Tissue insulin sensitivity was measured by the glucose clamp technique in 8 uremic insulin-dependent diabetic patients before and after 3 months on a low-protein diet (LPD) providing daily 35 kcal/kg body weight, 60% of the caloric supply being obtained from carbohydrates. An improvement in tissue insulin sensitivity was observed for each steady state of the clamp and daily insulin requirements decreased significantly from 38.3 ± 3.2 to 28.2 ± 2.5 units (p < 0.01) in spite of an increased carbohydrate intake. It is suggested that LPD lowers the production and accumulation of uremic toxins interfering with insulin sensitivity.
Cyclosporin A (CyA), an immunosuppressive agent, induces in vivo a severe nephrotoxicity with large decrease in renal hemodynamics correlated with in vitro glomerular contraction. The aim of this study is to show the ability of three xanthine derivatives, caffeine, theophylline and pentoxifylline, to diminish the CyA-induced in vitro glomerular contraction. The use of isolated glomeruli and cultured rat mesangial cells permits us to evaluate by quantitative and qualitative morphometric analysis the contraction elicited either with CyA alone or with previous treatment with nontoxic concentrations of xanthine derivatives. Indirect immunofluorescence of actin filaments makes it possible to appreciate qualitative morphometric changes in mesangial cells. A 10-min pretreatment with caffeine, theophylline or pentoxifylline (10-4 to 10-9M) abolishes the contraction elicited with 10-6 M CyA. CyA alone induces -13.9% compared to CyA with 10-6M pentoxifylline which induces only -3.2% of reduction of planar glomerulus surface area after 30 min. Similar results were provided with cultured rat mesangial cells. As shown by indirect immunofluorescence xanthine derivatives prevent the cytoskeletal reorganization (α-actin) of cultured mesangial cells which occurs with CyA. The marked constriction induced by CyA in isolated glomeruli and mesangial cells can be prevented by xanthine derivatives.
Cardiovascular morbidity and mortality in hemodialyzed patients are increased due to the frequently abnormal lipid metabolism. It has been reported that this abnormal lipid metabolism could be partially corrected by some highly permeable membranes, such as polysulfone or cellulose triacetate. We investigated the influence of 4 months of dialysis with a polyamide membrane upon the course of lipid parameters in 6 patients presenting a hypertriglyceridemia > 2 mmol/l while on bicarbonate dialysis with a cellulose membrane. Lipid parameters improved after 4 months of hemodialysis with a polyamide membrane. Serum triglyceride and cholesterol levels decreased, while HDL cholesterol and HDL levels rose significantly (p < 0.05). Apolipoprotein B decreased significantly (p < 0.05). Following heparin administration, lipoprotein lipase activity improved (p < 0.02), associated with a decrease in apolipoprotein C3 (p < 0.05). The fractional clearance rate of triglycerides rose significantly (p < 0.01). The use of highly permeable polyamide membranes results in a significant improvement in lipid disturbances of dialysis patients due to an increased lipoprotein lipase activity, induced perhaps by the removal of circulating inhibitors such as apolipoprotein C3.
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