Of human kidney with clinically nomal findings and with glomerulonephritic changes, the fine structure of tubular epithelial cells were examined through electronmicroscopy using ultrathin sections of biopsy specimens. In the normal kidney, proximal convoluted tubule, thin and thick segment of Henle's loop, convoluted tubule and collecting tubule were characterized morphologically. The brush border extensions of the proximal tubular epithelium do not seem to absorbe some particular substances from the tubular lumen, but to facilitate the process of absorption by providing the increased membrane area to which these substances can be absorbed. The small vesicular structures in the apical region of the cells indicate the cross sections of the tubular invaginations which are connected with the spaces between brush border extensions, and further with the tubular lumen. These structures are concerned directly with intake of some material (i. e. such as protein) in the tubular epithelial cells, suggesting the menbrane flow mechanism (as reported by Bennet) for pinocytosis of these tubular epithelial cells. Vacuole-, granule- and cytosome-like structures are differentiated in the proximal tubular cells. These cytoplasmic structures are all regarded as the developed forms of the tubular invaginations which directly help intracytoplasmic transport or metabolism of the pinocytosed materials. Basal intussusception (Peace) or basal infolding (Rhodin) is located in the basal region of the tubular epithelial cells, and is characteristically developed in the proximal tubular cells. Although many investigators regarded this structure to be composed of interdigitation of basal cytoplasmic lamellae of adjoining cells, the author is of opinion that some are intracytoplasmic menbrane structures of own cell. The author classified the tubular epithelial cells of proximal convolution into 8 kinds in 4 types, according to their morphological characteristics. 1) Type A : Cells which keep tightly packed brush border extensions in order, fully developd basal infoldings, abundant mitochondria, endoplasmic reticulum and cytoplasmic granules. They are observed chiefly in normal and elapsed cases of acute glomerulonephritis and in mild cases of subchronic glomerulonephritis, and are regarded as the highly energy-reserved form. 2) Type B-I : Cell, which have swollen cytoplasm; the cytoplasmic structures such as vesicles, mitochondria and endoplasmic reticula are decreased in number, brush border extensions often disappeared in these apical regions. However, destruction of the cell membrane is never seen. 3) Type B-II : Cells, which have increased cytosomes or vacuolar structures, abundant but irregularly disposed intracytoplasmic structures such as mitochondria, basal infoldings and other forms. 4) Type B-III : Cells, which have characteristically enlarged basilar extracytoplasmic spaces inside the basement membrane. Increase of intracytoplasmic vacuolar structures depresses the residual cytoplasm. Each cell of B-type is considered to be engaged vigorously in such activities as intracytoplasmic metabolism or transport across the cell. Cells of type B-I and B-II are observed numerously in elapsed cases of acute glomerulonephritis, and in mild cases of subchronic glomerulonephritis, but rarely in the cases of chronic glomerulo-nephritis. Cells of type B-III are noticed frequently in elapsed cases of acct e glomerulonephritis. Type C-I : Cells with partially destroyed membrane. Some of cytoplasmic elements such as mitochondria, cytoplasmic granules, vesicles and endoplasmic reticula, as well as a part of brush border extensions are discharged into the tubular lumen. Type C-II : Cells more severely destroyed than those of type C-I. Occasionally, the great part of cytoplasm with its cytoplasmic elements is carried away into the lumen, whereas the basement membrane is exposed directly to the lumen. These destroyed cells are always accompanied

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With the performance of percutaneous renal biopsy, the open renal biopsy is recently being carried out by us amounting totally to 27 cases up to date, 2cases of which were done bilaterally and 5 cases wore the case of being already oneside nephrectomised. Our open method is able to be performed under the direct observation on the kidney. Knives are available if necessary for getting the ample materials. Probably because the depth-accomodation of the puncture is easily feasible and styptic defence from the bleeding is comlete, the macroscopic hematuria is less found after the biopsy than percutaneous one and the microscopic hematuria disappears within 48 hours on the case of being unilaterally nephrectomised. Recently Morales et al. reported the method of the open renal biopsy like ours. Discussion of its safety, profiis and outline of the method will be introduced.

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Correlation of structure and function of the kidney which had been resected of 25%, 50% and 75% of renal tissue were studied and folloowing results were obtained. 1) In case of half resection of one side (25% reduction of nephron population), no marked changes were obtained both morphologically and functionally in the remaining nephron. 2) In case of exstirpation of one side (50% reduction of nephron population), both morpho-logically and functionally compensated changes appeared. 3) In case of half resection of one side and then exstirpation of the other (75% reduction of nephron population), these tendencies shown as follow became clearly. i) Functionally, 3 monthes after second operation, GFR of each nephron was increased 3 times to the control and the ability of glucose reabsorption increased also in the normal glomerular tubular balance. Though CH2O in diluting and T^c_mH₂O in concentrating increased significantly and the balance was well maintained in the normal range, urin from the hypertrophied nephron became isosmotically as a result of marked increased Cosm. ii) Morphologically, glomeruli hypertrophied in diameter 1.3 times to the control, proxymal convolutes 1.5 times with dilatated lumen and taller tubular epithelium then normal. Despite the enlarged distal convolutes in diametr, tubular epithelium was in the contraly flattened as a result of marked dilatation of the lumen. These findings of hypertrophied nephron following the decreased number of nephron population by the operation, functionally were similar to that of the human chronic renal disease. It is suggested that the function of the chronic renal disease is affected by mainly decreased numbers of hypertrophied nephrons.

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Oxygen consumption of the kidney has been found to be much higher than that of the liver. The present study was performed to clarify its biological significance related to its function, through the metabolic pattern of the nucleotides of the kidney, comparing with that of the liver. Male rats weighing 100-150 g, after administered iP³² (100μc/100 g) intraperitoneally, were decapitated and kidney and liver tissues were removed and immediately frozen. Oxygen consumption of both organs was determined by the Warburg's method. Acid soluble nucleotides were extracted with PCA from the frozen tissues and chromatographed through ion exchange resin column with formic system, then rechromatographed with formate system. Charcoal column chromatography or isobutanol extraction was applied for further purification of fraction of sugar phosphate or iP, respectively. Results obtained were as follows: 1) Kidney showed a much higher value in tissue respiration than that of liver. 2) Amount of total acid soluble nucleotides of the kidney was less than that of the liver. 3) Ratio of adenosine nucleotides to total nucleotides was 61.3% in the kidney and 60.5% in the liver, if respiratory cofactors (DPN, TPN, Ad-X) were excluded. That of uridine nucleotides was. w 30.7% in the former, while 35.5% in the latter, and that of guanosine nucleot ides 6.5% in the former, while 3.6% in the latter. 4) Kidney had more DPN than liver in its amount. 5) ATP/ADP ratio and ADP/AMP ratio were markedly lower in the kidney. On the contrary, UTP/total uridine nucleotides ratio was higher in kidney, and GTP/GDP ratio was almost the same between both organs. 6) The value of RSA(ATP) calculated by the incorporation of iP³² was much lower in the kidney (0.62/16 min., 1.04/25 min.) than in the liver (1.56/10 min., 1.78/15 mm.). 7) No retardation was found in the turnover between ADP and ATP even in the kidney accordingto SA(ADP)/SA(ATP). The ratio reached a higher value at 25 min, than that of the theoreticall equilibrium (2/3), while such a tendency could not be seen in the liver. 8) SA (nucleoside triphosphate)/SA(ATP) and SA(nucleoside diphosphate)/SA(ADP) ratio was close to 1 with uridine nucleotides and guanosine nucleotides in the kidney as well as in the liver. 9) The amount of hexose monophosphate was almost the same in both organs. In the kidney, the phosphte of hexose monophosphate and terminal phosphate of ATP were observed to be isotopically equilibrated in 25 min. When compared with the liver, the kidney could be characterized by its higher activity in tissue respiration associated with a low ATP/ADP ratio, as well as by markedly slow iP-ATP exchange (RSA(ATP)), representing an activity of oxidative phosphorylation in vivo. From these results and above-mentioned nucleotides pattern it seems possible that the kidney utilizess directly much more 'high energy intermediate of oxidative phosphorylation' other than ATP, probably as the source of energy in osmotic and transport work. In addition, a high activity of myokinase, and ATPase can be expected from above mentioned nucleotides pattern, and relatively slow ADP-ATP exchange observed will support such an assumption.

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I. Clearance analysis of sulfonamides tranport mechanism in the kidney. (i) Three sulfonamides with Fdifferent values of clearance .(sulfadimethoxine, sulfathiazole, sulfamethizole) and thiosulfate were administeredd orally and intravenously to healthy adults and patients with renal diseases respectively. The sulfonamides/thiosulfate clearance ratios were usually smaller than 1.0. As the value of thiosulfate clearance decreased to smaller than about 50, the ratios tended to increase, and especially the clearane ratio of sulfamethizole was larger than 1.0 in a few uses. The clearance values of acetylated sulfonamides were higher than those of free forms. It was indicated that both free and acetylated form of the sulfonamides were secreted and reabsorbed in the renal tubules. (ii) The sulfonamides (sulfadimethoxine, sulfathiazole) and inulin were administered intravenously to normal dogs. In this experiment, the sulfonamides/inulin clearance ratios were found to increase, when either tubular load of the sulfonamides or urinary pH was elevated, and especially the ratio of sulfathizole approached near 1.0. It was concluded that the sulfonarides were secreted and reabsorbed in the renal tubules in dogs too, considering that those drugs are partially bound to serum protein. II. Stopflow analysis of sulfonamides transport mechanism in the kidney. In an attempt to clarify the transport mechanism of sulfonamides (sulfadimethoxine, sulfathiazole), stopflow analysis was employed in normal dogs. From this study, it was found that both free and acetylated form of the sulfonamides were secreted in the proximal part and reabsorbed in the distal part, and that the secretory site of the sulfonamides was very near the secretory sites of PSP or PAH, and that the reabsorptive site of the sulfonamides was near the reabsorbed site of Na and the secretory site of K. The (U_S/S_S)/(U_IN/S_IN) ratio in the secretory case and the (U_S/S_S) ratio in the reabsorptive case have led us to assume that the active transport mechanism takes part in both secretory and reabsorptive cases of the sulfonamides. Further studies were made to confirm this assumption on the effects of acetate. NaHCO₃, and 2-4 DNP on the sulfonamides transport in the kidney.

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Amphenone 13, SU-4885, SU-8874, SC-8109, SC-9420 are known as having antagonistic activity to the aldosterone which plays important role to the Na balance in vivo. Real action mechanism of such agents still remains unknown. The purpose of this study is to reveal the effects of anti-aldosterone agents to the urinary electrelites excretions and various corticosteroids secretion by the lord of such substances to the dog.ResultsI. Change of urinary electrolite excretiona) By the Amph. B administration, urine volume and excretions of Na and Cl appeared to increase although no changes occured in the. K excretion and renal hemodynamics.b) By the SU-4885 administration, excretions of Na and Cl appeard to increase and urine volime increased slightly. No changes were observed in the K excretion and renal hemodynamics. In the cases administrated both SU-4885 and dexamethasone, urine volume and excretions of Na and Cl increased significantly. K excretion and renal hemodynamics remained in the no changes.c) By the SC-9420 administration which is under the dose of 20 mg, excretions of Na and K appeared to increase and urine volume remained in the no change. By the administration of over the dose of 40 mg, renal hemodynamics, urine volume and all of the electrolite excretions ecreased significantly. In the case administrated both SC-9420 and D. O. C., urine volume and excretions of Na and K increased significantly and K excretion decreased slightly.II. Changes of various cort costeroids secretiona) By the Amph. B administration, repressions of aldosterone, comp. B, comp. E, comp. F and 17OHCS secretion were observed. Addition of Amph. B to the A. C. T. H. administrated dog did not indicate any changes of the corticosteroids secretions.b) By the SU-4885 administration, significant decreases of aldosterone, comp. B, comp. E and comp. F were observed. And D. O. C., comp. S and comp. X appeared at this time. 17 OHCS remained in the no change. In the case administrated both SU-4885 and A. C. T. H. -Z, more significant decreases of comp. B, E and and more significant increases of comp. S and D. O. C. were observed. However, comp. X remained in the slight increased.c) By the SC-9420 administration, no significant changes of various corticosteroids secretions were occe red.

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This study was undertaken to investigate the relationship of the splanchnic nerve and the renal function, and its influence of the excretion of soidum, PAH and creatinine was observed by means of the renal clearance, TmPAH and the stop-flow analysis on the mongrel dogs. From 2 to 4 weeks prior to the experiment, unilateral splanchnic nerve resection (left side), denervation of renal nerve plexus and decapsulization were performed. All manipulations were carried out under sodium pentobarbital (Nembutal) anesthesia which was given intravenously in the dosage of 27mg per kg weight. Restlt: (1) the urinary volume and the concentration of sodium and potassium increased in the denervated side, but the concentration of creatinine decreased slightly in the denervated side and the concntration of PAH showed no significant difference in the denervated side in comparison with control side. (2) The GER increased slightly in the deneavated side, but the RPF showed no difference. (3) By the stop-flow analysis, the region of proxml tubule in the denervated side showed increased concentration of sodium and potassium and decreased concentration of creatinine. At the region of distal tubule, the concentrtion of creatinine indicated no difference Between denervated and control side, but this experiment revealed no conclusion concerning the excreation of sodium and potassium. (4) The analysis of the free flow of urine and the stop-flow analysis when administrated mercurial diuretics added to the denervated dogs, revealed the following results, the control side denervated side ratio of sodium, potassium and creatinine concentration was decreased and PAH concentration showed no differnce between denervated side and cotrol side. (5) The denervated side indicated slightly elevated TmPAH in comparison with the control side. However, GFR/TmPAH showed no difference. conclusion : As mentioned above, the increased urinary volume and the concentration of sodium and potassium on the denervated side could not be merely explained by the increase of GFR. The splanchnic nerve had a direct influence on the function of the tubules.

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