Nephrosis

NEPHROSIS. Contents: Definition ................. 830 Pathological anatomy ........... 831 Clinical forms: A. Acute nephrosis ............... 838 B. Necronephrosis ............... 839 C. Chronic, or lipoid nephrosis (including nephrosis with amyloid and amyloid nephrosis) ........ 840 Definition. According to the classical definition of Volhard and Fahr (1914), nephroses include all forms of Bright's disease of the kidneys characterized primarily by degenerative changes in the renal epithelium, or whose inflammatory character is in any case not indisputable; in a narrower clinical sense, nephrosis refers to those degenerative changes in the kidneys that proceed with massive edema and albuminuria in the absence of hematuria and elevated blood pressure. Historically, the differentiation of degenerative parenchymatous forms from the general complex concept of Bright's disease (see) and nephritis (see) was essentially carried out from the first years of the separation of Bright's disease. The edematous forms later named "nephroses" were described by French authors under the name of albuminous nephritis (Rayer, 1840), Bard's epithelial nephritis as a completely independent disease (une entité absolument autonome), and Dieulafoy's syphilitic nephritis as a purely epithelial lesion or chronic parenchymatous nephritis of the tuberculous (Landouzy, Bernard; 1901). However, Senator's classification, which dominated the clinic for many years, confused these purely degenerative forms with inflammatory ones under the name of acute and chronic "parenchymatous" nephritis. The further development of the doctrine of degenerative lesions of the kidneys was greatly facilitated by the work of Munk from Kraus's clinic, who studied the excretion of lipoids in the urine, disorders of lipoid and protein metabolism in edematous forms of renal afflictions, and discovered these lipoids in the renal epithelium in edematous and especially syphilitic lesions of the kidneys. Against the background of these achievements, Volhard and Fahr processed the anatomo-clinical material from Mannheim in their 1914 monograph, thereby making the question of purely degenerative forms of renal diseases—nephroses—topical, which it remains to the present time, continuing to develop and be intensely debated (see Nephritis, historical data). Furthermore, it became clear that in various forms of nephrosis (this was originally established for nephrosis of pregnancy), degenerative changes are also noted in the glomerulus ("glomerulonephrosis" of Fahr); in other forms of nephrosis—necronephroses, amyloidosis—the lesion affects the vessels to one degree or another, and even with minimal anatomical changes in the glomerular-vascular apparatus, the function of this apparatus can suffer significantly, which is clearly reflected in the clinical picture, distorting the typical picture of nephrosis. Finally, in the genesis of the clinical symptoms of nephrosis, especially edematous forms, a major, one might say predominant, role must be assigned to extrarenal factors, predominantly disturbances in metabolism.

E. Tareyev. Pathological Anatomy of Nephrosis. The exposition of the pathological anatomy of nephrosis encounters difficulties in connection with the continuing ambiguity of the concept of "nephrosis" and the circumstance that various investigators use this term in far from identical senses. While originally (F. Müller, Volhard, and Fahr) the designation "nephrosis" was intended to single out a primarily degenerative, non-inflammatory kidney disease within the framework of Bright's disease (see), subsequently two extremes emerged: a number of authors, predominantly pathomorphologists, among them Fahr, considered it possible to apply the term nephrosis generally to all degenerations and deposits in the kidneys without any regard to the clinical picture, i.e., whether the given kidney change is accompanied by albuminuria and edema; thus, in particular, Fahr also refers to nephrosis the most diverse processes of deposits in the kidneys ("Speicherungsnephrosen"): glycemic nephrosis (glycogen deposition), uric acid nephrosis (deposition of uric acid salts), calcareous nephrosis (lime deposition), hemoglobinemic nephrosis, etc. On the other hand, after elucidating the pathogenesis of chronic edematous nephrosis in the sense that in this case we are dealing with a general disease in which the kidney lesion is only one of the consequences of a general metabolic disorder, some clinicians developed a tendency to apply the term nephrosis only to diseases of the latter type, whereas in relation to other kidney degenerations, for example in infectious diseases, they use the name "nephropathies" or nephrosis in quotation marks. Both of these extreme points of view must be considered incorrect; on the one hand, it is impossible too broadly, without considering the clinic, so to speak in a narrowly morphological manner, to apply the term nephrosis in relation to all degenerative and infiltrative changes in the kidneys, and on the other hand, it is inexpedient to exclude from the concept of nephrosis various acute degenerative changes of an infectious-toxic character, even if they are not accompanied by edema; as yet it is impossible to completely deny that such acute degenerative changes, despite their reversibility, may turn out to be the initial stage of chronic edematous nephrosis. It is most expedient to understand by the name nephrosis a bilateral, uniform, and diffuse kidney disease with a primarily degenerative change in the parenchyma, and partly in their mesenchyme. A. Acute forms of nephrosis, observed in various acute infectious diseases and intoxications (infectious-toxic nephroses), have at their basis three stages, or rather three degrees of pathologico-anatomical changes: 1) in the earliest stages, the kidneys macroscopically may appear devoid of any changes, or their cortical substance is slightly swollen; in more severe cases, the kidneys are somewhat enlarged, the capsule strips off very easily, on section the cortical layer is widened, its tissue is clearly swollen and dull, its pattern is indistinct; the color of the cortex is greyish-pink, the medullary substance is sometimes red-purple, of a plethoric appearance. This picture of cloudy swelling (see) has at its basis corresponding microscopic changes. In the convoluted tubules of the first order, i.e., in the main parts of the tubules, the epithelial cells are enlarged, rounded, their protoplasm is granular (so-called albuminous, granular degeneration); the cell nuclei are mostly preserved, only in some are they absent; the lumens of the tubules due to the swelling of the cells are narrowed, in later periods widened and contain a granular protein mass. Sometimes in the epithelium of the convoluted tubules, besides protein granules, small fatty droplets pertaining to phosphatides and neutral fat are also found. In other tubule systems, in the glomeruli, and in the interstitial tissue, there are no changes. 2) The next degree of nephrosis is characterized by a more significant increase in the volume of the kidneys; their consistency is flabby, the cortex is broad, swollen, of a dingy grey hue, the medullary substance with a brown hue. Microscopically, along with granular degeneration, hyaline-droplet and vacuolar degeneration are found, as well as fat deposition, chiefly in the epithelium of the convoluted tubules; the disappearance of cell nuclei and complete cell breakdown are frequently observed; the lumens of the tubules are widened and filled with protein mass, the presence of the latter is sometimes observed also in the lumens of Bowman's capsule of the glomeruli. The glomeruli, interstitial tissue, and vessels are unchanged; only occasionally did Fahr find small infiltrates around the tubules clogged with casts. 3) The third degree of acute nephrosis manifests itself in widespread, often confluent necrosis of the epithelium of the convoluted tubules of the kidneys. In view of the fact that often these necrotic changes do not follow the first two stages, but develop immediately as such following the action of the causative agent, many single out this form into a special type of nephrosis under the name of necronephrosis or necrotic nephrosis; from the clinical point of view, this isolation of the form is supported by the fact that it usually presents signs of renal insufficiency. With the indicated necrotic nephrosis observed in certain poisonings, e.g., with salvarsan, acids, corrosive sublimate (so-called sublimate kidney), infectious diseases (cholera, diphtheria, typhoid, sepsis), in acute yellow atrophy of the liver, severe stagnant jaundice, etc., the kidneys are of normal size or somewhat enlarged, the cortical layer is slightly swollen, devoid of pattern, flabby, of a dingy yellow-grey color [see separate table (p. 359-360), Fig. 5]. Microscopically, confluent coagulation necrosis of the epithelium of the convoluted tubules, desquamation and breakdown of dead cells are found; sometimes necrotic changes are noted on the part of the epithelium and capillary loops of the glomeruli [see separate table (p. 295-296), Fig. 3]. In sublimate poisoning, subsequent deposition of lime in the necroticized cells is characteristic. B. Chronic forms of nephrosis are a manifestation of a disorder of general metabolism, with lipid metabolism disorder being of very great importance; in view of this, the majority of clinicians nowadays call these nephroses lipid nephroses. However, in view of the fact that at the basis of these nephroses lies a disorder not only of lipid, but also of protein, carbohydrate, and water-salt metabolism, this name cannot yet be considered entirely expedient and final. Chronic nephroses from a pathologico-anatomical point of view can be divided into two stages, or rather two forms of changes. 1) Lipid nephrosis. Macroscopically, the kidney is enlarged, of soft consistency; the capsule strips easily. The surface of the kidney is smooth, of a pale yellowish-grey color. On section, a significant widening of the cortical layer is visible, which is devoid of its pattern, moist, swollen, of a pale yellowish-grey color; peculiar yellowish strips and spots with a matte luster are often visible in it. The medullary substance is sharply separated from the above-described pale, swollen cortical layer by its violet-pink color with a brownish hue [see separate table (vol. XX, p. 103-104), Fig. 2]. Upon microscopic examination, one finds a combination of granular, hyaline-droplet, and vacuolar degenerations with lipid deposition, all these changes being concentrated predominantly in the convoluted tubules. The latter are usually strongly widened; the protoplasm of the epithelial cells is partly finely granular, partly in a state of hyaline-droplet transformation; besides, large vacuoles are visible in it, and special reactions reveal the presence of droplets of neutral fat in the basal parts of the cells; besides the latter, doubly refractive light-cholesterol-ester is also frequently encountered, which is located both in the epithelial cells and in the stroma, in which groups of so-called xanthoma cells are visible in such cases. In the widened lumens of the tubules there is a protein mass, partly finely granular, partly droplet-like, and various types of casts; in some nephroses, significant desquamation of the degenerated epithelium is observed. In the late periods of nephrosis, regenerative phenomena in the form of figures of karyokinetic division of the nuclei of preserved epithelial cells can be found in some tubules. The glomeruli in the majority of cases present no changes other than the sometimes existing presence of protein mass in the widened cavities of Bowman's capsule; however, in some cases, depositions of neutral fat and cholesterol-ester are observed in the epithelium of the glomeruli, and sometimes swelling and gluing of the capillary loops with their subsequent impermeability. Such kinds of changes in the glomeruli in nephrosis Fahr considers a nephrotic manifestation and refers to "glomerulonephrosis," observed alongside the usual tubular nephrosis. The renal stroma in lipid nephrosis is usually edematous, often contains lipids lying freely and in the form of groups of xanthoma cells; foci of lymphoid infiltration are sometimes encountered in the stroma. The renal vessels as a rule present no changes. The above-described pathologico-anatomical picture of the "large white kidney" (according to old terminology) is characteristic of the most frequently encountered forms of chronic edematous nephrosis, formerly bearing the name "chronic parenchymatous nephritis" and now called lipid nephrosis; in this picture, however, there are variants associated with one or another degree of degenerative changes in the parenchyma, edema of the stroma, etc., which gives one or another degree of increase in kidney dimensions, swelling and moisture of its cortical layer, etc.

Some variants of chronic nephrosis are based on the peculiarity that granular, hyaline-droplet, and vacuolar degeneration are weakly expressed, whereas the deposition of doubly refracting lipoids is of predominant importance; in such cases, the kidneys may be little enlarged, with the cortical layer only slightly expanded, showing on cross-section not a moist, but a dry surface, a greyish-yellow dull appearance with a characteristic yellowish speckling. These forms were at one time named lipoid nephrosis by Munk and separated from other types of nephrosis. At the present time, however (in view of the fact that in every chronic edematous nephrosis there is a disturbance of lipoid metabolism with hypercholesterolemia, and almost always in the kidney one or another amount of doubly refracting lipoids is observed, while on the other hand, in the form isolated by Munk, there are in the kidneys, besides lipoid deposition, other types of degeneration, although weakly expressed), the majority of clinicians (Volhard and others) do not perceive a fundamental difference between Munk's lipoid nephrosis and other chronic edematous nephroses, and unite all chronic edematous nephroses under the name of lipoid nephroses; among them, Munk's lipoid nephrosis is merely one of the variants. 2) Lipoid-amyloid nephrosis refers to those cases of lipoid nephrosis in which degenerative changes in the renal mesenchyme, in the form of amyloid deposition in it [see the separate table (pp. 295-296), figs. 1 and 2], are added to the aforementioned types of parenchymal degeneration. Amyloid appears in the vessel walls of the nephrotic kidney, in the walls of the glomerular capillaries, less frequently along the course of the proper membrane of the tubules and in the renal stroma, having everywhere the appearance of a homogeneous dense mass giving characteristic reactions (see Amyloid degeneration). Macroscopically, the appearance of the kidney in lipoid-amyloid nephrosis can vary depending on the degree of amyloidosis. Sometimes the presence of a small amyloid deposit in the kidney is obscured by the patho-anatomical picture pertaining to other degenerative changes, and then at autopsy the presence of amyloid in the kidney is established only on the basis of concurrent amyloidosis of the spleen and adrenals or is discovered only under the microscope. With more significant amyloid deposition, the kidney acquires the picture formerly designated as the "large lardaceous kidney." From the "large white kidney," characteristic of ordinary lipoid nephrosis, this picture differs in that the kidney is dense; on cross-section, the cortical layer does not bulge, but appears smooth, dry, has a pale yellowish-grey dull and translucent appearance; the presence of yellowish speckling testifies to significant lipoid deposition (sometimes directly within the amyloid substance itself). From these cases of nephrosis with amyloid or lipoid-amyloid nephrosis, in which amyloid deposition complicates nephrosis or occurs simultaneously with other nephrotic changes, the majority of investigators (Volhard and others) distinguish the amyloid kidney, or amyloid glomerulonephrosis, in which amyloid deposition occurs in the vessels and capillaries of the glomeruli of a healthy kidney or at any rate one not presenting nephrotic changes of the tubular system. These cases usually relate to generalized amyloidosis associated with various extrarenal processes. In the initial periods, the kidneys may appear macroscopically little changed; only the cortical layer proves to be pale grey and translucent. However, in the future, degenerative changes in the tubular parenchyma are added to the widespread involvement of the glomeruli by amyloid, and the picture becomes close to the "large lardaceous kidney," i.e., to the picture of lipoid-amyloid nephrosis. Therefore, in advanced cases, it is sometimes difficult to say whether one is dealing with lipoid-amyloid nephrosis or with an amyloid kidney with superimposed nephrosis. A certain nephrosis is also characterized by an o u t c o m e in shrinkage; in other words, with the gradual destruction of the parenchyma, a proliferation of the connective tissue stroma occurs. The kidneys hereby decrease in volume, become dense; the surface becomes uneven due to the appearance of depressions and retractions, usually unevenly distributed, partly larger and partly smaller; the capsule is fused in places with the surface. Upon microscopic examination, in the places of retractions, one finds collapse and disappearance of the tubules with proliferation of connective tissue between them. The corresponding glomeruli are reduced in volume, concentrically surrounded by connective tissue, not infrequently completely hyalinized; in glomerular amyloid, a gradual disappearance of amyloid is noted, as if under the pressure of the increasing connective tissue. In the uninvolved sections, a picture of nephrotic changes is observed, often with hypertrophy of the preserved glomeruli and strong dilatation of the tubules. Such an outcome of nephrosis into sclerosis and shrinkage (nephrotic nephrosclerosis, nephrotic contracted kidney) is rarely observed and is characteristic mainly of lipoid-amyloid nephrosis and that lipoid nephrosis which is accompanied by massive lipoid deposition and nephrotic involvement of the glomeruli. - There is still much that is unclear and controversial regarding the pathogenesis of nephrotic renal shrinkage. Leloir put forward the view that without glomerular involvement, the shutdown of the glomerulo-tubular systems and the proliferation of connective tissue cannot occur; this was confirmed by the fact that almost exclusively nephrosis with amyloid, in which glomerular involvement is precisely present, can progress to shrinkage. On the basis of this, for some time it was customary to view those nephroses in which, despite the absence of amyloid, there was a transition to shrinkage, with suspicion as to their belonging to nephroso-nephritids. In contrast to this, Aschoff expressed the opinion that besides the more frequent glomerular shrinkage, tubular shrinkage of the kidneys can also be observed in the absence of any changes in the glomeruli. This view is currently shared by Volhard as well; Fahr, who earlier stood at Leloir's point of view, has recently spoken of the possibility of a slowly developing proliferation of connective tissue associated with the obliteration and disappearance of the tubules. This is also confirmed by the experiments of Suzuki with uranium and Bahr with iodine, who obtained connective tissue proliferation as a result of experimental nephrosis without glomerular involvement, as well as the observations of Thannhauser and Krauss concerning the transition to shrinkage of nephrosis with Bence-Jones albuminuria. On the basis of the above, it must be thought that in certain cases pure tubular nephroses (without glomerular involvement) can be accompanied by connective tissue proliferation and shrinkage; such connective tissue proliferation is associated with degenerative changes in the tubules and stroma, the breakdown of degenerated elements, and the collapse of the tubules; it is very probable that the process is accelerated in those cases where the cessation of glomerular function is secondarily added to the obliteration of the tubules. It goes without saying that the presence of preceding glomerular involvement, as happens in nephrosis with amyloid and in certain lipoid nephroses, represents a particularly favorable basis for shrinkage and significantly accelerates the latter.

A. Abrikosov. I. Clinical forms. Clinical classification of nephrosis is difficult due to the fact that, as stated above, only a part of nephrosis gives characteristic clinical symptoms from the entire organism, while other types of nephrosis are predominantly limited to urinary symptoms. Therefore, most classifications emphasize this difference between the two large groups of nephrosis. Thus, Kollert distinguishes two major groups of nephrosis: a) purely local renal processes—febrile nephrosis, necrotic nephrosis (for example, bismuth nephrosis), and b) general diseases of the organism (with edema, cholesterolemia, and other general symptoms)—lipoid nephrosis, nephrosis of pregnancy. Volhard, in his latest classification (1931), distinguishes: A. Acute nephrosis with a necrotic sub-type. B. Chronic nephrosis with stages: initial, prolonged, and terminal. C. Nephrosis with amyloid and amyloid nephrosis. The last two forms proceed predominantly as a general disease of the organism. Munk's classification (1925) distinguishes nephrosis: febrile, necrotic, fatty, in acute infections, lipoid, syphilitic, of pregnancy, and amyloid; in this classification as well, the first half represents predominantly local diseases, while the second represents rather general diseases of the organism. More detailed classifications of nephroses, based in particular on the anatomical «stages» of tubular damage, hardly have a chance to hold their ground in the clinic, since these various stages (e.g., albuminous and fatty degeneration) are often indistinguishable in the clinic and essentially do not represent regular phases of the process's development in time (like, for example, the stages of typhoid fever adopted by the clinic), but are rather a manifestation of harmful agents of varying intensity. When describing individual clinical forms (e.g., lipoid nephrosis), indications of the possibility of distinguishing such anatomical stages will be provided. The classification of Volhard is taken as the basis of the further exposition. However, this classification is also not free from objections. The first category of «acute» nephrosis includes symptomatically completely different forms—febrile albuminuria (manifesting in the clinic only with a urinary syndrome) and necrotic nephroses of the corrosive sublimate kidney type (giving in the clinic a nephritic syndrome or renal insufficiency syndrome). It is unclear where nephroses such as nephrosis in Basedow's disease, diabetes, and cancerous processes should be assigned—clinically they are close to febrile albuminurias, but it is hardly possible to call them «acute» nephroses; apparently, Volhard generally considers it superfluous to create a clinical category for these predominantly anatomical forms. On the other hand, the second and third groups are clinically indistinguishable (both groups are characterized by an edema syndrome with the addition of a renal insufficiency syndrome in later stages); nephrosis of pregnancy should rightly be assigned to Volhard's second group: the term «chronic» in relation to this nephrosis is completely unjustified. However, replacing the definition «chronic» with the adjective «lipoid», which Volhard often resorts to in the text, represents a successful resolution of the issue. A. Volhard's acute nephrosis occurs in the majority of severely progressing infections, has as its anatomical substrate diverse, but superficially proceeding degenerations of the renal epithelium; clinically it is characterized only by urinary symptoms—albuminuria, casts, and renal epithelium in the sediment («febrile albuminuria»); urine of acid reaction, concentrated (as in all acute infections and febrile conditions). There is no edema, no rise in blood pressure, nor hematuria. If an increase in blood residual nitrogen is observed, it depends on the infection as such, on the large formation of nitrogenous slags (tissue breakdown), and not on renal retention. Similarly, the decrease in sodium chloride excretion during fevers, especially during lobar pneumonia, has nothing to do with impaired renal function (since blood chlorine drops simultaneously), but depends on pneumonic acidosis followed by a perversion of the serum ion concentration or on the accumulation of chlorine in the inflammatory exudate. The clinical course, prognosis, and treatment are determined by the underlying disease, and «nephrosis» is established only by urinalysis. In acute infections, albuminuria and other urinary symptoms appear and disappear together with the febrile period. In individual infections, in particular in typhoid fever and diphtheria, more severe nephroses with partial necrotization of the epithelium can be observed. However, blood pressure remains normal in these cases as well; edema readiness is insignificant, at most transitory, and cavity edema is more often of cardiac origin. Albuminuria can be higher and last longer (corresponding to the development of fatty degeneration); diphtheria can also lead to lipoid nephrosis with developed edema. In other infections, anatomical changes in the kidneys often present certain characteristic features; necrosis in the glomeruli can cause minor hematuria (Munk); sometimes focal nephritis is also added. Therefore, for a correct judgment of what is hidden under albuminuria or microhematuria in one infection or another, knowledge of the features of the anatomical picture of the corresponding most frequent renal lesions is required (see under individual infections). Fading diffuse nephritis, stagnant kidney can also proceed during infections under the guise of isolated albuminuria. From this, the illusory nature of the possibility of making a diagnosis of nephrosis in the clinic on the basis of albuminuria alone without other symptoms is clear. Moreover, in many chronic afflictions (cancerous tumors, Basedow's disease, diabetes), the microscope reveals degenerative lesions of the tubular epithelium without even albuminuria being observed in the clinic; the diagnosis of such «academic» nephroses is possible during life only on the basis of knowledge of the frequency of these anatomical changes in the named diseases. B. Necronephroses. Necrotic nephroses, or «necroses», are the term for the most severe anatomical changes of the renal epithelium occurring under the influence of various intoxications (partly toxico-infections) and expressed clinically by a severe general condition, albuminuria, hematuria, anuria, increased blood pressure, and retention of nitrogenous slags in the blood. A typical example of necronephrosis can serve as the «corrosive sublimate kidney». (See above pathological anatomy). — Histogenesis of the corrosive sublimate kidney. Most authors believe that the tubular epithelium is affected primarily, being damaged during its excretory function. Blood stasis in the glomerular system (Schlayer, Ricker) and changes in the glomeruli have been described; Volhard sees in this a secondary action of toxic substances formed in the dying epithelium. However, there are indications that the vascular apparatus can be affected primarily, in experimental animal poisoning already in the first hours (Photakis, Nikolaidis). It is conceivable that sublimate is excreted in the glomeruli and reabsorbed in the tubules (Kosugi); the lesion of the tubular epithelium is sharply expressed due to the greater concentration of poison in the tubules, and this can also explain the predominant lesion of the parts of the cells facing the lumen of the tubules. Clinically, in pronounced cases of corrosive sublimate kidney developing from sublimate poisoning, vomiting, bloody diarrhea (mercurial colitis), later loss of consciousness, increased blood pressure, leukocytosis (up to 40,000) are observed. Urine of low specific gravity, with a low content of nitrogenous slags and salts; its quantity is reduced down to multi-day anuria (polyuria is encountered only in the mildest cases). Protein in moderate quantities in the urine (can reach 20°/_oo), erythrocytes in small quantities in the sediment, hyaline, granular, epithelial casts, renal epithelium. Edema has not been observed even with prolonged anuria (except for cases by Ascoli and Volhard). In the blood, an increase in residual nitrogen, a drop in reserve alkalinity, hypochloremia (down to 240 mg%) (Goldblatt), an increase in cholesterol (Stasiak). In the most severe cases, sublimate poisoning rapidly leads to death; in subacute cases, prolonged anuria worsens the prognosis, although it still does not make it hopeless. Cases have been described with an increase in blood urea up to 726 mg% (Lemierre, Bernard) and even with the appearance of uremic pericarditis with seven-day anuria, which nevertheless ended in complete recovery. Sometimes a slight residual albuminuria remains for months. The pathogenesis of the corrosive sublimate kidney presents considerable difficulties if the entire picture is explained only by damage to the tubular epithelium. One might assume that the necrotic changes of the tubular epithelium would give the most clearly expressed typical picture of a nephrotic lesion, with edema, etc., but the clinical picture of the corrosive sublimate kidney actually approaches, as described above, acute nephritis. To reconcile clinical data with damage to the tubular epithelium, attempts were made to explain the pathogenesis of anuria in the corrosive sublimate kidney by the swelling of the tubular epithelium and the blockage of the tubules by necrotic masses; hematuria—by the significant desquamation of the tubular epithelium and the exposure of blood vessels as a result, with the exit of erythrocytes into the interior of the tubules; finally, the increase in blood residual nitrogen—by prolonged anuria (and extrarenal factors—significant breakdown of tissue protein).

However, in view of the determined disturbances of renal blood circulation and anatomical changes in the glomeruli, it is permissible to explain the development of pathological symptoms from the standpoint of impaired glomerular and tubular function, as in diffuse glomerulonephritis, which leads to hematuria, isosthenuria, etc. In particular, Lichtwitz explains anuria by glomerular damage. In addition to corrosive sublimate necrotifying nephrosis, necrotifying nephroses are also observed from bismuth (in the treatment of syphilis with soluble preparations) with albuminuria up to 17°/₀₀, from neosalvarsan (with characteristic hematuria), from inorganic arsenic, phosphorus, veronal, luminal, in a number of infections—severe typhoid and typhus, cholera, dysentery, malaria, diphtheria, pneumonia; in many experimental poisonings of animals with renal poisons (uranium, chromium). The diagnosis in the clinic is based mainly on knowledge of the etiology corresponding to the assumed anatomical picture (i.e., data on poisoning with corrosive sublimate, bismuth, etc.); from a purely symptomatological point of view, necrotifying nephroses are indistinguishable from inflammatory glomerulonephritides (or mixed forms) leading already in the acute stage to renal failure. Treatment of the corrosive sublimate kidney, in addition to prescribing a sparing diet as in uremia in general, aims to enhance diuresis. Physiological saline solution is administered (1.5–2.5 l intravenously + 3–4 l per rectum per day) (Hayman, Priestley), or better, a glucose solution (hypertonic into a vein, isotonic in an enema—Lermoyez and Bernard), alkaline solutions, soda lemonades internally. Large doses of bismuth internally (6–10.0 per day) are recommended to prevent septic ulcers; in fresh cases—hyposulfite into a vein or for duodenal washings; also bloodletting and hypertonic solutions of sodium sulfate and especially 20% NaCl into a vein ("rechloruration" of French authors), decapsulation with variable success, paravertebral anesthesia of the renal segments, X-ray therapy. B. Chronic, or l i p o i d N. Lipoid N. presents the most typical clinical picture of N., i.e., large edema with massive albuminuria and the absence of increased blood pressure and hematuria; the anatomical substrate on the part of the kidneys is fatty and lipoid degeneration of the renal epithelium—the large white kidney (corresponding to the initial stage); subsequently infiltration of the interstitial tissue by leukocytes (corresponding to the prolonged stage); and finally shrinking of the organ (corresponding to the terminal stage). In the doctrine of the pathogenesis of lipoid N. as a disease of metabolism not associated with lesions of a definite organ, the clinic has gone further than anatomical studies, which are so far riveted only to the study of the kidney suffering in the order of the impairment of its excretory function; therefore, the theory of lipoid N. at the present time is developing to a significant extent as a clinical rather than an anatomical problem (see pathogenesis). From the standpoint of nomenclature and for understanding the special world literature, it is important to note the tendency of many authors, in particular the Anglo-American and French schools, to apply the term N. only in relation specifically to lipoid N., in contrast to the bias observed in our practice to call N. any albuminuria without increased pressure and without hematuria. Amyloid degeneration of the kidneys, by virtue of the considerations indicated above, is considered in close connection with the presentation of lipoid N. One can distinguish three forms of amyloid kidney lesions (Volhard): 1) Pure amyloidosis of the renal vessels with insignificant spread of degeneration—clinically proceeds asymptomatically, being an unexpected anatomical finding. 2) N. with amyloid (lipoid-amyloid N.), clinically characterized by symptoms of lipoid N. with good renal function. In this combination, with a moderate development of amyloid infiltration, the clinic knows no symptoms on account of the amyloid itself. 3) Amyloid kidney, amyloid N., or amyloid glomerulonephrosis—those cases where a high degree of amyloid infiltration of the vessels disrupts renal blood circulation and causes the development of true renal failure. From a purely symptomatological point of view, it seems not easy to establish an amyloid complication, and this assumption arises either in the presence of a known definite etiology of a protracted course of edematous N. or, especially with the development of renal failure in a nephrotic, upon exclusion of inflammatory complications on the part of the glomeruli. Symptomatology. The leading symptom of lipoid N. is edema; they are located in the loose cellular tissue, especially on the face, predominantly on the eyelids ("renal edema"). In pronounced cases, the typical face of a nephrotic appears broad, of a lifeless pale color, the eyelids are swollen, translucent. Anasarca spreads to the entire body, affecting the shins, thighs, external genitalia; edematous infiltration accumulates in the lumbar region, on the hands, turning them into pillows. With large edema, patients retain up to 16–20 and more liters of edematous fluid, the skin may crack; the edematous fluid is watery, in a thick layer of a bluish-white color, as if several drops of milk had been added to it (pseudo-chylous fluid). Soon dropsy of the cavities develops; ascites, unlike cardiac dropsy, is not accompanied by swelling of the liver, on the contrary, in the epigastric region, marked tympanitis due to intestinal meteorism is noted. The amount of transudate in the abdominal and pleural cavity can reach many liters, it is almost colorless, with a low protein content (¹/₄–¹/₂%) and low specific gravity, weakly opalescent. Patients experience predominantly mechanical inconveniences from the mass of edematous fluid, tension in the skin, heaviness in the abdomen, etc.; however, in addition, there is often noted a decrease in appetite, general weakness, headaches, dragging pains in the lower back, often watery painless diarrhea. The urine at the height of the disease is scanty, of a saturated brown color, turbid, rich in urobilin, its specific gravity is increased—up to 1.030, sometimes up to 1.050 and higher. Upon boiling, the urine completely coagulates from a high protein content, reaching 30–50°/₀₀; sodium chloride in the urine may drop to traces at the height of the disease. In the sediment, renal epithelium, hyaline, granular, and less often waxy casts are found in varying amounts and inconstant from day to day. The renal epithelium, deposits on casts, or the casts themselves are often fatty degenerated; when viewed in a polarization microscope or when stained for lipoids, these fat droplets turn out to consist of double-refracting lipoids—cholesterol esters. There are no erythrocytes in the sediment or single ones are noted in the preparation, the number of leukocytes is also insignificant. In the clinical picture, besides the absence of hematuria, the absence of increased pressure is characteristic, or rather arterial hypotension, a normal fundus oculi, the absence of uremic symptoms (attacks of pseudo-eclamptic uremia were observed in pure nephrosis extremely rarely) (MacElroy, Murphy, Warfield). The course of lipoid N. is chronic, the onset is gradual. In the edematous stage, nephrotics are threatened by venous thromboses, and especially coccal infections, to which nephrotics are very prone and which usually assume a septic course in them. Diplococcal peritonitis, pneumococcal meningitis and sepsis are frequently observed, as well as streptococcal infections (peritonitis with hemolytic streptococcus), and especially erysipelas after scratching the edematous skin, etc. If patients survive this stage, the edema gradually disappears, and a tendency to edema still remains for a long time, appearing after eating salty food, cooling, and without apparent causes ("edema readiness"—Ödembereitschaft). Upon the subsiding of the edema, significant emaciation of the body is revealed, especially due to the loss of muscle substance. Patients gradually grow stronger, become within certain limits capable of work, and can lead a tolerable lifestyle for years, excreting all the time significant amounts of protein, true, smaller than in the acute edematous stage. Various infections, especially of the pharyngeal lymphatic ring, as well as other focal infections, often lead to the addition of a nephritic component (see Nephritis). Likewise, lipoid nephrosis joining inflammatory glomerulonephritis, the so-called secondary lipoid nephrosis, imposes a significant peculiar imprint on the course of the individual case, however, in its further course and in relation to the prognosis of the disease, it is entirely determined by this inflammatory process. A frequent complication of pure lipoid N. upon its prolonged existence, especially in the presence of such infections in the body as tuberculosis, lues, or septic foci, is amyloid degeneration—the so-called lipoid-amyloid N. arises; according to Epstein (A. Epstein), amyloidosis is only the highest stage of protein poisoning as a result of the same metabolic disorders of protein that nephrosis is. Pure lipoid N. can drag on for a large number of years and still end in complete recovery (even after 8 years of suffering, Steinitz); more often nephrosis leads to death from an intercurrent septic infection. Out of 18 cases by Christian, 15 died of infection. Schlayer saw only two cases of recovery.

In general, the poor prognosis of significant renal edema is justified. Conversely, Epstein considers recovery the rule; he has not observed fatal cases. Of 20 nephrotic children of Davison and Salinger, 6 recovered; of these, 5 enjoyed perfect health for 7 years or more. Unlike inflammatory forms, nephrosis is characterized by a low tendency to progress and to the development of renal failure. Even with a prolonged course, lipoid nephrosis may retain clinically and anatomically (mainly) the picture of a typically degenerative lesion without transitioning into contraction (with a course of up to 17 years), although cases of transition into a secondary contracted nephrotic kidney are also reliably known. More often, when signs of renal failure develop during the course of nephrosis (in the absence of symptoms of inflammatory glomerulitis), the anatomical substrate turns out to be amyloid-lipoid degeneration rather than a purely nephrotic contracted kidney; both of these forms are characterized by hyposthenuria, azotemia, and uremic symptoms in the absence of hypertension and fundus changes. Laboratory data and pathogenesis. Laboratory examination of cases of lipoid nephrosis clarifies the details of the clinical picture and provides the basis for various theories of the pathogenesis of this condition. Hematological analysis reveals practically normal numbers of erythrocytes and hemoglobin, in contrast to the anemia of nephrosis complicated by nephritis or amyloidosis; from the side of the leukocyte formula, there is lymphocytosis and eosinophilia. The erythrocyte sedimentation rate is sharply accelerated, often parallel to the degree of cholesterolemia (Tareev); sedimentation is slowed down as a result of treatment with urea, thyroidin, and novasurol. The blood volume in nephrosis is increased in a significant part of cases, especially when edema subsides—"oligocythemic hypervolemia." In the edematous stage, plasma proteins are sharply reduced, down to 2-3% instead of the normal 8%, and this decrease in proteins occurs mainly at the expense of the albumin fraction; as a result, a distortion of the normal albumin-globulin coefficient occurs, which is normally 1.5-2.3 and drops in nephrosis to 0.5-0.3 and even lower; less frequently, globulins increase absolutely as well. Fibrinogen is elevated, but obviously not as sharply as was erroneously determined by some authors. Blood cholesterol sharply increases, reaching 500-600 and even 1,000-1,500 mg %, and other blood fat fractions—lecithin and fatty acids—are also elevated. After a cholesterol load, its content in the blood increases. The milky color of the serum and transudates is probably due to special combinations of lipoids with proteins or to the flocculation of lipoids precipitating from an insufficient amount of protective colloids—blood proteins. The greater lability of blood colloids and their lower dispersion in nephrosis explain such properties as worse retention in plasma of colloidal dyes, for example, Congo red, which even in uncomplicated lipoid nephrosis leaves the bloodstream faster than normal. Blood sugar is lowered (in one case even down to 22 mg % in the absence of hypoglycemic symptoms) or is determined within the normal range, as is bound blood sugar. The determination of residual nitrogen and its various fractions in the blood gives normal figures (including for urea, amino acids, creatinine, aromatic bodies). The content of sodium chloride in the serum is normal or reduced (down to 455 mg %) or less often slightly elevated; serum calcium is reduced to 8-5 mg %. The dry residue and specific gravity of serum are reduced due to lower protein content. Urine analysis reveals a significant content of protein and nitrogenous slags. Fractional determination of albumins and globulins makes it possible to establish with certainty the predominance of the albumin fraction (constituting up to 94% of all urine protein; Tareev). The high specific gravity of urine depends only partly on the large amount of protein, but mainly on the increased excretion of urea, the amount of which in individual cases can reach 4.5%; the excretion of uric acid, creatinine, phosphates, sulfates, ammonia, and pigments also proceeds well. Most functional tests aimed at determining the excretion of nitrogenous slags give normal figures, including the Ambard coefficient and the determination of glomerular filtration volume according to Rehberg. The excretion of dyes—methylene blue in the Asher test, phenolsulfonphthalein, as well as other colloids—gum arabic after intravenous administration—is increased compared to norm. In nephrotics, alimentary glucosuria easily occurs (already after 50.0 of glucose), as well as phlorhizin glucosuria. The C/N coefficient of urine is elevated. The urine reaction is often shifted to the alkaline side due to excessive ammonia excretion; it changes to the acid side with difficulty after appropriate loads. The ammoniuria of nephrotics depends on excessive ammonia production in the kidney itself, rather than on the acid setting of general metabolism, as in diabetes (Magnus-Levy). The concentration test is superfluous, since the kidney reveals the hypersthenuric nature of its work even without a load. The dilution test gives various results depending on the stage of the disease; in the edematous stage, water excretion is significantly reduced, however, according to Yavein, the half-hour portions closest to water intake can be normally large. A sodium chloride load leads to the retention of salt and water. The degree of water metabolism disturbance with overt edema or "edematous readiness" is easily established in the clinic by the McClure-Aldrich tissue hydrophilicity test with the determination of the resorption time of the intradermally injected physiological solution; the resorption time is shorter the greater the edema, dropping even to 1 minute or less in severe nephrotic anasarca compared to the normal 60 minutes. After nutritional cholesterol loads, its increased excretion is revealed in the urine, especially apparent upon microscopic examination of the sediment. Of other laboratory methods, it can be pointed out that in nephrosis, basal metabolism can be determined as lowered (in 60% of cases Epstein found a decrease of 10-22% compared to norm; other authors as well). The pathogenesis of the nephrotic complex cannot be considered elucidated at the present time either. Various theories of nephrosis aimed to explain mainly the development of edema and albuminuria; as information accumulated on deeper metabolic disturbances in this disease, new theories tried to fully encompass the remaining symptoms (cholesterolemia, etc.). Classical theories linked the development of nephrotic edema with impaired renal function, assuming the primary loss by the kidney of the ability to excrete either water (Koranyi) or salt (Widal, Strauss). To this day, the brilliant observations of Widal and Javal have enormous clinical significance; they managed to induce with experimental precision the subsidence or reappearance of edema in an edematous renal patient using a salt-free diet, resp., a sodium chloride load. The second stage in the development of the doctrine of the genesis of renal edema can be characterized as tissue-based; at the same time, predominantly colloid-chemical changes in diseased tissues (M. Fischer) or a decrease in their elasticity (Landerer) were blamed. Volhard and Fahr also initially explained edema by changes in the periphery, namely by the lesion (degenerative) of the vascular wall. Finally, the third stage of the doctrine of nephrotic edema should be called humoral; essentially, it is a return to the doctrine of Bright and his immediate followers. At present, renal edema (especially nephrotic) is explained primarily by a decrease in the plasma protein content ("hypoalbuminemic edema"), consequently by a decrease in their colloid-osmotic, "oncotic" pressure (see Edema). A decrease in the oncotic pressure of plasma is constantly found in nephrotic edema, and a complete parallelism is observed between the degree of decrease in oncotic pressure and tissue hydrophilicity in nephrosis (Tareev). In the disturbance of protein metabolism, at present they see not only the cause of nephrotic edema, but also the essence of the entire condition ("diabetes albuminuricus" of Epstein). Nephrosis is beginning to be viewed as a disease of metabolism, primarily protein, lipoid, and water-salt metabolism, rather than as a kidney disease (Lowenthal). It is proposed to replace the term "nephrosis"—as associated with the concept of kidney disease and therefore incorrect—with broader terms that indicate more closely the essence of the disease, such as diabetes lipoido-proteinicus and others. A connection of individual cases of nephrosis with other disorders of lipoid metabolism is outlining, e.g., with hepatosplenomegaly of the Niemann-Pick type; treatment with novasurol, ammonium chloride, and thyroidin is essentially common both for "nephrosis" and for obesity. There are indications of the possibility of assuming at the root of the "nephrotic" metabolic disturbance a functional lesion of the liver; in favor of this opinion, Knauer cites the absence in nephrotics of the trypanocidal properties of serum (present under normal conditions), the presence of quinine-resistant lipase in the serum, water metabolism disorders, arterial hypotension, a pathological blood sugar curve after loads, and duodenal probing data.

Anatomical changes in the liver cells—atro-phy and degeneration—have also been detected as a possible manifestation of the functional overstrain of the hepatic parenchyma under the influence of blood protein loss, fatty degeneration, and lipoid infiltration. Schmidtmann blames the spleen in the pathogenesis of nephrosis. Behind the nephrotic metabolic disorder, a disturbance of endocrine-vegetative regulation may possibly be hidden. Epstein sees the connection of nephrosis with (relative) hypofunction of the thyroid gland in the lowering of basal metabolism, in the exceptional tolerance of nephrotics to thyroidin and adrenaline; he describes a case of nephrosis that turned into myxedema; three other cases of his developed during prolonged X-ray irradiation of the neck. Anatomical changes were found in the thyroid gland in nephrosis: absence of colloid, atrophy and desquamation of epithelial cells, which are a sign of functional exhaustion. Thyroidectomy in experiment led to degenerative changes of the tubular epithelium with simultaneous toxic fatty degeneration of the hepatic parenchyma. Ferrata (Pensa) treats arterial hypotension, bradycardia, asthenia, enophthalmos, and resistance to adrenaline observed in nephrotics as signs of adrenal damage and sees in nephrosis a pluriglandular thyroid-adrenal complex. Finally, Lichtwitz speaks of the pituitary-mesencephalic pathogenesis of nephrosis and the kidney of pregnancy. What is the participation of the kidneys themselves in the origin of the clinical symptoms of nephrosis? According to some authors, the "nephrotic metabolic disorder" with all clinical symptoms, on the one hand, and the anatomical "lipoid nephrosis," on the other, coexist as two pathological conditions, and it seems that even without characteristic anatomical changes in the kidneys, the entire clinical picture of a metabolic disease with edema, massive albuminuria, and lipoiduria can manifest (case of Labbé and coworkers). Indeed, the kidneys regarding their most important functions—the excretion of nitrogenous slag, pigments, foreign substances, and the regulation of acid-base balance—turn out as a rule to be undamaged in nephrosis; one can perhaps even speak of their increased permeability or of an increase in both filtration and reabsorption functions (Tareyev). However, opposing the kidney to the organism as a separate organ to the general metabolism, as a part to the whole, must not be done. The kidney affects the organism, and the organism affects the kidney. The increased work of the renal filter leads to the depletion of blood proteins and to the development of edema. At the same time, the depletion of blood protein caused by any means, for example, in experiments with healthy kidneys by blood washing, "plasmapheresis," leads simultaneously with the development of edema to the lipoid degeneration of the kidneys and albuminuria. The opposition of the kidney to the rest of the organism is also incorrect when Vollhard attempts to present in more detail the mechanism of edema formation; according to Vollhard, the kidney does not excrete water after a load because the water does not reach the kidneys, remaining in the tissues. However, from this point of view, the kidney, being not a tissue as an excreting organ, at the same time must be considered a part of the tissues, like any other water-retaining parenchymatous organ. It must be assumed that the kidney in nephrosis does not excrete water not because water does not reach the kidney, but because in nephrosis, with sufficient filtration, there are conditions of increased reabsorption, turning the increased function of the organ into a state reverse to excretion—into water retention in the organism (Tareyev). The pathogenesis of lipoid nephrosis should be conceived in such a way that the harmful agent acts on both the metabolism and the kidney simultaneously; subsequently, metabolic disorders increase the kidney damage, and the impairment of renal function increases the metabolic disorders (for example, by increasing the blood mass and thereby contributing to edema or contributing to the depletion of blood protein due to its loss with urine); a vicious circle is created, which is important to realize also from the standpoint of rational therapy. The etiology of lipoid nephrosis is insufficiently elucidated. Undoubtedly, infections play a major role, especially syphilis (leading generally to a significant disorder of lipoid metabolism), tuberculosis, purulent focal infection, pneumococcal infection, more rarely others; also lymphogranulomatosis, deforming arthritis. The named infections with prolonged and intensive exposure easily lead to the development of amyloid degeneration, which from a clinical point of view forces one to bring lipoid nephrosis close to this disorder of protein metabolism. On the other hand, it is important to note that, having arisen apparently under the influence of infection, nephrosis often develops further independently, and the removal of the infectious focus does not significantly alter the course of the disease; true, in amyloid degeneration, precisely in its very initial stages, such a connection appears more noticeably, in particular regarding the therapeutic effect. Moreover, patients with genuine lipoid nephrosis may experience improvement or more rarely complete recovery under the influence of an acute intercurrent infection, which obviously affects nephrosis—a metabolic disease—in the order of a factor normalizing metabolism—general metabolism and lipoid metabolism in particular; it is curious that in the casuistry of such cures of nephrosis from accidental infection, pneumococcal and streptococcal infections (which themselves cause nephrosis under other conditions) figure, pneumonia, pneumococcal peritonitis, empyema after tonsillitis, even erysipelas. Lipoid nephrosis is a rare disease, somewhat more frequent in children, especially boys (Davidson and Selinger on pediatric material had only 26 cases out of 54,000 patients). Predisposing to nephrosis are lymphatism and exudative diathesis. Among endogenous factors, importance is also attached to a certain set of the autonomic nervous system, in particular vagotonia; according to Hess, nephrosis is nephritis of vagotonics. Differential diagnosis. The diagnosis of pure lipoid nephrosis should be made with great caution, remembering the exceptional rarity of pathologico-anatomical findings of pure nephrotic forms; therefore, with a not entirely typical clinical picture, it is more logical to lean in favor of other diagnoses and first of all think of mixed forms—nephritis with secondary lipoid nephrosis. a) Such a "pseudonephrosis," or nephroso-nephritis, proceeding with the predominance of nephrotic symptoms, should of course be diagnosed in all cases proceeding with hematuria and hypertension, even with an insignificant transient increase in pressure (Vollhard) at the beginning of the disease or even with high normal figures of maximum pressure (hypotension is "typical for nephrosis"), as well as with any microhematuria, and all the more so with insufficient concentration of urine (with low specific gravity of urine in acute forms) or with other signs of nitrogen excretion impairment (increase of blood non-protein nitrogen). b) Distinguishing syphilitic nephrosis from other forms of lipoid nephrosis is allowed, apart from anamnesis and direct symptoms of luetic infection, by the stormy development of edema, very significant albuminuria (in exceptional cases up to 11°/₀₀ and even up to 13.7°/₀₀), sharp fluctuations in protein content (Yanovsky), turbidity of urine with an abundance of lipoid casts, high specific gravity and other typical signs of nephrosis. Of the various manifestations of syphilitic renal damage, nephrosis is the most characteristic; according to Munk, syphilitic nephrosis is generally the most typical example of lipoid nephrosis. However, mixed forms are not uncommon in syphilis: Bright's disease—nephroso-nephritides, or the addition of amyloid, transition into a contracted kidney, as well as, generally in syphilitic lesions, pluriviscerality of the suffering (hepatitis, etc.). The curability of syphilitic nephrosis is characteristic. However, improvement from mercury preparations, in particular from rubbing with grey ointment, cannot have decisive diagnostic significance (ex juvantibus), since it also occurs in nephrosis of another etiology (Munk); equally, at the root of a positive Wassermann reaction in lipoid nephrosis, besides specific infection, significant ongoing non-specific disturbances of lipoid metabolism of a non-specific character may have importance. c) The diagnosis of lipoid-amyloid nephrosis is based on the presence in the anamnesis of protracted suppurations (chronic empyemas, bone sequestra, cavernous tuberculosis, syphilis), on signs of amyloid degeneration of other organs (hepatomegaly and splenomegaly), persistent diarrhea, on greater persistence of edema and massive albuminuria. There is often anemia and other signs of cachexia as a consequence of the underlying exhausting disease. A relatively low specific gravity of urine and the development of insufficiency of the nitrogen-excreting function of the kidneys in the absence of glomerulonephritis also speak for the addition of amyloid; the urine in this case is weakly colored, the urine sediment under the microscope is scanty ("formule morte" of Vidal). The cholesterol content in the blood is lower than in pure lipoid nephrosis (depending on the cholesterol-lowering effect of cachexia and renal failure). Amyloid degeneration can also be diagnosed by a significantly greater excretion of globulins in the urine than in pure nephrosis.

(Senator and others, Tareyev), by the rapid disappearance of congo red from the bloodstream (Bennhold's test) upon intravenous injection of the dye (at least 60% of the dye one hour after injecting 10 cm³ of a 1% dye solution into a vein). d) Pregnancy kidney in the majority of cases proceeds under the clinical picture of nephrosis with edema, massive albuminuria, oliguria, high specific gravity, single erythrocytes in the sediment with a large number of casts (hyaline, granular, epithelial), and with lipoiduria. In far-advanced cases, a drop in concentration capacity may be observed. However, with pregnancy kidney, a number of symptoms are observed that are not usual for pure nephrosis, such as: elevated blood pressure, angiospastic states in the brain, changes in the fundus oculi—retinitis, hemorrhages. These symptoms are attributed not so much to the kidneys themselves as to general toxicosis (just like eclampsia); the urinary and general symptoms in the pure form of pregnancy kidney disappear after the natural or artificial termination of pregnancy (for details see Kidneys — pregnancy kidney). Nephrosis and working capacity. Acute nephroses arising in severe general infectious diseases cause a temporary loss of working capacity due to the underlying infectious disease and not due to the renal complication; the symptoms of nephrosis cease together with the cessation of fever, and therefore the presence of febrile nephrosis does not prolong the process of restoration of working capacity in those recovering from infectious diseases. In necronephrosis, the existing symptoms of general severe intoxication and renal symptoms make it mandatory to prescribe strict bed rest for the patient as long as oliguria, elevated blood pressure, elevated blood residual nitrogen, significant albuminuria, and hematuria are determined. With a favorable outcome of necronephroses, recovery from the disease proceeds at a rapid pace, and patients are soon able to return to their occupations. Residual hematuria and albuminuria may drag on for a longer period (for months) without affecting the patient's working capacity. The occurrence of necronephrosis in connection with the action of occupational hazards requires, of course, the transfer of the patient to another job. The greatest difficulties in assessing working capacity are presented by cases of chronic lipoid nephrosis. In the acute edematous stage, these patients must observe bed rest and therefore are completely incapacitated. When the disease transitions into the chronic non-edematous stage, albeit in the presence of continuing moderate albuminuria, patients partially restore their working capacity. In this respect, one must note, as a positive phenomenon from the standpoint of working capacity, firstly, the absence in pure nephrotic cases of a tendency to the development of renal failure and the development of a cardiovascular syndrome (i.e., elevated blood pressure, hypertrophy and dilation of the heart), and secondly, the considerable latitude of the diet permissible in cases of chronic nephrosis, in particular regarding protein food products. It is necessary to reckon with the favorable effect on the course of nephrosis of a dry and warm climate, a dry dwelling, etc. Taking into account the indicated circumstances, chronic non-edematous nephrotics may be allowed moderate physical labor, provided there are no particularly harmful moments of this labor, as well as with periodic control of urine and renal function (determination of blood pressure, condition of the heart, etc.). For mental workers, it is usually possible to allow a normal or slightly reduced work load. It should be especially emphasized that cases of albuminuria with edema, suspicious of amyloid degeneration, and even more so clear forms of amyloidosis, or the presence of a nephrotic contracted kidney, compel the patient to be placed in conditions of maximum sparing of the kidneys and the organism and almost completely deprive the patient of working capacity. In cases of mixed forms, i.e., nephrosonephritis or nephrosis with hypertension, the patient's working capacity is determined, apart from the acute edematous stage, predominantly by the degree of development and manifestations of the nephritic resp. hypertensive components. Treatment. For a correct approach to the treatment of cases of lipoid nephrosis, this disease should be viewed as differing significantly from banal inflammatory glomerulonephritis or from mixed forms that have a tendency to develop in the direction of renal failure. Therefore, one cannot speak of a "renal" diet or "renal diuretics" in general, since the diet and drug treatment in nephrosis are to a certain extent diametrically opposed to those in nephritis. Thus, the physician's responsibility increases: in cases incorrectly diagnosed or mixed, erroneous orientation of treatment can harm the patient. The diet of nephrotics has the purpose of making up for protein losses with the urine and counteracting the decrease in serum protein. Therefore, at present, a diet rich in protein, especially animal protein, containing 2–2.5 g and more of protein per 1 kg of the patient's weight is recommended. Epstein gives 120–240 g of protein per day. It should be remembered that already Widal and Javal (1903) in the treatment of the "chloruremic" syndrome introduced significant amounts of meat into the diet—400 g per day. The low-salt nature of the nephrotics' diet remains an obligatory rule; in edematous periods, it is necessary to introduce no more than 2–3 g of salt per day, for which salt-free bread, etc. should be given (see Dietotherapy). However, the actual anti-edematous agents at the disposal of modern clinics make it possible to significantly shorten the period of strict low-salt diet. The restriction of fats recommended by many authors to reduce the supply of cholesterol is of little practical importance. In any case, the physician must not support the view widespread among patients that for any kidney patient, protein is more harmful in the egg than the yolk; in relation to nephrotics, the question is decided rather the other way around. The amount of fluid introduced in the edematous stage should be restricted. Volhard allows the patient to drink as much urine as was excreted during the previous 24 hours. The regimen for edematous patients is bed rest. Dry-air and water baths are recommended not so much as a diaphoretic method, but to enhance skin function. For the prevention of secondary infections, in addition to general bodily cleanliness, patients should be placed in conditions that exclude influenza, erysipelas, and similar infections (isolation of nephrotics). After the subsidence of edema, movement, walks, and undemanding physical labor are permitted; during these periods, as well as with a still persisting edematous readiness, a stay in a warm, dry climate is advisable (among climatic stations in the USSR one can name Bayram-Ali, Firyuza, other localities of Central Asia; Sukhumi, Tiflis; the latter except for the early spring damp months). Among drugs, purine diuretics are of little effect, often even irritate the kidneys; in the first place in terms of effectiveness in nephrotic edema should be placed organic mercury compounds of the novasurol type, thyroidin, and urea. Novasurol (at a dose of 1–2 g of a 10% solution intravenously, as well as intramuscularly once every 4–7 days) causes a rapidly transient wave of diuresis in the coming 24 hours (en cascade, of French authors), reaching 5 or more liters per day; the excretion of chlorine and sodium in the urine increases, while albuminuria, on the contrary, drops. According to various theories, novasurol acts on the kidneys, tissues, or by stimulating the liver. Such is the action of novasurol analogs (merbaphen, novurit, salyrgan, neptal, 440 B.). All these preparations are not devoid of the toxic action of mercury, yet in pure nephrosis they are well tolerated. The action of novasurol is enhanced by glucose, and especially by ammonium chloride, prescribed 1–5 days before novasurol at a dose of 5 or more grams per day. Ammonium chloride causes acidosis, which promotes diuresis; however, this acidosis, especially in nephrosonephritis, can cause toxic symptoms, Kussmaul breathing with a drop in blood pH to 7.16; therefore, one should fear overdosage of ammonium chloride. Thyroidin acts as a dehydrating agent with prolonged use of large doses (0.4–0.8 and more per day) by improving protein metabolism, is very well tolerated by nephrotic patients, without causing tachycardia, etc. The apparent ineffectiveness of thyroidin often depends on insufficiently high dosage. When managing a case of nephrosis, the procedure is usually as follows: after removing the bulk of the edema with novasurol, for the subsequent months the patient is managed on thyroidin, establishing the actual dose depending on the case and phase of the disease. Urea has also been used by a number of authors with good results in large doses up to 50–100 g and more per day for several weeks. Meat diet acts as a diuretic partly due to the formation of a large amount of urea. Of other diuretics, potassium salts, calcium chloride are recommended; in isolated cases, success has been described from preparations of the liver, parathyroid glands, insulin, plasmochin, decapsulation of the kidneys, blood transfusions. In stubborn cases, mechanical removal of dropsical fluid is indicated.