Key words : Bright’s disease, Nephritis, Nephrosclerosis

The Life of Franz Volhard

Franz Volhard (May 2, 1872, to May 24, 1950) was a German clinician and researcher who contributed to the development of nephrology and hypertension through his extraordinary scientific and medical work. He was born in Munich, the fourth of 7 children. His father, Jacob Volhard, was a chemistry teacher and married Josephine Backofen, the daughter of the court painter Franz Backofen.

Franz Volhard completed his medical studies in Halle/Saale in 1897 and continued his successful academic career with a doctorate and about 200 scientific publications. In 1899, he married Else Toennies and started a family, which included 6 sons and 4 daughters.

During his illustrious career, he worked in many hospitals. In 1897/1898, he worked at the Pathology Department of Berlin-Friedrichsain and immediately afterward at the Medical University Clinic in Giessen. During his distinguished career, Volhard headed departments of internal medicine at the Luisen Hospital in Dortmund (1905-1910) and in Mannheim (1910-1918). He was then appointed full professor of internal medicine in Halle an der Saale (1918) and director of the university hospital in Frankfurt am Main (1927).

In 1931, he published one of his most important works, “Niere und Harnwege” (“Kidney and Urinary Tract”) in Bergmann and Staehelin’s Handbuch der Inneren Medizin.

During World War II, Volhard was exposed to the attacks of the Nazi regime. In fact, in 1938, he was forced to leave the post of director of the University Hospital Frankfurt am Main. Only in 1945, after the end of Nazi tyranny, did he return to his post as director. He died dramatically in a car accident in 1950 at the age of 78 years.

During his outstanding career, he received nume-rous awards and honors (Table 1).¹ The worldwide medical community has greatly appreciated the scientific contributions of Franz Volhard. He was posthumously given an award in his name from the International Society of Hypertension. In 1972, Sir George Pickering, Regius Professor of Medicine at Oxford, was the first recipient of this important award and delivered the first Volhard Lecture to the International Society of Hypertension. He described the eminent scientist as “one of the most handsome and the most impressive men that I have ever met. Outstanding, was his zest and joie de vivre. He noticed everything, and if it was good, enjoyed it hugely.”²

Franz Volhard and His Collaboration With Theodor Fahr

Volhard conducted important studies on kidney function together with his colleague Theodor Fahr. From 1909 to 1915, they investigated the mechanisms of Bright’s disease in Mannheim and developed a new classification of kidney diseases. In the monograph entitled Die Brightsche Nierenkrankheit. Klinik, Pathologie und Atlas (1914),³ Volhard and Fahr divided the collective term Bright’s disease into the 3 main forms: (1) degenerative diseases or nephroses, (2) inflammatory diseases or nephritides, and (3) arteriosclerotic diseases or scleroses. Arteriosclerotic diseases were divided into the simple benign sclerosis and the “Kombinationsform” (combinatory form or nephritis superimposed on the simple sclerosis). Fahr further subdivided benign sclerosis into the compensated and decompensated forms, depending on whether there was glomerular damage.

Volhard and Fahr also used the term “renal insufficiency” instead of the term “contracted kidney.” They distinguished 2 groups of hypertensive patients with nephrosclerosis. (1) The first group was with benign nephrosclerosis group. This group included patients with long-standing hypertension; death in these patients occurred mostly from cardiac or cerebrovascular disease, and renal failure was generally not observed. “Proteinuria may be completely absent in benign nephrosclerosis for many years and may develop only in trace amounts over many years.” (2) The second group was with malignant nephrosclerosis. This group included patients with abnormal hypertension, neuroretino-pathy, albuminuria, hematuria, progressive renal damage, and weight loss

Volhard and Fahr described the morphology of malignant nephrosclerosis by severe degenerative changes in the afferent arterioles (mainly fibrinoid necrosis), proliferative changes in the interlobular and arcuate arteries with marked thickening of the intima (edema and/or concentric onion-skin-like changes), and inflammatory and degenerative reactions of many glomeruli.

Volhard also distinguished between the pale and red forms of hypertension. (1) Pale hypertension was described as a general vasoconstriction manifested by pallor of the skin, constricted retinal vessels, and hypocirculation of the kidney. (2) The red form was defined as an expression of essential hypertension, initially finding no evidence of increased peripheral vascular resistance, but assuming decreased comp-liance of the great vessels.

Volhard emphasized the influence of heredity, age, obesity, lifestyle, and alcohol abuse on the development of hypertension. Taken together, these findings contributed significantly to a better understanding of the damage to kidney function and its treatment.

Volhard: A Pioneer of Hypertension

Volhard also assumed that hypertension in acute and chronic kidney disease is a consequence of diffuse involvement of the renal vessels. He wrote, “It is undisputed that with acute diffuse glomerulo-nephritis almost all glomeruli of both kidneys are found, so to speak, empty of red blood cells, not seldomly also the vasa afferentia.”

In 1942, Volhard went on to describe the mecha-nisms behind the different types of hypertension: “If the humoral mechanism of renally induced pale hypertension adds to red hypertension, high blood pressure is henceforth to be described as malignant. The progressive course of renal insufficiency is unavoidable, since the humorally caused general and renal vasoconstriction (induced by decreased renal blood flow) will further aggravate the disturbed circulation in the kidney – a true vicious circle just as with chronic nephritis, whose progression is to be understood only in this manner. Evident is the visible change of the background arteries of the eye. The later development of vascular changes, including thickening of the arterioles, could finally result in the development of pale hypertension.”

He further wrote, “Only some isolated glomeruli are still filled with blood. I have reason to assume that a contraction of the kidney vessels—possibly caused allergically—is a primary factor, ie, a functional occurrence. Supporting this is the fact that, after dying, the glomeruli are easily filled with and the vasa afferentia are often found empty of blood.”

Volhard emphasized that the increased vaso-constriction in pale hypertension is caused by a humoral factor released by the kidney after its ischemia. In fact, he explained, “Pale hypertension is caused by the kidney and acts humorally. Thereby, a vicious circle is induced with the consequent aggravation of hypertension and nephrosclerosis.” Volhard’s intuition essentially anticipated findings that would only be confirmed years later in larger experiments, making him a visionary pioneer of hypertension.

Volhard’s historical contribution to the elucida-tion of renal hypertension, especially on the basis of clinical observations, was acknowledged by Nobel Prize winner A. Houssay. He wrote in the preface of Braun-Menendez (Renal hypertension; 1946): “Much credit is due to the indefatigable investigations of Volhard, who was convinced that a vasospastic factor existed in the so-called pale hypertension, as was indicated by ocular and cerebral symptoms and by blanching of the vessels of the skin. Since he believed that the exaggerated contraction of these vessels was due to a substance circulating in the plasma, he devoted himself with the help of his students to a search for its presence.”

Volhard’s Classification for Uremia Symptoms and His Ideas on Nutritional Therapy

At the Congress of Internal Medicine in Warsaw in 1916, Volhard presented the treatment concept of “starvation, thirst and bed rest,” together with a brochure on the diagnosis and therapy of acute nephritis. This novel concept helped to reduce the mortality rate of “war nephritis” in the World War I and even in the World War II.

Volhard also extended nutritional therapy to hypertensive patients with chronic nephritis, recommending a low-sodium diet (1.5 g NaCl/day) and, at a time when there were no effective and nontoxic diuretics, the addition of fluid restriction. He explained, “In patients with diffuse nephritis and permanent hypertension, I have never seen a measure that has such a benefit as the reduction of fluid intake, which I recommend to relax the circulation and relieve the heart. The effect of this measure is extremely facilitated by a vegetarian diet.”

Volhard emphasized that reducing salt intake plays an important role in controlling extracellular fluid volume. Volhard observed not only better control of blood pressure but also an improvement in paroxysmal nocturnal dyspnea attacks in patients with renal dysfunction.

Volhard underlined the central role of adequate nutrition as a basic treatment for uremia-related symptoms and their progression. To better understand the treatment and management of uremia, he classified the clinical symptoms into (1) true uremia (resulting from retention of products normally excreted by the kidney) and (2) pseudo-uremia (symptoms that are not due to renal dysfunction).

For the treatment of true uremia, Volhard recom-mended a low-protein diet (especially vegetarian) with a normal calorie intake (2000 kcal/day). He wrote, “In patients with chronic renal insufficiency, it is possible to postpone the rise in serum urea concentration for a long time by reducing the daily nitrogen intake to 3-5 g (20-30 g protein). Sometimes we have even succeeded in lowering very high serum urea concentrations. Consequently, the uremic symptoms disappeared.”

This approach for patients with clinical manifes-tations of end-stage renal failure is an effective strategy to slow the progression of renal damage. These dietary strategies confirm the attention Volhard pays to the adequacy of nutritional status to minimize the complications of renal failure and to treat the complications associated with uremia.

Conclusions

Franz Volhard was a pioneer in the field of nephrology and hypertension. His commitment to research and clinical practice is a shining example of a scientific mind open to progress. At 150 years after his birth, the remarkable intuitions of this scientist are still valid and applicable in clinical practice and research today.

His contribution to the knowledge of hyperten-sion and the treatment of kidney disease was greatly appreciated by the scientific community worldwide, and his personality and attitude to research continue to be an inspiration to scientists worldwide years after his death.

References:

1. Luft FC, Dietz R. Franz Volhard in historical perspective. Hypertension. 1993;22(2):253-256. doi:10.1161/01.hyp.22.2.253
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2. Pickering G. The first Volhard lecture. Clin Sci Mol Med. 1973;45:1S-10S.
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3. Volhard F, Fahr T. Die Brightsche Nierenkrankheit. Klinik, Patholie und Atlas. Berlin, Germany: Springer; 1914.
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