We assessed the renal effects of chronic treadmill exercise in the remnant kidney model of chronic renal failure. Eight-week-old spontaneously hypertensive rats (SHR) were subjected to 5/6 nephrectomy by removal of the left kidney and infarction of two thirds of the right kidney . We performed two series of experiments. Firstly, we investigated the renal effects of chronic mild treadmill exercise in 5/6 nephrectomized SHR. The SHR were divided into 2 groups : a non-exercising group (Non-Ex) and a group conducting mild treadmill running at 20 m/min 0° grade for 30 min (Mild-Ex) 5 times/week for 4 weeks. Secondly, we investigated the effects of moderate or severe treadmill exercise in the rats. The SHR were divided into 3 groups : a non-exercising group (Non-Ex), a group conducting moderate treadmill running at 20 m/min 0° grade for 60 min (Moderate-Ex) and, a group conducting severe treadmill running at 35 m/min 0° grade for 60 min (Severe-Ex) 5 times/week for 4 weeks . Chronic treadmill exercise significantly attenuated the increase in proteinuria and serum total cholesterol levels intensity-dependently. These results were confirmed by morphological analysis of the kidneys. Moderate-Ex provided significantly effective protection against an increase in focal glomerular sclerosis . These results indicate that exercise did not worsen renal function and in contrast, suggest a renal-protective action in this rat model.

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The relationship between nitric oxide (NO) and blood pressure (BP) in deoxycorticosterone acetatesalt hypertensive rats (DOC) was investigated. Although urinary NO₂^- +NO₃^- (NOx) excretion (UNOXV) increased 2 weeks after surgery (2W-DOC), UNOXV decreased 4 weeks after surgery (4W-DOC) compared with that of the control. BP and UNOxV did not change in DOC after treatment with L-arginine (Arg-DOC) . Aorta from 4W-DOC and Arg-DOC had significantly decreased relaxation responses to acetylcholine.Deendothelialized aorta from 4W-DOC and Arg-DOC had significantly decreased relaxation responses to lipopolysaccharide. These data suggest that : 1) transient increase of NO synthesis is accompanied by elevation of BP, but long-term elevation of BP decreases NO synthesis in endothelium and smooth muscle cells ; 2) L-arginine supplement has no effect on the development of hypertension nor on NO production by endothelium and smooth muscle cells in DOC.

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Fibronectin glomerulopathy (FNG) is an inherited disease, characterized by massive Fibronectin (FN) deposits in the glomeruli. We semiquantitatively analyzed glomerular lesions and their progression in 5 cases with FNG from 4 different families : a 4 yearold male, a 19 year-old female, a 27 yearold male, a 58 year-old male (the father of the former case) and a 75 year-old male. All subjects showed a 201 times higher value of mean glomerular-tuft area (GA) and a 2.0 times higher mean number of mesangial cells (No. of MC) relative to control (p< 0.001). Strong positive correlations were observed between GA and the No. of MC (r=0.86, p< 0.001). The younger cases showed markedly higher value of GA and No. of MC than the older cases. Mean individual capillary luminal area was decreased in all but one case and the mean total capillary luminal area, which is roughly estimated as the glomerular filtration area, was less changed compared with the control. The number of capillary loops tended to increase, indicating elongation of the capillary loops. The fractional area of FN (%FN), collagen IV (%Coll. IV) and laminin (%Lam) were high in all cases except for the first Bx in the 27 year-old case. The %FN strongly correlated with %Coll. IV and %Lam (r=0.86, r=0.69, p< 0.001, respectively). Serial biopsy (Bx) with a 10 year interval was examined in the 27 year-old case and his father : GA and No. of MC were increased 1.4 and 1.9 times in the son, compared with his first Bx (p < 0.001, respectively), while no change was observed in the father. The %FN, %Coll. IV and %Lam were significantly increased in their second Bx (p<0.001). These results suggest that 1) enlargement of the glomeruli in FNG is caused by intraglomerular accumulation of FN, Coll. IV and Lam and proliferated mesangial cells, 2) there is a strong influence from the aging factor, and 3) compensatory elongation of the loops (increase in the capillary luminal area) may maintain the glomerular filtration.

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To investigate the role of thrombomodulin (TM) and tumor necrosis factor-α (TNF-α ) in hemolytic uremic syndrome (HUS), serum and urinary levels of TM and TNF-α were determined in patients with hemorrhagic enterocolitis (HC) of enterohemorrhagic E. coli O157: H7 infection. These patients were divided into two groups: an HUS group consisting of patients with HUS; an HC group consisting of patients without HUS. In the 10 days after the onset of diarrhea, the serum TM and TNF-α levels in the HUS group were significantly elevated compared with those in the control group but decreased after 11 days. The serum TM and TNF-α levels in the HC group were not elevated compared with those in the control group except for one case of TNF-α. It is suggested that the serum TM elevation showed the severity of endothelial cell damage. Urinary TM and TNF-α levels in the HUS group were significantly elevated in the first 10 days. The urinary TNF-α levels rapidly decreased after 11 days, while the urinary TM levels were persistently high. From these results, the sustained elevation of the urinary TM levels suggested the persistent presence of renal endothelial cell damage, and the decrement of urinary TNF-α levels suggested that TNF-α acted as a trigger of the renal endothelial cell damage in the first 10 days.

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Steroid therapy occupies a very important position in various types of kidney diseases in children . The period of steroid therapy in kidney disease tends to extend over a long time and the amount of medication tends to be high. Inhibition of the adrenal function because of steroid therapy is one of the major side effects requiring considerable care. In the present investigation, we examined the inhibition of adrenal function in various pediatric renal diseases using synthetic ACTH . In this study, we checked the serum 11-OHCS and cortisol levels and found that in nephrotic syndrome, the inhibition already existed at sideration. In other diseases we found inhibition of adrenal function using steroid and improvement of the function on reduction of the steroid dose. Patients who used steroid every other day showed better improvement. Therefore, we suggest that in nephrotic syndrome, the inhibition of adrenal function may participate in sideration in the syndrome. It was also found that reduction of the steroid given every other day inhibited the adrenal function to a lesser extent. We found that our challenge test using ACTH is safe and very useful for determining adrenal function .

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QT prolongation, a risk factor for arrhythmia and cardiac death, is observed in uremic patients. Though hypocalcemia, autonomic nerve dysfunction and cardiac hypertrophy are assumed to cause the uremic QT prolongation, the exact mechanism remains unspecified. We therefore examined factors related to the QT interval in chronic renal failure (CRF). Corrected QT interval (QTc) was significantly prolonged in CRF just before the induction of dialysis therapy (group A) compared with nephrotic syndrome with the intact or mildly impaired renal function (group B) . QTc was also prolonged in acute renal failure (group C). Cardio-thoracic ratio, serum albumin and Ca correlated with QTc in group A, but not in B or C. A single HD session in group A failed to shorten QTc, despite a significant increase in serum Ca⁺⁺ Autonomic dysfunction did not appear to be a major determinant of QT prolongation, since QTc was not different between diabetics and non-diabetics in group A and in chronic HD patients (group D). In group D, QTc did not correlate with SV₁+RV₅ on ECG or left ventricular wall thickness (LVWT) on echocardiography.In another group of chronic HD patients (group E), there was no significant correlation between QTc and the parameters of left ventricular mass, plasma brain natriuretic peptide (BNP). However, in the patients subjected to repeated echocardiography in group D, QTc and LVWT changed in parallel. In a retrospective analysis of QTc in group D, QTc was maximally prolonged at the time of starting HD therapy, and gradually improved in the following 1-5 years in both diabetics and nondiabetics. In contrast, chronic CAPD patients (group F) revealed no improvement of QTc. Thus, uremic QT prolongation cannot be explained simply by any of the previously assumed factors, but appears to be affected by multiple factors, which are partially correctable by chronic HD therapy.

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A 26-year-old woman who presented facial and lower leg edema associated with massive proteinuria was admitted to our hospital in Nine months before this admission, she exhibited myasthenia gravis and malignant thymoma, and underwent total thymectomy . On admission, there was no symptom of myasthenia gravis. She was diagnosed as having nephrotic syndrome and the first renal biopsy was performed. The histological findings showed membranous nephropathy . Immunofluorescent microscopy revealed that IgG and C3 were stained in a granular pattern in the periphery, and subepithelial deposits were observed in the basement membrane of the glomerulus by electron microscopy . With the administration of prednisolone, proteinuria disappeared and the nephrotic syndrome remitted . She was admitted again in due to proteinuria and lower leg edema following cystitis . The findings of the second renal biopsy were unremarkable . She was administered cyclosporin A to improve the nephrotic syndrome and to reduce the side effects of prednisolone . The proteinuria disappeared again and this effect was dependent on the dose of cyclosporin A . Since the first administration, no symptoms of myasthenia gravis or malignant thymoma have been observed . The relationships among myasthenia gravis, malignant thymoma and nephrotic syndrome were examined . Although the first renal biopsy findings showed membranous nephropathy, from the therapeutic responses of both prednisolone and cyclosporin A, the main course of proteinuria in this case may have been due to minimal change nephrotic syndrome . We consider this case of nephrotic syndrome to be important considering its etiology and the relationship between the histological findings and its clinical course .

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Focal segmental glomerulosclerosis (FSGS) associated with type C virus (HCV) hepatitis has not been described in the literature to date. However, we experienced a 30-year-old man, who had had HCV hepatitis, developed nephrotic syndrome and was admitted to our hospital . The first renal biopsy showed FSGS which was diagnosed by light, immunofluorescent, and electron microscopic study. FSGS diagnosis was based upon the findings of focal segmental glomerular sclerosis associated with hyalinosis and foamcells, segmental deposition of IgM and C₃ on glomeruli, and epithelial cell vacuolization in the Bowman's space. HCV hepatitis was treated with interferon -α (INF-α ) over 6 months. The treatment brought the disappearance of not only HCV-RNA from the blood, but also the manifestation of nephrotic syndrome. Therefore, the second renal biopsy was performed, but did not reveal any great pathological improvement. Five months later after the remission, he again had an elevated HCV-RNA level and a relapse of nephrotic syndrome. He was retreated with the same therapy and achieved a second remission of nephrotic syndrome. FSGS associated with HCV hepatitis is described first and the implication of INF-therapy in the improvement of proteinuria is discussed.

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We report the case of a 21-year-old man who had been developing acute renal failure with Methicillin-resistant Staphylococcus aureus (MRSA) colitis and sepsis. He was admitted for conscious-ness disturbance, nausea, vomiting, and diarrhea. Oliguria was also observed and his serum creatinine level was elevated to 10 mg/dl. Urinary protein was positive and an abundance of hyaline cast were seen in urinary sedimentation. Diarrhea and pyrexia were prolonged and serum C-reactive proteins were elevated, but lymphocyte and leukocyte counts temporarily decreased from the 3rd to the 6th hospital day and remained low until normalizing after the 14th day. His clinical symptoms improved with hemodialysis (HD) and effective antibiotic therapies. An MRSA strain producing toxic shock syndrome toxin-l (TSST-1), a super antigen which specifically stimulates human Vβ ₂-positive T cells, was separated from his feces and blood. To ascertain the cause of his renal dysfunction, a renal biopsy was performed on the 8th day. His renal histology revealed acute interstitial nephritis with severe inflammatory cell infiltration around the medullary areas without glomerular changes. Most of the infiltrated cells were small monocytes, and lymphoid cells were rich in the interstitium. With immunohistochemical staining, over 70 % of T-cells were Vβ₂-positive. TSST-1-producing MRSA was detected in his blood specimen. Furthermore, VR2-positive T cells were accumulated in the renal intersititium, and transient lymphocytopenia was observed. These data suggested the following possible pathogenesis for interstitial nephritis : TSST-1 acts as a super antigen in the renal interstitium where major histocompatibility complex (MHC) is class-2-positive, thereby resulting in interstitial nephritis with T cell migration.

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