Resolving an 80-yr-old controversy: the beginning of the modern era of renal physiology

Abstract

Marcello Malpighi discovered the glomerulus that bears his name in the 17th century, but it was not until the middle of the 19th century, in 1842, that William Bowman in London published his studies of the histological structure of the glomerulus and proposed that urine formation begins with glomerular secretion. At nearly the same time in Marburg, Carl Ludwig, unaware of Bowman's findings, proposed that urine formation begins with glomerular filtration followed by tubule reabsorption. The controversy lasted 80 yr. Prominent investigators weighed in on both sides. Rudolph Heidenhain's findings in 1874 swung the pendulum toward Bowman's theory until Arthur Cushny published his book, The Secretion of Urine, in 1917, in which he found the evidence insufficient to prove either theory. In 1921, a young physician, Joseph Wearn, began his postresidency training in the laboratory of Alfred N. Richards. He read Cushny's book and learned how to expose the glomerulus of a living frog. Richards proposed that Wearn use that experimental preparation to inject epinephrine into the glomerulus. Wearn proposed a different experiment: instead of using injection, collect fluid from the glomerulus and analyze it. Richards agreed, and the landmark results of that experiment, published in 1924, settled the controversy. The modern era of renal physiology was born.

Evolution, kidney development, and chronic kidney disease

“…Based on his anatomic study, Bowman in 1842 postulated that urine formation begins with glomerular secretion, whereas Carl Ludwig proposed glomerular filtration followed by tubular reabsorption [2]. The 20 th century saw rapid advances in renal physiology, with the demonstration of tubular secretion by Marshall in 1923, and the confirmation of filtration/ reabsorption by Wearn and Richards using micropuncture techniques in 1924 [2]. Equally important were the introduction of the concept of "clearance" by van Slyke in 1928 and of "homeostasis" by Walter Cannon in 1932.…”

Nephropathology: A Cornerstone for Understanding and Estimation of Recent Advances in Glomerular Diseases

“…Marcello Malpighi was the first to study not only the gross anatomy, but also the microanatomy of the kidneys and discover a part of its functional unit (i.e. the nephron), which he called a "gland" attached to arteries [4]. Malpighi assumed that it is the place of urine formation through a process of filtration from blood, according to substances' size and shape [4,5].…”

“…the nephron), which he called a "gland" attached to arteries [4]. Malpighi assumed that it is the place of urine formation through a process of filtration from blood, according to substances' size and shape [4,5]. Thus, it can be said that both renal pathology and renal physiology were born at that time.…”

“…During the same period, which can be designated as the pre-biopsy era (Figure 1), other important landmarks are the Richard Bright's basis of clinical nephrology (with his studies on kidney-related symptoms and the first attempt to classify kidney diseases), and the integration of clinical and pathologic findings which lead Sir Arthur Ellis to describe two types of nephritis (the first with glomerular hypercellularity and the second with glomerular sclerosis) [3,5]. Another forward movement took place that time in the field of renal physiology by the work of Carl Ludwig who applied the laws of physics (hydrodynamics) to explain the glomerular filtration process of urine formation [4]. His results were confirmed and further developed by the mic-ropuncture experiments of JT Wearn and AN Richards, which demonstrated a differential reabsorption of glomerular filtered solutes into the tubules, and hence put the basis of the modern renal physiology [4].…”

“…Another forward movement took place that time in the field of renal physiology by the work of Carl Ludwig who applied the laws of physics (hydrodynamics) to explain the glomerular filtration process of urine formation [4]. His results were confirmed and further developed by the mic-ropuncture experiments of JT Wearn and AN Richards, which demonstrated a differential reabsorption of glomerular filtered solutes into the tubules, and hence put the basis of the modern renal physiology [4]. At the beginning of the 20 th century, the first collaboration between a (renal) pathologist-Theodor Fahr and a clinician (treating internist)-Franz Volhard resulted in a new classification of kidney diseases driven by the combination of pathology findings and clinical signs of the disease: nephrosis-i.e.…”