Tsutomu Kuno

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.

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.

Increased Production of lnterleukin-1β and lnterleukin-1 Receptor Antagonist by Peripheral Blood Mononuclear Cells in Undialyzed Chronic Renal Failure

We investigated the cell content and production of IL-1beta and IL-1 receptor antagonist (Ra) by unstimulated and lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) obtained from 15 undialyzed patients with chronic renal failure (CRF; estimated GFR <10 ml/min), 15 patients on chronic hemodialysis (HD) and 15 healthy controls. These cytokines were measured by ELISA. The cell content of IL-1beta in freshly obtained PBMC was not detectable in any group. In contrast, that of IL-1Ra in CRF (1,807 +/- 370 pg/ml, p < 0.05) as well as in HD (1,791 +/- 151 pg/ml, p < 0.001) was significantly higher than that of the controls (907 +/- 156 pg/ml). In unstimulated cultured PBMC, spontaneous production of IL-1beta in CRF (66 +/- 13 pg/ml, p < 0.05) and in HD (81 +/- 29 pg/ml, p < 0.05) was significantly higher than that of the controls (26 +/- 3 pg/ml). In contrast, comparison of spontaneous production of IL-1Ra in the three groups was not significantly different. In LPS-stimulated PBMC, IL-1beta production in CRF (10,896 +/- 1,359 pg/ml, p < 0.01)and in HD(11,441 +/- 1,400 pg/ml, p < 0.01) was significantly higher than that of the controls (6,117 +/- 572 pg/ml). However, IL-1Ra production by LPS-stimulated PBMC in the three groups was not significantly different. Moreover, the spontaneous IL-1Ra/IL-1beta production ratio in CRF (140 +/- 16, p < 0.01) and in HD (142 +/- 19, p < 0.01) was significantly lower than that of the controls (294 +/- 41). The present study demonstrates that cytokine production by PBMC in undialyzed CRF patients as well as in hemodialyzed patients is heightened and may induce impaired function of the immunological system before CRF patients are introduced to dialysis.

Impact of the Fukushima Daiichi Nuclear Power Plant Accident on Hemodialysis Facilities: An Evaluation of Radioactive Contaminants in Water Used for Hemodialysis

Following the crisis at the Fukushima Daiichi Nuclear Power Plant caused by the 2011 Tohoku earthquake and tsunami, radioactive substances (131I, 134Cs, 137Cs) were detected in tap water throughout eastern Japan. There is now concern that internal exposure to radioactive substances in the dialysate could pose a danger to hemodialysis patients. Radioactive substances were measured in three hemodialysis facilities before and after purification of tap water for use in hemodialysis. Radioactive iodine was detected at levels between 13 and 15 Bq/kg in tap water from the three facilities, but was not detected by reverse osmosis membrane at any of the facilities. We confirmed that the amount of radioactive substances in dialysate fell below the limit of detection (7–8 Bq/kg) by reverse osmosis membrane. It is now necessary to clarify the maximum safe level of radiation in dialysate for chronic hemodialysis patients.

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.

Chronic Effects of Long-Term Acetate-Free Biofiltration on the Production of lnterleukin-1β and lnterleukin-1 Receptor Antagonist by Peripheral Blood Mononuclear Cells

The production of interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBMC) was examined in patients on long-term acetate-free biofiltration (AFB). Five stable patients on AFB were switched to bicarbonate hemodialysis (BCD) for a 2-week period using the same AN69 membrane dialyzer. IL-1beta and IL-1Ra production was measured by ELISA before and after dialysis in the last session of both treatments. Cytokine production by unstimulated PBMC did not differ significantly before and after both AFB and BCD. However, the spontaneous IL-1Ra/IL-1beta production ratio in AFB was significantly higher than that in BCD. These findings indicate that AFB may have more beneficial effects on cytokine production by PBMC compared to BCD.

Clinical benefit of preserving residual renal function in patients after initiation of dialysis.

Preserving residual renal function (RRF) after initiation of dialysis therapy is desirable for improving quality of life in ESRD patients. It has been believed that RRF declines more slowly in patients receiving continuous ambulatory peritoneal dialysis (CAPD) than in patients treated with other forms of maintenance dialysis. Episodes of intravascular volume depletion might be expected to cause more rapid loss of RRF, and are more frequent in patients on hemodialysis, which is intermittent therapy. However, recently it was demonstrated that in hemodialysis using high-flux biocompatible membrane and ultrapure water, RRF declines at a rate indistinguishable from that in CAPD. The HDF using ultrapure dialysate and the substitution fluid may show to preserve RRF as well as CAPD patients. In future, it might be a major concern for the assessment of the HDF by a multicenter clinical study for preserving RRF.

Oxidative stress on DNA in chronic renal failure: the influence of different hemodialysis membranes

AbstractsIt has been reported that uremia is a state of oxidative stress and may play an important role as a pathological cause of various uremic complications. Oxidative stress is known to increase conversion of deoxyguanosine to 8-hydroxy-2-deoxyguanosine (8-OHdG) in DNA, and 8-OHdG is used as a marker of oxidative DNA damage. We evaluated plasma and urinary concentrations of 8-OHdG in 49 patients (male 28, female 21; mean age 65 years; diabetic 27, nondiabetic 22) with chronic renal disease (CRD) and 22 patients (male 14, female 8; mean age 63 year; diabetic 7, nondiabetic 15) on maintenance hemodialysis (M-HD). Plasma concentrations of 8-OHdG were measured using a highly sensitive ELISA kit, and the urinary mean concentrations of 8-OHdG were measured using an ELISA kit. Plasma concentrations of creatinine (Cr), Urea nitrogen (UN), and β2-microgloblin (β2-MG) and 24-h creatinine clearance (CCr) were also measured in CRD patients. Furthermore, 8-OHdG was measured before the dialysis session in M-HD patients. The plasma concentration of 8-OHdG in patients on CRD was significantly correlated with serum-creatinine (S−Cr), serum-umea nitrogen (S-UN), and β-MG (P<0.0001) and also significantly negatively correlated with CCr (P<0.005), but was not significantly correlated with age, fasting blood suger (FBS), hemoglobin A1C (HbA1C), and urinary concentration of 8-OHdG were not correlated with S-Cr, S-UN, β2-MG, and CCr. The plasma mean concentrations of 8-OHdG in patients on CRD and M-HD were as follows: CRD (CCr>50 ml/min,n=12), 0.108±0.41 ng/ml; CRD (CCr<10 ml/min,n=9), 0.277±0.15 ng/ml; M-HD (n=22), 0.217±0.59 ng/ml (mean±SD). The mean plasma concentration of 8-OHdG was 0.296 ±0.75 ng/ml in patients on M-HD in the polysulfone mem-brane group, 0.304±0.122 ng/ml their cellulose membrane group, and 0.354±0.21 ng/ml their vitamin E-modified cellulose membrane group. This study showed that in CRD patients, oxidative stress on DNA increasesed with the progression of renal disease, and that end-stage CRD patients were already exposed to the same degree of oxidative stress on DNA as M-HD patients. In M-HD patients, oxidative stress on DNA was not related to the type of hemodialysis membrane.

Who Needs Acetate-Free Biofiltration?

Acetate-free biofiltration (AFB) is a hemodiafiltration (HDF) technique that is performed with a base-free dialysate and simultaneous infusion of sodium bicarbonate solution. In Japan 3 years ago, a new form of acetate-free dialysate containing 2.0 mEq/l citric acid was approved. Recently, we have had a 76-year-old male subject who switched from AFHD to AFB, mainly because of cardiovascular stability. Several factors may contribute to hemodynamic adaptation during AFB. One theory is that an increase in peripheral vascular tone and vascular refilling rate is caused by the high sodium concentration of the substitution fluid. AFB has all the premises for being a perfectly biocompatible technique capable of satisfying even the demands of critical patients laden with comorbidities.

The salvage of graft occlusion in a maintenace hemodialysis patient with tuberous sclerosis by percutaneous transluminal angioplasty using intravascular ultrasound: case report.

Abstract:  End‐stage renal failure due to tuberous sclerosis is rare and there is no previous report of a patient with tuberous sclerosis undergoing long‐term hemodialysis for over 18 years. The patency rate for a dialysis prosthetic graft is low, however, our patients graft survived over 16 years. For thrombotic occlusion of a graft, we performed percutaneous thrombectomy and balloon angioplasty and salvaged graft occlusion. Moreover, this case is the first report in which the interventional procedure (mechanical thrombectomy and balloon angioplasty) could be observed by intravascular ultrasound in addition to angiography.