Determination of the glomerular filtration rate (GFR): methodological problems, age-dependence, consequences of various surgical interventions, and the influence of different drugs and toxic substances.
Determinations of renal clearance of fluorescein isothiocyanate (FITC)-inulin were used for assessing the glomerular filtration rate (GFR) in rats and to characterize factors influencing the glomerular filtration capacity. In anesthetized rats, GFR develops after birth up to day 30. Thereafter, GFR remains relatively constant for up to 3 months of age and drops continuously until the 8th month. GFR can be determined in utero, already one day before birth, however, only at a very low level. It increases significantly on the first day of life. Even at this time the effect of furosemide on GFR can be proven. After reduction of renal mass, GFR is decreased in dependence on the extent of kidney tissue removal. However, within 2 days after unilateral nephrectomy (NX) or one week after 5/6 NX, GFR reaches values about 3/4 of the controls with two intact kidneys. Furthermore, the compensation of GFR after renal ischemia reaches 80% of baseline values after one week. On the other hand, GFR is enhanced after bile duct ligation as a model of hepato-renal failure. It has been shown in previous experiments that pretreatment with hormones can stimulate renal tubular transport processes. Pretreatment with dexamethasone or triiodothyronine after 5/6 NX improves glomerular filtration capacity whereas in animals with ligated bile ducts dexamethasone seems to prevent the increase in GFR. After subchronic treatment with epidermal growth factor (EGF) GFR is significantly reduced. A continuous infusion of amino acids does not change GFR in the controls but enhances the filtration capacity in EGF-treated rats. But immediately after bolus injection of amino acids GFR also increases significantly in the controls. Diuretics such as furosemide, most nephrotoxic agents (cyclosporine A [CsA], heavy metals) and imidazole reduce the GFR significantly. Diltiazem reported to act nephroprotectively in CsA nephrotoxicity in human beings was without beneficial effect in rats. This could be due to species differences in GFR because the rat is one of the species with the highest glomerular filtration capacity.
Fleck
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Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany.
D000375:Aging; D000818:Animals; D016572:Cyclosporine / Q000633:toxicity; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005919:Glomerular Filtration Rate; D006801:Humans; D007444:Inulin; D007668:Kidney / Q000503:physiopathology / Q000601:surgery*; D007674:Kidney Diseases / Q000139:chemically induced* / Q000503:physiopathology; D007700:Kinetics; D008670:Metals / Q000633:toxicity; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D014511:Uremia / Q000503:physiopathology
D008670:Metals; D016572:Cyclosporine; D007444:Inulin; D016650:Fluorescein-5-isothiocyanate