Biographical Memoirs Volume 63 (1994) / Chapter Skim
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1. Thomas Addis
1. Thomas Addis
Pages 1-47
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Biographical Memoirs VOLUME 63
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As a physicianscientist, he hack a distinctively quantitative and rigorous approach to clinical problems. His name is firmly connected to the study of kidney function and structure-function correlation and to the diagnosis and dietary treatment of the class of kidney disorclers once collectively known as Bright's disease.
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The new medical school dean, Dr. Ray Lyman Wilbur, brought Addis to Stanford on the recommendation of Sir Clifford Alibutt of the University of Cambridge, an event Wilbur
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AcIdis became professor of medicine in 1920 and served in that capacity until becoming professor emeritus in 1946. He also ran the Clinic for Renal Diseases at Stanford from 1921.
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the Thayer Lectures in 1931 and was visiting fellow at the Rockefeller institute in 1928. Addis was a member of the Association of American Physicians, the American Physiolo~ic~1 LSorietV the C,~cietv for Exnerimental Biolo~v and __ ~ ~ -- -I ~ ~ r ~ -- ~ -in -- Medicine, the American Society tor clinical investigation (president in 1930)
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He also published several studies on diabetes mellitus, including an analysis of the different clinical methods for estimating the degree of acidosis (this was just before the advent of insulin therapy) , a critique of the conventional preparation of the diabetic patient for surgery (which he held to be "a pure hypothesis, unsupported by any experimental work")
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, blooc! urea concentrations rise whenever renal excretory function is compromisecI.
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. AcIdis saw himself faced with "the problem of the relation between renal function en c!
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on was the ratio UV/B, the Adclis urea ratio, where Uis the urine urea concentration, Vis the urine volumetric flow rate, and B is the blooc! urea concentration.
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The discrepancy was rectified in a morphological study by Jean Oliver in which he showed that a disproportionately large amount of renal hypertrophy following uninephrectomy was clue to hypertrophy in the proximal convoluted tubules. At that time, renal excretory function was thought to be primarily a secretory process (the importance of giomerular filtration was not yet fully appreciated)
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eventually inuTin clearances as clinical anct research markers of gIomerular filtration. Although he continued to use the urea ratio as an index of the osmotic work of the kidney, Addis did adopt the creatinine clearance as a functional test, eventually contributing to the development of practical clinical methods for determination of the serum creatinine concentration.
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His approach to the clinical classification of Bright's disease was therefore twofold: quantitative examination of the urinary sediment (the Acldis county indicatecl the nature of the lesion, en cl the urinary urea clearance (the Adclis urea ratio) indicated the extent of the lesion.
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that followed Toss of renal mass, but Fahr and Smadel (1939) soon demonstrated that high-protein diets also increase the rate of renal destruction in rats with Masugi nephritis (now called nephrotoxic serum nephritis)
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. Thus, the early conception of renal work as urea secretion by the proximal convoluted tubules eventually evolved into the idea of renal work as water extraction from an increasingly concen
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His approach took into account not only the principle of minimization of renal work but also the effect of urinary protein losses, the likelihood that with decreased appetite in renal disease less than the prescribed amount of protein would actually be ingested, vitamin supplementation in light of a restricted food intake, and the special requirements for growth in children (for whom Addis ore · ~ -r rip ~m ~-~ - ~ scribed up to 2 grams/kilogram of body weight per day, almost four times the adult level)
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Although the thermodynamic definition of renal work played a major theoretical role, it also tract limitations. The iclea of organ weight as an inclirect measure of organ work was therefore exploitecl.
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"In this endeavor nothing is more likely to still curiosity and initiative than a nomenclature that implies knowledge where only ignorance exists." Even so, growth of the remaining nephrons following partial nephrectomy seemed to Addis to lower the urea work load per gram of remnant nephrons and thus be an adaptive response to an increase in renal work per nephron. MECHANISMS OF PROTEINURIA ~ ~ 9 3 2 - 49 3 The final major topic that Adctis investigated was the relationship between proteinuria and kidney disease.
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rip "For no matter how well supported by reason and buttressed by fact a new method of treatment may be, there is no sure foundation for clinical action other than clinical experience." The book has a strongly philosophical tone and thus also serves as a vehicle for an exposition of AcIdis's philosophy of clinical medicine and scientific research. in addition, Richard W
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In fact, his clinic at Stanford always primarily saw patients with nephritis or with kidney diseases simulating it. This is the reason patients were referred to Aciclis.
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Since the most obvious consequence of a high-protein diet for the kidney is also excretion of larger amounts of urea (the final breakdown product of protein in the hotly anal the major urinary solute) , it was incleect logical for Aciclis to at least consicler the osmotic excretory work of the kidney as a major factor in causing renal hypertrophy ant!
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The objection itself is based on analogy and arises because of a difficulty in conceiving that a small change in energy relations may sometimes leac! to large material results." The above-mentioned similarities between renal growth after nephrectomy and- growth on a high-protein diet supported his iclea of the "effectiveness" of renal osmotic work.
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My edema was high, over twenty pounds, as was my urinary protein loss, about twenty g per clay. r was placecl on a salt-free cliet, which eliminated the edema in four months, and on a rigorous minimum-protein diet, which ~ followecl for fourteen years.
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~~ ~ human suffering. To Arthur ~— Bloomfielc3 his relations with his patients were marked by "deep friendship and concern." Despite the efforts of Aciclis and his colleagues, many patients eventually died of renal disease.
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When Scribner left the lab in 1945 for an internship at San Francisco County Hospital, Aclclis gave him the laboratory's electric pH meter (a valuable piece of equipment in those clays) to use on the personal laboratory "cart" that Scribner had put together.
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his research work, and the Clinic for Renal Diseases at Stanford University held its sessions right in the laboratory, in the mictst of experiments ("we can't On clinic days the laboratory was a sight to be remembered. It was humming with activity.
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positivist"; all the studies of renal function are just "means to his end, which is action, not knowledge." He is, in fact, "obliged to be more than scientific": while the scientist is always attempting to generalize his or her understanding, the clinician must individualize his or her understanding to each particular patient. Although Addis could be found in his laboratory any day of the week during an experiment, life in the barnlike lab retained a pleasant and cultured atmosphere.
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Addis was onetime chairman of the San Francisco chapter of Physicians' Forum, a national organization favoring national health insurance. Such activities cost several phy
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He expressed surprise as well as pleasure with the Festschrift in his honor published in the Stanford Medical Bulletin (1948) "because I have spent thirty-five years .
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There was also a renewed appreciation of the acute effects of dietary protein loads on kidney filtration rate. In 1982 a hypothetical mechanism was proposed that tied dietary protein intake and compensatory "hyperfunction" itself to progression of a large number of renal diseases, as well as the slow Toss of renal function with age.29 Since that time, interest in the dietary treatment of chronic renal failure has increased enormously in the United States.
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(Department of Medicine and Alumni Association, Stanford University School of Medicine, 1984~. "Festschrift for Thomas Addis," Stanford Medical Bulletin, 6 (February 1948)
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clarified the relative roles of the three factors in urinary excretion: glomerular filtration, tubular secretion, and tubular reabsorption. The principal drawback in fact to
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6. It has been proposed that more information about renal function capacity could be obtained if creatinine or inulin clearances were determined before and after an acute dietary protein load, allowing assessment of basal function and the renal reserve 0.
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H Hostetter, "Dietary Protein Intake and the Progressive Nature of Kidney Disease: The Role of Hemodynamically Mediated Glomerular Injury in the Pathogenesis of Progressive Glomerular Sclerosis in Aging, Renal Abla ~ I,.
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THOMAS ADDIS 35 tion, and Intrinsic Renal Disease," New England journal of Medicine, 307(1982)
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1:30534. 1909 The effect of the administration of calcium salts and of citric acid on the calcium content and coagulation time of the blood.
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24:203-20. The effect of intravenous injections of fresh human serum and of phosphated blood on the coagulation time of the blood in hereditary hemophilia.
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- III. The effect of changes in blood urea concentration on the rate of urea excretion.
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6:20912. Renal function and the amount of functioning tissue.
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NIII. The effect of various factors other than blood urea concentration on the rate of urea excretion.
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MacKay. Influence of age on degree of renal hypertrophy produced by high protein diets.
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MacKay. The degree of compensatory renal hypertrophy following unilateral nephrectomy.
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MacKay. The degree of compensatory renal hypertrophy following unilateral nephrectomy.
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37:458-60. The osmotic work of the kidney and the treatment of glomerular nephritis.
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Yuen. The relation between the serum urea concentration and the protein consumption of normal individuals.
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The relation between protein consumption and diurnal variations of the endogenous creatinine clearance in normal individuals.
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