Vital staining of the kidney was performed to classify the cells of glomeruli and to study the mechanism of the staining of the epithelial cells of proximal convolutions. Two hundred and forty seven rats and 45 rabbits were injected intravenously or intraperitoneally with acid dyes (trypan blue, Evans blue, lithium carmine, Congo red, methyl blue, and acid fuchsin), suspensoid substances (colloid silver, carbon black, and saccharated iron oxide), basic dyes (neutral red and Janus green), phenolsulfophthalein, and heterologous proteins (egg white and human hemoglobin). The kidneys were studied histologically, cytologically, histochemically and electron microscopically. In the rabbits injected with trypan blue, Evans blue, lithium carmine, and PSP, the disappearance from plasma and the excretion into urine of the dyes were examined. The results obtained are summarized as follows. (1) In the order of Evans blue, trypan blue, lithium carmine, , and PSP, the urinary excretion of the dyes was decreased and the retention in the blood increased. (2) Glomerulus: In vital stainings, especially when stained with suspensoid substances, four kinds of cells were differentiated in glomerular tufts : (i) glomerular epithelial cells negative to vital stain, (ii) common capillary endothelial cells, nearly or perfectly negative, (iii) mesangial cells, weakly positive, (iv) phagocytic endothelial cells, markedly positive.Similar phagocytic endothelial cells were also found in the peritubular capillaries of the renal cortex. These phagocytic cells are assumed to have the function to clear the foreign substances im-permeable through the glomeruli. (3) Renal epithelial cells of proximal convolution: (i) In the epithelial cells of the rats injected with saccharated iron oxide, egg white, and human hemoglobin, the vacuoles first appeared just under the brushborder of the cells. They then shifted deeper into the cell body, fusing together and condensing their contents, and finally fused with lysoso-mes or transformed into the lysosome-like bodies, where the phagocytized substances were digested. The substances not digested were eliminated into the luminal cavity of the tubules. The authors con-sidered this series of phenomena as a light microscopic expression of reabsorption. (ii) When rats were injected with PSP, the dye granules appeared throughout the epithelial cells of proximal convolution immediately after the injection and soon disappeared. They were minute in size and showed no relation to lysosomes. The authors interpreted these features as a light microscopic manifestation of renal epithelial secretion. (iii) When rats were injected with trypan blue and Evans blue, the dye stuffs appeared in renal epithelial cells in 6 hours and showed a series of reabsorption. In the case of lithium carmine, it ap-peared primarily in lysosome in 1 hour and thereafter followed the same course as seen in the case of trypan blue and Evans blue. Congo red and methyl blue did appear neither in the urine nor in the renal epithelial cells, Acid fuchsin and neutral red were excreted in the urine in large amount, without staining the renal epithelial cells. (iv) The results of this study and of the previous works on the binding of the dyes and plasma protein indicate that there is a close relation between the binding power of the dyes and their ability to stain vitally the renal epithelial cells. (v) From these observations and the findings of other investigators using electron microscopy, micropuncture and renal perfusion techniques, it may be concluded that the renal epithelial cells reab-sord (probably by pinocvtotic process) trypan blue and Evans blue as a complex with plasma albumin, Is in the case of the cells of reticulo-endothelial system. In other words these dye stuffs seem to serve ;o visualize the movement of the plasma albumin in the nephron. (vi) The mechanism of the vital staining with lithium carmine is necessary further to be

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In an attempt to identify the effects of orthostasis on the renal function, alteration in (1) renal clearances, (2) the rates of urinary excretion of protein as well as (3) red blood cells were measured serially on a ) 10 normal children, b ) 56 children with acute glomerulonephritis (AGN), c ) 35 chil-dren with idiopathic nephrotic syndrome (NS) and d) 26 children with postural proteinuria (PP). 1) The glomerular filtration rate (GFR) of children with renal diseases in orthostasis compared to the rate obtained in supine position was: (all values of the clearance studies in orthostasis hereafter are expressed as the percentage of the values in supine position) (1) normal controls: 93.9±3.7%*, (2) cases with postural poteinuria:a) lordotic type: 85.9±3.7%, b ) orthostatic-lordotic type: 98.2 +4.6%, (3) acute stage of AGN: 77.7±4.10, (4) acute stage of NS: 78.5±4.5% and (5) so-called chronic type of NS: 78.1+5.5%, The decreased GFR noted in (3), (4) and (5) returned to normal with the clinical improvement. (6) convalescent stage of AGN: 93.8±3.30, (7) AGN, clinically healed: 94.7+3.0%, and (8) NS in remission: 90.4±0.9%. 2) The renal plasma flow (RPF) of normal individuals in orthostasis was 83.1±5.4% of that in supine position. The decrease in RPF is significantly greater than that in GFR. Also in patients with renal diseases the decrease in RPF is significantly greater than in normal controls. RPF in orthostasis: (1) acute stage of AGN: 64.1+2.8%, (2) AGN in convalescence: 65.6±3.5%, (3) AGN, clinically healed: 80.6+3.6%, (4) NS in acute stage 66.1+6.40, (5) NS in remission: 77.7±5.3%, and (6) so-called chronic type of NS: 63.8+7.2%. 3) Greater increase in filtration fraction (FF) (as calculated from the data given above) was noted in patients with renal diseases than in normal controls when orthostatic position was assumed. 4) However, in severe cases of AGN in which the GFR in supine position was less than 50 ml. / min., orthostasis exerted little effects on the renal function as seen in GFR: 95.0±3. 2% and RPF 84.7±7.9%. 5) The urine flow in normal control decreased during orthostasis. Especially in the acute active stage of the renal diseases, it was decreased both in supine and orthostatic positions and started to increase as the clinical condition improved. 6) The alteration of GFR in orthostatic position is believed to give an answer to the question of when to ambulate the nephritic as well as nephrotic patients. 7) The urinary protein concentration increased during orthostasis. However, due to decrease in urine flow, the net protein excretion rate (urinary protein concentration in mg, f ml.×urine flow in ml. /min.×1/100) did not show a significant alteration, often resulting in slight decrease. 8) The total protein clearance (Cpr) in many cases showed a small decrease, while the minimum concentration of protein in the glomerular fluid (as expressed by UprV/GFR where Upr is the urinary protein concentration in mg. /ml. and V is the urine flow in ml. /min.) and the total protein clearance/ sodium thiosulfate clearance ratio (Cpr/GFR) remained unchanged in a great majority of the cases with proteinuria. In postural proteinuria, the two indices increased and the increase was greater in ?cases with orthostatic-lordotic type of PP, 9) The number of red blood cells (rbc) excreted in urine by normal individuals was less than 6 per mm3 in a random voided specimen and the urinary rbc excretion rate was less than 4.5 rbc f min, without a significant alteration during orthostasis. Half of normal children showed no rbc in urine both in orthostatic and supine positions. Essentially similar observations were made in postural prote-inuria. 10) In renal diseases the number of rbc in urine did not necessarily increase during orthostasis and the urinary rbc excretion rate remained unchanged or decreased slightly. 11) To discuss the urina

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The pathogenesis of hyperlipemia observed in the nephrotic syndrome has been the subjects of many papers. It has been indicated that one factor contributing to this abnormality is a decreased rate of removal of serum lipid from the circulating blood. Moreover, the suggestion has been made that the release fat of from adipose tissue increases in the nephrotic syndrome. In the present study, attention was directed to the ability to remove circulating lipid by peripheral tissues and to the mobilization of fat from adipose tissue in the nephrotic syndrome of human beings (lipoid nephrosis and glomerulo nephritis) and of experimental nephrotic rats produced by subcutaneous injection of aminonucleoside (AN-rats). The results were as follows. 1. ¹³¹I-Triolein preparation was orally administered to analyze for whole blood ¹³¹I and lipid-bound ¹³¹I radioactivities. In the nephrotic patients, the maximum level of lipid-bound 1311 activity was higher than that of normal controls and the activity disappeared from the circulating blood of nephrotic patients at a slower rate, comparing with other groups. The ratio of lipid-bound ¹³¹I radioactivity to whole blood 1311 concentration was considerably higher in nephrotic patients than in normal controls and patients with chronic glomerulonephritis and minimum value was obtained in a group of patients withh cirrhosis of the liver. These results obtained in nephrotic patients may be presumptive evidence of, , a) increased synthesis of lipid in the liver, b) increased intry of synthesized lipid into the circulation, , . c) impaired ability to remove circulating lipid at the periphery, or d) a combination of these factors 2. The maximum level of heparin-induced plasma lipoprotein lipase (LPL) activity was lower is nephrotic patients than in normal controls. An inhibitor to LPL was observed in all plasma of nephrotic patients. Transitional changes with time of plasma LPL activity following the injection of heparin in patints with chronic glomerulonephritis were extremely characteristic. The maximum activity of plasma LPL was significantly correlated with such clinical parameters as serum total protein, albumin and cholesterol levels for diseased groups, but no correlation was found for nephrotic patients. The role of albumin and heparin in the pathogenesis of nephrotic hyperlipemia was discussed. 3. In vitro, the liberation of LPL from the epididymal fat pads and kidneys by heparin was redu-ced in AN-rats, although the release of LPL from the cardiac muscle showed no significant difference at 5% level in two groups. The impaired ability to remove circulating lipid by LPL mechanism in the nephrotic syndrome was ascertained in vivo and in vitro studies. The etiology of such reduced LPL activity in the nephrotic syndrome was a-lso discussed. 4. The lipase activity participating in the release of free fatty acids from adipose tissue was mar-kedly increased in the epididymal fat pads of AN-rats. This suggests the possibility that mobilization of fat from adipose tissue may be accelerated in the nephrotic syndrome, and also new concept that mobilization hyperlipemia is responsible for the pathogenesis of nephrotic hyperlipemia. However, this concept is inconsistent with the data reported hitherto and remains to be determined.

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Renal pressor factor, angiotensin, acts directly on the adrenal cortex to increase the secretion of aldosterone and produce marked electrolyte changes which influence arterial blood pressure. Experiments were performed by intravenous injection of synthetic angiotensin, synthetic aldos-terone in the adrenalectomized dogs and normotensive subjects who took spironolactone to know whether electrolyte changes might be caused directly by angiotensin or by hypersecretion of aldosterone. These results lead to the following conclusion : Synthetic angiotensin I and synthetic aldosterone decreased urine flow and the excretion of Na, Cl. However, the excretion of K was reduced by angiotensin, whereas it was increased by aldosterone. Marked effect of electrolyte excretion was observed in both. Therefore on the one hand the action of electrolyte excretion was done through aldosterone and, on the other hand, it was done directly by angiotensin. Since same effect was observed in the normo-tensive subjects who took spironolactone, it is obvious that angiotensin acts directly on the tubular.

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The principal purpose of this study is to investigate the kinetics of ¹³¹I-hippuran in the human body, in order to obtain the informations about renal circulation and tubular excretion, which may be used as a quantitative evaluation of renal function. After a single injection of ¹³¹I-hippuran, the disappearance curves of ¹³¹I-hippuran from blood were shown to be represented as the sum of 3 exponentials on the semilogarithmic graph. Consequently, it was assumed that a three compartment model should be adopted for the study of kinetics of ¹³¹I-hippuran. The existence of an extravascular body compartment omitting the kidneys showed that ¹³¹I-hippuran could disperse and distribute into the body tissue. And the fact that the values of extraction ratio obtained by renal catheterisation decreased in the course of time after a single injection of ¹³¹I-hippuran, might be explained only by application of a multi-compartment model. From these considerations, a following new mathematical model was proposed for the kinetics of I-hippuran.
Qi: Radioactivity in the compartment i.Kij : Intercompartmental rate constant from compartment j to i.The simultaneous differential equations to describe the transfer of radioactivity are shown as follows. dQ₁/dt=-K₂₁Q₁-K₃₁Q₁+K₁₂Q₂+K₁₃Q₃
dQ₂/dt=K₂₁Q₁-K₁₂Q₂
dQ₁/dt=K₃₁Q₁-K₁₃Q₃
Therefore, on the basis of this model, intercompartmental rate constants could be calculated from the data obtained by analysis of the blood disappearance curve. And effective renal blood flow can be calculated from the following formula. E(t)⋅F⋅Q₁/V₁=K₂₁Q₁-K₁₂Q₂
E(o)⋅F=K₂₁V₁
Where, F: total renal blood flow.E(t) : extraction rate at a given time t.V1 : distribution volume ¹³¹I-hippuran in the compartment 1. This kinetics study as made in the cases of normal and diseased subjects and the results are summerized in the table. For another application of this kinetics study, the author described a new method using double isotope technique for simultaneous studies on the circulatory and excretory functions of both the kidney and the liver. According to the kinetics model of ¹³¹I-hippuran, the renogram curve is corresponding with the transition of radioactivity in the kidney compartment and is explained principally on the same basis of the kinetics study mentioned above. From this point of view, finally, the application of analogue computor as a trial for the theoretical analysis of the renogram was investigated.

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