The use of a high-flux membrane, which eliminates larger molecular weight solutes with better biocompatibility, has steadily increased since the discovery of beta-2 microglobulin (beta 2m) amyloidosis in 1985. The long-term effects of a dialyzer membrane on morbidity and mortality are not completely understood. To examine the membrane effect as a factor of carpal tunnel syndrome onset and mortality, multivariate Cox regression analysis with time-dependent covariate was conducted on 819 patients from March 1968 to November 1994 at a single center. Two hundred and forty-eight of the patients were either switched from the conventional to high-flux membrane or treated only with a high-flux membrane. Fifty-one patients underwent a CTS operation and 206 died. Membrane status (on high-flux or on conventional) was considered as time-dependent covariate and risk was adjusted for age, gender, type of renal disease and calendar year of dialysis initiation. The relative risk of CTS was reduced to 0.503 (P < 0.05) and mortality 0.613 (P < 0.05) by dialysis on the high-flux membrane, compared to the conventional membrane. Serial measurements of beta 2m indicated significantly lower beta 2m to persist in patients on the high-flux membrane. The high-flux membrane decreased the risk of morbidity and mortality substantially. Larger molecule elimination was shown important not only for preventing beta 2m amyloidosis, but for prolonging survival of dialysis patients as well.

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.

Background Patients on long-term hemodialysis become deficient in carnitine and are frequently treated with carnitine supplementation to offset their renal anemia, lipid abnormality and cardiac dysfunction. The therapeutic value of carnitine supplementation on left ventricular hypertrophy (LVH) in patients with normal cardiac systolic function remains uncertain. Methods and ResultsThe cardiac morphology and function of 10 patients given 10 mg/kg of L-carnitine orally, immediately after hemodialysis sessions 3 times per week for a 12-month period were compared with 10 untreated control patients. Using echocardiography, left ventricular fractional shortening (LVFS) and left ventricular mass index (LVMI) were measured before and after the study period. As a result, amounts of serum-free carnitine increased from 28.4±4.7 to 58.5±12.1 mol/L. The LVMI decreased significantly from 151.8±21.2 to 134.0±16.0 g/m 2 in treated patients (p<0.01), yet the LVMI in untreated control patients did not change significantly (ie, from 153.3±28.2 to 167.1±43.1 g/m 2 ). However, LVFS values remained unchanged in both groups. Although L-carnitine promoted a 31% reduction in erythropoietin requirements, hematocrit and blood pressure did not change during the study period. Conclusions Supplementation with L-carnitine induced regression of LVH in patients on hemodialysis, even for those with normal systolic function. (Circ J 2008; 72: 926 -931)

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)

The genotype of HCV (III) and a reduction in the core antibody titre appear to be useful parameters for predicting the response to IFN-alpha therapy.