Introductory Chapter: Modern Diagnostics with the Ancient History

1. Introduction

Urinary tract (UT), in its entirety, has a long and interesting history extending far beyond modern times. The first written mention of UT and especially kidneys reaches ancient Egypt, as kidneys together with the heart, were the only organs not removed from the mummified bodies [1]. It was believed that the kidneys are the means of judgment in the afterlife, the proverbial guide for the heart’s decisions. The fundamental role of kidneys and heart for humans’ afterlife fate was not only Egyptian domain as it was also a common belief among other ancient civilizations and religions, such as Semitic Tradition and Old Testament [2, 3].

The fact that the kidneys were not removed from dead bodies before mummification and burial has been the reason for today’s existence of the archaic samples of those organs with, e.g., renal cysts and stones [1, 4]. As such, the knowledge of urinary tract infections (UTIs) also reaches ancient times. They were not called UTIs but were well defined nonetheless, together with very specific ways of treatment (e.g. [1]). The first written mention of UTI dates back again to ancient Egypt and the Ebers Papyrus from 1550 BC, where UTI is described as ‘sending forth heat from bladder’ [5]. It is worth underlining that the actual role of UT was far from correct in those ancient times, but still, the aforementioned Ebers Papyrus contains interesting descriptions of maladies such as urethritis, prostatitis, or cystitis and procedures such as uroscopy, which will be the modern urinalysis [1]. Later on, but still, in Antiquity, despite very limited and often quite erroneous knowledge of urinary tract functioning, Hippocrates and his successors were able to perform a rudimental urinalysis, noting such features as color, consistency, sediment, odor, and volume [6]. Corpus Hippocraticum presented many known renal afflictions today, such as renal colic, chronic renal infection, renal tuberculosis, and UTI symptoms, e.g., urinary incontinence and urinary retention [4].

The historical breakthrough for the UT elements and their role in physiology dates back to the brilliant scientist Galen of Pergamon, who was the first to claim and prove that the main role of kidneys, not the bladder, is to produce urine [7]. Even though the exact mechanism of urine formation remained a mystery to this scientist because the function was described as ‘the separation of excess and poorly concocted bodily humors’, the impact of Galen on nephrology cannot be diminished both in the case of uroscopy and the structure of the kidneys [7]. What is even more important, when it comes to Galen’s impact on nephrology, is his contribution to its pathology. Galen is, e.g., credited for the first differential diagnosis and work-up of anuria and oliguria. His work also details the approach to a patient with such conditions as diabetes mellitus and diabetes insipidus, even though the exact pathomechanisms of those diseases themselves were a mystery at that time [8].

An even more detailed description of kidneys and UT was created by Oribasius from Pergamum, the Byzantine scholar who, apart from his impact on nephrology development, was remembered as the writer of Collectiones Medicae [4, 9], preserving the ancient medical knowledge. His descriptions of the nephron structure, together with a detailed illustration of its blood circulation, were the most detailed at the time. His proposed treatment options for hematuria, both acute and chronic nephritis and nephrolithiasis, even though they are not on par with today’s practice, emphasized the role of physiotherapy and phytotherapy in nephropathology of that time [9]. Another Byzantine scholar – Avicenna – preserved the at the time known practices and knowledge from Greek and Far Eastern regarding urinalysis [10]. He said that ‘urine is a faithful guide for the knowledge of the illness’, which is a succinct description of the idea standing behind urinalysis.

2. Postantiquity advances in nephrology

Beginning from the Renaissance, the modern history of nephrology started. It still greatly drew from the knowledge of ancient scientists and physicians, in part mentioned above, but the new equipment allowed the previously unattainable precision in human anatomy and physiology observation [4]. Andreas Vesalius, the Belgian anatomist, and Roman Bartolomeo Eustachio working separately at more or less the same time, based their discoveries on direct observations of humans’ and dogs’ kidneys. Their meticulous work allowed them to correct many of the mistakes of their predecessors (and still, they had different results regarding some of the anatomical features of analyzed kidneys, e.g., the position of the right and left one in the human body) when it comes to the anatomy of the kidney [11]. Where Vesalius and Eustachio were quite ignorant of the function of the kidney itself [12], Neapolitan physicist and mathematician Giovanni Borelli was vitally interested in mechanisms explaining the mechanics of the body, among them kidney functioning, stating that the kidneys play the role of sieve filtering blood and excreting the elements which need to be eliminated [11]. Marcello Malpighi and Lorenzo Bellini, other renowned physicians, who were additionally armed with magnifying lenses and microscopes, were able to perform even more detailed observations of renal structure and function, especially Malpighians’ body of the kidney [13]. Bellini, Borello, and Malpighi though, even with all the advances in their observations, still believed that urine is created in purely mechanistic or hydraulic ways [11, 14]. The concept of ultrafiltration as the means of urine formation was first described by Archibald Pitcairne, even though it was properly termed almost 150 years later [11]. The final touches to the kidney anatomy and function were added by William Bowman, who, armed with a microscope far better than Malpighi’s and Bellini’s described the existence of Bowman capsule surrounding the Malpighi’s body. That in itself added the missing element to the urine formation hypothesis [15].

Richard Bright is considered the father of modern clinical nephrology. Together with other famous physicians, Thomas Hodgkin and Thomas Addison, they developed knowledge about specific pathologies; some were even named after them [4]. Bright discovered that the presence of albuminuria and edema is always linked with kidney disease [16]. He described such conditions as acute nephritis, nephrotic syndrome, and uremia. Additionally, he found and explained the link between kidney disease and enlarged ventricles of the heart [17].

Urinalysis remained largely unchanged at the time. As a visual science, it linked the observed changes in color, consistency, sediment, odor, and taste with specific diseases. And diabetes mellitus and diabetes insipidus are the best in proving the need for tasting the sample as the first means ‘sweet as honey’ and the second ‘without taste or perceptible flavor’ [18]. What is worth mentioning, though, is that with uroscopy becoming more and more popular, there were regions around the world where uromancy developed [19]. Many of those not knowledgeable enough made it a practice to diagnose various diseases based on information from pamphlets containing elaborate charts allowing comparing the color of the urine to diagnose assorted diseases [20]. Later on, it led to the need for uroscopy regulation, and some statutes were formulated trying to regulate the art of uroscopy [21].

3. The dawn of modern urinalysis

Together with the anatomical and functional advances of nephrology, also nephropathology and diagnostics started to develop. The autopsies of dead bodies brought many pathologies to light. Interesting results were revealed by, e.g., Malpighi’s body autopsy [22]. He suffered from chronic kidney disease and supposedly hypertension, and his autopsy results were published together with over 2000 others in Theophile Bonet’s Sepulchretum sive anatomia practica ex cadaveribus morbo denatis. The first such extensive collection of postmortem reports [22]. In turn De Sedibus et Causis Morborum per anatomen indigatis published almost 100 years later by Giovanni Morgagni, is considered the foundation for the classification of kidney diseases based on gross anatomy and clinical symptoms [23].

The development of physiology and pathology was accompanied by the advances in chemistry of urine. The first ones mentioning the exact parameters of urine, such as specific gravity, hematuria, or proteinuria, were Paracelsus and his two followers, Joan Baptista van Helmont and Herman Boerhaave [24, 25]. The chemistry knowledge in those days was not on par with physiology development though [26]. The dominant role of alchemy at the time had some impact on that. The beginning of actual urinalysis based on actual chemical structure is set in the seventeenth century. It was then that chemistry was freed from the influences of mystic alchemy and started to make headways. Many manuals were published about the principles of basic chemical methods, such as distillation and sublimation but also many others. Christofle Glaser, Nicolas Lemery, and aforementioned Herman Boerhaave should probably be mentioned as the ones (but not the only ones) who impacted chemistry the most at the time [25, 27]. The chemicals in the urine were divided into nonvolatile acidic residues, identified as chloride salts later on, and ‘volatile alkali’, ammonium carbonate, or urea. The aforementioned Bellini and Thomas Willis should probably be credited to be the ones of first authors of quite extensive descriptions of changes in urine (its’ color, taste, and odor) depending on the urine’s composition and clinical condition [18]. Willis was also the one involved in regulating uroscopy, mentioned earlier, by clearly stating that the observed changes in urine’s color, taste, and odor reflect those of the blood, not mystic humors [28]. The link between blood and urine and the need to analyze them both to get a clear picture of various illnesses was also later underlined by others, e.g., Robert Boyle and Browne Langrish [25, 29]. The last one even said ‘the study of the proportions of several principles of blood and urine, both in sound and disease state, will be highly useful in investigating the causes and the phenomenon of disease’ [29].

The inauguration of biochemistry is dated to the beginning of the nineteenth century. Probably the most important milestone from that time is the identification of a vital element of urine – urea. It was identified and characterized by William Prout and synthesized by Friedrich Wöhler [30, 31]. Quite quickly, urea was linked with several pathologies, and the term ‘uremia’ was coined. The first disease in which an elevated level of serum urea was noted was mentioned earlier Bright’s disease (or nephritis), but soon the urea level started to get measured in many other kidney diseases [32]. But what is most important about the research regarding urea is its role in the development of the concept of dialysis and artificial kidney [33].

The first complete compendium about the analysis of urine, Quantitative Clinical Chemistry, was published at the beginning of the twentieth century by John P. Peters and Donald D. Van Slyke [34]. It contained a detailed description of blood and urine chemical composition and the rules for standardized measurement of such parameters as electrolytes concentration, especially K⁺, and Na⁺. That allowed for assessing conditions such as hyponatremia, respiratory and metabolic acidosis, and effective osmotic pressure [35, 36]. As all of them are linked with renal state, Peters insisted on combining clinical laboratory and clinical investigation. That way, laboratory diagnostics became vital to clinical diagnosis [34]. By the end of the 30s of the 20th century, urinalysis started to become a common routine in medical examinations [37].

Almost 100 years later, urinalysis is still considered one of the most important tools implemented in standard medical examination. This period was filled with an intense development of that branch of the diagnostic laboratory. Many new techniques were developed, increasing the sensitivity and specificity of performed tests and making it easier to interpret obtained results even in specific and demanding groups of patients, e.g., pregnant women.