The etiologic relationship between glomerulonephritis with nephrotic syndrome and the so-called lipoid nephrosis has not been established. The author divided their two forms of nephrotic syndrome into four types. Then, an attempt was made to clarify the mechanism of proteinuria, and study was carried out on the method of treatment, its effect on various types of disease, the mode of action of the hormones, and their side-effects. (1) The types divided into are: 1. nephrosis with glomerulonephritis (la. nephrosis in acute glo merulonephritis and 1b. nephrosis in chronic glomerulonephritis) and 2, chronic nephrosis (2a. mixed type and 2b. pure type). Nephrotic syndrome may occur in the acute stage of glomerulonephritis. Except for severe cases, prognosis of this type is generally favorable. Nephrosis in chronic glomrulonephritis has the worst prognosis of all the four types. The mixed type of chronic nephrosis consists of those cases that have sy, ptoms found in all the types from pure type to nephrosis in chronic glomerulonephritis. (2) Hypermermeability of the walls of glomeruli to protein is thought to be mainly responsible for proteinuria. The contention that decreased protein reabsorption by the renal tubules may also concern in the mechanism of proteinuria is entertained. Protein loading tests carried out in three patients revealed a reabsorptson rate of 8 mg./min, in the patient, but the measurements failed in the remainder of the cases. (3) Three different schedules for administration of prolonged intermittent ACTH and Steroid therapy are described. The therapy had a marked effect on many of the cases belonging to the pure type of chronic nephrosis and nephrosis in acute glomerulonephrosis, but provided no improvement in many of the cases of nephrosis in chronic glomerulonephritis. Steroids achieved a slightly better result than ACTH. The effect of ACTH and Steroides seems to depend on their action to decrease aldo-sterone and improve glomerular function. The patients investigated did not always benefited from relief of both or either of these conditions. Steroids had a side-effects of causing gastrointestinal diso rder; repeated administration of ACTH caused shock to occur in one patient.

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Applying biopsy in clinical studies, the latters were carried out (1) to investigate natural history of glomerulonephritis, (2) to predict the effect of ACTH and Steroids on nephrotic syndrome and to examine the changes in kidney function and biopsy findings before, during and after the course of the therapy, and (3) to clarify diabetic nephropathy based on the study of the triad of proteinuria, hype-rtension and diabetic retinopathy. The following conclusions were reached:(1) Glomerulonephritis. (a) Normalization of kidney function occurred, and kidney function tests often showed raised values in the transitionary period from the acute to the chronic stage. Biopsy revealed a histologic picture of mild changes in many cases, but a picture consisting of a mixture of variable changes ranging from a mild damage to destruction of the tissue was revealed in a few cases. (b) Severity and duration of glomerulitis, and exacerbation and duration of an extrarenal focus are thought to be the factors concerned in the prognosis of glomerulonephritis. (c) Some cases of glomerulonephritis in which preceding infection was unknown showed a histologic picture of chronic nephritis, though early diagnosis of glomerulonephritis was made clinically.(2) Nephrotic Syndrome. (a) Biopsy findings seemed to serve as a more reliable guide to the result of ACTH and steroid therapy than renal clearance values. (b) When ACTH and steroid therapy had been effective, renal clearance values, GFR inn particular, rose. However, biopsy with light microscope revealed no structural changes in the glomeruli that were attributable to the hormones. (3) Diabetic Nephropathy. (a) One or more of the triad were found in the majority of cases of diabetic patients, Frequ-ency of Patients with proteinuria was 28.6 Per cent. (b) Diabetic patients with hypertension or those with hypertension and retinopathy had aa high incidence of proteinuria. However, renal clearance values and biopsy findings of the former differed from those of the latter. (c) Nodular Intercapillary Glomerulosclerosis were found in patients with the triad, while: arteriolo-nephrhsclerosis was the predominant change in patients with proteinuria and hypertension.

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By observing renal function in the diseased kidney and histological changes in the proximal convoluted tubule, the author carried out clinical and experimental studies, with the following results, in an attempt to seek the relation between morphological changes in mitochondria and renall function. 1) Changes in mitochondria in the proximal convoluted tubule in the diseased kidney can be roughly divided into four types. 2) When changes in mitochondria were analysed by the disease, it was found that acute nephritis produces almost normal findings, while chronic nephritis brings about types I-IV. Types I, II and IV took place in nephrotic syndrome; types III and IV in essential hypertension and types I-III in the diabetic kidney. 3) Types I, II and IV were observed in many cases which showed a great excretory amount of protein in the urine. 4) Many cases of the diseased kidney associated with a decreased RPF and hypertension exhibited types III and IV. 5) When type III and IV were studied in their relation to the clinical course, it was shownn that type III was observed when the interval between the onset of the disease and the biopsy of the diseased kidney was long; wherease type IV was produced when the interval was short. 6) Type IV also occurred in the case of advanced proteinuria and the interruption in renal blood circulation. 7) Regarding changes in the proximal convoluted tubule in plasma loaded dogs. Changes of types I and II were visible in many of them. Changes of type IV took place in many of experimental ishemic kindney in dogs. From these findings, morphological changes in mitochondria which belong to types I and II cann be interpreted as being due to the reabsorption of protein by the proximal convoluted tubule, while those which come under type III can be regarded as being due to the chronic interruption in renal blood circulation. Sience changes of type IV occurs in the cases of both marked proteinuria and the interruption of renal circulation, it may be presumed that changes of IV type easily take placer by other complicated factors.

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92 cases of glomerulonephritis which were confirmed both by clinical course and by histological findings of renal tissues obtained by biopsy were studied. From histological findings, they were clas-sified as acute, elapsed acute, subacute, subchronic, chronic, chronic sclerosing and nephrotic glomerulo-nephritis. In acute glomerulonephritis, mild acute form, which had not almost been known, was observed and presence of subclinical form was proved. Acute inflammatory change was still observed in the glomeruli after 4-9 months following acute attack. The histolytic alterative lesion coexisting with exudative and proliferative change of glomerular capillaries indicated the chronic tendency of glomerulonephritis. In elapsed acute glomerulonephritis, subclinical form which mildly progressed from the onset was observed besides repairing stage of acute form, histological findings of kidney of the cases with clinical course of Volhard's "healing nephritis with a defect" were not so constant in focall lesion of glomeruli as he stated but rather showed diffuse slight lesion of them. The author found that subacute glomerulonephritis had to include severe type of subchronic glo-merulonephritis as well as traditional Lohlein's fulminant type, and that preceding to these stages there was a process called acute extramembranous glomerulonephritis.. From above results acute glomerulonephritis may be classified as benign and malignant by its clinical course and moreover classified to intramembranous and extramembranous type respectively. In subchronic glomerulonephritis the author described diffuse, axial and peripheral sclerosing types which developed on the process to the glomerular sclerosis. In the renal functions of chronic glomerulonephritis the differences between individuals were mar-kedly noticed. This fact can be explained from that the preservation of renal function for considerable period of time when glomerular change consists chiefly of axial sclerosis, and capillaries are kept dilated. 2 cases of secondary sclerosing glomerulonephritis without history of renal disease were thought to be essential malignant hypertension at first, but were diagnosed as secondary sclerosing glomerulonephritis by renal biopsy. In nephrotic glomerulonephritis the author showed that nephrotic syndrome could coexist with all types of glomerulonephritis except acute type, and concluded that nephrotic stage of glomerulonephritis was not proper concept. Among the cases which showed symptomes of lipid nephrosis clinically, 2 cases with subclinical and elapsed acute glomerulonephritis were diagnosed by renal biopsy. It is imagined that when these cases are exposed to nephrotic stimmulation, socalled lipid nephrosis and corresponding histologicall change may develop. From above mentioned various cases and types, the author studied the clinical developmental mode of human glomerulonephritis

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For the exploration of the vascular changes of the intrarenal blood vessels from three dimensional viewpoints were available 12 kidneys of, autopsy material which have been assumed as malignant hypertension in clinical and pathological aspects. For this purpose reconstrution methode by means of semiserial sections of the diseased kidney was employed. It is found that there are three fundamental structural types of renal change: 1. Specific arteritic type characterised by the presence of so-called concentric arteritis of the middle and small arteries, 2. Hypertrophic medial type showing prominent hypertrophic muscle in the media accompanied by less predominent muscle hypertrophy, and 3. Atrophic medial type bearing less prominent muscle in its entire length of artery. In addition to these is found a peculiar type which exhibits the type closely resembling the intercapillary glomerulosclerosis. Whitin the first type threr are two subdivided types present; arteriolitic type and arterial one. The former shows intense fibrinoid necrosis and concentric arteriolitis of the arteriole entering the vascular pole of the glomerulus and the latter reveals concentric arteritis of rather larger sized artery. Considering the pathogenesis of these lesions the hypertrophic medial type is thought to be explained with angiospasm of larger sized artery as Volhard and others have postulated. The ischemic change will play a main role at that occasion. It is, however, neccessory to take other factors in consideration for understanding their pathogenesis because of the fact that other types of the hypertension cases can not be covered in the pathogenesis with ischemia due to vasocontraction. The atrophic medial type possesses less amount of muscle which seems to be unable to warrant so severe ischemia in its peripheral field as to cause the specific changes of blood vessel. Also should be paid attension to different portions of vascular tree which responds to the same stimulus with different types of tissue reaction. At the same time collateral channels established in the kidney by changes antecedent to the last ones would be thought to play a role.

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In order that the relationship between systemic circulation and renal one might be clarified, the alteration of renall blood flow by the reflectoric changes in systemic blood pressure was measured with electromagnetic flow meter. Methods: 23 dogs, weighing 8 to 15 kgs, intraperitoneally anesthetized with 35 mg/kg of nembutal sodium were divided into three groups, of which carotid occlusion was preformed in the 1st group, stimulation of the central end of cervical vagal nerve in the 2nd group, and stimluation of the central end of the sciatic nerve in the 3rd group. The one end of the cannula equipped with the electrode of electromagenetic flow meter was inserted into the left renal vein, and the other into the right jugular vein so thet the shunt could be made from renal vein to jugular vein, and the renal vein blood flow was measured by electromagnetic flow meter. The systemic blood pressure was measured with mercury manometer in the right femoral artery.The renal vascular resistance was calculated from the following equation: mean arterial pressure (mmHg)/renal blood flow in cc/min×1332×60dynes⋅sec⋅m^-5 The carotid occlusion was carried out by clamping bilateral common carotid artery for 30 seconds. The electrical stimulation of the nerve was made with square waves, 30-60cycles/sec, and 5-50volts, for 15-20 seconds. Results: 1) In the carotid occlusion, slight increase in both renal vascular resistance and renal blood flow was observed accompanied with the increased systemic blood pressure. The increased renal blood flow might be considered to be caused by insufficient constriction of renal blood vessels. 2) By stimulating the central end of the cervical vagal nerve, pressor, biphasic pressor-depressor, or depressor responese occurred. In the pressor response, renal blood flow did not always show consistent changes. In the depressor response, renal blood flow always decreased. 3) In most cases of the elevation of systemic blood pressure by stimulation of the central end of the sciatic nerve, renal blood flow decreased remarkably, which showed a contraction of the renal vascular bed. Conclusion: It is suggested that renal circulation will not maintain a constant state irrespective of the changes in the systemic circulation, but will be influenced by the reflecroric alteration of the systemic blood pressure. The mode of changes in the renal blood flow can be modified by the nature of the reflex or individual difference of the animal used.

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For the purpose of exploration of the renal vasculature at its benign contraction 17 autopsy cases were avaii.able with procedure of making serial sections focusing the deviation of blood vessel tree in three dimensional spaces. Conclusively the renal contraction is thought to be a reconstruction charac-terised by deviation of the renal vasculature and by forming arteriovenous shunt at the corticome-dullary junction. There are three types of deviation of renal vasculature, especially of interlobular ones including vasa afferentia: 1, obliquely running type, 2 breaking type and 3, archiforme type. These are seen at varying stages of renal contraction and consist, therefore, criteria for classification of contracted kidney. The oblique type can be seen at early stage of contraction and is followed by breaking type vasculature and finally by archiforme one at its advanced stage. The medial muscle coat which is well preserved in the obliquely running type minishes in the distal extent of interlobular artery at its breaking point. This is thought to mainly due to ischemia by narrowing of the lumen. On the contrary the medial coat of the archiforme artery is focally well preserved. This spe-aks for the fact that the vessel still holds capacity of control for blood vessel stream. At its late sta-ge communication of interlobular artery including its branches with venous system, especilally with Venae corticales profundae is finally established. This fact substanciates that the renal contraction should be assumed as reconstruction of the kidney like liver cirrhosis.

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1. Annria developed in patients whose the left kidney has been removed for nephrolithiasis 25 years ago. On examination biliary calculi were found. 2. After fourty days rabbits were subjected to removal of one kidney and to operation, a 6 per cent lycopodium suspension prepared with physiological saline was injected directly into the liver in order to cause liver impairment. Oliguria or anuria was also observed. 3. After the removal of one kidney, the compensatory hypertrophy of the remaining kidney usually takes place. However, such a hypertrophy did not take place in the kidney of rabbits whichh were affected with oliguria or anuria. This might be due to the fact that experimental hepatic impairment prevents the remaining kidney from performing its compensatory function. 4. Various qualitative tests were repeatedly carried out in the urine of rabbits in which the experiments were performed. Study of the urine for protein and indican alone revealed positive. Generally speaking, there were no such findings as were interpreted as abnormal. 5. Rabbits in which anuria or oliguria developed showed an increase in the non-protein nitrogen value. An increase in the urinary nitrogen value took place in moiety of the rabbits. An increase in the non-protein nitrogen value is due to liver insufficiency, whereas an increase in the urinary nitrogen value is due to renal insufficiency. 6. The testing of liver function by the schema of Bruger and Oppenheim showed that alkaline ph.osphatase activity markedly diminished. Even if the liver is impaired, its conservative function is so high that tests do not easily produce abnormal results. 7. As an indicator of liver insufficiency, Ratliff paid an attention to be important to an increase in amount of amino-acid nitrogen and a decrease in the blood sugar level following hepatorenal syndrome. However, a decrease in the blood sugar level did not occur at all in our experiments. 8. As for electrolytes in the blood, there was an increase in amount of kalium and a decrease in amount of natrium. These findings were similar to those which were encountered in the case of acute renal insufficiency. 9. Pathohistological examination of the kidney affected with anuria or oliguria disclosed the swelling and hyaline droplet degeneration of the renal tubular epithelium. Well-defined patches of coagulation necrosis were noted at the site of injection in the liver. On Glisson's capsule an infiltration of a small number of round cells was accompanied by the muitiplication of minute biliary ducts. 10. The 24-hour urinary excretion of 6-hydroxyindole acetic acid lays in a normal range.

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The author has produced alloxan diabetes in hypertensive rats experimentally established by the method of Abrams and Sobin. Comparing these rats with the simple alloxan-diabetic and the solely hypertensive animals, histopathological investigations were carried out mainly on kidney, and the obtained results were considered in connexion witn some of the clinical manifestations of the animals, to give the following conclusion. 1. Alloxan-diabetic rats developed diabetic glomerulosclerosis of the kidney, showing nodules similar to that found in the Kimmelstiel-Wilson syndrome in human, and the hyperplasia of mesangium which might be the precursory stage of the nodule. 2. Lipohyaline globules were found in the glomeruli of the kidney, in alloxan-diabetic rats as well as in rats developing simple hypertension. 3. In alloxan-diabetic rats, glomerulosclerosis was found more frequently in the animals treated to develop hypertension beforehand, than in those left without prior manipulation. 4. There was a tendency to maintain higher blood pressure in rats with glomerulosclerosis than those without it. 5. Glomerulosclerosis was more frequently encountered in animals showing relatively low levels of blood and urine sugar, and longer survival.

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Paper electrophoresis and quantitative clearance test of the kidney have been applied to the serum and the urinary protein on healthy individuals in Comparison with various cases of proteinuria. The effect of diuresis upon the group of nephrotic syndome is also evaluated in view of protein filtration by the same means. In these studies conclusions are made as the followings. 1. The urine of healthy individual contains small amount of protein. By concentrating the urine 5, 000 to 6, 000 x, fractional study of the protein reveals identical constitution of albumin, α₁-, α₂- β-and γ-globulin as the serum protein. However, quantitatively, globulin is usually more than albumin, and the average A/G ratio is 0.55 in total of five individuals. This indicates that before the se-rum protein pass through as the urinary protein, the major portion of serum protein is to be reabso-rbed by renal tubules. Reabsorption of albumin is much more than that of globulin. 2. Fractional study of the Urinary protein in cases of proteinuria also reveals identical fractional pattern to that of the serum, although total amount of the urinary protein is much less than that of the serum. This indicates the urinary protein in these cases is also derived from the serum protein. 3. There are many differences in fractional patterns of urinary protein among proteinuria of various causes. However, generally globulin is depressed and mainly incresed in albumin; A/G ratio being over in most of the cases. The ratio is highest in nephrotic syndrome and lesser in acute glomerulonephritis, chronic glomerulonephritis, essential hypertension and in recovering period of acute glomerulonephritis accordingly. 5. Fractional renal protein clearance test shows also highest clearance of each fraction in cases of nephriotc syndrome. Less clearance is noted in acute nephritis, and the least is in essential hype-rtension. In instances, the ratio of each fraction of globulin against albumin is highest in α₁-glo-bulin and lowest in α₂-globulin as the following, coresponding to the order of molecular weight of each globulin.
Alb.≥α₁>β≥γ>α₂-globulin
5. The above findings indicates that protein of smaller molecular weight is higher in clearance than that of larger ones. It is, therefore, assumed increase in permiability of the glomerular filter plays an important role in development of proteinuria. 6. In nephrotic syndrome, administration of steroid hormons and/or chlorothiazide increases uri-nary output remarkably as well as improves clinical pictures. Inspite of this increased urinary out-put, marked depression of proteinuria is found by administration of the former, resulting in prominentt increase in serum albumin and/or A/G ratio. In addition, administration of steroids hormoris demons-trates evident separation of α₂ and β-globulin in fractional pattern of electrophoresis.

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