Classics in clinical science: The concept of renal clearance

Abstract

A major share of the advances in medical knowledge has come about through the work of clinical investigators who applied the methods of science to the study of disease. Their skill in identifying important problems at the bedside and constructing practical solutions which enlarged the scientific base of medical practice, has resulted in tremendous advances in the armamentarium of every physician. In the climate of today, when the clinician eagerly utilizes the methods of the laboratory, it is difficult to believe that early in this century clinicians looked with suspicion upon newfangled things and basic scientists had disdain for research carried out by clinicians. This earlier attitude of clinicians is typified by the story told David L. Edsall by President Eliot of Harvard. Mr. Eliot had forced through the faculty of the Harvard Medical School the establishment of a course on bacteriology and the appointment of Dr. H. C. Ernst, who had recently returned from study in Europe, as the teacher of the subject. There had been violent opposition to the establishment of a course in so new a subject of questionable value and a professor of pediatrics had been especially violent in opposition. Methods for demonstration of the diphtheria bacillus were already available for diagnosis, and soon after Ernst’s appointment the use of diphtheria antitoxin was introduced. Dr. Ernst was the only man in the city who knew how to recognize the bacillus or to make an antitoxin. One day Mr. Eliot met the professor of pediatrics coming from Dr. Ernst’s laboratory, and said to him: “Doctor, isn’t this an odd place for you to be?” He replied: “Yes, but nowadays one has to come here for a diagnosis and now we have to come here for our treatment.” This attitude continued in some degree, however, for long afterwards. When Edsall went to Harvard as Jackson Professor of Medicine in 1912 Mr. Lowell, who had been president of Harvard University for three years, told him that at faculty meetings the clinicians sat on one side of the table, the laboratory men on the other, and each opposed the other in everything. A physician-scientist who was equally at home at the bedside and at the laboratory bench was Thomas Addis [l]. Born in Edinburgh in 1881, he came to this country in 1911 to take over the clinical laboratory at Stanford under Ray Lyman Wilbur. Addis’ genius for research soon led him to cast off the burdens of the routine laboratory and within a short time his important studies on the kidney were launched. In collaboration with various associates, his investigations of renal disease brought a continual output of excellent work until his retirement in 1948. He first studied the physiology of the kidney but soon embarked on investigations of disordered structure and function in Bright’s disease. Addis and others at Stanford were stationed at Camp Lewis, Washington, during World War I. While there they made important observations on blood pressure and pulse rate, similar to those made by Horace Smirk on basal blood pressure many years later. It was after his return to Stanford at the end of the war that Addis began his investigations into urinalysis and renal function. One of his classic contributions appeared in the first issue of the Journal of Urology in 1917 [2] entitled “The Ratio Between the Urea Content of the Urine and of the Blood After the Administration of Large Quantities of Urea. An Approximate Index of the Quantity of Actively Functioning Kidney Tissue.” This paper began with a penetrating review of the previous work on the testing of renal function and then was followed with Addis’ own rationale for developing the “urea ratio “: “the ratio between the urea content of the urine and of the blood (UV: B) expresses the number of times by which the urea excreted in the urine during a certain period of time exceeds the amount of urea present in 100 cc of blood supplied to the kidney during