We studied 40 patients (18 males and 22 females) with IgA nephropathy out of 105 primary renal diseases Biopsy materials from the patients were examined by immunofuorescence (IF) and light microscopy. The average age at the biopsy is 30 years (15-52 years), whereby 67% of the patients are between 20 and 39 years old. The initial clinical symptoms of the disease were chance proteinuria and/or hematuria (50%), gross hematuria (25%) and others (25%). Ten patients experienced gross hematuria during the course of the disease The gross hematuria was predominant in females (4:1). The impairment of the renal function was observed in 37% of the patients and males were percentually more predominant than females. There was a good correlation between the amount of proteinuria and the severity of the glomerular disease, Gross hematuria was more frequently found in patients with a mild glomerular lesion By IF, the deposition of IgA in the glomeruli was slight in the early stage of the disease and increased as the disease advanced, In some cases the deposition was also found along the capillary walls, however, the deposition decreased as the glomeruli were sclerosing. In the sclerosing area of the glomeruli, IgA was not stained however IgM and C3 were strongly positive just like in case of focal glomerular sclerosis, No protein components were found n the completely fibrosed glomeruli. These data suggest that IgA has already been deposited in the mesangial area subclinically. Upper respiratory tract infection (URTI) makes the disease manifest to cause gross hematuria. The interval between the onset of the preceding URTI and gross hematuria is too short to cause an immume complex disease ; moreover, many patients were pointed out proteinuria and/or hematuria before URTI or gross hematuria. To elucidate the etiology of IgA nephropathy, genetic factors should also be detected.

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Present studies dealing with focal glomerular lesion of Wistar rat were divided into three groups such as untouched group, saline group and unilateral nephrectomy group. It appears to us that in the first glomerular lesion shows loss of negative charge in GBM and gradually developing in the increased segmental mesangial matrix, and adhesion between Bowman's capsule and glomerular capillaries. In our examination, unilateral nephrectomy group showed highest incidence of FGS and also most severe urinary protein excretion. In addition, in this group was accompanied by severe tubulo-interstitial lesion showing lymphocytic infiltration and tubular damage. The linear regression line of all Wistar rat was revealed that glomerular trend was higher than tubular ones. Therefore we were suggested that primary glomerular damage result in secondary tubular damage. We could reject our null hypothesis that correlation between glomeruli and tubulo-interstitium is not at the 1% level. Also the presence of correlation between glomeruli and arteries in unilateral nephrectomy group was suggested that alteration of renal hemo-dynamics was attributable to glomerular damage. Immunofluorescent, optical, electron microscopical findings were nearly corresponded to previous investigators of experimental and human FGS.

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The mechanism initiating compensatory renal hypertrophy is not fully known yet. The present investigation was performed to elucidate wheather humoral factor is involved in compensatory renal hypertrophy in unilaterally nephrectomized rats. The effect of rat serum on the rate of incorporation of ³H-thymidine into DNA or ¹⁴C-uridine into RNA was studied in rat renal cortical cells in primary monolayer culture. The following results were obtained:1) The rate of 3H-thymidine uptake by rat renal cortical cells was significantly stimulated in the presence of rat serum in culture media.2) Uninephrectomy resulted in the significant increase in the weight of remaining kidney in rats 48 hours after operation.3) The stimulating effect of serum from uninephrectomized rats on ³H-thymidine or ¹⁴C-uridine uptake was not significantly different from that of control rats. These results suggest that humoral factor may not be a major stimulator in the development of comensatory renal hypertrophy in rats after uninephrectomy.

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11 adult female dogs were given periodic intravenous injections of urauyl nitrate (UO₂ (NO₃)₂·6H₂O) to create a syndrome of chronic uremia. After the initial injection, there was an abrapt fall in creatinine clearance and rise in plasma urea nitrogen. Low and relatively constant creatinine clearance (10.2±2.7ml/min mean±S.D) were easily maintained with furhher injections. Dogs developed proteinuria, aminoaciduria, weight logs, and plasma amino acid levels similar to those of chronically uremic humans and rats, therefore, net production and utilization (Qmet) of amino and ammonia were assessed in the left kidney of 11 normal and 8, chronically uremic female dogs induced with uranylnitrate. Studies were conducted at the end of two 120-min infusions, first with half-normal saline and then with amino acids which increased plasma concentrations to postprandial levels. In the normal dogs, Qmet for a number of amino acids and ammonia was significantly positive (net production) or negative (net utilization). Qmet became more negative with the amino acid infusion. In the uremic dogs, Qmet for amino acids and ammonia was qualitatively similar to normal and tended to change in the same direction with the amino acid infusion. Although the absolute values for Qmer were usually less in the uremic dogs, with the amino acid infusion their mean fractional Qmet (Qmet/creatinine clearrance) were often greater. A substantial proportion of the infused amino acids were removed by the kidney in both groups of dogs. In the uremic dogs, there was evidence for preservation of glomerular-tubular balance between the filtered load of amino acids and tubular reabsorption. Those findings indicate that the dog kidney may make an important contribution to total synthesis or metabolism of certain amino acids by the body and may slso affect plasma concentrations of some amino acids. Durino acid infusions, the kidney plays a major role in removal of the added amino acids. In renal failure these functions are decreased, but compared to the fall in glomerular filtration rate, they are relatively well preserved.

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Borah, et al, demonstrated that HD is a severe catabolic stress to N-metabolism. EAA loss during HD has been speculated as a stress. In order to study this mechanism, AMIYU® (contained 8 EAA and His. 7% solution, Morishita Pharm. Co. Ltd., ) was infused into venous line throughout 5 hrs. HD with the speed of 40 ml/hr. (study A) and during the last 1 hr. of 5 hrs. HD with the speed of 200 ml/hr. (study B) . The time courses of urea generation rate (Gu.), aminogram and N-balance were compared among control, study A and study B-HD. There were no significant changes in EAA level during control HD suggesting that EAA loss was replacedd by protein catabolism. Gu. (mg/min) during 4 hrs, after control HD (20.1±1.2) was significantly higher than predialysis value (4.7±0.1), indicating the catabolic stress due to HD. Gu. after study A-HD (17.3±1.3) was significantly lower than that after control HD. But Gu. after study B-HD (23.0±0.9) was significantly higher than that after control. HD. This shows that the high dose of EAA administered during the last 1 hr. of HD is not lost into dialysate but is degradated to urea about a half because the last 1 hr, in 5 hrs. HD may be already the catabolic phase. N-balance was -3.6±0.8 (g/day) on control HD day and improved by EAA supplementation throughout HD (-2, 1±0.8). Plasma total. EAA and nonEAA levels significantly increased during 4 hrs. after control HD, suggesting that amino acids were supplied through protein degradation. But in study A, plasma total nonEAA level significantly decreased during HD, indicating that protein catabolism was suppressed by EAA supplementation throughut HD. From these results, HD itself is shown to be the strong catabolic stress to N-metabolism. The rapid decrease in plasma EA.A level due to EAA loss during HD would be one of this factor. The low dose administration of EAA throughout HD is considered to be not only replace the EAA loss, but also suppress this catabolic stress.

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Biosynthesis of guanidinosuccinic acid (GSA) increases in renal failure, and the mechanisms of its synthesis has been thought to be closely related to the urea cycle. To clarify the pathway of GSA synthesis and the mechanisms of its increased synthesis in renal failure, the effect of urea cycle members and D, L-norvaline, an inhibitor of urea cycle enzymes on GSA synthesis was studied in isolated hepatocytes prepared from normal rats. GSA was separated by high pressure liquid chromatog-raphy, using a cation exchange resin column for amino acids analysis. It was measured fluorometrically after reacting with 9, 10-phenanthrequinone which selectively reacts with mono-substituted guanidine derivatives. We previously reported that isolated hepatocytes (7×10⁶ cells) which were incubated in 6 ml of Krebs-Henseleit bicarbonate buffer (+3% bovine serum albumin and 10 mM sodium lactate) synthesized GSA at a rate of 40 nmol/10⁸ cells/4 h in the presence of 36 mM urea, but a detectable amount of GSA was not synthesized in the presence of 10 mM NH₄CI. The effect of other urea cycle members on GSA synthesis was also examined. In the presence of 1 mM carbamyl-phosphate, 10 mM citrulline, 10 mM argininosuccinate, 5 mM ornithine or 10 mM NH₄CI + 5 mM ornithine, hepatocytes did not synthesize a detectable amount of GSA. In the presence of 10 mM NH₄Cl and 36 mM urea, 0.5 mM of ornithine or arginine inhibited GSA synthesis by 63%. When the ammonium chloride was omitted, GSA synthesis increased with 36 mM urea, was strongly inhibited by 1 mM arginine, but was little inhibited by 1 mM ornithine. In the presence of NH₄CI, 1mM and 5 mM citrulline inhibited GSA synthesis by 33% and 85%, respectively. D, L-Norvaline (5 mM), an inhibitor of urea cycle enzymes (ornithine transcarbamylase, arginin-osuccinate synthetase and arginase), strongly inhibited GSA synthesis stimulated by urea with or without 10 mM NH₄Cl. These results suggest that GSA synthesis stimulated by urea is competitive with urea synthesis and that the synthesis of the former is partly catalyzed by the urea cycle enzymes.

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The biosynthesis of guanidinosuccinic acid (GSA), implicated as a uremic toxin, has been reported to be closely linked with the urea cycle. Our previous report of increased GSA synthesis by urea in isolated rat hepatocytes prompted us to study in vivoo To investigate the relation between urea synthesis and GSA synthesis, ornithine, a stimulator and D, L-norvaline an inhibitor of urea synthesis were administrated to normal rats and hepatic GSA levels were determined At the same time, the hepatic concentrations of arginine and aspartate which are the members of the urea cycle and were also proposed to be the precursors of GSA were determined to clarify the metabolic pathway of GSA synthesis. GSA was determined fluorometrically using HPLC with a cation exchange regin column (Hitachi 2610, 4X125mm). Amino acids were determined by an amino acid analyzer (JLC6AH). Three hours after the intraperitoneal injection of urea (1mg N/g body weight), hepatic GSA level increased to 48 nmol/g wet liver which is about 7 times that of the control rats fasted for 15 hours. By the intraperitoneal injection of ornithine (20μmol/g body weight), the increase of hepatic GSA level by urea was inhibited by 51% and by D, L-norvaline (7.5μmol/g body weight), the increase of hepatic GSA level by urea was also inhibited by 71%. By the injection of urea, the hepatic concentration of arginine also remained at the undetectable level and that of aspartate decreased from 2.1 to 1.4μmol/g wet liver, By the injections of ornithine plus urea and D, L-norvaline plus urea, the hepatic concentration of arginine increased to 0.013 and 0.04μmol/g wet liver, respectively, and that of aspartate did not change by the former and decreased to. 0.6μmol/g wet liver by the latter. These results indicate that the change of the concentration of arginine and aspartate did not correspond to the change of hepatic GSA level and also they suggest that GSA synthesis is competitive to urea synthesis and some steps of GSA synthesis are catalizad by the urea cycle enzymes inhibited by D, L-norvaline.

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The therapeutic effect of calcitonin in renal osteodystrophy(ROD) is controversial. A nephritogenic glycopeptide (crude glycopeptide : GP) was extracted by the method of Shibata and was injected to rats to get azotemic animals. These rats were divided 1st) normal control group, 2nd) GP control group, without administration of VD derivatives and eel calcitonin derivative(ECT), 3rd) 1α-OH-D₃ group, 4th) 1α-OH-D₃+ECT group, 5th) ECT group, 6th) ECT group with long term administration. In the 1ast group, injection of ECT (250m MRCunit/kg. 3 times/week) was carried out from 120th to 285th day. In 3rd, 4th, and 5th groups, the administration of 1α-OH-D₃ (0.05μg/kg), ECT (250mMRC unit/kg) plus 1α-OH-D₃ (0.05μg/kg), ECT (250mMRCunit/kg) were performed from 230thto 285 th day respectively. Mean BUN in control group was 17, 3±2.5mg/dl, whereas that in 2nd group was 41.8±11.1mg/dl (P, 0.001) at 285th day. Cortical thickness of femur in the control group was 27.4±2.0%, whereas in 2nd, 3rd, 4th, 5th, and 6th group, it was 20.9±3.9% (P<0. 001), 27.5±2.0% (ns), 24.7±4.9% (ns), 24.2±3.3% (ns), 26.3±3.3% (ns) respectively at 285th day. Bone density of femur in the control group was 2.31±0.14mm Aluminum (mm Al), whereas inn the 2nd, 3rd, 4th, 5th and 6th group, it was 1.95±0.14mmAl (P<0.001), 2.20±0.15mmA1 (ns), 2.02± 0.12mmAl (P<0.02), 2.11±0.19mmAl(ns), 2.15±0.18mmAl (ns) respectively at 285th day.Urinary hydroxyproline in the 2nd group was 1904±431μg/day, whereas in the control, 3rd, 4th, 5th, and 6th group, it was 399±85μg/day (P<0.001), 440±67μg/day (P<0.001), 440±242μg/day (P<0.001), 933±424μg/day (P<0.01) 670±117μg/day (P<0.001) respectively at 285 day. The present data suggest that ECT might be effective in protecting ROD in these experimental condition, although curative effect of 1α-OH-D₃ was considered to be more remarkable.

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It is known that nocturnal penile tumescence (NPT) occurs physiologically during REM sleep. In order to differentiate an organic impotence from psychogenic one, the author has practiced REM-penogram in which NPT is measured simultaneously with cerebral wave in all night sleep. REM-penogram was conducted on 12 hemodialysis patients of impotence, 10 patients of psychogenic impotence and 10 patients of organic impotence. As the results it was found that in the case of dialysis patients total REM-sleep time is reduced while REM latency is prolonged. With dialysis patients complaining total impotence, NPT was not recognized and those complaining partial impotence schowed less frequency of NPT. In the case of dialysis patients reduction of REM-sleep is often recognized. For the diagnosis of impotence not only NPT but also simultaneous recording of cerebral wave in all night sleep is necessary.

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To clarify the relationship between changes in renal sodium handling and blood pressure by the dietary sodium restriction in patients with essential hypertension, dietary sodium was restricted for 7 days (from 10g/day to 2g/day) in 30 mild to moderate hypertensives. Fifteen patients were balanced of sodium intake and excretion within 7 days (group A). Others were continued negative sodium balance at the end of the period of dietary sodium restriction (group B). There were no significant difference in age, sex, blood pressure, and severity of hypertension between two groups. By the dietary sodium restriction, the average mean blood pressure of group A was significantly reduced from 117±2.9mmHg to 106±3.4mmHg (p<0.05), but not in group B. Body weight and plasma volume were significantly reduced in both groups. Hematocrit was increased in group but not in group A. Cardiac index was reduced, and peripheral vascular resistance and urinary norepinephrine excretion were increased in group B but not in group A. We suggest that mild to moderate essential hypertensives who continued negative sodium balance during a week of sodium restriction may have disturbance of renal sodium handling and volume-pressure control mechanism, and therefore can't reduce blood pressure by the dietary sodium restriction.

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We have been investigated clinical course and prognosis of glomerulonephritis and chronic renal failure clinico-pathologically. As the parameters, acute phase reactants (APRs) were picked out. They were a1-Antitrypsin (α₁-AT), α₁-Acid-glycoprotein (α₁-AG), α₂-macroglobulin (α₂M) and Haptoglobin (Hp) respectively.The results obtained were as follows.(1) APRs correlated well with the clinical course of acute glomerulonephritis. They normalized with improvement of histological findings.(2) In severe persistent proteinuria group (both proteinuria and hematuria) of chronic glomerulonephritis (CGN) showed all high levels.(3) APRs were increased in histologically severe CGN.(4) In the group exhibiting high urine FDP were increased α₁AT.(5) The higher creatinine level was, the lower albumin and transferrin. However, the latter improved up to normal limits on hemodialysis.(6) α₁AT and α₁AG revealed relatively good correlation with creatinine. In the former, r=0.532, and r=0.474 in the latter.(7) In chronic renal failure, BUN/Cr ratio lowered with Transferrin on low protein and high calorie diet over 3 months, while α₁AT increased.

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