CAPD therapy, in spite of its possible adverse effects in patients with atherosclerotic disease, has been shown to improve insulin resistance in adult uraemic patients, similarly to HD therapy.
The pharmacokinetics of meropenem were studied after intravenous infusion in 13 patients grouped according to the impairment of their renal function. Creatinine clearance (CLCR) was greater than 50, 50 to 30, and less than 30 ml/min in groups I, II, and III, respectively. Two other groups, groups IV and V, each comprising four patients with end-stage renal disease (CLCR, < 5 ml/min), were also studied, the former on days off of hemodialysis and the latter on days of hemodialysis. The elimination half-lives of meropenem were 1.54 +/- 0.70 h in group I patients, 3.36 +/- 1.02 h in group II patients, and 5.00 +/- 1.05 h in group III patients. Cumulative urinary excretion accounted for 48.5% of the dose in group I patients and decreased progressively with a decline in renal function. Hemodialysis shortened the elimination half-life of meropenem from 7.0 h to 2.9 h. H-4295, the main metabolite of meropenem, had a peak level in plasma of 0.5 to 1.0 h in patients with renal failure. The level of H-4295 decreased with hemodialysis. The dosing interval of meropenem should be prolonged in a regular proportion to the decline in CLCR (12 h in group II patients and 24 h in group III patients). In patients receiving hemodialysis, dosing after each hemodialysis session is recommended.
The passage of various endogenous proteins [such as albumin, transferrin, immunoglobulin G (IgG), and immunoglobulin M (IgM)] across GBM was studied in vivo in normal Munich-Wistar rats. Glomeruli were fixed by three different methods: in situ drip-fixation, perfusion- and immersion-fixation; then they were processed for immunogold electron microscopy. The most reproducible results were obtained with in situ drip-fixation. Albumin, transferrin and IgG penetrated into GBM, but IgM did not. Morphometry revealed that density of albumin increased towards the inner 1/5 to 1/3 of GBM (junction of lamina rara interna and lamina densa) and decreased towards the subepithelial region of GBM, whereas density of IgG and transferrin was the highest at the subendothelial site and declined towards the subepithelial side of GBM. These findings suggest that central and/or outer zone of GBM constitute the main filtration barrier for albumin, and that subendothelial zone may contribute also to the charge-selective barrier. It is also suggested that the subendothelial zone acts more effectively as a filtration barrier for IgG and transferrin than for albumin. In the outer zone of GBM, which roughly corresponds to lamina rara externa visualized by conventional electron microscopy, the relative density of IgG and transferrin was higher than that of albumin. Since the pI of albumin was lower than that of IgG and transferrin, this finding suggests that subepithelial zone of GBM also acts as a charge-selective barrier. In conclusion, the main GBM filtration barrier for albumin might be the central and outer zones of GBM, and that for transferrin and IgG might be the entire width of GBM.(ABSTRACT TRUNCATED AT 250 WORDS)
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