Renal biopsies were performed on 25 patients with reflux nephropathy to clarify the relationship between the pathological findings and clinical parameters. Biopsy specimens were obtained at anti-reflux operation by open renal biopsy. Glomerular lesions were classified as focal, diffuse, segmental and global sclerosis. Tubulo-interstitial changes were defined according to the principle advocated by Cotran and expressed as the percentage of the lesions. The clinical parameters consisted of the grades of VUR, the grades of renal scarring, renal function and the daily urinary protein excretion. A significant relationship was noted between the grades of VUR and those of renal scarring. The percentage of global sclerosis in the kidney revealed a close relationship with the grades of VUR and the percentage of tubulo-interstitial changes but not with the renal function or the daily urinary protein excretion. Focal segmental hyalinosis and/or sclerosis (FSHS) lesions were presented in 3 of 25 cases (12%). The pathological findings of the FSHS lesions had a close relationship with the renal function and the daily urinary protein excretion and the prognosis of the kidney. The other patients without FSHS lesions displayed an unchanged renal function. Based on these observations, it is clear that the prognosis of the patients with vesico-ureteral reflux could be predicted from the histopathological findings; the presence of FSHS lesions suggests a poor prognosis for the kidney. The degree of daily proteinuria represents a useful parameter for evaluating the progression of the reflux nephropathy.

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In relation to the phenomenon in which IgA nephritis is carried over from childhood to an adult age, pathohistological analysis was performed to elucidate the age-related character of the expression of the disease based on renal biopsy specimens from different age groups. A significant difference in the glomerular lesions was noted between the age groups under 15 yrs (15±2.1 yrs) and over 18 yrs. In the younger age group, the disease became manifest with lesser glomerular sclerosis and segmental lesions, whereas mesangial proliferative and sclerosing lesions were evident with increasing segmental lesions in the adult-onset disease. It is suggested that some of the childhood cases of IgA nephritis with progressive mesangial sclerosis could be carried over to an adult age.

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Antithrombin III (AT III), a plasma inhibitor of coagulation factors, was evaluated for its inhibitory effects on the development of glomerulonephritis induced by antibasement membrane antibody in rats. AT III was administered intravenously at 250 and 1000 Units/kg to rats once a day for 14 days after intravenous injection of rabbit antiserum against the rat glomerular basement membrane. In the rat model, the high dose of AT III reduced the urinary total protein, plasma total cholesterol and plasma phospholipid, and tended to lower the incidence of fibrin deposits in Bowman's space, cell proliferation in the glomeruli, and PAS-positive granules (absorption droplets) in the glomerular epithelium. The above results suggest that AT III is effective in inhibiting the development of glomerulonephritis.

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An NADPH-ferredoxin reductase (EC 1.6.7.1) was purified from bovine kidney mitochondria and its physicochemical properties were investigated. The ratio of the absorbances at 272 and 450 nm was 8.8, and the enzyme had a specific activity of 5, 850 nmol/min/mg for the reduction of cytochrome c. We determined the molecular weights of the NADPH-ferredoxin reductase as 53, 000 and 34, 000 Da by SDS-PAGE and HPLC analysis, respectively. Renal ferredoxin was substituted by adreno-ferredoxin, but spinach ferredoxin was not. The reductase formed an immuno-precipitin line against antibody of the adrenal reductase on Ouchterlony double-diffusion analysis. The sequences of amino acid residues of this reductase in the amino-terminal regions were identical. The amino-terminal region of the reductase may thus play an essential role in the enzymatic function.

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The effects of chronic phosphate depletion on vasopressin (ADH) secretion and kidney tissue ADH concentration were examined in rats fed on a diet containing 0.26% phosphorus (LP) or 0.99% phosphorus (NP). The concentration of plasma phosphorus (P) fell significantly in the LP rats after a 4-week period on the experimental diet. There was no significant difference between the LP and NP rats as regards their plasma ADH concentrations and kidney tissue ADH concentrations in normal hydration after a 4-week period on the experimental diets. Following hypertonic saline tests, the plasma ADH concentrations increased significantly in the LP and NP rats, but there was no significant difference between the groups. The kidney medulla and papilla ADH concentrations increased significantly with plasma ADH elevations in both groups. Again, no difference could be found in the cortico-medullary ADH concentration gradients between the two groups. These results indicate that chronic hypophosphatemia in phosphate depleted rats may not be related to ADH secretion and the distribution or tissue concentration of ADH in the kidney. Further, our data suggest that a low plasma P does not influence the ability of ADH to bind to kidney receptor in rats.

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Various guanidino compounds were determined in 48 non-dialyzed patients with chronic renal failure. The patients were divided into two groups, as follows: group A, chronic glomerulonephritis and polycystic kidney; and group B, diabetis nephropathy, lupus nephritis and renal amyloidosis. Six kinds of guanidino compounds in the serum were measured by high performance liquid chromatography. Although guanidinosuccinic acid (GSA), methylguanidine (MG) and taurocyamine (G-TAU) were inversely related to deterioration of renal function, arginine and guanidinoacetic acid were not correlated with the serum creatinine and urea nitrogen (SUN) levels. GSA was increased exponentially with decrease in renal function as compared to SUN. The ratio of methylguanidine to creatinine (MG/CRN) was significantly higher in the patients of group B than those of group A (P <0.05) in the range of creatinine 2.0-8.0 mg/dl. MG/CRN showed a negative correlation with the progression rate of renal dysfunction (P<0.01). It is suggested that GSA might be a more sensitive marker for renal dysfunction than SUN at the end stage of chronic renal failure, and MG/CRN might represent another indicator reflecting the activity of the causal renal disease and progression rate of renal failure. Furthermore, G-TAU could be a potent substance indicating the disease state. From these results, it is concluded that determinations of guanidino compounds in the serum might be useful for recognizing of the state of chronic renal failure.

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Hypotension is an important clinical problem for safe dialysis. In the present study, we divided dialysis patients into two groups according to their clinical features: stable (7 cases) and unstable (7 cases). The serum catecholamine levels were measured every hour during dialysis while monitoring the blood pressure and heart rate. At each time, the plasma noradrenaline levels were found to be significantly higher in the unstable group. However, these levels declined significantly at 3, 4 and 5 hours after the commencement of dialysis, and corresponded to the fall in blood pressure. In contrast, the plasma adrenaline levels revealed no significant difference between the two groups.

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We described a radioimmunoassay system for measuring blood erythropoietin (Epo) levels using recombinant human Epo and evaluated the regulatory mechanisms of Epo in dialysis patients. A satisfactory dose-response relationship for Epo levels was observed within the wide range of 3-250 mU/ml with a sensitivity of approximately 5mU/ml. The Epo levels were found to be 16.1 ± 8.6 mU/ml (m ± SD) in 422 uremic patients on maintenance dialysis and 17.1 ±7.2 mU/ml in 86 normal subjects. The Epo levels were not statistically different between the two groups, although the hematocrit was significantly lower in the dialysis patients. No correlation was observed between the Epo levels and hematocrit in the dialysis patients. Patients with polycystic kidneys had higher hematocrits and Epo levels than patients with chronic nephritis. No changes in Epo levels were observed with age and with the period of dialysis. Diurnal variations in the Epo levels revealed a significant increase after hemodialysis, and an acute reduction in hematocrit following massive hemorrhage raised the Epo levels up to 3, 180 mU/ml. These findings indicate that the Epo levels in dialysis patients are inappropriately low for the severity of anemia and suggest that a negative feedback mechanism of the hematocrit on the Epo secretion may exist in uremic patients as well as in normal subjects and that the threshold for Epo secretion might be 'reset' at a low hematocrit level.

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Since it remains unclear how the regulatory mechanism of blood pressure and volume is associated with the renin-angiotensin system, the sympathetic nervous system, and atrial natriuretic peptide (ANP), we examined the changes in blood pressure and vasoactive hormones occurring in 12 patients with end-stage renal failure. They were divided into two groups, those who were anuric (group A, n=7), and those who had a daily urine volume of more than 700 ml (group B, n=5). The changes in the mean blood pressure (MBP) and these vasoactive hormones were observed during hemodialysis with water removal in group A and without water removal in group B, and during blood pressure reduction with sodium nitroprusside in group A. The basal levels of ANP in groups A and B were twice as high as those of normotensive subjects. During hemodialysis, MBP did not reveal any changes in both groups. In group A, ANP and body weight (BW) decreased, whereas the plasma renin activity (PRA) and norepinephrine (NE) increased. In group B, ANP remained stable during the first 3 hr and decreased at the end of hemodialysis. However, BW, PRA, and NE were unchanged. In group A, significant correlations were observed between the changes in BW and those in ANP (r=0.52, p<0.05), PRA (r=-0.57, p <0.01 ), and NE (r=-0.76, p<0.01 ). During blood pressure reduction, MBP decreased with accompanying increases in NE and PRA. However, ANP did not show any change. Significant correlations were noted between the changes in MBP and those in PRA (r=-0.87, p<0.01) and in NE (r=-0.75, p<0.01), but no significant correlation was found between the changes in MBP and in ANP. These results suggest that in patients with end-stage renal failure, the renin-angiotensin system and the sympathetic nervous system are activated to counteract either a blood pressure or blood volume reduction to maintain the blood pressure, and the regulation of ANP depends mainly on the volume rather than on the blood pressure.

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The prevalence of hepatitis C virus (HCV) infection in patients with long-term hemodialysis (HD) in Japan was assessed using an Ortho HCV Antibody ELISA TEST system. Out of 51 patients, 48 of whom had a history of blood transfusions, 15 (29%) were positive for anti-HCV. This figure is much higher than that in other countries (1-20%), and the difference may reflect a select population. Six (33%) of 18 HD patients with chronic hepatic disease were anti-HCV positive. On the other hand, the prevalence of hepatitis B virus (HBV) markers was 39% (20/51), and 7 (35%) of these 20 with HBV markers were also positive for HCV. The prevalence of anti-HCV showed no relation to the duration of HD treatment. Although a correlation between the prevalence and the blood units transfused was not demonstrated, anti-HCV positive patients had received blood transfusions amounting to significantly more units than those given to negative patients. Anti-HCV was detected in approximately one-third of patients with long-term HD, indicating a lower prevalence of HCV infection as compared to that of HBV infection, and patients with hepatitis of type C accounted for about one-third of HD patients with chronic hepatic disease.

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It has been reported that Neurotropin can markedly improve pruritus in patients undergoing hemodialysis (HD). In order to elucidate the probable causes of pruritus and the antipruritic effect of Neurotropin, various biochemical parameters in the plasma of patients before and during HD were investigated. Forty-three patients undergoing HD were divided into three groups. Eighteen patients had suffered no episode of pruritus (group A), 17 patients had on-going pruritus (group B) and the remaining 8 patients had experienced improvement of pruritus following Neurotropin treatment (group C). The mean concentration of substance P was in only B group significantly increased with HD only in B group, indicating that substance P could be one of the causes of pruritus in patients undergoing HD. Neurotropin appears to exert its antipruritic effect by lowering the level of substance P. The change in parathyroid hormone (PTH) level during HD was not significant in any of the groups, but the mean concentration of PTH in group B was higher than that of group A, indicating that PTH may also be one of the causes of pruritus.

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The V₁ vasopressin receptor antagonist, d(CH₂)₅Try(Me)AVP, enhanced the vasopressin-stimulated osmotic water flow in the toad bladder and inhibited the vasopressin-induced prostaglandin E₂ production at 1 × 10^-9 M. It is well known that prostaglandin E₂ inhibits the vasopressin-induced water flow in the toad bladder. These results indicate that the V₁ vasopressin receptor is possibly present in the toad urinary bladder.

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Using anti-Tamm-Horsfall protein (THP) immunohitochemical study was performed to analyse the relationship between intrarenal reflux and induced nephropathy in surgically resected kidney tissues including hydronephrosis, renal calculi and trauma. With the increase of the histological grade of hydronephrosis intrarenal reflux was observed in two ways. Extratubular efflux of THP was seen to correlate with mononuclear and lymphocytic interstitial inflammation with the initiation by cellular immune response. The reflux of THP was also observed in the Bowman's space, but this did not seem to result in glomerular lesions including adhesion and/or sclerosis.

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A case of Wegener's granulomatosis with renal dysfunction is described. Granulomatous lesions of the lung, left eyelid and left leg, and chronic sinusitis were observed at the time of admission. Renal and skin biopsy specimens revealed typical features of Wegener's granulomatosis on light microscopy and immuno fluorescence microscopy. A dramatic response occurred following cortico steroid and cyclophosphamide therapy, characterized by improvement of proteinuria and renal function, and disappearance of the granulomas and 67gallium citrate accumulations in both the eyes and nose. Further-more, the levels of anticytoplasmic antibodies (ACPA) in the serum samples were significantly decreased after such therapy. It appears that combined therapy with corticosteroid and cyclophosphamide can be effective in improving proteinuria and renal dysfunction, and in reducing of ACPA in patients with Wegener's granulomatosis.

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This report describes an investigation of 128 patients on maintenance hemodialysis. Their serum bone Al-P isoenzyme (Al-P III) values were measured by the Rosalki method, and simultaneous estimations were made of their serum osteocalcin levels as a diagnostic indicator of renal osteodystrophy (ROD). ROD was evaluated clinically from Jensen's criteria, based on a four-stage classification of the radiographic evidence for subperiosteal resorption: no change (stage 0), minor change (stage I), and definite change (stages IIa and IIb). The serum AI-P III levels in the stage ha and lib patients showed significantly elevated values (p <0.01), i.e., 4.98 ± 6.23 and 20.51 ± 13.46 KAU, respectively. In contrast, their serum osteocalcin levels were not appreciably different. Patients with elevated N-PTH values of 0.30 ng/ml or more were found to have serum AI-P III levels of 20 KAU or more, and all of these patients were categorized under the stage IIb classification. It is concluded therefore that in chronic renal failure patients on hemodialysis, measurements of the serum AI-P III are highly useful for diagnosing ROD, and may also be considered as a critical parameter for assessing the indication for parathyroidectomy (PTX).

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