measurement (BIA) has been proven as a non-invasive and accurate method for measuring intracellular and extracellular fluid spaces in man. In addition, plasma atrial natriuretic peptide (ANP) and cyclic guanosine monophosphatase (cGMP) concentrations have been shown to reflect central venous filling. Using these methods, we compared body fluid status between stable patients on haemodialysis and peritoneal dialysis. METHODS: Thirty-nine chronic haemodialysis patients, 43 chronic peritoneal dialysis patients and 22 healthy controls were included in the study. Multifrequency BIA was performed using the Xitron BIS4000B device (frequencies from 5 to 500 kHz were scanned and fitted) in patients before and after haemodialysis. Peritoneal dialysis patients were measured after drainage of the dialysate. Plasma ANP and cGMP levels were measured in plasma using a (125)I solid phase RIA. Serum albumin concentrations and serum osmolality were measured in all patients. The body fluid data were analysed in relation with the clinical findings. RESULTS: Total body water (TBW) was 0.471+/-0.066 l/kg before haemodialysis and 0.466+/-0.054 l/kg after haemodialysis. Peritoneal dialysis patients had a TBW (0.498+/-0.063 l/kg) that was greater than the before and after dialysis values of haemodialysis patients. The extracellular body fluid (V(ecf)) was increased pre-haemodialysis. It was even greater in peritoneal dialysis patients compared with patients both pre- and post-haemodialysis (pre 0.276+/-0.037 l/kg; post 0.254+/-0.034 l/kg; peritoneal dialysis 0.293+/-0.042 l/kg, P<0.05). However, plasma ANP concentrations (representing intravascular filling) in peritoneal dialysis patients were comparable with post-haemodialysis values (284+/-191 pg/ml vs 286+/-144 pg/ml). The correlation coefficient between sysRR and V(ecf) was r=0.257 in haemodialysis (P=0.057) and r=0.258 in peritoneal dialysis (P<0.05). A significant negative correlation was found between serum albumin and V(ecf)/TBW in peritoneal dialysis patients (r= -0.624). CONCLUSION: Body fluid analysis by BIA demonstrated that TBW and V(ecf) were increased in peritoneal dialysis patients, and were comparable or even greater than values found before haemodialysis. However, plasma ANP levels indicated that intravascular filling was not increased in peritoneal dialysis. The ratio of V(ecf) to TBW was correlated to systolic pressure and negatively to serum albumin in peritoneal dialysis patients.     

Insulin action on glucose and protein metabolism during L-carnitine supplementation in maintenance haemodialysis patients.

BACKGROUND: Impaired protein anabolism and insulin resistance are characteristic features of maintenance haemodialysis patients. We have used a randomised, matched-paired, double-blind, placebo-controlled experimental design to determine the capability of intravenous L-carnitine supplementation to modify insulin resistance and protein catabolism in non-diabetic patients with end-stage renal disease (ESRD) undergoing chronic haemodialysis treatment. METHODS: L-carnitine (20 mg x kg(-1)) (n = 9) or placebo (n = 10) were given intravenously at the end of seven consecutive dialysis sessions. Whole-body protein and glucose metabolism were assessed on interdialytic days by the L[1-(13)C]leucine and the [2,2-(2)H(2)]glucose kinetic models in the postabsorptive state and during euglicemic hyperinsulinemic clamp studies at baseline and at the end of the treatment period. RESULTS: L-carnitine supplementation was associated with lower (P < 0.05) rates of leucine oxidation (-11 +/- 12%) and appearance from proteolysis (-6 +/- 2%) during the clamp studies than after placebo supplementation. The rates of glucose appearance in the postabsorptive state did not change significantly in the patients receiving L-carnitine treatment. Insulin-mediated glucose disappearance was improved by L-carnitine only in those patients (n = 5) (+18 +/- 3%, P < 0.05 vs placebo group, n = 5) with greater baseline insulin resistance, selected according to the median value of insulin sensitivity before treatment. CONCLUSIONS: L-carnitine supplementation was associated with protein-sparing effects in maintenance haemodialysis patients during hyperinsulinemia.     

Dietary potassium and laxatives as regulators of colonic potassium secretion in end-stage renal disease.

BACKGROUND: In end-stage renal disease (ESRD), colonic potassium (K+) secretion increases as renal K+ excretion declines. The nature of this adaptive process is poorly understood, but post-prandial increases in plasma K+ concentration may be a determining factor. In addition, even though colonic K+ secretion increases in ESRD, interdialytic hyperkalaemia is a serious problem in haemodialysis patients, which might be reduced by stimulating colonic K+ secretion still further using laxatives. METHODS: Plasma K+ concentrations were measured in the fasting state, and for 180 min after the oral administration of 30 mmol of K+ to nine control subjects and 16 normokalaemic patients with ESRD (eight "predialysis" patients and eight patients undergoing continuous ambulatory peritoneal dialysis (CAPD)). Plasma K+ concentrations were also monitored for 180 min in fasting controls and ESRD patients who were not given the oral K+ load. To study the effect of laxatives on interdialytic hyperkalaemia, plasma K+ concentrations were measured in eight control subjects and 13 haemodialysis patients before and during 2 weeks treatment with bisacodyl (a cAMP-mediated laxative) and in five haemodialysis patients before and during 2 weeks treatment with lactulose (an osmotic laxative). RESULTS: Oral K+ loading caused plasma K+ concentration to rise within the normal range (3.5-5.1 mmol/l) in control subjects, while significantly higher concentrations were achieved in the "predialysis" patients and sustained hyperkalaemia developed in the CAPD patients. Bisacodyl treatment had no effect on plasma K+ concentrations in control subjects, but significantly decreased the mean interdialytic plasma K+ concentration (from 5.9+/-0.2 to 5.5+/-0.2 mmol/l, P<0.0005) in haemodialysis patients, whereas plasma K+ concentration did not change during lactulose treatment. CONCLUSIONS: Higher plasma K+ concentrations after food may help to maintain K+ homeostasis in ESRD by enhancing colonic K+ secretion. Bisacodyl may be useful for reducing interdialytic hyperkalaemia in patients undergoing haemodialysis.     

The outcome of chronic dialysis in infants and toddlers--advantages and drawbacks of haemodialysis.

BACKGROUND: Improvements in dialysis technology allow replacement therapy for even the youngest of children with end stage renal disease. Nevertheless, the cumulative experience in this age group is limited. METHODS: We compared the outcome of 20 children who initiated chronic dialysis before the age of 1 year (weight 4.9 +/- 2 kg, Group 1), with a particular focus on those under the age of 1 month (eight children, weight 2.9 +/- 0.34), to that of 14 patients, aged 1.1-3 years when starting dialysis (weight 10.1 +/- 1.7, Group 2). RESULTS: The outcome was poor in the youngest age group; only 3/8 survived to 3 years. Of those who started dialysis between the ages of 0.3 and 3 years, 84% underwent kidney transplantation. One-, three-, five-, and eight-year patient survival was 96%, 88%, 84% and 84% respectively [corrected] Severe co-morbidities were present in almost half of those who died. Hospital stay was 3.5 times longer in Group 1 than in Group 2 during the first 3 months of dialysis. Permanent central venous catheters inserted under ultrasound guidance resulted in a 4.4-fold increase in catheter survival compared to non-cuffed catheters. Marked blood loss at beginning of haemodialysis (HD) is attributable to residual volume in the dialysis system (15.7 mL/kg/month) and frequent blood tests (12.1 +/- 5.9 mL/kg/month). These values decreased 2-fold after 8 months of treatment. CONCLUSIONS: The main factors determining the poor outcome of infants on dialysis are extremely young age at initiation and severe co-morbidities. Despite some disadvantages, HD may be successfully implemented in infants and toddlers, in highly specialized centres with a well-trained nursing staff.     

An integrated analysis of glucose, fat, and protein metabolism in severely traumatized patients. Studies in the basal state and the response to total parenteral nutrition.

A series of isotopic infusions were performed in 43 severely ill patients suffering from blunt trauma (mean injury severity score of 31). The patient data have been compared with data obtained from 32 normal volunteers, and in addition the metabolic response of the trauma patient to total nutritional support (TPN) has been assessed. The rate of VO2 was elevated in the trauma patients compared with that of the volunteers (160 mumol/kg/minute vs. 103 mumol/kg/minute). Glucose production was significantly increased in the patients compared with the volunteers (21 +/- 2 mumol/kg/minute vs. 14 +/- 1 mumol/kg/minute), but the trauma patients had an impaired capacity to directly oxidize plasma glucose. The percentage of glucose uptake oxidized in the volunteers was 36 +/- 2%, and the percentage of glucose uptake recycled was 10 +/- 1%. By contrast, in the trauma patients, 23 +/- 4% of the glucose uptake was directly oxidized, and 29 +/- 11% was recycled. The rate of glycerol turnover in the trauma patients (5.3 +/- 0.3 mumol/kg/minute) was significantly elevated compared with the volunteer value (2.2 +/- 0.1 mumol/kg/minute), and the basal rate of fat oxidation was twice as high in the patients as in the volunteers (2 mg/kg/minute vs. 1 mg/kg/minute). The rate of whole body protein catabolism was significantly higher in the patients (5.8 +/- 0.7 g/kg/day vs. 4.3 +/- 0.3 g/kg/day), and as a result, the rate of net protein catabolism was significantly elevated in the patients. The response to TPN (amino acids and a 50:50 mixture of glucose and fat) included an increase in the percentage of glucose uptake oxidized (up to 45 +/- 12%), a decrease in the oxidation of fat (up to 0.8 mg/kg/minute), and a significant increase in whole body protein synthesis (up to 6.1 +/- 1.1 g/kg/day) so that the rate of net protein loss was minimized but not prevented. (The rate of net protein catabolism during TPN was 1.3 +/- 0.5 g/kg/day.) There was no correlation between the injury severity score (ISS) and the degree of metabolic abnormality. The rate of NPC in the patients with ISS less than 20 was higher than in the volunteers (ISS = 0), but the values for NPC in patients with ISS 21-40, and ISS greater than 40 were virtually identical to the corresponding values in patients with ISS less than 20. It is concluded from these studies that: 1) Trauma patients have a high rate of VO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of biochemical, haematological and volume parameters in two treatment schedules of nocturnal home haemodialysis

BACKGROUND: The biochemical, haemodynamic, clinical and nutritional benefits of nocturnal home haemodialysis (NHHD) compared with 4 h, three times per week conventional haemodialysis are well known and accrue by increasing dialysis time and frequency either for 8 h alternate night per week (NHHD3.5) or for 8 h six nights per week (NHHD6). However, there are little data comparing NHHD3.5 with NHHD6. METHOD AND RESULTS: Thirteen patients on NHHD6 were compared with 21 patients on NHHD3.5, all with similar demographic profiles. Pre- and post-dialysis phosphate (PO4) control was ideal between the groups. However, all NHHD6 needed PO4 supplementation compared with 4/21 (19%) NHHD3.5. In the present study, 8/21 (38%) NHHD3.5 needed PO4 binders whereas none was required with NHHD6. The pre-haemoglobin (Hb) 122.8 g/L (NHHD6) versus 124.9 g/L (NHHD3.5) and the pre-albumin 38.31 g/L (NHHD6) versus 37.71 g/L (NHHD3.5) were not significantly different. NHHD6 had significantly lower pre-blood urea and creatinine (10.16 vs 19.54 mmol/L and 437.0 vs 812.3 micromol/L, respectively). Less interdialytic urea and creatinine fluctuation were also noted in NHHD6. Of major significance was the significantly lower ultra filtration rate and intradialytic weight gains (mean +/- SEM) of NHHD6 (249 +/- 76 mL/h and 2.0 +/- 0.65 kg) versus NHHD3.5 (425 +/- 168 mL/h and 2.9 +/- 1.2 kg). CONCLUSION: The authors conclude that NHHD6 offers the optimum biochemical, volume and clinical outcome, but NHHD3.5 has additional appeal to providers seeking home-based therapy cost advantages and consumable expenditure control. A flexible dialysis programme should offer all the time and frequency options of NHHD but in particular, should support NHHD at a frequency sympathetic to the clinical rehabilitation and lifestyle aspirations of individual patients.     

Aseptic hip necrosis after renal transplantation

To help determine the etiology of posttransplant aseptic hip necrosis, 11 stable renal allograft recipients (group A) who developed aseptic hip necrosis were compared with 89 patients (group B) without this complication. A comparison of mean age, duration of dialysis, mean daily prednisone dose, and incidence of rejection in the first year following transplant, sex, donor source, incidence of posttransplant parathyroidectomy, and mean serum calcium and alkaline phosphatase levels identified no significant differences between groups A and B. The mean serum creatinine value at three (2.2 +/- 0.31 mg/dL [190 +/- 30 mumol/L] vs 1.9 +/- 0.10 mg/dL [170 +/- 10 mumol/L]) and 12 (2.3 +/- 0.35 mg/dL [200 +/- 30 mumol/L] vs 1.9 +/- 0.10 mg/dL [170 +/- 10 mumol/L]) months and the serum phosphate value at three (3.0 +/- 0.19 mg/dL [0.97 +/- 0.06 mmol/L] vs 2.8 +/- 0.08 mg/dL [0.90 +/- 0.03 mmol/L]) and six (3.2 +/- 0.25 mg/dL [1.03 +/- 0.08 mmol/L] vs 2.9 +/- 0.25 mg/dL [0.94 +/- 0.08 mmol/L]) months were significantly greater in group A. Eight patients in group A underwent 13 total hip replacement an average of 16.5 +/- 3.1 months following transplant without significant complications. In conclusion, posttransplant aseptic hip necrosis occurs frequently, and renal allograft dysfunction may contribute significantly to its pathogenesis. When indicated, total hip replacement is both safe and effective.     

Elimination of intravenously administered ibandronate in patients on haemodialysis: a monocentre open study.

BACKGROUND: Ibandronate is an inhibitor of osteoclast-mediated bone resorption. This therapeutic effect is utilized in the treatment of osteoporosis and metastatic bone disease. The effect of ibandronate in patients on haemodialysis with renal osteopathy has not been studied since the pharmacokinetics of ibandronate under haemodialysis are unknown. METHODS: We analysed the removal of ibandronate from the plasma by haemodialysis in 12 chronic haemodialysis patients suffering from end-stage renal disease (ESRD). After intravenous administration of 1 mg ibandronate, the plasma concentration of ibandronate was determined in plasma samples drawn before entering (inflow) and after passing through (outflow) the haemodialyser, and in the dialysate at 1, 2, 3 and 4 h during the first haemodialysis session, and after 1 and 4 h during the second and third dialysis sessions. RESULTS: The back-extrapolated initial ibandronate plasma level was 38.9+/-15.9 ng/ml; this decreased during first haemodialysis (after 4 h) to 4.9+/-0.9 ng/ml and after two subsequent haemodialysis treatments to 0.38+/-0.16 ng/ml. Ibandronate concentration was reduced by 47% with every passage through the dialyser. The total decrease of ibandronate plasma concentration during the first 4 h of haemodialysis was 78% of plasma peak levels. The ibandronate dialysis plasma clearance was determined at 92+/-19 ml/min. The total amount excreted at the first dialysis using the recovery rate measure was 364+/-98 microg and using the mean difference in inflow/outflow (arteriovenous) concentration (A-V difference method) it was 371+/-132 microg. About 36% of the total amount of ibandronate administered (1 mg) was removed by the first dialysis treatment. CONCLUSION: Ibandronate was efficiently removed by haemodialysis. After three haemodialysis sessions the ibandronate plasma levels were close to quantification limit. One monthly dose of 1 mg ibandronate would not result in elevated plasma levels in patients with ESRD on haemodialysis treatment three times a week. In haemodialysis patients, ibandronate should be administered after the haemodialysis session.     

Glucose and urea kinetics in patients with early and advanced gastrointestinal cancer: the response to glucose infusion, parenteral feeding, and surgical resection

We isotopically determined rates of glucose turnover, urea turnover, and glucose oxidation in normal volunteers (n = 16), patients with early gastrointestinal (EGI) cancer (n = 6), and patients with advanced gastrointestinal (AGI) cancer (n = 10). Studies were performed in the basal state, during glucose infusion (4 mg/kg/min), and during total parenteral feeding (patients with AGI cancer only). Patients with early stages of the disease were also studied 2 to 3 months after resection of the cancer. Basal rates of glucose turnover were similar in volunteers and in patients with EGI cancer (13.9 +/- 0.3 mumol/kg/min and 13.3 +/- 0.2 mumol/kg/min, respectively) but were significantly higher in patients with AGI cancer (17.6 +/- 1.4 mumol/kg/min). Glucose infusion resulted in significantly less suppression of endogenous production in both patient groups than that seen in the volunteers (76% +/- 6% for EGI group, 69% +/- 7% for AGI group, and 94% +/- 4% for volunteers). The rate of glucose oxidation increased progressively in proportion to the tumor bulk. In the volunteers the percent of VCO2 from glucose oxidation was 23.9% +/- 0.7%, and in EGI and AGI groups the values were 32.8% +/- 2.0% and 43.0% +/- 3.0%, respectively. After curative resection of the cancer, glucose utilization decreased significantly (p less than 0.05). The rate of urea turnover was significantly higher in the AGI group (8.4 +/- 1.0 mumol/kg/min) in comparison with the volunteer group value of 5.9 +/- 0.6 mumol/kg/min (p less than 0.03). Glucose infusion resulted in a significant suppression of urea turnover in the volunteers (p less than 0.02), but in the AGI group glucose infusion did not induce a statistically significant decrease. We conclude from these studies that the presence of even a small, potentially curable gastrointestinal cancer is associated with a loss of the normal host-regulatory mechanisms designed to conserve body resources; this effect is more marked as the tumor bulk increases; increasing tumor bulk effects a progressive increase in glucose utilization and in protein breakdown.     

Difference in the homocysteine-lowering effect of folic acid in haemodialysis patients with and without occlusive vascular disease.

BACKGROUND: Hyperhomocysteinaemia has been identified as an independent cardiovascular risk factor and is found in more than 85% of patients on maintenance haemodialysis. Previous studies have shown that folic acid can lower circulating homocysteine in dialysis patients. We evaluated prospectively the effect of increasing the folic acid dosage from 1 to 6 mg per dialysis on plasma total homocysteine levels of haemodialysis patients with and without a history of occlusive vascular artery disease (OVD). METHODS: Thirty-nine stable patients on high-flux dialysis were studied. Their mean age was 63 +/-11 years and 17 (43%) had a history of OVD, either coronary and/or cerebral and/or peripheral occlusive disease. For several years prior to the study, the patients had received an oral post-dialysis multivitamin supplement including 1 mg of folic acid per dialysis. After baseline determinations, the folic acid dose was increased from 1 to 6 mg/dialysis for 3 months. RESULTS: After 3 months, plasma homocysteine had decreased significantly by approximately 23% from 31.1 +/- 12.7 to 24.5 +/- 9 micromol/l (P = 0.0005), while folic acid concentrations had increased from 6.5 +/- 2.5 to 14.4+/-2.5 microg/l (P < 0.0001). However, the decrease of homocysteine was quite different in patients with and in those without OVD. In patients with OVD, homocysteine decreased only marginally by approximately 2.5% (from 29.0 +/- 10.3 to 28.3 +/- 8.4 micromol/l, P = 0.74), whereas in patients without OVD there was a significant reduction of approximately 34% (from 32.7+/-14.4 to 21.6+/-8.6 micromol/l, P = 0.0008). Plasma homocysteine levels were reduced by > 15% in three patients (18%) in the group with OVD compared with 19 (86%) in the group without OVD (P = 0.001), and by > 30% in none of the patients (0%) in the former group compared with 13 (59%) in the latter (P = 0.001). CONCLUSIONS: These results indicate that the homocysteine-lowering effect of folic acid administration appears to be less effective in haemodialysis patients having occlusive vascular disease than in those without evidence of such disease.     

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.