One of the most common problems in the blood-access for hemodialysis is clotting. Urokinase (UK) is routinely used as a thrombolytic agent for peripheral or cardiac thrombosis at present. Digital manipulation is added to UK-thrombolysis (UKTM) for the patients with clotted blood access for hemodialysis. The average age of those patients was 62.5 years. The total dose of UK was 180, 000 units in average. The overall recanalization rate was 71.4% (25/35), 75% (18/24) in patients with PTFE grafts, and 63% (7/11) in those with native arteriovenous fistulas. As complications following UKTM, ecchymoses were seen in 24/25 (92%), local pain in 23/25 (92%), re-clotting with in 24 hours in 2/35 (5.7%). No serious bleeding complications nor pulmonary embolism were seen. UKTM is a safe, easy, and effective modality to treat the clotting blood access as a first choice of treatment options.

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We examined the usefulness of dual energy X-ray absorptiometry (DXA) for nutritional evaluation in 34 male hemodialysis patients (mean age 55.2±12.3 years, mean duration of hemodialysis 119.6±71.2 months). The underlying renal diseases included chronic glomerulonephritis in 28 patients, nephrosclerosis in 5, and polycystic kidney disease in 1. The correlations between the percent Fat (%Fat), lean body mass (LBM) and bone mineral content (BMC) measured by DXA were examined between either the body mass index (BMI) or arm muscle circumference (AMC) calculated by the anthropometric method. There were significant positive correlations between BMI and %Fat (r=0.773, p<0.001), and AMC and LBM (r=0.608, p<0.001). %Fat in patients undergoing hemodialysis for over 10 years was significantly higher than that in patients receiving hemodialysis for less than 10 years (p<0.05). These results suggest the usefulness of DXA as a nutritional index in hemodialysis patients.

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Silkworm larvae plasma (SLP) reagent is activated by peptidoglycan (PG), a fragment of both the gram-positive and the gram-negative bacterial cell wall, as well as β-glucan (BG), a component of fungi. It is possible to measure contamination by PG quantitatively by combining the limulus amebocyte lysate (LAL) and SLP measurement methods. Therefore, a more accurate analysis of a dialysate can be made by using both SLP and LAL methods to detect endotoxin (ET) and/or PG contamination. We studied the effects of contaminated dialysates on human peripheral blood mononuclear cells (PBMC) by measuring production of various cytokines in vitro. Muramyl dipeptide (MDP) was used as the biologically active minimum constituent of PG. A total of 54 dialysate samples were obtained in sterile conditions from 4 sites, 1) a reverse osmosis-treated water system, 2) a central dialysate proportioning system, 3) a multiple patient station, 4) a personal patient station, at 9 dialysis facilities. To detect bacterial contamination, the samples were measured by the LAL (C), LAL (G) and SLP methods. PBMC were collected from 10 healthy controls and from 10 hemodialysis patients and cultured for 24 hours with lipopolysaccharide (LPS), MDP, LPS+MDP and a contaminated dialysate. Levels of IL-1 Ra, IL-1 β and TNF-α in the culture medium supernatants were measured by ELISA. PG was not detected in dialysates from site 1) or site 2). However, dialysates from the inlets of the dialyzer at a bedside monitor of the central patient stations and the personal patient stations showed 4.1±6.1ng/ml at site 3) (in 3 out of 18 samples 17%) and 3.3±4.6ng/ml at site 4) (in 7 out of 18 samples 39%). Not only contamination by PG alone but also combined contamination by PG and ET were detected. Furthermore, IL-1 Ra, IL-1 β and TNF-α production by PBMC increased in accordance with the concentrations of MDP. Cytokine production was 5 to 10 times higher where MDP and ET coexisted than where either MDP or ET existed alone, showing a synergic effect of MDP and ET. On the basis of these results, there is a high possibility that PG may also be a pyrogen, although ET has been considered the only pyrogen in dialysates. Therefore, it is essential to recognize the presence of both ET and PG in investigating dialysate contamination.

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We have developed a charge selectivity index (CSI) for estimating the indicator of peritoneal function. The calculation formula is as follows: [CSI {glutamate (Glu)/glutamine (Gln)}: Glu D/P ratio÷Gln D/P ratio, CSI {lysine (Lys)/glutamine (Gln)}: Lys D/P ratio÷Gln D/P ratio].
Furthermore, we determined the CSI by using neutral IgG1 and acid IgG4, which had different isoelectric points despite their equal molecular weight. The formula of this measurement is as follow: [CSI (IgG4/IgG1): IgG4 D/P ratio÷IgG1 D/P ratio]. The CSI was determined in two groups. One was a group of 50 outpatients who had been enrolled in this study, in whom no episode of peritonitis was recognized within a year prior to the study (normal group). The other was a group of 16 patients who had an episode of peritonitis within the previous month (peritonitis group). Following the standard peritoneal equilibration test (PET), 2 liters of a 2.5% glucose dialysate was injected into and held in the peritoneal cavity for exactly 4 hours. Dialysate samples were collected at 0 and 4 hours. A single serum sample was obtained at the midpoint of the procedure. Peritoneal transport was estimated from the dialysate (D) to plasma (P) ratio of amino acid (Glu, Gln, Lys), IgG1, IgG4, creatinine (Cr), β₂-microglobulin (β₂-MG), and albumin (Alb) at 4 hours. The D/D₀ glucose ratio was calculated, and then each CSI was calculated.
The results of the study were as follows: (1) D/P ratios of Glu, Gln, Lys, IgG1, IgG4, Cr, β₂-MG and Alb were significantly increased in the peritonitis group. (2) CSI (Glu/Gln), CSI (Lys/Gln), and CSI (IgG4/IgG1) were significantly increased in the peritonitis group. (3) A significant correlation was obtained between the CSI (Glu/Gln) and D/D₀ glucose ratios, CSI (IgG4/IgG1) and D/P ratios of Alb. (4) A significant correlation was obtained between CSI (IgG4/IgG1) and CSI (Glu/Gln), or CSI (Lys/Gln). (5) A significant correlation was obtained between CSI (Glu/Gln), CSI (Lys/Gln), CSI (IgG4/IgG1), D/P ratios of Giu, D/P ratios of Cr, D/D₀ glucose ratios, and dialysis duration among the normal group.
Those CSI's indicated a new test to estimate peritoneal membrane function.

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The dose dependency of falecalcitriol (ST-630), an analogue of the active vitamin D₃, which has very strong biological activity, was investigated for treatment of secondary hyperparathyroidism in patients undergoing hemodialysis in a double-blind, multicenter study. The final global improvement rating was assessed by using the percent change in serum level of HS-PTH (44-68 midregion PTH) as an index. The rates of “improved” or better were 31% for the 0.05μg/day group, 38% for the 0.15μg/day group, and 59% for the 0.3μg/day group. The serum HS-PTH levels showed a significant increase (average increase 20%) in the 0.05μg/day group, and a tendency toward increase in the 0.15μg/day group, but a decrease (average reduction 10%) in the 0.3μg/day group, with a significant difference between the 0.05μg/day and 0.3μg/day groups. Falecalcitriol thus showed dose-dependent suppression in HS-PTH. C-PTH displayed the same changes as HS-PTH, and the decrease in C-PTH was statistically significantly more pronounced in the 0.3μg/day group. In overall safety rating, the unsafe rates (cases assessed as “almost safe” or less) were 2% in the 0.05μg/day group, 9% in the 0.15μg/day group, and 20% in the 0.3μg/day group. Major adverse reactions in the 0.3μg/day group were hypercalcemia (3 patients) and bradycardia with an abnormal feeling in the chest (1 patient). The highest level of serum calcium (albumin-adjusted value) among the patients with hypercalcemia was 12.3mg/dl, but in all three patients the level returned to normal within 20 days, and no particular problems were observed. The mean serum calcium levels in the 0.3μg/day group remained within the normal range throughout the treatment period, and there was no rise in mean serum phosphate concentration in any of the three groups. A serious adverse reaction involving hepatic dysfunction was noted in 1 patient of the 0.15μg/day group, but it improved when treatment was discontinued. As these findings show, falecalcitriol showed outstanding efficacy in the treatment of secondary hyperthyroidism in chronic renal failure. When efficacy and safety were taken into consideration, the optimal dose was assumed to be 0.3μg/day. However, hypercalcemia requires adequate attention, and monitoring of serum calcium levels at suitable intervals is considered important, in order to ensure safety. Further studies considered necessary, are an objective comparison of the optimal dose established in this study with a control drug; an investigation of efficacy and safety during long-term administration; and an investigation of the effect on bone lesions.

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Endotoxin (ET) levels in the dialysate must be determined by an accurate and precise assay. For validation, three commercial kits, Endospecy (Seikagaku, Tokyo), ET single test-ES (Wako, Osaka) and Kinetic QCL (BioWhittacker, Maryland) were tested for interference. The dilution series of the dialysate, bicarbonate and acid concentrate were made between 1- and 80-fold, which were spiked with U.S. Pharmacopoeia reference standard ET (USP RSE). The recovered activity for ET in each series was evaluated versus the theoretical value of 50EU/L. The dilutions which overcame interference with Endospecy were 1, 40 and 20 in the dialysate, acid concentrate and bicarbonate, respectively. Likewise, 1:4, 1:40 and 1:40 dilutions were necessary to overcome inhibition with ET single test-ES. With Kinetic QCL, there was no interference in the undiluted dialysate; however, enhancement was observed between 2- and 16-fold dilution. The dilution which overcame interference in the bicarbonate was 40-fold with Kinetic QCL. Even the 80-fold dilution of the acid concentrate failed to overcome inhibition with Kinetic QCL. Clinical dialysate samples were also measured for ET activity by Endospecy and ET single test-ES kit in parallel. The ET single test-ES kit gave significantly lower values (44%) than the Endospecy kit (p<0.05). In addition, the stabilizing agent for preventing ET in the dialysate from loss of activity through inactivation and adsorption was shown to be effective, as the recovered ET activity in the dialysate was kept within the range of 100±25% of the initial value as long as 7 days.

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Preoperative autologous blood donation its an alternative to allogeneic blood transfusion in patients scheduled for surgery. However, in anemic patients such as patients on hemodialysis, the ability to donate sufficient autologous blood can be limited by inadequate stimulation of erythropoiesis. We herein report two hemodialysis patients donating autologous blood preoperatively and successfully treated without allogeneic blood transfusion. The first patient was a 45-year-old woman who had suffered from bilateral leg pain. She had been receiving hemodialysis regularly since 1979. Magnetic resonance imaging (MRI) in August 1995 revealed disk herniation, and partial laminectomy was performed in September 1995. Four units of autologous blood was collected preoperatively. The second patient was a 51-year-old man complaining of macroscopic hematuria. He had been receiving hemodialysis regularly since 1991. Cystoscopy in April 1996 revealed a large bladder tumor centered on the posterior wall. The biopsy specimen of the tumor revealed squamous cell carcinoma, and total cystectomy was performed in May 1996. Six units of autologous blood was preoperatively collected. Both patients donated 2 units of autologous blood immediately after hemodialysis weekly and received 24000IU of recombinant human erythropoietin (rHuEPO) subcutaneously after each donation. No significant decrease in the hematocrit associated with autologous blood donation was evident in these two patients. They required no allogeneic blood transfusions and made an uneventful recovery. These cases suggest that it is possible for hemodialysis patients to donate sufficient autologous blood preoperatively with administration of rHuEPO and normovolemic phlebotomy, even if the hematocrit level is below 33% prior to the first donation.

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We report a case of pheochromocytoma in a patient with a single adrenal gland on long-term hemodialysis. The patient was a 56-year-old man who had been on hemodialysis since January 1978. He was operated on radically for right renal cell carcinoma in Febrary 1995 (RCC, papillary and common type, granular>clear cell subtype, G₂, pT₂, N₃). In August, a left adrenal tumor (φ2cm) was incidentally discovered on a follow-up CT scan for renal cell carcinoma. The tumor was found to be hypovascular by selective arteriography and had not larged since the preoperative CT scan. In December, he complained of paroxymal hypertension with palpitation just over the regular dialysis, and was diagnosed as having pheochromocytoma by I¹³¹-MIBG scintiscanning. The tumor was successfuly enucleated from the adrenal cortex on 27 Febrary 1996.
In spite of successful resection of the tumor, elevated levels of plasma vanillylmandelic acid (VMA) persisted. So, the plasma VMA levels of patients on hemodialysis without pheochromocytoma were measured, and ranged from 110.1 to 416.8ng/ml (243.6±94.2). From these findings, the normal upper limit of plasma VMA was determined as 432ng/ml (mean+2SD) in patients on hemodialysis without pheochromocytoma.

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A case of central pontine myelinolysis (CPM) caused by hyponatremia in a patient on regular hemodialysis (HD) is reported. A 51-year-old woman with a history of diabetes mellitus for 15 years started HD in July 1995. There were no serious clinical problems, except for intermittent diarrhea due to a previous operation for a thrombus of the supraintestinal artery and a poorly controlled blood glucose level. General fatigue occurred around August 10, 1996. A few days later, gait disturbance and dysarthria appeared, while a brain computerized tomography revealed no abnormalities. Additional intake of salt was recommended, because hyponatremia of 125mEq/l was also found. Magnetic resonance imaging on August 21 revealed a low intensity area in the central pons. Several lines of evidence led to the diagnosis of CPM. The deliberate slow correction of serum sodium concentration by administration of sodium (170mEq/day), reinforcement of medication for diarrhea, control of water volume and strict correction of the blood glucose level improved the neurological disorders. It was considered that loss of sodium due to intermittent severe diarrhea and anorexia as well as water excess due to inadequate dry weight and hyperosmolarity with high blood glucose level were the main causes of her hyponatremia. There was also a possibility that unexpected rapid correction of her serum sodium concentration by the normal dialysate composition (Na; 140mEq/l) during HD caused or exacerbated the CPM. In conclusion, it is necessary to diagnose immediately and to treat deliberately a case of CPM, because HD therapy has a tendency to bring on an imbalance and unexpected rapid correction of electrolyte concentration.

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