The state of the electrical charge of serum and urinary albumin was investigated in both the nephrotic and remission stage of idiopathic nephrotic syndrome (INS), using isoelectric focusing (IEF). 1) Both a b2 band (a main albumin band appearing at the site of isoelectric point:pI4.7), and a b3 band (a more anionic albumin band than the b2 band) were detected commonly in all samples of urine and serum of INS patients in nephrotic and remission stages and of healthy volunteer controls even if the applied albumin in urine and serum amounted to 20μg or 100μg. 2) When applied albumin amounted to 20μg, bl bands (less anionic albumin bands than the b2 band) were detected between pI 4.7 and p16.5 in urine and in both serum and purified albumin fractionated from serum of INS patients in the nephrotic stage. However, b1 bands were not detected at all in the urine and serum of either INS patients in remission stage and healthy volunteer controls. 3) When applied albumin amounted to 100μg, bl bands were detected also in serum of healthy volunteer controls. From these results, it was confirmed that less anionic albumin existed also in the serum of healthy volunteer controls although the amount was extremely small. Moreover, it was suggested that less anionic albumin appeared in greater quantity in the serum of INS patients in the nephrotic stage than in serum of healthy volunteer controls, and that this increased amount of less anionic albumin would leak more easily into urine through the anionic charge barrier of the glomerular basement membrane than the main albumin (b2 and b3 bands) would.

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To study the role of reactive oxygen species (ROS) in chronic renal disease, we studied the localization of Cu, Zn-Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in glomeruli of patients with IgA nephropathy by immunohistochemical method. Thirty three kidney specimens were used consisting of 28 IgA nephropathy and, normal parts of the 5 resected kidneys with renal tumors as controls. To evaluate the change of renal function and renal histological grade, creatinine clearance (Ccr) and histological grade were assessed at the time of biopsy. In normal kidney, Cu, Zn-SOD and GSH-Px was localized in tubular cells, and not in glomeruli. In the kidney with IgA nephropathy, Cu, Zn-SOD and GSH-Px were detected in epithelial side of the glomerular capillary wall in addition to the tubular cells. The positive correlation was observed between the glomerular localization of Cu, Zn-SOD and that of GSH-Px. As for the relation between the extent of localization of these enzymes and clinical findings at the time of biopsy, the following results was obtained. When Cu, Zn-SOD and GSH-Px was strongly stained in glomeruli; histological change of glomeruli was milder. These results suggest that Cu, Zn-SOD and GSH-Px have the beneficial actions for renal function as anti-oxidative factors.

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The effect of AST-120 was examined in the rat model of CRF induced by adriamycin (ADM), which is known to induce focal glomerular sclerosis (GS). ADM (2mg/kg) was injected intravenously twice at a 3-wk interval. After 14 wks, rats were paired with control (C) and AST-120 (A) groups according to levels of BUN and proteinuria. Then, the rats were fed regular rat chow with (A, n=1O) or without (C, n10) AST-120. After 28 wks, there were more GS in C. Averaged sclerosis index(SI, 0-4scale) in C was 1.97 (0.94-3.22), while 1.61 (0.60-2.97) in A. When GS was advanced in C (SI>2.0), largely ameliorated SI was noted in A (2.61 vs.1.97, C vs.A, p<0.05 by paired W-test, n=5 each). Also, in these rats, BUN, serum creatinine and Ht were all improved in A (p<0. 05). Thus, AST-120 was effective in CRF rats induced by ADM when uremia was advanced. The data also indicates that a reduction of uremic toxins could improve glomerular histology and renal function in CRF.

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This study was designed to determine changes in one of metabolic functions, gluconeog-enesis after ischemic renal injury. Right kidneys of SD rats were removed and a vascular clamp was placed across the left renal artery and vein for 0, 10, 30, 60 and 90 min. On 1, 3 and 7 days after the treatment, tubule suspensions were prepared by collagenase treatment of left kidneys and incubated with or without 2mM pyruvate or malate aerobically. After the incubation, glucose contents were assayed photometrically. Serum creatinine was also determined. In addition, morphological changes were observed under light microscopy to examine the relationship between metabolism and morphology. The tendency of increase of gluconeogenesis was observed on day 1 and 3 after 10, 30, 60 min of ischemic time. On the other hand, gluco-neogenesis decreased significantly on day 1 after 90 min treatment. In contrast, on day 1 and 3 after treatment, serum creatinine levels showed no difference from control at the groups of 10 and 30 min ischemia. Whereas it rose significantly at the group of 60 min ischemia, showing a different tendency from that of the increase of gluconeogenesis. Moreover, morphologic damage was observed on day 1 and 3 after ischemia of 30 and 60 min. The morphologic damage was found more advanced in the corticomedullary region than those of the cortex which has the high gluconeogenic activity and which thus showed relativly limited damage. These results suggest that renal gluconeogenesis is relatively insusceptible to ischemic injury. The fact that it increased up to 60 min of ischemia could be conceived as the reactions by acidosis, compensation for tissue damage, supplement energy for ATP decrease and for further regeneration as emergency responses and the actions for maintaining the blood glucose level.

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Renal size reduction accompanied by the decrease of renal function was evaluated by ultrasonography in 30 normal controls, 45 patients with chronic renal diseases (CRD) and 22 patients with diabetic nephropathy (DN). In controls, significant positive correlation was observed between sectional areas of right kidney and creatinine clearance (Ccr) (r=0.794, p<0.001), suggesting that the decrease of renal function due to aging was accompanied by the renal size reduction. Significant correlation was also found between the size and Ccr in CRD (r=0.814, p<0.001) and DN (r=0.640, p<0.01). No significant difference was observed between controls and CRD in the reduction rate of renal size per unit change of Ccr, which suggested that the renal size reduction accompanied by the decrease in Ccr was the same in controls and CRD. In contrast, in DN, renal size reduction accompanied by the decrease in Ccr was smaller than controls or CRD. When renal sizes were compared in patients, whose Ccr were equal or less than 20 ml/min, renal sizes were significantly larger in DN than CRD (p<0.001). The duration of illness from the onset of proteinuria was longer in CRD than DN (13.5 years and 4.7 years, respectively). The difference of renal sizes, however, can not be fully explained by the differences in the length of illness, since the renal size was larger in DN than CRD even when we compared the patients with the similar length of illness. In conclusion, renal size decreased with the reduction in the renal function in controls, CRD and DN. The decreasing rate in renal size was the same in controls and CRD, but was low in DN. The difference in reduction in renal size can not be fully explained by the difference of the duration of illness.

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Small molecular weight uremic toxins, guanidino compounds and aliphatic monoamines, were measured in the serum of chronic and acute renal failure (CRF and ARF) patients. A close correlation was noticed between guanidinosuccinic acid (GSA) and serum urea nitrogen (BUN) and also between methylguanidine and serum creatinine (Cr) in nondialyzed and dialyzed CRF patients. The same relation was seen in ARF patients showing rapid change of metabolic conditions, which suggested the tight linkage between guanidino compounds and protein metabolites. On the other hand, dimethylamine (DMA) was related with Cr in CRF patients, however, not in ARF patients. Since the production of DMA from Cr is carried out mainly, but relatively slowly, by bacterias in the intestine, the rapid metabolic change of ARF may not affect DMA synthesis. Furthermore, the DMA synthesis from trimethylamine-N-oxide (TMA-N-O) was studied using liver homogenate. The liver homogenate produced DMA by adding TMA-N-O as substrate. However, the kidney homogenate could synthesize it even without substrate. Therefore, the kidney seems to be a major site of DMA production as well as the intestine.

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The activities of N-acetyl-β-D-glucosaminidase (NAG), r-glutamyl-transpeptidase (γ-GTP) and NAG isoenzyme were measured in the urine of 20 patients with multiple myeloma (IgG/IgA type/Bense Jones type ; 15/1/4 cases) and 25 healthy controls to evaluate these activities as indicators of renal disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary NAG activity in the patients with myeloma was significantly higher than that in the controls (20.1±3.3 vs 4.3±0.3U/g.cr; p<0.001). Urinary NAG activity in these patients correlated positively with the dose (mg/g. cr) of urinary protein (γ=0.755; p<0.01), most of which were considered to be light chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme fraction (NAG-1, -2, -3) was higher in the patients than that in the controls, and especially NAG-2 fraction (A form) showed a highly positive correlation with the dose of urinary protein. Urinary r-GTP activity in the patients did not differ from that in the controls, but urinary NAG/γ- GTP ratio was higher in the patients, and reversely correlated with creatinine clearance (r=-0.721; p< 0.01). It is suggested that the elevation of urinary NAG activity results from the damage of lysosome in proximal tubular cells by urinary light chain protein and its degradation products. Therefore, urinary NAG activity may be a good index for proximal tubular disturbance, and NAG/r-GTP ratio may be an index for the extenisive damage of nephrons in addition to the damage of tubular cells in multiple myeloma.

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There have been a number of case reports on nephrotic syndrome with histological findings of minimal change on light microscopy and mesangial IgA deposition on fluorescent microscopy. The pathogenesis of these cases is, however, yet to be clarified. Here, we report a case of minimal change nephrotic syndrome (MCNS) associated with IgA nephropathy, which developed later in the course of MCNS. The patient was 18 years old male with steroid-responsive nephrotic syndrome. First episode of proteinuria occurred when he was 4 years old. On the fourth episode of proteinuria, renal biopsy revealed minimal change on light microscopy and no evidence of deposition of immunoglobulins or complements on immunofluorescent and electron microscopy. On the fifth relapse of MCNS, microhematuria developed concomitantly with massive proteinuria. Renal biopsy, then, showed light microscopic findings of mild focal segmental glomurulonephritis. Significant mesangial IgA deposition was observed on immunofluorescence study. Electron microscopy revealed electron dense deposit in the mesangial and paramesangial area. The patient was well-responsive to steroid although microhematuria persisted after disappearance of proteinuria. We concluded that IgA nephropathy may have developed subsequently in the course of MCNS in our case.

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We report a case of 10-year-old boy with chronic tubulo-interstitial nephritis (TIN). He had febrile convulusion and received sodium valproate (VPA) treatment. l8months later, he had developed Fanconi syndrome. On admission, he also had evidence of tubular and glomerular dysfunction. Renal biopsy revealed interstitial nephritis with linear tubularbasement-membrane deposition of IgG and C₃ and dominant infiltration of CD4 positive cells in interstitium. Although there is not a positive proof of the etiology in the relationship between TIN and VPA, it is likely that VPA is a possible cause of chronic TIN from his past history.

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Tissue renin content within the kidney decreases from outer to inner cortex. However, it is not known whether this gradient is due to a decrease in the number of afferent arterioles from the outer to inner cortex or the decrease in renin content per afferent arteriole. Furthermore, it is still controversial whether sodium depletion increases or decreases this gradient. According to Taugner et al., sodium depletion induces the extension of renin positive part of afferent arterioles from vascular pole toward interlobular artery. Since the length of extension may differ among superficial, midcortical, and juxtamedullary afferent arterioles, the observed gradient may vary depending on whether the entire afferent arteriole or only the vascular pole is examined. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined tissue renin content. We studied: 1. whether tissue renin content per afferent arteriole decreases from the outer to inner cortex. 2. whether sodium depletion affects the gradient of tissue renin content within the cortex. In result, we reached the conclusions, as follows: 1. Tissue renin content per afferent arteriole decreases steeply from superficial to midcortical to juxtamedullary afferent arterioles. 2. The absolute difference in renin content among the three types of afferent arterioles becomes greater during sodium depletion. The internephron heterogeneity of tissue renin content may contribute to functional heterogeneity.

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Though renin release from a single superficial afferent arteriole has been studied extensively, there is no report on renin release from a single midcortical or juxtamedullary afferent arteriole. In the present study, we microdissected the entire afferent arterioles from superficial, middle, and juxtamedullary cortex of rabbit kidney, and examined renin release from a single afferent arteriole. In result, we got the following conclusions. 1. Basal renin release per afferent arteriole decreases steeply from superficial to midcortical to juxtamedu-llary afferent arterioles during both normal and low sodium intake. 2. Isoproterenol (l.6×10^-4M) significantly stimulates renin release from all three types of arterioles on either diet; however, only in the superficial arterioles is the increase (Δ) greater with dietary sodium restriction. These findings indicate substantial heterogeneity of basal and isoproterenol-stimulated renin release, and response to chronic sodium depletion.

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