MO1031FROM MARCELLO MALPIGHI THROUGH JEAN REDMAN OLIVER AND JOSEP TRUETA: A CONTINUING CONTRIBUTION TO THE “BLACK BOX” CLINICAL PREDICTION MODELS IN NEPHROLOGY

Background and Aims The modern development of the black box approach in clinical nephrology is inconceivable without a logical theory of renal function and a comprehension of anatomical architecture of the kidney, in health and disease: this is the undisputed contribution offered by Malpighi, Oliver and Trueta starting from the seventeenth century. The machine learning model for the prediction of acute kidney injury, progression of renal failure and tubulointerstitial nephritis is a good example of how different knowledge about kidney are an indispensable tool for the interpretation of model itself. Method Historical data were collected from literature, textbooks, encyclopedias, scientific periodicals and laboratory experimental data concerning these three authors. Results The Italian Marcello Malpighi (1628-1694), born in Crevalcore near Bologna, was Professor of anatomy at Bologna, Pisa and Messina. The historic description of the pulmonary capillaries was made in his second epistle to Borelli published in 1661 and intitled De pulmonibus, by means of the frog as “the microscope of nature” (Fig. 1). It is the first description of capillaries in any circulation. William Harvey in De motu cordis in 1628 (year of publication the same of date of birth of Italian anatomist!) could not see the capillary vessels. This thriumphant discovery will serve for the next reconnaissance of characteristic renal rete mirabile.in the corpuscle of Malpighi, lying within the capsule of Bowman. Jean Redman Oliver (1889-1976), a pathologist born and raised in Northern California, was able to bridge the gap between the nephron and collecting system through meticulous dissections, hand drawn illustrations and experiments which underpin our current understanding of renal anatomy and physiology. In the skillful lecture “When is the kidney not a kidney?” (1949) Oliver summarizes his far-sighted vision on renal physiology and disease in the following sentence: the Kidney in health, if you will, but the Nephrons in disease. Because, the “nephron” like the “kidney” is an abstraction that must be qualified in terms of its various parts, its cellular components and the molecular mechanisms involved in each discrete activity (Fig. 2). The Catalan surgeon Josep Trueta I Raspall (1897-1977) was born in the Poblenou neighborhood of Barcelona. His impact of pioneering and visionary contribution to the changes in renal circulation for the pathogenesis of acute kidney injury was pivotal for history of renal physiology. “The kidney has two potential circulatory circulations. Blood may pass either almost exclusively through one or other of two pathways, or to a varying degree through both”. (Studies of the Renal Circulation, published in 1947). Now this diversion of blood from cortex to the less resistant medullary circulation is known with the eponym Trueta shunt. Conclusion The black box approach to the kidney diseases should be considered by practitioners as a further tool to help to inform model update in many clinical setting. The number of machine learning clinical prediction models being published is rising, as new fields of application are being explored in medicine (Fig. 3). A challenge in the clinical nephrology is to explore the “kidney machine” during each therapeutic diagnostic procedure. Always, the intriguing relationship between the set of nephrological syndromes and kidney diseases cannot disregard the precious notions the specific organization of kidney microcirculation, fruit of many scientific contributions of the work by Malpighi, Oliver and Trueta (Fig. 3).