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H Dieperink

Publications and source records attributed to H Dieperink.

48 records · Page 3Linked to original sources

Glomerulotubular function in cyclosporine A treated rats.

A total of 178 rats treated with Cyclosporine A (CyA, dose range 0-50 mg/kg/day) during 14 days were investigated with clearance methods (inulin, lithium, sodium and potassium), serum CyA and plasma renin concentration (PRC). Inulin clearance (Cin) decreased to a mean of 68% of the control value in the 12.5 mg/kg/day group, 44% in the 25 mg/kd/day group and 47% in the 50 mg/kg/day group, respectively. Lithium clearance (CLi) was reduced in all CyA treated groups, while the absolute proximal tubular reabsorption as calculated from Cin-CLi was decreased during increased fractional proximal reabsorption (1-CLi/Cin). As proximal intratubular hydrostatic pressure has been shown to be low in the normal range (excluding tubular obstruction) these findings are considered due to a decrease in ultrafiltration pressure. Furthermore we found the reabsorption of sodium distal to the proximal tubule to be decreased, both absolute (PNa X (CLi-CNa)) and fractional to the delivery from the end of the proximal tubule (1-CNa/CLi). Also the distal potassium reabsorption was decreased PK X (CLi-CK). These findings were not primary, but rather secondary, to the altered proximal function, since it has been shown that i.v. CyA immediately produces increased fractional proximal reabsorption. PRC was increased from a mean of 2.5 to 4.9 and 5.3 X 10(-4) Goldblatt units (GU)/ml (12.5 and 25 mg/kg group, respectively), to be explained by the decreased sodium delivery to the macula densa region and/or by a direct CyA effect. In conclusion CyA reduces the net ultrafiltration pressure, and due to an insufficient decrease in absolute proximal tubular reabsorption, fractional proximal reabsorption increases.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Xeno- and auto-perfusion of rabbit kidney. Machine perfusion with blood at 37 degrees C.

Five rabbit kidneys were perfused with human blood and another five with their own blood in a re-circulating oxygenated system at 37 degrees C. The flow decreased to 2 ml/min. within 30 min. in all xenoperfusions, while none of the autoperfused had decreased to this level by 60 min. Endothelial damage, exudation, and IgG deposits along the basement membrane of the glomerular capillaries were the discriminative features of the xenoperfusion. In these experiments, we were unable to demonstrate any major role of platelets in the process leading to decreased blood flow.

Animals↗

Glomerulotubular function in cyclosporine-treated rats. A lithium clearance, occlusion time/transit time and micropuncture study.

Sprague-Dawley rats treated with cyclosporine (Cys) and appropriate controls were investigated with inulin, lithium and sodium clearances. It was found that Cys depressed glomerular filtration rate (GFR) and absolute proximal tubular reabsorption, while fractional proximal reabsorption was increased. As a normal proximal tubular reabsorptive capacity was found after volume expansion, and the intratubular pressure was normal, tubulotoxicity or obstruction of the tubular system by Cys was excluded. Increased fractional proximal reabsorption was also found with the occlusion time/transit time method. Intravenous Cys resulted in instantaneous renal functional changes qualitatively identical to those of prolonged Cys treatment. It was concluded that Cys nephrotoxicity is due to decreased ultrafiltration pressure, most probably due to a reversible spasm in the afferent glomerular arteriole.

Animals↗

Pinacidil--effects on function and perfusion of normal kidneys and renal xenografts.

Pinacidil is a new vasodilating compound claimed to increase renal perfusion and function. A preliminary study showed that pinacidil did not sustain renal perfusion through a period of increasing renal vascular resistance in pig-to-rabbit renal xenotransplantation. Accordingly, the effect of pinacidil on renal function in conscious catheterized rats was studied. Pinacidil 0.12-0.18 mg/kg i.v. caused a moderate reduction in mean arterial blood pressure (14-17 mmHg), a decrease in inulin and PAH clearances (50-65%), and sodium and water retention. The sodium clearance/lithium clearance ratio decreased, suggesting increased sodium reabsorption in the distal nephron during pinacidil administration. Thus the results are in accord with those obtained with several other vasodilators, but not with those obtained in mongrel dogs during pinacidil administration.

Animals↗

Effects of cyclosporin A, gentamicin and furosemide on rat renal function: a lithium clearance study.

1. This study applied clearance methods of inulin, lithium, potassium, sodium and para-aminohippuric acid (PAH) for investigation of the effects of cyclosporin A (CyA), furosemide and gentamicin on rat (n = 92) renal function. The drugs were dosed for 2 weeks; CyA 12.5 mg/kg per day, gentamicin 32 mg/kg per day and furosemide 5 mg/kg per day. 2. The questions asked were: could these methods differentiate the effects of drugs with different sites of action, and would gentamicin or furosemide exaggerate the nephrotoxicity of CyA? 3. Furosemide increased sodium clearance (CNa) 74% and fractional sodium clearance (FENa) 105%, while fractional sodium reabsorption in the distal nephron (FDNR) was reduced, compared with placebo-treated controls. 4. Gentamicin reduced CPAH 29% and Cin 37%, while FENa increased 335%. Proximal fractional reabsorption (PFR) and absolute proximal reabsorption (APR) decreased. 5. CyA depressed CPAH 32% and lithium clearance (CLi) 56%, and increased PFR. 6. The effects of CyA and furosemide in reducing renal function were not additive. 7. CyA plus gentamicin reduced CPAH to 35% of the value in untreated controls, equal to 52% of the CPAH of CyA-treated rats; Cin was reduced to 46% of the Cin of CyA-treated rats. 8. Rats given CyA, furosemide and gentamicin had decreased Cin, CPAH and CLi compared with rats given either CyA plus furosemide or gentamicin plus furosemide. 9. Thus, in this investigation of drugs known to have different sites of actions, the differences in renal and tubular function were discernible with the lithium clearance method. 10. The nephrotoxicities of CyA and of gentamicin were additive, while furosemide did not aggravate CyA nephrotoxicity.

Animals↗

Nephrotoxicity of cyclosporin A and contrast media. A comparison between diatrizoate and iohexol in rats.

Urine profiles (albumin, glucose, NAG, LDH, GGT and sodium) were followed for 22 h or 8 days after intravenous injection of diatrizoate, iohexol or saline in 30 adult Wistar rats in which nephrotoxicity was induced by daily peroral administration of 25 mg/kg body weight cyclosporin A over a 14-day period. Another 10 rats which had the vehicle of the cyclosporin A solution (placebo) and saline injected intravenously served as controls. The effect of iohexol and saline on the albumin excretion was similar, whereas diatrizoate increased it significantly. Both contrast media caused significantly increased excretion of all three enzymes. The contrast media had no effect on the excretion of glucose and sodium. Except for the fact that the excretion of NAG was significantly higher following iohexol than following diatrizoate 24 to 46 h after injection no significant differences between the two media were found from 24 h after injection among the rats given cyclosporin A. No contrast medium related changes were found by light microscopy of the kidneys. Neither iohexol nor diatrizoate potentiate acute cyclosporin A nephrotoxicity.

Acetylglucosaminidase↗