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Franz Volhard and Theodor Fahr: Achievements and Controversies in Their Research in Renal Disease and Hypertension

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Franz Volhard and Theodor Fahr: Achievements and Controversies in Their Research in Renal Disease and Hypertension Journal of Human Hypertension (2001) 15, 5–16 2001 Macmillan Publishers Ltd All rights reserved 0950-9240/01 $15.00 www.nature.com/jhh REVIEW ARTICLE Franz Volhard and Theodor Fahr: achievements and controversies in their research in renal disease and hypertension A Heidland1, W Gerabek2 and K Sebekova3 1Department of Internal Medicine, 2Institute of History of Medicine, University of Wuerzburg, Germany; 3Institute of Preventive and Clinical Medicine, Bratislava, Slovakia The clinician, Franz Volhard, and the pathologist, ischaemic kidney(s) contributing – via a vicious circle – Theodor Fahr, worked closely together in Mannheim to a further rise in blood pressure with subsequent reno- from 1909 until 1915 and introduced a novel classi- vascular injury and aggravation of hypertension. This fication of renal diseases. In the monograph entitled ‘Die hypothesis was supported in 1930 by initial experiments Bright’sche Nierenkrankheit, Klinik, Pathologie und of his collaborator, Hartwich (demonstrating in dogs a Atlas’ (1914) they differentiated between degenerative mild rise in blood pressure after ligation of branches of (nephroses), inflammatory (nephritides) and arterio- the renal artery) and definitively proven by Goldblatt sclerotic (scleroses) diseases. Nephrosclerosis was div- (1934) in dogs by induction of severe and persistent ided into the benign and malignant form, of which the hypertension after clamping of both renal arteries. The latter stood the test of time as a new disease entity. Fahr consequent detection of the renin angiotensin system further divided benign nephrosclerosis into the com- was the final confirmation of Volhard’s postulated renal pensated and decompensated form – depending on the pressor substance. In the pathogenesis of red presence or absence of glomerular injury. In the patho- (essential) hypertension, Volhard stressed the role of genesis of malignant nephrosclerosis, Volhard stressed hereditary factors, age, obesity and potentially of severe the decisive role of severe blood pressure elevation, alcoholism. He emphasised a premature reduction of while Fahr postulated an inflammatory mechanism, a vascular distensibility (due to elastosis of the concept later confirmed by Adalbert Bohle for at least a prearterioles), a high cardiac output as well as a damp- minority of patients. A very far reaching concept of ening of baroceptor function. Additionally, Volhard Franz Volhard was his idea that pale (renal) hyperten- made crucial advances in cardiology and pneumology. sion results from a pressor substance released from Journal of Human Hypertension (2001) 15, 5–16 Keywords: Franz Volhard; Theodor Fahr; classification of renal diseases; glomerulonephritis; benign nephrosclerosis; malig- nant nephrosclerosis Introduction attempted to unfold the heterogeneity of Bright’s dis- ease. However, the description of the various renal In the 19th century medicine evolved into a natural lesions by pathologists and clinicians was confusing science, true scientific standards were introduced. In and chaotic. A real breakthrough (‘breath of fresh air’, particular, novel investigative tools had an enormous Sir George Pickering5) was the novel classification by impact: urine analysis (by microscopy and protein 1 Volhard and Fahr in their famous monograph ‘Die determination), estimation of renal function (by Bright’sche Nierenkrankheit, Klinik, Pathologie und measurement of urine osmolarity and determination Atlas’, 1914.6 of blood urea nitrogen),2 indirect measurements of blood pressure (by sphygmomanometry)3 and evalu- ation of the eye ground (by opthalmoscopy).3 Patho- Franz Volhard logical anatomy had been revolutionised by the intro- Was born in Munich on 2 May 1872, the son of the duction of light microscopy combined with new well-known Professor Jacob Volhard, later Director of techniques for tissue staining.4 Numerous studies the Institute of Chemistry at the University of Erlangen and Halle.7,8 He started studying medicine in 1892 at the University of Bonn, where August Ke´k- Correspondence: Dr A Heidland, Department of Internal Medi- cine, University of Wuerzburg, Josef-Schneider-Str. 2, 97080 ule´ and Eduard Pflu¨ ger were among his teachers. He Wuerzburg, Germany continued his studies in Strasbourg with Oskar Min- Received 20 March 2000; revised and accepted 25 July 2000 kowski, Bernhard Naunyn, Richard von Rec- Achievements and controversies in renal disease and hypertension A Heidland et al 6 klinghausen and Oswald Schmiedeberg. In 1897 Vol- hard graduated from the University at Halle and subsequently completed his dissertation on ‘Experi- mental and clinical studies on the pathogenesis of eclampsia’. After a short stay at the Pathological Insti- tute in Friedrichsheim/Berlin, he was trained in internal medicine at the University of Gieβen (1898– 1905) under the chair of Franz Riegel. This decision was not purely coincidental, since in that clinic being unmarried was not a prerequisite for an assistant’s position – quite in contrast to most other clinics in Germany. During his stay in Gieβen, Volhard started scientific research in various fields, including cardio- vascular, renal and gastroenterological problems. His faculty rank (habilitation) in 1901 concerned the ‘Lipid splitting enzyme of the stomach’. In 1905 Volhard was asked to be Director of the Clinic of Internal Medicine of the Luisenhospital in Dortmund. At this time he had already become specifi- cally interested in nephrology and hypertension. Inspired by the cryostatic measurements of the urinary osmoregulatory function by Sandor von Kora´nyi, Vol- hard introduced the urinary concentration and dilution test by measuring specific gravity as an overall para- meter for evaluation of renal function. In 1908 Franz Volhard became Director of the Town Hospital of Mannheim which at the time was in a catastrophic state. Here he attracted the atten- tion of the young pathologist Theodor Fahr, who had very similar scientific interests, in particular of renal vessels. A close partnership developed which was to have an enormous impact on research devel- opment of nephrology and hypertension. Volhard Figure 1 Franz Volhard (1872–1950) as Director of the Clinic of Internal Medicine at the University of Frankfurt/Main (Source: B and his collaborators participated in all autopsies Oslen, MD, Department of Internal Medicine, University of Halle). and in the microscopic evaluation of renal tissues. As a result, their monography on Bright’s disease became the ‘bible of nephrology’ for several decades. Gießen, where he completed his dissertation (1903). In 1918 Volhard was named Director of the Clinic For further training, he moved to Simons and of Internal Medicine at the University of Halle and Deneke in Hamburg and later on to Iljitsch Metsch- in 1927 of the University of Frankfurt/Main (Figure nikow at the Louis Pasteur Institute in Paris. He con- 1). His most important work at this time was the tinued his career at the Institute of Pathology of the publication ‘Kidney and Urinary Tract’ (1826 pages) Hafenkrankenhaus in Hamburg. From 1909 till 1915 in Bergmann and Staehelins’s Handbook of Internal he remained with Volhard in Mannheim, where a Medicine (1931).9 tight collaboration and lasting friendship developed. Volhard was in trouble with the Nazi regime for, Afterwards he returned to the Pathological Institute unfortunately, his independent opinion. As a conse- of the University Hamburg/Eppendorf, where he quence, he was forced to leave his position as Director was given the chair of general pathology in 1924. of the Clinic in 1938 in a humiliating manner. After There he continued his research on diseases of the the end of the Nazi tyranny in 1945, he was reinstated kidney, heart and blood vessels. His most significant as Director and was extremely active until his acciden- publications included the pathological anatomy of tal death (car crash) at the age of 78 in 1950. Volhard, Morbus Bright, kidney tumors and the cardiovascu- the genius scientist, outstanding physician and brilli- lar system. Fahr died in Hamburg in 1945 (Figure 2). ant speaker, had exceptional humanitarian qualities. Among his hobbies, the love of music has to be Elucidating concepts in the acknowledged; Volhard was both an enthusiastic heterogeneity of Bright’s disease in the singer as well as a talented violinist, heading his own family orchestra with his 10 children. 19th century In 1836 Richard Bright (Guys Hospital in London) Theodor Fahr described the association of bilateral diffuse renal Was born in Pirmasens on 3 October 1877 and stud- diseases with albuminuria, oedema and myocardial ied medicine in Munich, Berlin, Kiel and lastly hypertrophy and differentiated them into inflam- Journal of Human Hypertension Achievements and controversies in renal disease and hypertension A Heidland et al 7 chronic interstitial and chronic parenchymatous nephritis.13 Parenchymatous nephritis (also known as tubular nephritis or great pale kidney) with oed- ema and proteinuria was attributed to epithelial degeneration and subdivided into the hypertensive and normotensive forms. Interstitial nephritis, asso- ciated with hypertension and heart hypertrophy, was separated into groups with and without renal impairment. In 1904 Sandor von Koranyi coined the term ‘renal insufficiency’, characterised by loss of renal functional variability as determined by urinary osmolarity.19 In another categorisation of Senator (1896) the hematogenous non-purulent nephritides were divided into acute nephritis, chronic non- indurative
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