Polymethylmethacrylate (PMMA) membranes were first developed in Japan in 1977. Over its 30-year history, use of PMMA has given rise to a new generation of dialysers and continues to evolve. In long-term observation of patients treated with PMMA membranes (BK series), it has been found that serum beta2-microglobulin is maintained at a significantly lower level than in haemodialysis (HD) patients undergoing treatment with conventional cellulosic membranes. Regarding long-term side effects, radiolucent bone cysts (RBC) and carpal tunnel syndrome (CTS) have developed in relatively few patients undergoing HD with PMMA membranes. The profiles of various proteins in the blood of HD patients differ from those in normal subjects. PMMA membranes remove a wide variety of solutes not only via permeation, but also adsorption. Numerous reports have noted that pruritus can be ameliorated with the use of slightly anionic PMMA membranes (BG series). We have been performing proteomic analysis of plasma from HD patients with pruritus. We have confirmed that slightly anionic PMMA membranes can adsorb components with a molecular weight of 160,000 Da, which have stimulatory effect on mast cells from pruritus.

The concentration of carnitine, which is essential to fatty acid metabolism, can decrease markedly in patients on long-term hemodialysis coincident with life-threatening cardiac damage. However, administration of L-carnitine improves the myocardial function of these patients. To evaluate the underlying events of this phenomenon, we used recently developed technology, ¹²³I-labeled β-methyl-p-iodophenyl-pentadecanoic acid (BMIPP) myocardial scintigraphy, as a test of myocardial fatty acid metabolism. Our results showed that the free carnitine concentration (19.2 ± 6.5 μmol/l) was lower in 11 chronically dialyzed patients than in 8 healthy controls (49.3 ± 7.7 μmol/l, p < 0.0001). Additionally the heart to mediastinal ratio (H/M) of BMIPP was higher for these patients than for the controls (1.91 ± 0.19 vs. 1.52 ± 0.24, p < 0.005), and the patients’ washout rate (WOR) of BMIPP was lower (17.2 ± 6.0 vs. 22.8 ± 4.2%, p < 0.05). After L-carnitine was administered orally to the patients at doses of 1 g/day for 1 month and 0.5 g/day for the following month, the concentration of free carnitine in their sera increased to 85.4 ± 27.0 μmol/l (p < 0.0001). Although the H/M ratio did not change (1.89 ± 0.20) with this treatment, their WOR increased to 21.9 ± 6.6% (p < 0.001), similar to that of controls. The left ventricular end-diastolic dimension and left ventricular fractional shortening remained unchanged, as shown by echocardiography. The results presented here denote that a carnitine deficiency in chronically hemodialyzed patients disrupts their myocardial fatty acid metabolism, which is improved by L-carnitine supplementation.

Ultrasonography to Calculate Carotid Maximum IMTB-mode ultrasonography of the extracranial carotid artery was performed with a high-resolution, real-time scanner equipped with a 7.5-MHz imaging transducer (SSD 650 CL, Aloka, Tokyo, Japan). One trained physician, who was blinded with regard to the subjects' clinical Jpn Circ J 1999; 63: 692 -696 (Received March 19, 1999; revised manuscript received June 2, 1999; accepted June 10, 1999 Accelerated atherosclerosis is a major risk for uremic patients undergoing long-term hemodialysis. Because hyperhomocysteinemia may influence this condition, 168 such patients were examined for a possible association between plasma total homocysteine concentration (tHcy) and conventional cardiovascular risk factors. Generalized atherosclerosis was indicated by excessive intimal-medial wall thickness (IMT) of the extracranial carotid artery as measured by B-mode ultrasonography. The results documented tHcy in these patients of 33.0±16.9 mol/L, a significantly higher amount than that of healthy subjects (11.0±3.1 mol/L, p<0.0001). The patients' carotid maximum IMT was 1.79±1.16 mm. In multiple regression analyses with forward elimination procedure, carotid maximum IMT was clearly related to age (r=0.417, p<0.0001), systolic blood pressure (r=0.262, p=0.0043), smoking (r=0.177, p=0.0076), duration of hemodialysis (r=0.083, p=0.0045), and tHcy (r=0.195, p=0.0021). These 5 factors accounted for 36.0% of the variation in carotid maximum IMT. Factors determined as unrelated were male gender, diastolic blood pressure, body mass index, total and HDL cholesterol, triglyceride, lipoprotein(a), uric acid, calcium, inorganic phosphate, and parathyroid hormone. Therefore hyperhomocysteinemia, along with advanced age, systolic hypertension and smoking aggravates atherosclerosis in chronic uremic patients. (Jpn Circ J 1999; 63: 692 -696)

As compared to Europe and USA, the survival rate of chronic haemodialysis (HD) patients in Japan is demonstrated by the Japanese Registry to be high. However, another Japanese Registry nationwide survey on their quality of life revealed serious osteoarticular disorders increasing with the duration of HD. Selecting plasma beta2-microglobulin (beta2-M) as a marker, a prospective study on the long-term clinical effect of a beta2-M-removable membrane (PMMA BK membrane) has been performed and the changes in joint pains and plasma beta2-M have been followed for 5 years. In addition, the incidence of carpal tunnel syndrome (CTS) and bone cysts among 225 patients maintained on HD with BK membrane was analyzed retrospectively. By continued use of BK membrane, plasma beta2-M was maintained at a significantly lower level than that in HD with conventional cellulosic membranes. The total score of joint pain in HD patients treated with BK membrane was significantly decreased and maintained at this low value throughout 5 years. In HD patients treated with BK membrane for a long period, the occurrence of CTS and bone cyst was less and postponed, as compared to patients on HD with conventional cellulosic membranes. HD-related amyloidosis had not been observed for 5 years in patients treated with BK membrane from the introduction of haemodialysis.

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Earlobe creases are surrogate markers for high risk of cardiovascular disease. There is no data concerning earlobe creases among hemodialysis patients, who have an increased risk of cardiovascular disease. A cross-sectional study was conducted to determine the prevalence of earlobe creases and their association with prevalent cardiovascular disease among hemodialysis patients. Patients undergoing hemodialysis were recruited from five outpatient hemodialysis centers. Both earlobes were photographed during a dialysis session with the patient in a supine position and the photos evaluated independently by two experienced nephrologists blinded to the participants' clinical characteristics. Prevalent cardiovascular diseases were defined as a history of myocardial infarction, cerebrovascular accident, or peripheral vascular disease. Sensitivity, specificity, and positive and negative predictive values for detection of prevalent cardiovascular disease were calculated. Logistic analysis was used to examine the association between earlobe creases and prevalent cardiovascular disease. Earlobe creases were identified in 24.5% of 330 hemodialysis patients (200 men; mean age, 67.8 years). The prevalence of earlobe creases increased with age for men (P for trend <0.0001), but not for women (P for trend = 0.07). Sensitivity, specificity, and positive and negative predictive values were 30.9% (95% confidence interval, 21.9-41.6), 77.5% (71.9-82.3), 30.9% (21.9-41.6), and 77.5% (71.9-82.3), respectively. Multivariate logistic analyses indicated the prevalence of earlobe crease was not associated with prevalent cardiovascular diseases. The prevalence is similar to that previously reported for Japanese individuals not undergoing dialysis. No association between earlobe creases and prevalent cardiovascular diseases was identified.

Dear Sir, Ulinastatin with a molecular weight of 67,000 is a trypsin inhibitor which was purified from fresh human urine. It has a broad spectrum of enzyme activity inhibi tion: trypsin, chymotrypsin, elastase, etc. [1][2][3]. It has already been reported that ulinastatin had effectiveness in the treatment of pancreatitis and traumatic, hemor rhagic, and endotoxic shock [4,5].The effects of ulinastatin on oliguric acute renal fail ure were assessed in this study. Five cases of oliguric acute renal failure were treated. There were 3 males and 2 females, age ranging from 58 to 78 years. The mean age was 69.0±(SE)4.0 years. Serum creatinine and blood urea nitrogen levels ranged from 2.0 to 8.4 and from 71 to 121 m g/dl, respectively. The mean of serum creatinine and blood urea nitrogen levels were 5.4± 1.2 and 90 ± 10 mg/dl. Mean (± S D ) arterial pressure and heart rate were 88.6 ±23.0 mm Hg and 75 ± 24 beats/min, re spectively. For these 5 cases, an intravenous bolus injec tion of ulinastatin (20 x 10I * * 4 U) in saline (2 ml) was admin istered [6], Before and after the ulinastatin injection, other medications for treatment of oliguric acute renal failure were continued. Then urinary volume, blood pres sure, and heart rate were measured every I h. Urinary volumes were corrected with transfusion volumes. The corrected urinary volumes (cUV), calculated using the equation cUV = UV (ml/h) transfusion volume (ml/h), are presented in figure 1. The cUV values were signifi cantly higher than the values before ulinastatin injection. Furthermore, the increased cU V had been retained for at least 4 hours. On the other hand, mean arterial pressure and heart rate did not significantly change after ulinas tatin injection.Ulinastatin 20X104U

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