The present series of work were undertaken in order to clarify some of the clinical problems, such as modes of administration, refractriness and side effects. Among the various diuretics, acetazoleamide, mercurials and chlorothiazide were chosen, since these are used most widely and have most interesting problems about their actions. I studied the mechanism of the action, the electrolyte dirturbances caused by them and the factors influencing the action. Studies on the mechanism of the action were made mainly by the stop-flow method, which were proved as a reliable and excellent method to study the localisation of the reabsorption and secretion in the nepheon. The action of mercurials on the potassium excretion was examined by other methods, because the stop-flow method is not proper to examine the potasium transport. As a factor influencing the action of diuretics, I layed emphasis on the intracellular potassium and hydrogen ion metabolism, which is the most direct circumstance where diuretics preform their actions.(1) Acetazoleamide depresses the reabsorption of bicarbonate in both proximal and distal tubules, but depresses the reabsorption of sodium only in the proximal tubule. Mercurials depress the reabsorption of sodium in the proximal tubule. The secretion of potassium is depressed by mercurials, and the reabsorption of potassium is also considered to be depressed by the mercurials. such an action on the potassium excretion is specific to mercurials, but are influenced by the adrenal cortical hormones. Chlorothiazide enhances the excretion of sodium, potassium, chloride and bicacbonate. The mechanism to increase the potassium excretion, however, is different from that of acetazoleamide, and the mechnism to increase the chloride excretian is different from that of mercurials. The data suggest that chlorothiszide depresses the reabsorption of sodium and chloride not only in the proximal tubule, but in the distal tubule. (2) Acetazoleamide may cause hypokalemic acidosis, mercurials hypochl.oremic alkalosis, and Chlorothiazide hypokalemic alkalosis. (3) Acidifing salts depress the action of acetazoleamide, and increase the action of mercurials. Alkalinizing salts depress the action of mercurials and increase the action of acetazolea-mide. Chlorothiazide are scarecely influenced by either salts. (4) The intracellular potassium concentration are influe need by the change of acid-base balance, and reveresely the ineracellular acid-base balance is influenced by the change of potassium metabolism. These intracelluar electrolyte metabolism must be considered as an important factor which influences the acitons of acetamoleamide and mercurials. (5) DOCA and Pitressin have no influence on the mercurial diuresis. DOCA, horever, can influence the mode of electrolyte excretion during the mercurial diuresis.
Taking up acute nephritis and the nephrotic syndrome as the edema of renal origin, the abnormalities of the electrolyte, metabolism in these were researched. Because of having being unsettled the results about them as yet, the electrolyte metabolism in these were observed on the clinical data & then on the experimental data. As the cause for edema in acute nephritis, the capillary permeability by the antigen antibody reaction has much weight, the other hand, in the nephrotic syndrome, the hypoosmolality by hypoproteinemia. For these reasons, the electroly-te metabolism in anaphylaxy & plasmapheresis were observed. 1) The clinical data about acute nephritis was as follows. The decrease in total serumprotein & albumin fraction were comparatively slight. When the renal in-sufficiency was severe, the plasma k concentration was increased during the oliguric phase and then became low at the wend of the polyuric phase. But if the reneal isuff'iciency was relatively slight, it was in-creased after the onset of diuresis. The plasma Na & C1 concentration were high during the oliguric phase, became low at the end of the polyuric phase & then recover, d the normal value. The plama Ca concentration were low during the oliguric phase & then became normal after the onset of diuresis. The urinary excretion of Na & C1 had the peak of that during the polyuric phase and the peak of K excretion was always several days later. The peak of 17 ketosteroid excretion coincided mostly with that of K, which speaks the adreno-cortical hormone take part in these changes. 2) The early change of dogs in anaphylactic shock was mainly due to the liver congestion. When the severity of shock was slight, dogs relatively lived long & the capillary permiability was prominent. This time, the Hematocrit value was high, the total serum protein was decreased, the plasma Na & Cl concentration were elevated and the plasma K concentration was decreased. 3) Acute nephritis was induced in dogs by the antikidney serum. The change of electrolyte metabolism was similar to that in men. The early change of it was almost equal to the change in anaphylactic dogs which relatively lived long. 4) The clinical data about the nephrotic syndrome was as follows. The plasma Na concentration was decreased, which seems to be inversely interdepenent to the total serum cholesterol. Hypoproteinemia was attended mostly by the higher plasma C1 concenration. When the renal damage was severe, the plasma K concentration was elevated. During diuresis following the steroid therapy, the plasma K & C1 concntration became low, but Na concentration high. Comparing the ACTH the rapy with the Prednisolone therapy, the former had the inclination of keeping water & Na in the body before diuresis. 5) Hypoproteinemia was induced in dogs by plasmapheresis. The total serum protein & the albumin fraction were depressed much, neverthless, the total serum cholesterol wsa not so increased. They had no edema & no oliguric phase in spite of hypoproteinemia. The plasma Na concentration was slightly increased, but C1 & K concentration moderately decreased. 6) The experimental nephrotic syndrome was induced in rats by aminonucleoside. Hyperlipemia was observed, but the plasma electrolyte concentration had little change. The electrolyte contents of edematous tissues were as follows. The liver has little change. The Na & Cl content were increased in the muscle as well as in the kidney, but K content decreased in the former as it was increased in the latter. Considered as the carcass, total body Na & C1 appeared to be increased with water, but this tendency keep back by the NaCI defecit diet. The Ascitic fluid had the lower concentration than the plasma in Na, K & Cl concentration, bnt as to the Cl concentration, often became higher.
The purpose of this study was clinical observations on the protein metabolism in nephritis, especially on correlation between proteinuria, serum protein fractions and severity of renal lesions. The histological findings of kidney was made by needle biopsy specimens. The following results were obtained; 1) Urinary protein excretion showed no difference in each group of nephritis except in nephritis with nephrotic syndrome. 2) Serum protein ranged as follows; total protein decrease slightly in acute nephritis, markedly in nephritis with nephrotic syndrome and normally in the other groups. Accordingly to longstanding of nephritis, serum protein fractions showed marked abnormality, that is, hypoalbuminemia, hyper-alpha-globulinemia and hyper-beta-globulinemia and in addition hypo-gamma?globulinemia in nephritis with nephrotic syndrome. 3) Total cholesterol level increased slightly in chronic nephritis, markedly in nephritis with nephrotic syndrome and almost normally in the other groups. Esterization of cholesterol ranged normally in each group, but chronic nephritis with slight increase in the esterization. 4) There was no correlation between proteinuria and serum protein fractions but total cholesterol level increased in the patients with much proteinuria. 5) It appeared difficult to explain the severity of renal lesions from the range of proteinuria or the abnormality of serum protein fractions.
RPF, GFR together with TmG were measured 24 times, and TmPAH was measured 21 times in altogether 47 cases of diabetes.Glucose titration curves were determined in 2 cases of mild diabetes.Besides, renal function was observed in 3 cases of renal diabetes.1) There were many servere cases in the group whose GFR was normal or in the upper limits of normal. As Tm G and TmPAI were either normal or in the lower limits of normal in this group, GFR/TmG became increased and GFR/Tm PAx were in the upper limits of normal.2) There were more cases with milder symptoms in the group whose GFR was in the lower limits of normal. Tm value were within normal limits. GFR/Tm G, GFR/Tm PAR were also normal.3) In the diabetic cases with slightly decreased GFR, GFR/Tm G and GFR/Tm PAR were normal.4) There were relatively larger number of cases of diabetes with long histories among those whose GFR was more than moderately decreased. Although the values of their fasting blood sugar were variant, the amount of urinary sugar output was less than 20 grams per day, GFR/ Tm G and GFR/TmPAH were only slightly decreased.5) All of those who had old age, hypertension, albuminuria, changes in fundus of the eye espe-cially with changes of K. W. III and upward, the complication of myocardial damage and long histories of diabetes showed decreased renal function. In many of the above cases, the urine sugar was less than 20 grams per day. GFR/Tmn and GFR/TmPAH were within normal limits.6) In three cases of renal diabetes, RPF and GFR were normal, whereas Tm G values were all markedly decreased.7) Glucose titration curves were determined in 2 cases of mild diabetes indicating the results that tmg was equal to 0.6……1.7 times Tm G and was within normal limits.
Changes in blood pressure, blood non-protein nitrogen, albuminuria, urinary concentration, PSP excretion, urea clearance, glomerular filtration rate, renal blood flow and filtration fraction were followed with advancing age in normal subjects, patients with chronic nephritis and patients with essential hyperrension.Gradual decrease of renal function was generally observed. Except the concentrating ability which showed more marked decrease with age than normal in both nephritis and essential hypertension, the decrease of renal function with advancing age was more pronounced inpatients with chronic nephritis than in normal subjects or patients with essential hypertension.