In an attempt to clarify the Clinico-pathological characteristics of IgA nephropathy with acute onset, comparative studies among patients with IgA nephropathy with acute onset (group I) and with incidious onset (group II), and patients with Henoch-Schönlein purpura nephritis (HSPN) were carried out. Of 135 patients with immuno-pathologically proven IgA nephropathy, 12 patients, 5 males and. 7 females, ages ranging from 6 to 63 years, with a mean of 25 years, manifested an abrupt appearance of acute nephritic syndrome such as macroscopic hematuria, massive proteinuria and edema. They revealed a larger amount of urinary protein of 2.3±0.4 g/day (mean±SEM, p<0.01) including 7 nephrotic patients (58%, p<0.01) as compared to group II, which showed a urinary pro-tein level of 1.2±0.1 g/day including 9 nephrotic patients (7%). Thirty-nine patients with HSPN revealed urinary protein of 1.4±0.2 g/day and of nephrotic range in 10 patients (26%, p<0.01). Regarding the pathological findings, glomerular crescents were found in 9 patients (75%) in group I and 18 (46%) in HSPN, showing a significantly higher in-cidence compared to group II (32/123, p<0.01, p<0.05, respectively), although the grade of mesangial proliferation did not differ among the three groups. The immuno-fluorescence study disclosed IgA deposits along the glomerular capillary wall as well as in the mesangial area in all group I patients, in 45 (37%) group II patients, and in 20 (5100, ) patients with HSPN. As for the clinical courses, 3 patients died in group I within one year, but the clinical status in the other 9 patients in this group improved within 3 years. The clinical status in patients with HSPN similarly improved within 3 years with no patients getting worse, but 4 patients died in this group. On the contrary, no apparent change of clinical status was observed in group II during a 5-year follow up. These results suggest that patients of group I IgA nephropathy and HSPN flare up in the early phase of the disease, but follow an improving clinical course when having escaped from development of chronic renal failure in the early phase. This is in contrast to group II IgA nephropathy who showed no changes of clinical status during the follow-up period.

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The mucosal IgA immune system may play a role in the pathogenesis of IgA nephro-pathy. In the first experiment, the author examined whether or not oral administration of bovine gamma globulin (BGG) can induce glomerulonephritis in rabbits. Six rabbits received water alone (Group A) and 6 rabbits received BGG in daily drinking waterr in a 0.1% solution (Group B) for 20 weeks. After 4 weeks, serum IgA antibody and IgG antibody against BGG began to be detectable by ELISA in the orally administered Group B and gradually increased to about 5 times the background amounts in non-administered Group A, but there were no glomerular immune deposits and glomerular damages. In the second experiment, 8 rabbits received intravenous injections of 0.5 mg of BGG once a week (Group C) and 12 rabbits received BGG in daily drinking water in a 0.1% solution (Group D). After 8 weeks, the rabbits in both groups received daily intravenous injection of BGG for 12 weeks and the dose was gradually increased from 0.5 mg to 10 mg. After pre-immunization, serum IgA antibody and IgG antibody against BGG were detectable in all rabbits by ELISA, but the ratio of IgA antibody to IgG antibody in Group D (1.00±0.14: M±SE) was significantly higher than that in Group C (0.41±0.09). At the end of experiment, 7 rabbits in Group D showed mesangial or mesangiocapillary IgA deposits in addition to IgG deposits: they showed mesangial proliferation with small crescents on lightmicroscopy and mesangial electron dense deposits with small subepitherial deposits on electronmicroscopy. On the other hand, 3 rabbits in Group C showed capillary IgG deposits without IgA deposits and little glomerular damages. ELISA for IgA-BGG complex showed elevated serum levels in the rabbits with IgA deposits on glomeruli. These results suggest that oral administration of antigens in serum sickness rabbits induces specific IgA antibody and glomerulonephritis which is similar to human IgA nephropathy.

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A total 24 cases with orthostatic proteinuria and 5 each of normal healthy subjects and chronic glomerulonephritis patients in clinically stable state were examined their changes of urine protein components before and after forced lordosis. In all of the analysis of urine protein components of resting and spot urines, the major component was albumin accompanied with small amount of alpha-1 acid glycoprotein and IgG globulin where no noticeable difference was observed among the above three clinical conditions. Only increases of the amounts of albumin were seen in the orthostatic proteinuria and chronic glomerulonephritis therefore, it was impossible to differentiation the two by means of analysis by spot urine. When forced lordosis was applied, there was no change of urinary protein excretion and components in healthy subjects before and after lordosis whereas in orthostatic proteinuria and chronic glomerulonephritis, increases of total protein excretion, especially that of albumin, were observed. Before and after the lordosis, no change of urine protein components were observed in chronic glomerulonephritis while in orthostatic proteinuria, along with a remarkable increase of protein excretion a transient low/non-selective proteinuria was observed after 30 minutes of lordosis as compared with the high selective proteinuria that was a charac-teristic change observed in all of the cases of orthostatic proteinuria. From this results thus above, when the cases that orthostatic proteinuria are suspected, it is useful for the confirmation of diagnosis of the disease, to perform, together with routine analysis, the forced lordosis and to analyse the urine protein components before and after lordosis.

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In phylogenetically and ontogenetically immature glomerulus of chicken embryo mesonephros, development of the glomerular capillary wall forming filtration barrier was observed with an electron microscope and the factors participating in its selective permeability were studied. In addition, in each developmental stage of primitive glomerular basement membrane (PGBM) of the mesonephros, the permeability of PGBM was studied with anionic ferritin and anionic site of PGBM were observed with cationized ferritin and polyethyleneimine. Simultaneously, participation of the size selective barrier and charge selective barrier in PGBM was studied and the following conclusion was obtained. (1) The PGBM of the mesonephros consisted mainly of epithelial basement membrane. With development of the glomerulus, PGBM of the mesonephros increased its thickness and became electron dense. Study on permeability for anionic ferritin revealed only extremely rough formation of the size selective barrier in PGBM. (2) Similarly to the metanephros of the higher mammals, anionic sites were ovserved in the lamina rarae of PGBM in the mesonephros at the early stage of glomerular development. However, in this experiment, it was not clear whether the anionic substance forms the charge selective barrier or not. (3) The endothelial fenestrae and their diaphragm and epithelial slit pore were confirmed to make morphological change similar to that in mammals metanephros. I was suggested that endothelial fenestrae and their diaphragm might play an important role as filtration barrier in PGBM of the mesonephros with immature size and charge selective barriers.

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Helix pomatia agglutinin (HPA) recognizes terminal N-acetyl-D-galactosamine residues, which are "masked" by sialic acid in normal rat glomeruli. Digestion in vitro or in vivo with neuraminidase (NRD) resulted in exposure of HPA receptors on the surface of glomerular endothelial cells (GEN). Experimental glomerulonephritis (GN) was induced by intravenous injection of rabbit-anti-HPA serum (AHPAS) before perfusion, ex vivo perfusion of left kidney with NRD and HPA (perfusate was recovered from the renal vein), reestablishment of blood circu-lation, and intravenous injection of AHPAS after perfusion. 15 minutes after revasculization, accumulation of platelets in the glomeruli was seen and immune deposits containing rabbit IgG, rat C3 and HPA were present in the sub-endothelial space. 2 days later, immune deposits were recognized mainly in the sub-epithelial space in finely granular pattern. 7 days after revasculization, these subepithelial deposits increased in their size and mild GBM thickening was observed. In the rats which were not treated with NRD, immune deposits localized in the mesangium and were not observed in GBM 2 or 7 days after revasculization. In the rats which were not treated with HPA, or in the rats treated with normal rabbit serum instead of AHPAS, no immune deposits were formed. Only the group of rats treated with AI-IPAS, NRD and HPA developed mild to moderate proteinuria. Rat IgG was negative in glomeruli throughout the experiment. These results suggested that this experimental model was characterized by (1) initiation of immune reaction on the surface of GEN, (2) movement of immune deposits across GBM from luminal side to epithelial side. Glomerular filtration pressure, NRD treatment, and mediators from platelets might contribute to the immunopathologic change in this model.

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Hyperuricemia and urinary uratic sedimentation due to hyperuricaciduria are conceivably main factors in the onset and aggravation of renal disorders in gout. We have measured intrarenal uric acid concentrations in the autopsied patients with primary gout in an attempt to clarify a mechanism in the onset and aggravation of renal disorders. The subjects were 7 patients with primary gout, 7 with chronic renal insufficiency exhibiting secondary hyperuricemia in a non-dialyzed group, 9 in a dialyzed group and 11 in a control group (serum uric acid not more than 7 mg/100 ml and Ccr not less than 60 ml/min), Uric acid concentrations in the renal cortex, juxtamedulla and medulla were measured by the HPLC-ECD method. As a result, intrarenal uric acid concentrations in a group of gout were higher than that in a control group in any of these regions, and the intrarenal uric acid concentrations were higher in the medulla than in the cortex and 3 times higher in the medulla than that in a control. Although serum uric acids showed higher levels in a non-dialyzed group, intrarenal uric acid concentrations were almost similar to that in a control, and tended to be lower in the medulla than in the cortex. This trend was more significant in the dialyzed group than in the non-dialyzed group. intrarenal uric acid concentrations in the patients with gout were also proved higher even when histological uric acid and urate deposit could not be verified. Thus, the measure-ment of uric acid concentrations were considered useful for clarifying a mechanism in the development of renal disorders in the patients with gout.

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We noticed the downward tendency of blood pressure in chronic hemodialysis patients whose anemia was improving. To evaluate the relationship between anemia and blood pressure in chronic hemo-dialysis patients, we examined hemodynamics on 26 patients, and found negative correla-tion between hematocrit value (Ht) and blood volume (BY), while positive one between BV and mean blood pressure. These results indicate that the decreasing of BV coincides with the improvement of anemia, and lowers blood pressure. Although the cause of the reduction of BY was not conclusive, we speculated that the increasing of fatty tissue weight due to increment of diet, frequently observed in patients whose anemia was improving, might decrease BY consequently when their weights kept constant.

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84 normotensive healthy children aged 12 to 15 years were studied. Erythrocyte Na/K flux ratio was examined in relation to serum Na, K, total and HDL cholesterol, and blood hemoglobin concentration. Erythrocyte Na/K flux ratio showed a significant positive correlation with blood hemoglobin concentration, and a negative correlation with serum K level. A strong family history of essential hypertension was associated with the decreased ratio of ery-throcyte Na/K flux. These findings suggest that erythrocyte Na/K flux ratio may be a genetic marker for essential hypertension. However, careful consideration might be needed to evaluate this ratio, since it may be affected by serum K or blood hemoglobin concentration.

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Effects of OKY-046, a specific thromboxane (Tx) synthetase inhibitor, on blood pres-sure, Tx synthesis in blood platelet, kidney slice and aortic strip were evaluated in adult spontaneously hypertensive rats (SHR). OKY-046 was dissolved into drinking water with the concentration of 1, 10, 100 mg/dl. The averaged intakes of OKY-046 were 1.4±0.1, 13.0±1.1, 147±12 mg/kg/day, in rats who had taken 1, 10, 100 mg/dl of OKY-046 solu-tions for drinking water, respectively. The systolic blood pressure was significantly decreased by 34 mmHg only with high dose of OKY-046 (147 mg/kg/day). OKY-046 suppressed the platelet aggregability to ADP with low dose upto 1.4 mg/kg/day. Release of Tx B₂, a stable metabolite of Tx A₂, from blood platelet was attenuated with moderate dose of OKY-046 (13.0 mg/kg/day), while the release of Tx B₂ from the kidney slice was suppressed only with high dose of OKY-046. The release of Tx B₂ from aortic strip was not changed with high dose of OKY-046. OKY-046 had no effect on release of 6-keto-PG F_1α, a stable metabolite of prostacyclin, from aortic strip or kidney slice. These results suggest that the effect of OKY-046 on Tx synthesis has organ specificity and that the antihypertensive effect of this drug in SHR is related to its decreasing action of renal Tx synthesis.

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To examine the role of prostaglandins (PGs) in the macula densa mechanism of renin release, rabbit afferent arteriole (Af) alone and afferent arteriole with macula densa attached (Af+MD) were microdissected and incubated consecutively. Hourly renin release rate from a single Af (or Af+MD) was calculated and expressed as ngAI·h^-1·Af^-1 (or Af+MD^-1)/h (where AI is angiotensin I). Basal renin release rate from Af was 0.84±0.14ngAI·h^-1·Af^-1/h (X±SEM, n=23) and remained stable throughout the incubations. Basal renin release rate from Af+MD was 0.33±0.04ngAI·h^-1Af+MD^-1/h (n=17), which was significantly lower (p<0.01) than that from Af. When furosemide (1.5 mM) was added to Af, no significant change in renin release rate was observed. However, when furosemide was added to Af+MD, renin release rate increased from 0.40±0.05 to 1.59±0.15ngAI·h^-1·Af+MD^-1/h (n=10, p<0.01). After the pretreatment with indomethacin, a cyclooxygenase inhibitor, furosemide still increased renin release rate from 0.17±0.02 to 0.56±0.09 ng AI·h^-1·Af+MD^-1/h (n=5, p<0.05) ; however, indomethacin pretreatment reduced both basal and furosemide-stimulated renin release rate (p<0.05). In the presence of PGI₂ (10 μM), renin release rate from Af increased from 0.45±0.14 to 1.49±0.53 ng AI·h^-1·AN/h (n=9, p<0.05), and further increased to 4.50±1.24 ng AI·h^-1·Af^-1/h (p<0.02) after removal from PGI₂. When PGE₂ (10 μM) was added to Af+MD, renin release rate increased from 0.54±0.09 to 1.26±0.24ng AI·h^-1Af+MD^-1/h (n=8, p< 0.05). However PGE₂ had no effect on renin release rate from Af alone. We concluded that (1) the prostaglandin system may be a modulating factor of response in the macula densa mechanism of renin release, (2) PGI₂ has direct action on renin release from affer-ent arteriole, and (3) PGE₂ may participate in the control of renin release through the action on the macula densa.

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Low protein diet and captopril administration were demonstrated to decrease proteinuria of DN respectively. It was considered that the mechanism of each treatments was related with the improvement of intra-renal hypertension. We studied the combined effect of low protein diet and captopril on the proteinuria of DN. Subjects were 7 type 2 diabetic patients with nephropathy (serum Cr, 1-4 mg/dl, μ-protein, 1.3-7.6 g/day) fed 60-70 g/day protein diet. They were fed low protein diet 35 40 g/day) for 3 weeks and followed by oral captopril administration (37.5 mg/day) for more 3 weeks. Tatal urinary protein was significantly reduced from 3.85±1.85 g/day to 2.76±1.53g day (p<0.01) by low protein diet. And it decreased significantly to 2.32±1.62g/day by combination of low protein diet and captopril (p<0.05). Serum albumin level, serum K were remained constant. Ccr did not significantly changed (27.5±20.1→30.8±15.9 ml/min) by these treatments. In conclusion, combination therapy of low protein diet and captopril reduces renal albumin clearance in DN additionary. It is considered that low protein diet relieves glomerular hyperfiltration and captopril enhances it.

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We analysed the changes in serum creatinine concentration (Scr) in 24 patients with polycystic kidney disease whose Scr is higher than 1.5 mg/dl for over 3 times. Using the linear regression analysis, time and the reciprocal of Scr (1/Scr) as well as time and the logarithm of Scr (logScr) showed significant correlation in 19 patients, correlation coefficient (r) ranged from -0.8031 to -0.9912 and from 0.81576 to 0.99115, respectively. When predicting the time at which dialysis would be required, frequent determination of Scr is recommended after Scr begins to elevate. LogScr and 1/Scr are plotted against time, and prediction of the time is carried out as follows: (1) When a single straight line is described either on reciprocal or on logarithmic plot, the time is calculated using the single straight line. (2) When a straight line is not evident, the time is calculated on reciprocal plot as a single straight line, and (3) when a new line can be easily recognized, using the new line. Assessing the effect of therapy on progression of the disease remains to be defined.

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A case of idiopathic acute interstitial nephritis with Fanconi syndrome and uveitis was presented, The serial changes of some renal tubular functions were followed for one year. A 45 year-old woman complained of malaise and heart burn, and referred to our institution because of renal insufficiency and bilateral renal accumulation on ⁶⁷Ga-scan at the examination in another hospital. Laboratory studies on admission showed glycosuria, proteinuria, panaminoaciduria and metabolic acidosis. GFR, concentrating capacity, %TRP, uric acid clearance (C_UA/Ccr), TmG and TmHCO₃- were all reduced. The renal biopsy specimen revealed tubulo-interstitial nephritis with marked infiltration of neutrophils, eosinophils and plasma cells, although no remarkable changes in glomeruli were present. IF studies were negative in both glomeruli and tubules. Uveitis occured two months after the onset of the interstitial nephritis, and resolved gradually by local steroid therapy. No granulomata was found in bone marrow specimens. We could not find out any etiological factors which might involve uveitis and interstitial nephritis in this case. Serum pH and bicarbonate concentration had, however, recovered within a month, and %TRP and C_UA/ Ccr were gradually recovered within a year after admission without systemic steroid therapy. A further renal biopsy preformed 15 months after the onset of the disease revealed interstitial fibrosis and mild interstitial infiltration of small lymphocytes, plasma cells and fibroblasts. But no evidence of tubulitis was found. On the otherhand, hyperaminoaciduria was still observed, and decreased TmG were not improved at all even after a year. In summary, this is a very rare case which showed the discrepancy in the recovery of some renal tubular dysfunctions in idiopathic interstitial nephritis with Fanconi syndrome and uveitis.

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We conducted renal biopsy on a 36-year-old male patient with hypothyroidism accompanied by proteinuria (0.3-0.4/day) and renal failure (Ccr 41.2 ml/min). Light microscopically, thickening of glomerular capillary wall, expansion of mesangial area and seal-engraving change due to the deposition of lipid were observed both diffusely and globally. Electron microscopically, loosening of GBM (Lamina rara interna) and mesangial matrix, and vacuolization of mesangial cell were noted. Based on the literature available heretofoe, glomerular plathology of nephropathy is considered to have been caused by hypothyroidism. We decided to report on this case inasmuch as, to the writer's knowledge, findings on the relationship between hypothyroidism and renal pathology are scarce both home and abroad.

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