Yuji Nagura

Dialyzability of gadodiamide in hemodialysis patients

PurposeThe aim of this study was to evaluate the contrast enhancement, pharmacokinetics, dialyzability, and safety of gadodiamide in patients on hemodialysis.Materials and methodsThirteen hemodialysis patients with abdominal disease were examined after receiving intravenous gadodiamide (0.1 mmol/kg body weight) by magnetic resonance imaging (MRI) and were dialyzed at l, 3, 5, and 8 days. Blood samples were obtained immediately before, during, and at the end of the first hemodialysis session and immediately before and at the end of the next three sessions. The complete blood count, blood biochemistry, β2-microglobulin, and gadolinium were measured. Dialysis of urea, creatinine, and gadolinium during the first hemodialysis session was assessed. Precontrast and postcontrast MRI and Gd-enhanced MR angiography (MRA) images were reviewed and visually evaluated by two radiologists; their evaluation was based on consensus.ResultsGadodiamide did not cause any changes in renal function. An average of 73.8%, 92.4%, and 98.9% of the gadodiamide dose was eliminated by the end of the first, second, and third hemodialysis sessions, respectively. The average half-time of gadodiamide was 1.93 h (SD 0.55). The mean clearance of gadodiamide during hemodialysis was 63.5 ml/min (SD 21.9). There were no side effects related to the injection of gadodiamide. In all cases, diagnosable MRI and MRA images were obtained after gadodiamide injection in the hemodialysis patients.ConclusionIn hemodialysis patients, gadodiamide achieves diagnosable images. It is dialyzable and can be used safely without measures to increase excretion.

An Overview of Regular Dialysis Treatment in Japan (as of 31 December 2004)

Abstract:  A statistical survey of 3932 nationwide hemodialysis (hereafter, dialysis) facilities was carried out at the end of 2004, and 3882 facilities (98.73%) responded. The population undergoing dialysis at the end of 2004 was 248 166, an increase of 10 456 patients (4.4%) from that at the end of 2003. The number of dialysis patients per million people was 1943.5. The crude death rate of dialysis patients from the end of 2003 to the end of 2004 was 9.4%. The mean age of patients who underwent dialysis in 2004 was 65.8 years, and that of the total dialysis population was 63.3 years. The percentage distribution of patients who underwent dialysis according to a newly underlying disease showed that 41.3% of patients had diabetic nephropathy and 28.1% had chronic glomerulonephritis. The frequency of calcium carbonate use for dialysis patients was 75.1% and that of sevelamer hydrochloride use was 26.2%. The frequency of sevelamer hydrochloride use does not necessarily have a strong correlation with the dose of calcium carbonate. Patients who received high doses of sevelamer hydrochloride tended to have a low concentration of arterial blood HCO3–. Approximately 15% of dialysis patients used an intravenous vitamin D preparation, generally maxacalcitol. The longer the patients had been on dialysis, the higher the frequency of use of an intravenous vitamin D preparation. When the concentration of serum intact parathyroid hormone (PTH) was more than 200 pg/mL, the frequency of use of an orally administered vitamin D preparation decreased; but that of intravenous vitamin D preparation increased. The percentage of dialysis patients who received percutaneous ethanol injection therapy (PEIT) was 1.4%. The percentage was more than 50% in the patients who had been on dialysis for more than 10 years. The percentage of patients who received PEIT again was 35.0%. The percentage of patients who had been on hemodialysis for more than 10 years and received PEIT again was more than 50%. 

Factors influencing long-term survival in patients on chronic dialysis

Japan has the highest prevalence of dialysis patients in the world. According to the Annual Report of the Japanese Society for Dialysis Therapy (JSDT; 2002), the total dialysis population was 229 538 (1801.5 patients per million population) at the end of 2002. The annual crude mortality rate has been less than 10%. Survival rates in the incident dialysis patients were 0.874 for 1 year, 0.609 for 5 years, and 0.391 for 10 years. Despite the increased acceptance for dialysis of elderly patients, those with comorbid conditions, and those with diabetes mellitus, the adjusted hazard ratios for death have been improving since 1983. This improvement was obtained by delivering a dialysis dose of Kt/V 1.33 and dialysis sessions of 4 h. Independently of the JSDT registry, there exists a local dialysis registry in Okinawa, the Okinawa Dialysis Study (OKIDS) registry, in which are filed the records of every chronic dialysis patient from the beginning of dialysis therapy in 1971 to the end of 2000. Several outcome studies have been conducted to determine the factors related to survival, using the data in that registry. There are distinct differences in environmental and socioeconomic conditions and lifestyles within a given country, and between countries and ethnic groups, that may affect the survival of dialysis patients. In this article, both the JSDT registry and OKIDS data are reviewed in order to identify factors related to the survival of chronic dialysis patients.

Comparison of the Effects of Cellulose Triacetate and Polysulfone Membrane on GPIIb/IIIa and Platelet Activation

Background: During hemodialysis session, several adverse reactions can occur on platelets, which are attributable to bioincompatibility of the dialysis membrane. Glycoprotein IIb/IIIa (GPIIb/IIIa) is the receptor for fibrinogen, which mediates platelet aggregation and adhesion. Accordingly, we compared the influence of a cellulose triacetate (CTA) and polysulfone (PS) membrane on GPIIb/IIIa and platelet activation. Methods: Blood samples from 5 patients on hemodialysis were taken at 0 time, 15 min, 30 min, 60 min and 240 min, during a single hemodialysis session, by a crossover design using CTA or PS. Platelet count and plasma concentration of GPIIb/IIIa, β-thromboglobulin (β-TG) and platelet factor 4 (PF-4) were measured. GPIIb/IIIa was measured by flow cytometry. β-TG and PF-4 were measured by ELISA. Results: There was no significant change in the total amount of GPIIb/IIIa during dialysis session between the CTA and PS. However, the level of bound GPIIb/IIIa was significantly (p < 0.0002) increased from 1,426 ± 435 to 40,446 ± 2,777 mol/PLT with PS. In contrast, there was no significant change with CTA (3,258 ± 1,469 to 4,301 ± 1,422 mol/PLT). The platelet counts and β-TG and PF-4 behavior during the dialysis session did not show significant change between the PS and CTA. Conclusion: The characterization of changes in platelet membrane receptor (GPIIb/IIIa) may be a useful marker for studying the biocompatibility of dialysis membranes. On platelet aggregation, CTA might be more biocompatible membrane than PS.

Sclerosing Encapsulating Peritonitis: Regional Changes of Peritoneum

Sclerosing encapsulating peritonitis (SEP) is characterized by the diffuse appearance of marked sclerotic thickening of the peritoneal membrane. We experienced a case with SEP accompanied by regional changes of peritoneum. A 37-year-old woman with end-stage renal failure was started on continuous ambulatory peritoneal dialysis in 1985 and was transferred to hemodialysis in 1997. She was admitted because of ileus in 1998 with SEP and died of septicemia. The diagnosis of SEP was confirmed via the autopsy. The root of the mesentery was retracted and shortened. Since the peritoneal change was marked in the regions with free margin of mesentery and was less apparent in the regions not adhered to mesentery, it is indicated that mechanical stress also contributes to the occurrence of SEP. Since calcification and ossification were only seen in a free margin of small bowel from mesentery, it is suggested that there is a close relationship between calcification and ossification. Since fibrosis invaded into the muscle layer, dysfunction of bowel movement as well as bowel obstruction contributed to the appearance of ileus. It is suggested that mechanical stress by the root of mesentery which is retracted and shortened also contributes to the appearance of SEP.

Increasing gender difference in the incidence of chronic dialysis therapy in Japan.

Abstract:  The incidence of chronic kidney disease and its progression to end‐stage renal disease (ESRD) differs between genders, so it can be surmised that the incidence of ESRD is different between men and women. We analyzed the annual incidence of ESRD by gender for a 20 year period, from 1983 to 2002, using Japanese Society for Dialysis Therapy (JSDT) registration data. The annual incidence of ESRD was calculated as the number of incident dialysis patients divided by the census population of the previous year in each gender, and expressed per million of each population (male and female). In men, the incidence of ESRD increased from 99.9 in 1983 to 330.2 in 2002, whereas it was 66.6 in 1983 and 184.9 in 2002 in women. The difference of incidence of ESRD from men to women increased from 33.3 in 1983 to 145.3 in 2002. The mean age at the start of dialysis was 51.5 years (men) and 52.5 years (women) in 1983, it increased to 63.8 years (men) and 66.1 years (women) in 2002. The difference in mean age increased from 0.9 years in 1983 to 2.3 years in 2002. There was no clear relationship between the available dialysis station per 100 000 population and the men to women ratio in the prevalent dialysis patients among the 47 prefectures. The acceptance of dialysis therapy might not be strong enough to explain the increasing difference in ESRD incidence between men and women in Japan. Differences in the socioeconomic conditions and lifestyles between men and women, which might be related to the gender difference in incidence in ESRD, should be studied further.

A Comparison of Bicarbonate Hemodialysis, Hemodiafiltration, and Acetate-free Biofiltration on Cytokine Production

Abstract:  Acetate‐free biofiltration (AFB) is a special hemodiafiltration (HDF) modality performed with a base‐free dialysate and simultaneous injection of non‐pyrogenic sodium bicarbonate solution. The purpose of this study was to investigate the difference of cytokine production by conventional bicarbonate hemodialysis (BCD), standard HDF and AFB in the same patients. Eight stable hemodialysis patients were treated in random order with BCD, HDF and AFB every 4 weeks. The production of interleukin‐1β (IL‐1β) and interleukin‐1 receptor antagonist (IL‐1Ra) by peripheral blood mononuclear cells (PBMC) was investigated without stimulation and with stimulation by a small amount of endotoxin (ET)‐contaminated β2‐microglobulin (β2M) and lipopolysaccharide (LPS) before and after dialysis treatment in the last sessions during all periods. To serve as controls, 14 healthy volunteers participated in this study. In spontaneous IL‐1Ra production, the values of before and after AFB were not significantly different from that of the controls, and the values of before and after BCD and before HDF were significantly higher than that of the controls. In LPS‐stimulated PBMC, IL‐1β production before and after AFB was not significantly different from that of the controls, and before and after BCD and HDF was significantly higher than that of the controls. In ET‐contaminated β2M‐stimulated PBMC, IL‐1β production before and after AFB was not significantly different compared to the controls, and the production was significantly lower than that before and after BCD and HDF. In addition, IL‐1Ra production after AFB was not significantly different from the controls, and the production was significantly lower than that before and after BCD and HDF. It was concluded that a lower cytokine production by AFB may have the effect of preventing dialysis‐related complications.

Impaired Cell-Mediated Immunity in Focal Glomerular Sclerosis

Cell-mediated immunity (CMI) was evaluated in 8 patients with focal glomerular sclerosis (FGS), 50 patients suffering from chronic mesangial proliferative glomerulonephritis without renal insufficiency and 24 healthy controls. The following parameters were measured: delayed skin reactivity to purified protein derivative, circulating lymphocytes, lymphocyte cell-surface markers (neuraminidase-treated sheep erythrocyte and erythrocyte-antibody-complement rosettes) and functional markers (mitogenic responses to concanavalin A and phytohemagglutinin). The FGS patients with nephrotic syndrome (NS) had a significant depression in CMI, characterized by decreased responses of the lymphocytes to both concanavalin A and phytohemagglutinin, impaired delayed hypersensitivity to purified protein derivative and a decreased proportion of T lymphocytes as compared with normal subjects. In contrast, the levels of all CMI parameters studied in FGS patients in remission and in patients with chronic glomerulonephritis with or without NS did not differ from normal subjects. Thus, the majority of FGS patients with NS demonstrated an impaired response in a CMI assay system. The possible significance of these phenomena in the pathophysiology of FGS is discussed.

Relationship between Insulin Resistance and Uremic Toxins in the Gastrointestinal Tract

The relationship between insulin resistance and local uremic toxins was examined using an oral adsorbent. Fourteen rats demonstrating a diabetic state underwent two-thirds, nephrectomy and were divided into two groups. The control group was fed standard rat chow, and the test group was fed standard rat chow containing 5% AST-120. The target level of blood glucose was achieved by controlling the dosage of exogenous insulin. All rats were sacrificed at week 6. Body weight, blood glucose level, and renal function at week 6 were not significantly different between both groups. However, the mean blood glucose level and the mean dose of exogenous insulin in the AST-120-fed group were significantly reduced as compared with the control group. The results of the present study indicate that administration of an oral adsorbent in diabetic nephropathy decreases the doses of exogenous insulin and improves insulin resistance, and that uremic toxins which exist in the gastrointestinal tract play important roles.

Evaluation of Serological Diagnosis Tests for Tuberculosis in Hemodialysis Patients

Abstract:  Patients receiving hemodialysis are generally considered to be at increased risk of developing tuberculosis. In the current study, in order to evaluate the usefulness of serological tests in dialysis patients, serum antibodies for tuberculous glycolipids antigen (TBGL) and for lipoarabinomannan (LAM) were measured in hemodialysis patients. The present study included 243 hemodialysis patients. Serum antibodies for TBGL and LAM were measured. Tuberculin skin tests were carried out and chest X‐rays evaluated at the same time. There were no patients with active tuberculosis at the time of blood sampling. Thirty‐six patients (14.8%) and 25 patients (10.3%) were positive for anti‐TBGL antibody and anti‐LAM antibody, respectively. One hundred and fifty‐five patients (63.8%) were positive for tuberculin skin testing and 123 patients (50.6%) had old pulmonary tuberculosis on their chest X‐ray. There was no significant correlation between the results of anti‐TBGL antibody and anti‐LAM antibody. There were no relationships among the results of tuberculin skin test and the two serological tests. However, positivity of anti‐TBGL antibody and anti‐LAM antibody was significantly higher in patients with findings of old tuberculosis on the chest X‐ray than those without findings. The current results show that these serological tests are positive more frequently in hemodialysis patients without any proof of active tuberculosis than in healthy subjects (2%) and careful interpretation is necessary for relevant results.