Effect of hyperfiltration, proteinuria and diabetes mellitus on the uptake kinetics of gentamicin in the kidney cortex of rats.
The influence of hyperfiltration-hypertrophy, proteinuria and glucosuria on the renal cortical uptake of gentamicin was studied in several experimental models. Two groups of remnant kidney rats, one fed a standard protein diet and one a low protein diet, heavy proteinuric rats (adriamycin) and diabetic rats, each with their own control group, were treated with increasing doses of gentamicin, given as a continuous infusion over 6 hr. The relationship between increasing steady-state serum levels (ranged from 1 to 100 micrograms/ml) and the cortical gentamicin concentrations at the end of the infusions was examined by means of Michaelis-Menten kinetics. The uptake curves were compared to their respective control curves. It was demonstrated that gentamicin uptake was reduced in remnant kidney rats fed standard diet (showing hyperfiltration and heavy proteinuria), in adriamycin rats (showing heavy proteinuria in the absence of hyperfiltration) and in diabetic rats. Uptake of gentamicin in remnant kidney rats fed low protein diet (showing hyperfiltration and slight proteinuria) was comparable to controls. It appeared that among the pathophysiological factors examined, proteinuria is the most important in decreasing the cortical uptake of gentamicin. It is suggested that high levels of proteins in the proximal tubular fluid interfere with the adsorptive endocytic process, involved in the uptake of both proteins and gentamicin.
Pattyn
V M
VM
Department of Nephrology-Hypertension, University Hospital Antwerp, University of Antwerp, Edegem, Belgium.
Verpooten
G A
GA
Giuliano
R A
RA
Zheng
F
F
De Broe
M E
ME
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005260:Female; D005839:Gentamicins / Q000493:pharmacokinetics*; D005919:Glomerular Filtration Rate; D006984:Hypertrophy; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000378:metabolism*; D011507:Proteinuria / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D005839:Gentamicins