The Renal Clearance of Endogenous "creatinine" in Man.

The existing methods for the analysis of inulin, as well as the requirements for the continuous intravenous infusion of this material, place the inulin clearance method for measuring the glomerular filtration rate beyond the reach of practicality for many laboratories and in general limit clearance observations to relatively short intervals of time. There is a requirement for a simpler clearance method of at least approximate accuracy by which observations can be made continuously for periods of 24 hours or longer. Endogenous "creatinine" appears to offer possibilities in this direction, since it would obviate the necessity for intravenous infusions, frequent withdrawal of blood and elaborate analytical procedures. The nature of the endogenous substance or substances which yield color with Jaffe's alkaline picrate reaction for creatinine has long been a matter of controversy. The literature on this subject is reviewed by Miller and Dubos (1, 2). These authors, using an allegedly specific enzymatic method on 1:5 plasma filtrates prepared with 10 per cent sodium tungstate and 0.66 N sulfuric acid, concluded that in normal human plasma, creatinine constitutes 80 to 100 per cent of the chromogenic substance, although in renal disease, where the chromogen is elevated, the plasma may contain relatively large amounts of non-creatinine chromogenic material. Exogenous creatinine is excreted in man both by glomerular filtration and tubular secretion. Crawford (3) has recently adduced new evidence on this point by showing that the exogenous creatinine/inulin and the exogenous creatinine/thiosulfate clearance ratios are reduced by saturation