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The present experiment demonstrated that an irreversible glomerulosclerosis could be induced in the rat through repeated intravenous administrations of OX-7 (a monoclonal anti-Thy-1.1 antibody). Rats were injected with 0.2 mg of affinity-purified OX-7 at 1-week intervals for a period of 4 weeks. Glomerular damage was periodically examined at light-microscopic level. Thirty-five days after the initial injection (7 days after the final injection), capillary aneurysms and expansion of the mesangial areas with hypercellularity were frequently observed. Similar glomerular damage was also observed in rats 7 days after they received a single injection of either 1.0 or 0.2 mg of OX-7. After repeated injections, 112 days from the initial administration (84 days after the final injection), approximately 60% of the glomeruli had expanded mesangial areas with an apparent increase in the mesangial matrix. The result contrasts sharply with that obtained from a single injection of OX-7 in that more than 85% of the glomeruli showed no abnormalities 84 days after the injection. This chronic model, as a result of repeated injections of the antibody, could serve as a potential for further investigation of the mechanisms involved in the development of chronic glomerulonephritis.

We analyzed the rebound pattern of plasma beta 2-microglobulin (beta 2-m) concentration from 4 h after completion of hemodiafiltration until the start of the next treatment according to the one-pool beta 2-m kinetic model so as to determine beta 2-m generation rate and whole-body beta 2-m clearance. Next, we obtained the whole renal beta 2-m clearance as the product of renal creatinine clearance and the glomerular sieving coefficient of beta 2-m. Then, extrarenal beta 2-m clearance was calculated as the difference between whole-body beta 2-m clearance and whole renal beta 2-m clearance and renal beta 2-m clearance due to tubular absorption was taken to be the difference between whole renal beta 2-m clearance and renal beta 2-m clearance due to urinary excretion. The results showed that the higher the patients' plasma beta 2-m concentration was, the lower was the whole-body beta 2-m clearance. Moreover, in the present study, an inverse correlation was found between the following respective factors: plasma beta 2-m concentration and whole renal beta 2-m clearance; plasma concentration and renal clearance due to tubular absorption; plasma concentration and renal clearance due to urinary excretion. However, there was no correlation between plasma beta 2-m concentration and extrarenal beta 2-m clearance. The findings indicate that the variation of plasma beta 2-m concentration with the individual patient is solely attributable to the variation in residual renal function in terms of beta 2-m elimination.

The purpose of the study is to investigate the effects of L-carnitine on the exogenous acetate metabolism during hemodialysis together with the triglyceride and free fatty acid metabolism. Sixteen chronic renal failure patients on acetate dialysis were orally administered 1,200 mg of L-carnitine chloride per day for 12 weeks. Plasma triglyceride concentrations at 30 and 60 min following initiation of hemodialysis were significantly lower than before hemodialysis, while the plasma concentrations of free fatty acid at the same points into hemodialysis were significantly higher than before hemodialysis, whether L-carnitine chloride was being given or not. This is attributed to the enhanced degradation of triglyceride and the increased generation of the free fatty acid with heparin administration during hemodialysis. The L-carnitine chloride treatment did not affect the plasma triglyceride concentrations at 30 and 60 min into hemodialysis, whereas the free fatty acid concentrations at the same points into hemodialysis were significantly lower after L-carnitine chloride administration commenced than before it. This is attributed to the fact that fatty acid oxidation was enhanced following the L-carnitine chloride treatment. Compared to before the drug administration, the whole body clearance of exogenous acetate was significantly increased after the drug was given, and the plasma acetate level during hemodialysis fell accordingly. This is attributed to the fact that with L-carnitine chloride administration, the amount of accumulated acyl-CoA in the cytosol decreased and consequently the citrate cycle function increased.