Masamiki Miwa

Health-related quality of life among dialysis patients in Seattle and Aichi

We used the 36-item Short-Form Health Survey to compare health-related quality of life (HRQOL) between 104 dialysis patients in Seattle, WA, and 2,178 patients in Aichi, JAPAN: Compared with Aichi patients, Seattle patients had lower scores on three scales related to physical HRQOL: Physical Functioning (PF; P = 0.03), Role-Physical (RP; P = 0.004), and Vitality (VT; P < 0.001). However, scores related to mental HRQOL were higher for Seattle patients compared with those of Aichi patients, which included scores for Role-Emotional (RE; P = 0.005) and Mental Health (MH; P < 0.001). Scores for Bodily Pain, General Health Perception, and Social Functioning did not differ significantly between the two groups. These differences persisted even after potential confounding factors were controlled for. However, after taking into account national norm data for the United States and Japan, differences in PF and VT disappeared, whereas differences in RP, RE, and MH persisted. These results suggest that the higher scores for PF and VT in Aichi patients were partly explained by the higher physical HRQOL of the Japanese general population. Although these data may not be representative of the total dialysis populations in the United States and Japan, they suggest potential differences in HRQOL between patients in the two countries. Additional research is needed to confirm these results and understand the factors associated with these differences. The findings suggest the need for further attention to the physical limitations of US dialysis patients and the mental health of Japanese dialysis patients.

Platelet GPIIb/IIIa Is Activated and Platelet-Leukocyte Coaggregates Formed in vivo during Hemodialysis

Background/Aim: During hemodialysis, platelets and leukocytes are activated and form platelet-leukocyte coaggregates in which GPIIb/IIIa (CD41/CD61) and CD62P (P-selectin) are involved. However, it is still controversial whether platelet activation and platelet-leukocyte coaggregate formation are dependent on the dialyzer membrane material. Method: We examined the appearance of activation-dependent antibody on platelets as an index of platelet activation, and the appearance of platelet-specific antigen on leukocytes as an index of platelet-leukocyte coaggregation, during hemodialysis in 7 patients treated using regenerated cellulose (RC) membrane and next using polysulfone (PS) membrane. In order to reduce the influence of factors other than dialyzer membrane material, this study was conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate. Moreover, flow cytometric techniques with whole blood were employed, which reduce artificial cell activation during the cell or plasma separation procedure. The platelet-specific monoclonal antibodies used in this study were anti-CD61, PAC-1 (which recognizes only the conformationally activated GPIIb/IIIa) and anti-CD62P. Results: Changes in the percentage of PAC-1-positive platelets were significantly greater during hemodialysis with RC than with PS. However, changes in the percentage of CD62P-positive platelets were not significantly different between hemodialysis with RC and PS. Changes in the percentage of CD61- or CD62P-positive leukocytes were significantly greater during hemodialysis with RC than with PS. Although changes in percentage of PAC-1-positive platelets did not parallel those of CD62P-positive platelets during hemodialysis, there was a significant positive correlation between the percentage of CD61-positive leukocytes and the percentage of CD62P-positive leukocytes. Conclusion: This study, conducted in a prospective crossover fashion using a pyrogen-free bicarbonate dialysate in order to reduce the influence of factors other than the dialyzer membrane material, demonstrated that both the degrees of GPIIb/IIIa activation and platelet-leukocyte coaggregation were greater during hemodialysis with RC than PS.

Changes in Mac-1 and CD14 Expression on Monocytes and Serum Soluble CD14 Level during Push/Pull Hemodiafiltration

Background/Aim: Employment of treated dialysate as replacement fluid raises concerns about exposure of patients to pyrogenic substances. This study was undertaken to evaluate the safety of treated dialysate as the replacement fluid for push/pull hemodiafiltration. Methods: In the present study, changes in the expressions of Mac-1 and CD14 on monocytes, which are upregulated by monocyte activation, were analyzed by flow cytometry, and the serum level of sCD14 which elevates by monocyte activation was measured by enzyme-linked immunosorbent assay (ELISA) during treatment in 7 patients on hemodialysis with regenerated cellulose (RC) membrane, polysulfone (PS) membranes and by push/pull hemodiafiltration (HDF) with PS membranes in a cross-over fashion. Results: During hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration with PS, both Mac-1 and CD14 expressions on monocytes significantly increased by passing through the artificial kidneys, and, accordingly, the respective values downstream of the artificial kidneys were significantly higher than the predialysis values, even when the lipopolysaccharide level in dialysate was not detectable by Limulus assay. There was no significant variation in serum sCD14 levels during any of the hemodialysis with RC, hemodialysis with PS or push/pull hemodiafiltration. However, during hemodialysis with PS or push/pull hemodiafiltration with PS, changes in Mac-1 and CD14 expression on monocytes were significantly smaller than those during hemodialysis with RC. Conclusion: Monocytes are activated to a greater extent during hemodialysis with RC membranes than during push/pull HDF with PS membranes. We consider that push/pull HDF may be safer than hemodialysis with RC membrane and that it is as safe as hemodialysis with the PS membrane in terms of monocyte activation, when pyrogen-free dialysate is employed.

Predialysis serum albumin concentration and creatinine generation rate do not reflect the same pathophysiologic status

BackgroundWhereas the creatinine generation rate may reflect only the protein nutritional status by way of muscle mass, the predialysis serum albumin concentration may well reflect a variety of aspects of a patients pathophysiologic status, including the protein nutritional status. The aim of this study was to clarify whether or not serum albumin concentration and the creatinine generation rate reflect the same pathophysiologic status.MethodsThe risk of death associated with the creatinine generation rate was studied with and without adjustment for the serum albumin concentration in 1588 patients undergoing hemodialysis. A comparison was also made between the death risk associated with serum albumin concentrations with and without adjustment for the creatinine generation rate. Possible correlations between the creatinine generation rate and serum albumin concentration were evaluated.ResultsThe death risk associated with the creatinine generation rate was little changed when adjusted for serum albumin concentration. However, the death risk associated with serum albumin concentration remained high even after being adjusted by the creatinine generation rate. Moreover, the correlation was very weak between the creatinine generation rate and the serum albumin concentration.ConclusionsSerum albumin concentration and the creatinine generation rate do not reflect the same pathophysiologic status.

Involvement of oxidative stress in the accelerated formation of pentosidine in patients with end‐stage renal failure

SUMMARY: Advanced glycation end products (AGEs) have been found to accumulate in the amyloid deposits, skin and plasma of haemodialysis patients (HD), implicating the possible involvement of AGE‐modified protein in pathogenesis in dialysis‐related amyloidosis. Pentosidine, an AGE cross‐link, is a specific marker for AGEs. Plasma pentosidine levels in HD patients were increased dramatically. In the present study, plasma pentosidine, fructoselysine, advanced oxidation protein products (AOPP) and glutathione peroxidase (GSHPx) levels were measured to elucidate the role of oxidative stress in pentosidine formation in nondiabetic HD patients. Plasma pentosidine did not correlate with fructoselysine; plasma AOPP levels were significantly higher than those in normal subjects (201.45 ± 57.93 vs. 55.91 ± 6.57 μmol/L, P<0.001) and correlated positively with plasma pentosidine in HD patients (r=0.52, P<0.005); plasma GSHPx levels were significantly lower than those in normal subjects (168.40 ± 65.08 vs. 348.87 ± 86.10 U/I, P<0.001) and correlated negatively with plasma pentosidine (r=0.54, P<0.001) in HD patients. Decreased GSHPx levels may lead to the accumulation of hydrogen peroxide. These findings implicate the involvement of oxidative stress in the accelerated formation of pentosidine in uraemia and suggest that pentosidine could be considered as an oxidative stress biomarker to estimate the degree of oxidative‐stress‐mediated protein damage.

lpr T cells have lower ability to maintain bcl-2 expression ex vivo.

Autoimmune-prone lpr mice develop lymphoproliferative disorders, whereas their lymphocytes show accelerated apoptosis in culture. To elucidate whether the bcl-2 protein, a repressor of apoptosis, is critical to the discrepancy between in vivo and in vitro survival, we examined bcl-2 expression in T cells from +/+ and lpr mice during culture. The expression levels of bcl-2 in cultured T cells from lpr mice were significantly down-modulated compared to those from +/+ mice and freshly obtained T cells. Besides, the reduction of bcl-2 protein levels was inhibited in T cells cultured in the presence of T cell receptor (TCR) signalling. These results suggest that lpr T cells might be susceptible to apoptosis in vitro due to down-modulation of bcl-2 by withdrawal of TCR signalling.

Application of Buttonhole Cannulation Technique to Surgically Superficialized Arteries.

In Japan, use of a surgically superficialized brachial artery is recommended for vascular access in patients who are either unable to tolerate hemodialysis because of reduced cardiac function or who do not have vessels suitable for creation of an arteriovenous fistula. Superficializing a brachial artery involves relocating a portion of the artery into subcutaneous tissue and immobilizing the artery at that location. Superficialized artery access can result in certain serious complications, such as an aneurysm and/or stenosis. In order to avoid such complications, we attempted applying the buttonhole method to this vascular access. A buttonhole track was created slightly distal from the center of the superficialized portion of a brachial artery approximately 2 weeks after superficialization. When arteriosclerosis was evident in that location, we tried to find a less sclerotic portion, under ultrasonography guidance, for creation of the arterial-side buttonhole track. For returning extracorporeal circulated blood, a normal vein on the arm with a superficialized brachial artery was cannulated with a sharp needle. Recently, however, we attempted to create a buttonhole track also on a vein for venous-side buttonhole cannulation. The brachial artery was superficialized in 5 patients. In all patients, buttonhole cannulation was successfully performed with the artery access. Buttonhole cannulation had been performed on these patients for 8-54 months. No serious complications such as a pseudoaneurysm were found in these patients. Serious complications specific to the superficialized artery access may be prevented by application of the buttonhole method.

Causes and Solutions of the Trampoline Effect

A trampoline effect may occur mainly when a buttonhole tract and the vessel flap fail to form a straight line. Certain findings, however, suggest another cause is when the vessel flap is too small. The frequency of the trampoline effect, for example, is lower when a buttonhole tract is created by multiple punctures of the arteriovenous fistula (AVF) vessel than when it is done by one-time puncture of the vessel. Lower frequency of the trampoline effect with multiple punctures of the AVF vessel may be due to enlargement of the initial puncture hole on the vessel every time the vessel is punctured with a sharp needle. Even if aiming at exactly the same point on the AVF vessel every time, the actual puncture point shifts slightly at every puncture, which potentially results in enlargement of the initial hole on the AVF vessel. Moreover, in some patients, continued use of a buttonhole tract for an extended period of time increases the frequency of the trampoline effect. In such cases, reduction of the incidence of the trampoline effect can be achieved by one buttonhole cannulation using a new dull needle with sharp side edges that is used to enlarge the vessel flap. Such single buttonhole cannulation may suggest that the increased frequency of the trampoline effect also potentially occurs in association with gradually diminishing flap size. As a final observation, dull needle insertion into a vessel flap in the reverse direction has been more smoothly achieved than insertion into a vessel flap in the conventional direction. A vessel flap in the reverse direction can be adopted clinically.

New rinsing-back method for blood tubing using blood tubings with a line bypassing the blood pump segment

バイパス付き血液回路は，通常の血液回路に血液ポンプをバイパスする回路が付加されていることを特徴とする．バイパス付き血液回路を使用しての返血操作では，人手を要する血液回路のクランプ操作と開放操作とが返血工程初期の短時間に集中している．そして，これらの操作が終了すれば，その後の返血は放置しておいても自然に進行していく．生食ソフトバッグからシャント血管内腔までの落差圧が20mmHg以上の23名の患者を対象にした研究では，透析スタッフが直接操作を行う初期操作時間は26.6±5.2秒であり，返血が自然に進行していくその後の返血工程に要した時間は3.67±0.66分であった．この結果は，バイパス付き血液回路を使用する新しい返血法では，25～30秒間を要する返血工程のいくつかの初期操作が終了すれば，透析スタッフはほかの患者の状態の急変など，緊急事態に対応するために返血中の患者のベッドを離れることも可能になることを示している．また，停電や地震などの災害時にも，バイパス付き血液回路を使用する新しい返血法では，リンス液ラインとの接続部よりも動脈針側の血液回路を充填している16～36mLの血液の損失も受け入れるならひとりの患者につき4～5秒間の操作で30名程度の患者の返血をひとりの透析スタッフが3～4分間で行うことができると計算される．

Which Kt/V Is the Most Valid for Assessment of Both Long Mild and Short Intensive Hemodialyses?

It is unclear at present which mathematical modeling Kt/Vurea is valid for assessment of both long mild hemodialysis (HD) and short intensive HD, the single-pool modeling Kt/V (Kt/Vsp) based on the pre- and postdialysis serum urea concentrations, double-pool modeling Kt/V (Kt/Vdp) based on the predialysis concentration and the estimated postdialysis equilibrated concentration, or Kt/V calculated on the basis of dialyzer urea clearance, HD session duration and urea distribution volume (Kt/Vdl). Thus, the respective Kt/V during a short intensive HD was compared with its counterpart Kt/V during a long mild HD, where the same amount of urea is removed during both HD treatments. It was found that the Kt/Vsp and Kt/Vdl during short intensive HD were significantly greater than the respective Kt/V during the long mild HD. On the other hand, there was no significant difference in the Kt/Vdp between the long mild and short intensive HDs. In conclusion, Kt/Vdp may be more valid for assessment of both long mild and short intensive HDs.