Creatinine clearance was used as a measure of glomerular ifitration rate (G.F.R.), since it is known to remain constant during short-term experiments, and to be independent of variations in plasma creatinine concentration (Eggleton, 1944). The use of inulin clearance for this purpose has been under investigation, but preliminary results indicate a behaviour so irregular in relation to the steadiness shown by creatinine clearance that the latter has been retained. The experiments were of two main types. In a few, a first rapid infusion of creatinine and sodium thiosulphate (freshly prepared) was followed by a continuous slow infusion and, when urine flow was steady, two consecutive samples were collected, followed by a blood sample. In the majority ofexperiments, a single injection was made either of creatinine, ofthiosulphate, or of both together;the first blood sample was taken 5-30 min. after the end of the infusion and at intervals thereafter, the clearance during the collection of the intervening urine samples being calculated from the concentration in the plasma at the mid-point of each sample. It is unorthodox to attempt sampling before equilibrium has been attained between blood and tissues, and we were first driven to this expedient when using small injections of thiosulphate, since this substance disappeared too rapidly
Inulin is used at present for the measurement of glomerular filtration rate (G.F.R.) in most species of laboratory animal, including man, and the evidence in favour of the hypothesis that it is freely filtered at the glomerulug and neither secreted nor reabsorbed by the tubule cells is apparently strong (Smith, 1937). Certain other substances have the same clearance as that of inulin in certain species, e.g. creatinine and ferrocyanide in the dog, but not in man, and creatinine has been used for measurement of G.F.R. in the cat (Eggleton & Habib, 1949a), since its clearance was found to be independent of changing creatinine concentration in the plasma. This clearance has now been compared with that of inulin over as wide a range of concentrations of the two substances as possible and with the concentrations both increasing and decreasing.The two clearances were identical under certain conditions, but under others the creatinine/inulin clearance ratio varied between 0-65 and 1-7. When the two are not identical, the evidence suggests that creatinine clearance is the more probable measure of filtration rate.
METHODSThe general experimental technique has been already described (Eggleton & Habib, 1949a). A few experiments were performed under chloralose and urethane anaesthesia, but nembutal was used in the majority and in the few experiments performed on dogs. In the latter, urine was collected from one kidney only, by cannulation of the ureter near its upper end, and blood obtained from a femoral artery. Inulin (Kerfoot) was administered intravenously in concentrations ranging from 1 to 20%, either in a single dose, or by constant infusion from a motor-driven syringe following a small initial dose. Creatinine was injected intravenously when a high concentration was required; when a low steady concentration was needed, it was given by the subcutaneous route.Creatinine was estimated as the alkaline picrate, inulin by Cole's modification (unpublished) of Roe's method (1934). In both, colour comparison was made by use of a photoelectric colorimeter.
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