Excretion of Exogenous Creatine by the Guinea Pig Kidney

Abstract

In the search for substances suitable for measurement of glomerular filtration rates, tubular secretion of exogenous creatinine was discovered in the aglomerular fish (1, 2 ) , dogfish (3)(4)(5), frog (6, 7), snake (8), chicken (9), kangaroo rat (10) as well as the albino rat (11)(12)(13)(14), sheep and goat ( 1 5), dog [under the special condition of stopflow analyses (16, 17)], primate (18, 19), and man (20,21). In earlier work on guinea pigs, the present authors noted a disparity between inulin and creatinine clearance. Examination of this revealed that the guinea pig kidney tubules also secreted exogenous creatinine. Oyen and Boylan ( 2 2 ) had also obtained evidence for tubular secretion of exogenous creatinine by this species, but a curious depression of the clearance of inulin by creatinine observed by these investigators had vitiated an analysis of the tubular mechanism involved. In the present investigation, a detailed analysis of the mechanism of excretion of exogenous creatinine was made. In particular, the role of tubular secretion was analyzed in a wide range of plasma creatinine concentrations.Methods. Experiments were performed on 58 male and 9 female guinea pigs of mean body weight for these experiments of 892 (544.5-1 172). A total of 223 clearance observations was made. I n reporting the results, females were separately grouped, while the males were distributed throughout other groups according to specific experimental maneuvers or procedures used in analyses. Food and water were allowed ad libitum. All animals were anesthetized with Nembutal (24-48 mg/kg ip). The left external jugular, right common carotid, trachea, and ureters (suprapubically) were catheterized. Ringer's solution containing 6% inulin and varied concentrations of creatinine was constantly in-* Supported by USPH Grant HE 09553. fused intravenously at 0.08 ml/min. Blood pressure was recorded at 5-min intervals from the common carotid with a mercury manometer fashioned from PElOO polyethylene tubing. A three-way stopcock placed in series with the manometer and carotid catheter permit ted blood sampling. Finally, body temperature was recorded with a small animal thermometer inserted into the suprapubic incision.Protocols of the experiments may be described in general with variations which will be noted in discussions of each group. All animals were infused 1 hr prior to the start of the first urine collection period. Bood samples were collected at midpoints. Reasonable steady state conditions with regard to plasma concentrations were believed to exist, with maximal deviation from the mean of 17% in the longer experiments. Filling the arterial catheter with 2.5% mannuronate or 1% heparin in Ringer's sufficiently heparinized the animal through interchange with the arterial blood so that additional anticoagulant was unnecessary. Clearance periods were 15 or 30 min in length. At the conclusion, the kidneys were removed, cleared of fat and fascia, blotted dry, and weighed.Analytical methods. Creatinine was determined by the technique of...