We examined the role of the sympathetic nerve activity in the pathogenesis of hyperr tension by acute salt loading. Male white rabbits underwent partial nephrectomy (removing 70-80% renal mass). Hypertonic sodium chloride (50 ml/kg/hr) was infused intraR venously into α-chloralose.anesthetized, partially nephrectomized rabbits over a 60.min period. By the infusion of 015 M-NaCI, blood pressure was significantly elevated by 704+ 2a mmHg and plasma sodium was greatly increased to 187.2±4.2 mEq/L, Plasma norepinephrine was dose.dependently increased by salt loading. Plasma norepinephrine on 0.75 M-NaCI loading was twofold increase as compared with that on physiological saline loading. While, infusion of hypertonic urea solution induced neither hypertension nor elevated plasma norepinephrine. However blood pressure and plasma norepinephrine were significantly decreased by clonidine or hexamethonium, plasma norepinephrine was significantly increased following infusion of hypertonic sodium chloride. It is suggested that blood pressure elevation induced by acute salt loading might be associated with increased peripheral sympathetic nerve activity.

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Kindney functions immediately after living, donor transplantation were studied in seven pediatric recipients weighting less than 30 kg. Blood and timed, urine samples were colh lected succesively for 24 hours, and urine volume (UV), creatinine clearence (Ccr) and fractional excretion of sodium (FENa) were measured, FENa of the first urine was invariablly high (27±18%), and it decreased exponentially (11±7% at 3 to 6 hours postoR peratively and 3.9±2.1% at 18 to 24 hours postoperatively). UV decreased from 5.2± 2.2 ml/min (0 to 6 hours postoperatively) to 2.5±1.6 ml/min (18 to 24 hours postopera-tively) during the observation period. Within 6 hours after revascularization, Ccr was not correlated with UV (r=0.19, p>0.2). Non-oliguric renal failure (delay of the decrement of serum creatinine levels) was observed in two cases early postoperatively. In the remaining five, serum creatinine levels decreased exponentially. From 6 to 24 hours after revascularization, the relationship between Ccr and UV was as follows: Ccr was 27±15 ml/min when UV ranged less than 1 ml/min, 40±10 ml/min when UV ranged from 1 ml/min to 1.5 ml/min (this difference was statistically significant; p<0.05), and no further increm ment of Ccr was observed when UV increased more than 1, 5 ml/mina Above observation suggests that (1) the duration on non-oliguric renal failure and/or persistence of extremely high FENa after livingmdonor transplantation is limited, and (2) the fluid replacement therapy "chasing" one hour UV to keep large UV (more than 1 ml/min) might be necessary for only a few hours immediately after revascularization in otherwise uncomplicated pediatric recipients.

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In order to study the characteristics of oxalate transport across the brush border membrane, we studied oxalate uptake by rat renal cortical brush border membrane vesicles (BBMV). Vesicles were prepared with MgCl2 precipitation method and oxalate was measured by a modification of the millipore filtration technique, Transport of oxalate by these vesicles was non-saturable under the condition of salt and anion free medium indicating passive diffusion, The maximum uptake in BBMV at 30°C was obtained at 10 min incubation. Low temperature experiments showed gradual increase of oxalate accumulation into BBMV up to 90mine The rate of oxalate transport by the vesicles was decreased by the presence of both the Na and K gradient (in<out). The extravesicular Cl ion stimulated the accumulation of oxalate into BBMV significantly. The hypotonic lysis indicated the temperature dependent efflux of oxalate from osmotically sensitive intra vesicular space. The existence of extravesicular 5 mM paraaminohippurate (PAH) decreased oxalate uptake in BBMV and inhibited the efflux of oxalate from BBMV significantly.

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Active oxygen plays an important role in tissue injury. We have reported that methylguanidine (MG), a uremic toxin, is formed by active oxygen from creatinine (Cr) in vitro and in isolated rat hepatocytes. In this study, we investigate the role of active oxygen in the synthesis of guanidine (G) of which serum level increased in uremics. Substances were incubated with active oxygen sources in 50 mM phosphate buffer (pH 7.4 at 37°C). We used xanthine oxidase system for the superoxide radical, hydrogen peroxide (H₂O₂) and H₂O₂ + FeC1₂ for the hydroxyl radical (OH) as active oxygen sources. G was formed from various guanidino compounds including arginine, guanidinoacetic acid (GAA), canavanine, creative, Cr and MG by OH. And G synthesis from arginine and GAA by every kind of active oxygen was inhibited by the addition of corresponding scavengers. Among active oxygen species OH produced the largest amount of G. These results indicate that G is formed from various guanidino compounds as a result of active oxygen.

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In order to clarify the role of cell-mediated immunity in primary glomerular diseases (PGD), we investigated interleukin-2 (IL-2) production and IL-2 response by peripheral blood lymphocytes (PBL) R Moreover, lymphocyte subpopulations and IL-2 receptor (IL 2R) expression were examined by flow cytometryR The subjects included 4 cases of minimal change nephrotic syndrome (MCNS), 24 of membranous nephropathy (MN), 8 of membrano-proliferative glomerulonephritis (MPGN), 22 of IgA glomerulonephritis (IgA-GN) and 50 of healthy volunteers as controls, The PBL of the study subjects were cultured with PHA for 4s hrs, then the IL-2 activity of the supernatants was determined by using an IL-2 dependent human adults' leukemic cell line, ILKT-1. Proliferative response to recombinant IL-2 in Con A activated PBL was measured by the ³H-thymidine incorporation. The patients in nephrotic stage of MCNS and MN untreated with prednisolone, and nephrotic stage of MPGN demonstrated a significantly reduced IL-2 production, while the remission stage of MCNS, MN and MPGN, and IgA-GN showed no difference in their IL-2 production, In patients with MCNS and MN, IL-2 production demonstrated a significant positive correlation with both CD4 and CD4/CD8, and negative correlation with CD8. Furthermore, the response to IL-2 and the ability to express IL-2R in patients with MCNS were significantly decreased compared to the healthy controls. These results suggest that defective production of and response to IL-2 may be important in the pathogenesis of PGD.

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To understand the normal or abnormal glomerular function of the kidney, it is very important to obtain the precise information from the cultured mesangial cell. After cultivation of mesangial cell from the isolated rat glomeruli, profiling analysis of the organic acids in the cultured medium was studied using GC-MS, and the specific metabolites of the mesangial cell was determined. Significantly high concentration of lactyl lactate was detected only in the cultured medium from the mesangial cell, but not from the cultured medium without cell (control), epithelial cell or other cell lines originated from various organs. Therefore, it is concluded that lactyl lactate might be one of the specific metabolites of the mesangial cell during cultivation. It is also suggested that lactyl lactate in the cultured medium could be used as a specific marker of the mesangial cell.

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Fifty-four patients with IgA nephropathy were examined by electron microscopy to clarify the significance of gaps of the glomerular basement membrane (GBM) in lgA nephropathy. Gaps of the GBM were observed in 17 cases. The findings of gaps of the GBM were divided into three groups. In the first group, the gaps of the GBM were covered by epithelial and/or endothelial cells, and the original capillary lumen was pre-served. In the second group, wide gaps of the GBM were observed, and the capillary lumen was partially collapsed. In the third group, the capillary lumen was almost filled with basement membrane-like materials and cells. Spherical microparticles were seen at the gaps of the GBM in 2 cases. Patients with gaps of the GBM showed a tendency to have a higher incidence of microscopic hematuria of greater than 20 red blood cells per high-power field of vision. Decreased creatinine clearance (less than 80 ml/min) were more frequently seen in patients with gaps than in those without (p<0.01) . Diffuse mesangial proliferation was more frequently observed in patients with gaps than in those without (p<0.05). Marked local thinning or splitting of the GBM and electron dense deposits or spherical microparticles on peripheral capillary walls were more frequently observed in patients with gaps of the GBM than in those without (p<0.01, <0.01, <0.01 and <0.05, respectively).

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We studied 230 patients with primary IgA nephropathy to clarify the correlation between renal function and clinicopathological features in IgA nephropathy. In 42 among those patients, the characterization of the light chains in the glomerular IgA deposits was also studied. GFR was normal in 203 patients, and decreased in 27 patients at the time of biopsy. The amount of proteinuria and the frequency of arterial hypertension were greater in the patients with renal dysfunction than in the patients with normal renal function. The severity of intracapillary proliferation, the extent of glomerular obsolescence, the severity of interstitial change and the severity of arterioscrelosis were greater in the patients with renal dysfunction. In immunofluorescent findings, neither intensity of the deposits of IgA, IgG, IgM, C3, Clq and fibrinogen nor presence of loop deposits were associated with renal dysfunction; nevertheless, the patients with predominant kappa light chain IF had a significantly lower renal function than those with predominant lambda light chain IF or identical light chain IF score. In conclusion, in adition to clinico-pathological features previously reported, the type of light chains in glomerular IgA deposits was thought to be a indicator of progression of this disease.

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Intraplatelet serotonin (5-HT) levels were measured in 46 patients with SLE, 20 with IgA nephropathy and 57 with other diseases. SLE patients had a lower mean serotonin level, 0.24±0.12 pmol/10⁵ plts, compared with that of controls, 0.34±0.098 pmol/10⁵ plts. In some patients with SLE, there was a significant correlation between clinical activity and intraplatelet serotonin levels. When the patients clinical state became serious, the intraplatelet serotonin level was depressed, although no increase occurred in plasma serotonin levels. Exogenous 5-HT uptake by platelets is not disturbed in patients with SLE. It is unlikely that failure of 5-HT uptake plays a role in the depletion of intraplatelet serotonin in SLE. However, in IgA nephropathy, both intraplatelet serotonin levels and exogenous 5-HT uptake by platelets are elevated, The mechanism of this elevation is not yet clear. When plasma β-TG levels were measured in SLE patients, no correlation between intraplatelet serotonin levels and plasma β-TG values was found.

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Clinical feature and incidence of hypocomplementemia from 752 MPGN patients were examined. The Japanese school general medical examination system and private and government examination available for company employees revealed 60.6% of these patients Percentage of subtypes was type I 68.1%, Type II 5%, Type III 10.6%, unknown 16.3%. First examinations found, clinical features were acute nephritic syndrome 17.5%, Rapidly progressive Nephritic Syn. 2%, Recurrent or Persistent Hematuria 7.5%, Chronic Nephritic Syn. 41.6%, Nephrotic Syn, 31.4%. Cases of Acute Nephritic Syn. and Recurrent and Persistent Hematuria were more prevalent in the younger age groups than the other syndromese The course of complement level (C) was classified into 4 groups. They are persistent hypocomplementemia 34.5%, hypocomplementemia and after rising to normo complementemia 29.8%, occasional hypocomplementemia 11.4%, and the total percentage of hypo-complementemia in the course of the disease in the 4 groups was about 90%. With regard to the therapy, clinical improvement was 49, 1% and pathological improvement was 18.6%. Younger age groups (<15Y.) were responded better to the therapy than older age groups (≥15Y.). The general medical examinations revealed several cases in the early stages, therefore early treatment was possible. The results show that the early diagnosis and early treatment are important to improve the prognosis, and The examination of complement level and its course are effective for the diagnosis and treatment.

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Blood levels of β₂-microglobulin (β₂-M) in patients suffering from chronic renal failure (CRF) [57 cases under conservative therapy and 23 cases under hemodialysis therapy upto 2 months] were compared between patients administered oral adsorbent AST420 (AST group) and those not administered (control group). Increase of β₂-M levels following progression of renal failure was rather moderate in AST group compared to control group and the difference between the two groups was enhanced as Cr level increased. In patients whose clinical data were available until initiation of hemodialysis, the period to initiation of hemodialysis was found to be longer together with lower levels of β₂-M in AST group than in control group. In addition, β2-M were also found to below in patients under hemodialysis therapy who were administered A T420, with statistically significant difference from control group. These results were likely to be explained by preventive effect of AST420 on proo gressive deterioration of renal function in CRF, according to previous studjes on AST-120 in basic and clinical research. That is to say, the suppression of increase of β₂-M level could be resulted by administration of AST420 due to not only maintenance of glomerular filtration but also, to a certain extent, peritubular uptake of 132-M followed by decomposi-tion of β₂-M in tubular enzymes. In conclusion, it was clinically supported in this study that AST-120 could serve for maintenance and/or improvement of renal function including metabolic function.

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Ofloxacin is a newly developed ginolone antibacterial agent with high degree of activity against a wide variety of gram-positive and gram, negative bacteria, The major route of elimination of ofloxacin is urinary excretion, and it would e expected that renal impairment would prolong ofloxacin elimination In this study, the pharmacokinetics of ofloxacin after 100 mg oral dose were investigated in patients with chronic renal failure (CRF) whose Ccr were lower than 20 ml mm. The t 1/2 was significantly prolonged with decreasing renal function from 2.90 hr for normal to 23.06 hr for CRF. In the CRF patients, C max and AUC 0-∞ were greater than in normal. There were no significant differences in Vd between normal and CRF. The renal clearance of ofloxacin decreased from 261.0 ml/min. for normal to 8.0 ml/min, for CRF, and correlated significantly with Ccr in CRF (r=0.88 p<0.001). There were no significant differences in non renal clearance between normal and CRF. The 24 hr renal excretion of ofloxacin averaged 91.9±5.4, 14.1±5.5% of the dose in normal and CRF. In three hemodialysis patients, the dialysance of ofloxacin was 66.0, 465, 43.2 ml mm, respectively (creatinine dialysance 90.0-114.9 ml/min, ). Based on the above findings, a reduction in the dose of ofloxacin is necessary in patients with severe renal impairment. In the hemodialysed patients, its high dialysa-bility should be considered in the dose.

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Recently, it has been hypothesized that proteinuria, glomerulosclerosis and progressive renal insufficiency might result from hemodynamic changes in glomeruli adapting to reduction in renal mass. Our aims were to evaluate the effects of high oral protein loading in healthy subjects and patients with IgA nephropathy on creatinine clearance (Ccr), urinary excretion of albumin (Alb), NRacetyl-D-glucosaminidase (NAG), α-1-microglobulin (α1MG), and β-2-microglobulin (β2MG). Three groups of subjects were examined as follows: N=normal subjects; PI=IgA nephropathy patients with less than 30% of glomeruli showing crescents or sclerosis, PII= patients with more than 30% of glomeruli affected. All subjects orally received an acute protein load (40-60 g). Following hydration, urine and blood samples were collected for Ccr and urinary excretion of microproteins before loading and for four hours there after. (1) Ccr significantly inR creased after loading in groups N and PI (p<0.01), but not in group PII, and the increase in groups N and PI was also significantly greater than that in group PII. (2) U-Alb/cr and u-NAG/cr were unchanged in groups N and PI, but significantly increased in group PII (p<0.05), and the increases were significantly greater than in groups N and PI (p< 005). (3) In group N, u-α1MG/cr and u- β2MG/cr also significantly increased (P<0. 05) . These results suggest that changes in Ccr, u-Alb/cr and u-NAG/cr after a high oral protein load are useful parameters of glomerular damage in IgA nephropathy.

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Rats with puromycin-aminonucleoside (PAN) induced nephrosis (PAN rats) exhibit disruption of the components of the GBM, visceral epithelial glycocalyx, loss of podocyte pedicles, and degeneration of renal tubules. NAG activity and proteins in urine were assayed to evaluate the degree of renal tubular damage in PAN rats. PAN nephrosis was induced in male wistar rats weighing 150 g, with the cutaneous injection of 0, 5 mg/100 g Ba W. PAN for 7 days. The NAG activities in urine and renal tissue were assayed by MCP-NAG methods. Urinary protein was analyzed by SDS-PAGE. Urinary NAG activity significantly increased from the 5th day with its peak on the 14th day. The NAG activity was detected not only in the cortical tissue but also in iso-lated glomeruli The NAG activity in renal tissue was decreased from the 2nd to 4th weeks after PAN injection as compared with that in the normal control rats, However, the activity was recovered to the normal control level by the 9th week, The major component in the urinary proteins of PAN rats was albumin in the majority of the rats, but in several rats, low molecular weight proteins (37 K, 52 K daltons) were detected as the major components in the early stage after PAN injection, Chemical analysis of these low molecular weight proteins were performed, Immunoblotting indicated that these proteins were also found in the serum, However, the following evidence indicates that these proteins are apparently derived from renal tissue: 1) Very small amounts of these proteins are found in the blood. 2) In the urine of some rats, these proteins were found at higher levels than albumin. 3) These proteins are also found in renal tissue.Further investigation is necessary to characterize these proteins.

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