Motoyoshi Sato

Effects of L-Carnitine Supplementation on Cardiac Morbidity in Hemodialyzed Patients

Cardiac diseases are well known among patients on maintenance hemodialysis (HD), and carnitine deficiency may be an important factor in cardiac morbidity. We studied the effects of low-dose L-carnitine treatment (500 mg/day) on chest symptoms (dyspnea on exertion, chest pain, palpitation), cardiac function, and left ventricular (LV) mass in 9 HD patients with reduced ejection fraction (EF). After 6 months of L-carnitine treatment, most patients had at least some improvement in chest symptoms, while LVEF was increased and LV mass was decreased. Carnitine fractions increased and reached plateaus at 2–3 times the baseline levels. These results suggest that prolonged low-dose L-carnitine treatment can improve the cardiac morbidity by restoring decreased carnitine tissue levels and impaired oxidation of FFA.

Factor(s) present in sera from patients on long-term hemodialysis increase(s) mRNAs for collagenase and stromelysin in synovial cells

Rheumatic disorders are common complications in patients on long-term hemodialysis (HD), and abnormalities of collagen metabolism in the musculoskeletal system have been suggested in these patients. Since collagenase, which catalyzes the initial step in the proteolytic degradation of collagen, plays an important role in the metabolism of collagen, the present study investigated whether factor(s) present in the sera from patients on long-term HD stimulates collagenase gene expression in synovial cells. The addition of sera from 8 patients on long-term HD resulted in 1.5- to 4.0-fold increases in the collagenase mRNA level in human synovial cells as compared with that of sera from normal subjects. The collagenase-inducing factor(s) in uremic sera is more than 3,000 D in molecular mass and shows no binding to heparin. Uremic sera also increased stromelysin mRNA, but failed to exert any effect on mRNAs for tissue inhibitor of metalloproteinases and pro alpha 1(I)collagen. Our findings suggest that there exists a factor(s) to enhance degradation of synovial collagen in sera from long-term HD patients.

Changes in Oxidative Stress and Microcirculation by Low‐density Lipoprotein Apheresis

Abstract:  Low‐density lipoprotein apheresis (LDLA) leads to an improvement of microcirculation during the very early stages of treatment, and continued treatment may produce antiatherogenic effects in patients with peripheral arterial disease (PAD). Suppression of oxidative stress, improvement of endothelial functions and alteration in the action of vasoactive compounds may occur with the improvement of the rheological property of blood as a result of aggressive removal of atherogenic factors including LDL, possibly resulting in the suppression of development of atherosclerosis. As these effects of LDLA may ameliorate not only PAD but also ischemia in other organs, it is suggested that repeated LDLA prevents the progression of atherosclerotic diseases and probably improves the long‐term prognosis of patients with PAD.

Interleukin 8 and Biocompatibility of Dialysis Membranes

To determine whether interleukin 8 (IL-8) can be used as an index of biocompatibility of dialysis membranes, the effects of hemodialysis (HD) on plasma IL-8 levels and the expression of IL-8 mRNA in peripheral blood mononuclear cell (PBMC) were compared among regenerated cellulose (RC), polyacrylonitrile (PAN) and polymethylmethacrylate (PMMA) dialyzers. HD using RC dialysers significantly increased plasma IL-8 levels and induced abundant expression of IL-8 mRNA in PBMC. HD using PMMA dialyzers also increased plasma IL-8 levels and induced slight expression of IL-8 mRNA. In contrast, HD using PAN dialyzers neither increased plasma IL-8 levels nor induced the expression of IL-8 mRNA. In vitro studies demonstrated that IL-8 was considerably adsorbed by PAN membranes and not at all by RC and PMMA. These studies indicate that plasma IL-8 level and expression of PBMC IL-8 mRNA can be used as indices of biocompatibility of dialysis membranes.

Survey of the Effects of a Column for Adsorption of β2-Microglobulin in Patients With Dialysis-Related Amyloidosis in Japan

Dialysis‐related amyloidosis is a serious complication of long‐term hemodialysis. Its pathogenic mechanism involves accumulation of β2‐microglobulin in the blood, which then forms amyloid fibrils and is deposited in tissues, leading to inflammation and activation of osteoclasts. Lixelle, a direct hemoperfusion column for adsorption of β2‐microglobulin, has been available since 1996 to treat dialysis‐related amyloidosis in Japan. However, previous studies showing the therapeutic efficacy of Lixelle were conducted in small numbers of patients with specific dialysis methods. Here, we report the results of a nationwide questionnaire survey on the therapeutic effects of Lixelle. Questionnaires to patients and their attending physicians on changes in symptoms of dialysis‐related amyloidosis by Lixelle treatment were sent to 928 institutions that had used Lixelle, and fully completed questionnaires were returned from 345 patients at 138 institutions. The patients included 161 males and 184 females 62.9 ± 7.7 years age, who had undergone dialysis for 25.9 ± 6.2 years and Lixelle treatment for 3.5 ± 2.7 years. Based on self‐evaluation by patients, worsening of symptoms was inhibited in 84.9–96.5% of patients. Of the patients, 91.3% felt that worsening of their overall symptoms had been inhibited, while attending physicians evaluated the treatment as effective or partially effective for 72.8% of patients. Our survey showed that Lixelle treatment improved symptoms or prevented the progression of dialysis‐related amyloidosis in most patients.

Randomized Pilot Trial Between Prostaglandin I2 Analog and Anti-Platelet Drugs on Peripheral Arterial Disease in Hemodialysis Patients

The effect of the prostaglandin I2 analog, beraprost sodium (BPS), on hemodialysis (HD) patients with peripheral arterial disease (PAD) has not been fully elucidated. The effect of BPS was compared to that of PAD drugs in HD patients with PAD in a multicenter randomized prospective interventional pilot study (J‐PADD). Seventy‐two PAD patients on HD were entered and randomly divided into two groups; that is, BPS group (Group A: n = 35) and PAD drug (cilostazol or sarpogrelate) group (Group B: n = 37). Primary endpoint was changes in skin perfusion pressure (SPP). Kidney Disease Quality of Life (KDQOL) score, cardiovascular events, PAD events, and adverse events were also evaluated. SPP increased significantly in both groups at 24 weeks from their basal levels. The absolute increase of SPP in Group A and Group B were 15.4 ± 30.0 mm Hg (P < 0.0001) and 20.2 ± 22.1 mm Hg (P = 0.025) (instep), and 13.8 ± 19.3 mm Hg (P < 0.0001) and 9.2 ± 16.3 mm Hg (P = 0.041) (sole), respectively. Changes of KDQOL score showed significantly better result in the role of physical score in Group A compared with Group B. Although heart rate was unchanged in Group A, 9.3/min increase was seen in Group B patients who received cilostazol. There was no intergroup difference in cardiovascular events and/or PAD events between the two groups during the study period. This exploratory pilot study suggested BPS was as effective as anti‐platelet drugs in improving microcirculation in HD patients.

Plasma Interleukin 8 Levels Are Increased by Hemodialysis

The effects of hemodialysis on plasma interleukin 8 (IL-8) levels and the expression of IL-8 mRNA in peripheral blood mononuclear cells (PBMC) were studied in uremic patients undergoing maintenance hemodialysis (HD) using regenerated cellulose dialyzers. The plasma IL-8 levels in the patients after HD sessions were significantly higher than before HD. Comparison of the IL-8 mRNA levels obtained from PBMC before and after HD indicated that the expression of IL-8 mRNA was increased by HD. The enhancement of production of IL-8 in PBMC during HD may be responsible for inflammatory complications and impaired host defense in HD patients.

Short-Term Biological Effects of a New and Less Acidic Fluid for Peritoneal Dialysis

Background: Conventional peritoneal dialysates are potentially bioincompatible and seem to be a causative factor for peritoneal sclerosis. Recent studies demonstrated that a new type of dialysate has a positive long-term clinical effect on dialysis patients. Methods: In this study, to elucidate the short-term biological effects of a newly developed dialysate of higher pH on the peritoneal membrane, we assessed macrophage proportions and several markers (inflammatory cytokines, cancer antigen 125 (CA125) and albumin) in spent dialysates before and 2 weeks after the change to the new fluid from a conventional fluid. Results: We found that the use of the new dialysate decreased intraperitoneal levels of inflammatory cytokines, CA125 and albumin associated with the decrease of macrophage populations in dialysis effluents. Conclusion: These observations suggest that a new and less acidic fluid reduces pro-inflammatory potential in the peritoneum, and thus affords better preservation of peritoneal membrane integrity in uremic patients on peritoneal dialysis.

Development and evaluation of new devices for use in the central venous catheter system

The central venous catheter (CVC) is considered the most reliable type of temporary blood access, and longer-term blood purification has become possible with its improvement. We report the clinical evaluation of a new CVC, the Tornado catheter, and discuss complications associated with the long-term use of the CVC (L-CVC). We placed Tornado catheters in the internal jugular vein for 1–2 weeks in 10 patients. L-CVC were employed in 14 patients undergoing maintenance hemodialysis (HD). In only 2 of 10 patients with a Tornado catheter, the blood flow was decreased during HD due to clot formation on the arterial side. No patients had other complications. In patients with L-CVC, poor blood flow often occurred. In two patients with cardiac dysfunction, we have been using CVC for more than 12 months. The development of a CVC that will serve as a permanent blood access is expected.The central venous catheter (CVC) is considered the most reliable type of temporary blood access, and longer-term blood purification has become possible with its improvement. We report the clinical evaluation of a new CVC, the Tornado catheter, and discuss complications associated with the long-term use of the CVC (L-CVC). We placed Tornado catheters in the internal jugular vein for 1–2 weeks in 10 patients. L-CVC were employed in 14 patients undergoing maintenance hemodialysis (HD). In only 2 of 10 patients with a Tornado catheter, the blood flow was decreased during HD due to clot formation on the arterial side. No patients had other complications. In patients with L-CVC, poor blood flow often occurred. In two patients with cardiac dysfunction, we have been using CVC for more than 12 months. The development of a CVC that will serve as a permanent blood access is expected.