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.

We investigated the clinical efficacy of direct hemoperfusion with a beta2-microglobulin (beta2-m) adsorption column for the treatment of patients with dialysis-related amyloidosis. A 2-year prospective controlled study was performed to compare the effects of passaging blood through a (beta2-m) adsorption column (Lixelle) before it is passaged through the dialysis polysulfone membrane on the severity of amyloidosis in these individuals. Patients (n = 22) whose blood went through the Lixelle column prior to dialysis had a higher beta2-m removal rate compared to an equal number of controls, and they showed earlier improvement in their symptoms which included impaired daily activities, joint stiffness, and pain. The appearance of additional bone cysts was prevented in pre-adsorbed patients but not in the controls. Thus, the Lixelle column is useful in preventing the progression of dialysis-related amyloidosis and in ameliorating or arresting the progression of the symptoms of this disorder.

Spontaneously developing focal and segmental glomerulosclerosis (FGS) in Buffalo/Mna rats was studied. There were no differences in the occurrence of the disease between male and female rats. Plasma macromolecules were detected in the urine samples of 2-month-old rats using sodium dodecyl sulphate polyacrylamide gel electrophoresis. All 4-month-old animals had proteinuria in excess of 30 mg/24 h. At the age of 4 months, sclerotic glomeruli were rarely observed. At the age of 6 months, all animals had a few sclerotic glomeruli in every kidney section examined. Animals which were 22 months old had sclerotic lesions in 37.8–52.1% of the glomeruli. Ultrastructural examination revealed that alterations in epithelial cells, such as effacement of foot processes, vacuolization, and a podocytic membrane-like structure, were found at the age of 2 months. The animals examined were neither uremic nor hypertensive. Our present study showed that female as well as male Buffalo/Mna rats had an earlier onset of the disease than the other strains of rats and that alterations in glomerular epithelial cells were first detected in the early stage of the disease.

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