This study was designed to determine whether or not the appearance of type I or type III collagen in glomeruli and serum procollagen III peptide (PIIIP) concentration are affecting the prognosis of patients with IgA nephropathy. In cases with reduced creatinine clearance (Ccr<80 ml/min) at the time of renal biopsy, the appearance of type III collagen increased, and subsequently type I collagen appeared as Ccr decreased. In addition, We measured serum PIIIP concentration in these cases. The increase of serum PIIIP correlated with the decrease of Ccr. These results suggest that theappearance of type I and III collagen in glomeruli and the increase in serum PIIIP concentration might be a useful marker to predict the outcome of IgA nephropathy.

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Autoantibody formation and lymphocytes proliferative response to tubular basement membrane (TBM) antigen were examined to clarify the pathogenesis of gold nephropathy, in rheumatoid arthritis patients. The existence of tubulopathy was ascertained by urine protein analysis, electrophoresis and urine TBM antigen titration. Circulating antibody to human TBM antigen titrated by enzyme immunoassay was significantly elevated in patients with gold tubulopathy, and mitogenic stimulation with TBM antigen of peripheral lymphocytes specifically responded in the early stage after receiving gold, but then clearly decreased after the cessation cessation of gold. But, when the lymphocytes had been passed through a nylon wool column, the reaction was remarkably high even in the later stage after receiving gold, suggesting that another suppressive population of lymphocytes became trapped in the nylon wool column. This evidence suggests that gold compounds definitely act as initiating and promoting agents, and the development of tubular disorders induced by gold are likely related to the cellular recognition of effector Tcells to the TBM antigen, following the strong effect of gold on the cellular immune system.

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In an attempt to clarify the indication and efficacy of the methylprednisolone pulse therapy (1000mg x 3times) for rapidly progressive glomerulonephritis (RPGN), 3 patients with the disease were carefully followed and the clinical course during and after the treatment were precisely analysed. According to the declination rate of reciprocals of serum creatinine(1/Cr), one patient were divided into the acute type (-1.00x10-2dl/mg/day or less) and the others into the subacute type (more than 1.00 × 10-2 dl/mg/day). In the patient of acute type, renal biopsy revealed cellular crescent formation in 93.8% of glomeruli observed. One course of the pulse therapy resulted in a decrease in Cr from 3.0mg/dl to 1.3mg/ dl and transformation of cellular crescents to fibrocellular or fibrous crescents. In the other two patients of subacute type, crescents were observed in 72.7% and 72.0% of glomeruli observed, and 87.5% and 38.9% of them were composed of cellular crescents respectively. lnitial courses of the pulse therapy resulted in decreases of Cr from 3.5mg/dl to 2.4mg/dl and from 3.0mg/dl to 1.4mg/dl respectively. Additional courses, given because of insufficient reduction of Cr in the former, induced a further lowering to 1.3mg/dl, and because of re-elevation of Cr to 2.2mg/dl and remaining of cellular crescents in 20% in the latter, induced a decrease of Cr to 1.5mg/dl and disappearance of cellular crescents. These results suggest that the methyl prednisolone pulse therapy has apparent and prompt effects on RPGN administered when the disease is in an active phase indicated by linear declination of 1/Cr and presence of cellular crescents in glomeruli, and the additional course administered when the disease activity persists indicated by re-elevation of Cr in addition to remaining of cellular crescents, but no more course may be necessary when Cr has been stable.

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We investigated to confirm the biochemical mechanisms of the hypothesis that lipid peroxidation participates in the pathogenesis of aminoglycoside-induced nephrotoxicity. Male Sprague-Dawley rats were injected with gentamicin (GM), 300mg/kg per day. Twenty-four hours after the injection the rats were killed and the renal cortex was processed for glutathione (GSH), malondialdehyde (MDA), phospholipase A₂ (PLA₂), phosphatidylcholine (PC), sphingomyelin (SPH) and phospholipids (PL). And we also studied the GSH reduced rats by buthionine sulfoximine (BSO) administration, to compare the biochemical differences with these parameters in two groups. GM induced a significant decrease of PLA₂, SHP/PC ratio and GSH. Marked elevation of MDA (lipid peroxidation) and PC were observed after a single injection of GM. In contrast, BSO injected rats were not showed increment of tissue MDA, in spite of marked reduction of renal GSH. These data support the conclusion that accelerated lipid peroxidation occurs early in the course of GM administration and inhibition of lysosomal PLA₂ activity involved in the degradation of lysosomal membrane which consisted of phospholipids.

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Thirty-one autopsy cases of beta 2-microglobulin (β2M) amyloidosis were pathologically investigated in comparison with 17 autopsy cases of AA or AL amyloidosis. In 20 cases (65%, 20/31) of β2M amyloidosis, inframmatory cells, mainly macrophages were seen infiltrating around jS2M amyloid in intervertebral disks. The more β2M amyloidosis advances, the more macrophage infiltration tends to be prominent. In cases of severe β2M amyloidosis, the cytoplasm of macrophages around amyloid deposition were swollen with engulfed amyloid substance and were often transforming to foreign body multinucleated giant cells. In addition, granulation tissue was formed with infiltrating macrophages, foreign body multinucleated giant cells, capillary proliferation and fibrosis around β2M amyloid deposition.On the other hand, inframmatory cell infiltration around amyloid deposition was scarcely seen in AA or AL amyloidosis. Ultrastructurally, macrophages were abandant in phagocytic vacuoles containing amyloid fibrils. These macrophages were immunohistochemically positive for CD68, IL-1 β and TNF-α. Thus, macrophage infiltration around β2M amyloid is thought to be responsible for local pain and tissue destruction of dialysis patients.

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We conducted a multiplecenter joint study on the effects of recombinant human erythropoietin (rEPO) for predialysis patients. rEPO was intravenously administered to 42 predialysis patients (13 males and 29 females) with hematocrit (Ht) levels of less than 30%. The subjects were divided into group A (28 cases)in which rEPO was administered twice a week, and group B (14 cases) with rEPO administration once a week. The initial adminis-tration dosage was 60001U/week. The Ht levels were 22.6±3.3% for group A and 23.2±2.7% for group B before the administration of rEPO, and increased to 31.0±4.0% and 27.7±3.7% respectively twelve weeks after initiating administraion. The levels of effective improvement on anemia included 'markedly effective' in 17 cases (80.9%) and 'effective' in 2 cases (9.5%) in group A, and 'markedly effective' in 5 cases (41.7%) and 'effective' in 3 cases (25.0%) in group B. No significant change was seen in serum creatinine (Cr) levels during the study period. In the evaluation of renal function by reciprocal serum creatinine (1/Cr), a consistent tendency was not recognized; thus, suggesting that the rEPO administration had no effect on the renal function. No variation of blood pressure was seen. As far as side effects were concerned, headache and heavy headedness were recognized in four cases. There were, however, no cases in which the severity of the side effects dictated the discontinuation of the rEPO administration. In conclusion, rEPO was judged to be a safe and effective treatment for the anemia of predialysis patients.

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The marvelous effect of recombinant human erythropoietin (EPOCH) on the anemia of the patients suffering from chronic renal failure had been already reported even in the predialysis patients. However, the influence on residual renal function as well as pharmacokinetics of EPOCH in predialysis patients was not clarified yet. Therefore, we made a clinical study of EPOCH in 10 predialysis patients to investigate the clinical effect as well as pharmacokinetecs. EPOCH was administered intravenously once a week with the dosage of 3, 000-9, 000 IU for 8 weeks. All patients showed prominent improvement of anemia. Though no patient show serious adverse effect, two patients showed controllable hypertension accompanying with the increase of hematocrit. Meanwhile, the speed of the deterioration of residual renal function obtained from the regression line by reciprocal of the serum creatinine was not aggravated by the correction of anemia. Pharmacokinetic study revealed that the halflife of EPOCH was extended compared to normal but the degree of extension was same as that of in dialyzed patients. The plasma concentrationtime curves showed the pattern of monoexponential disappearance and the area under the curve (AUC 0 to 48 hr.) showed dose-response increase. However, both parameters mentioned above as well as systemic clearance rate did not show any change between those of on day 0 and on day 56. These results no long-term accumulation of EPOCH, though the level of intrinsic erythropoietin was decreased after EPOCH treatment. Thus, the beneficial effect of EPOCH on the correction of anemia was revealed even in the predialysis patients without affecting on residual renal function.

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A 59-year-old male was admitted to our clinic for further examination of the calcified renal cyst discoverd incidentally on medical workup elsewhere. CT showed a left renal cyst associated with calcification. Ultrasound-guided puncture of the renal cyst was not successful because of thickness of the cystic wall. Renal angiography showed hypervascularity of the cystic wall. Association of renal cell carcinoma could not be ruled out, therefore the exploration was performed. Histological examination revealed benign renal cyst with calcification. A 27-year-old male presented with the chief complaint of left flank pain. Following examinations by US, CT and MRI, a renal cyst associated with renal cell carcinoma was highly suspected. Subsequent exploration revealed cluster of cysts with a yellowish lesion a few mm in diameter. Frozen section, revealed no malignancy, and cystic fluid was not hemorrhagic. Therefore as many cystic walls as possible were removed without nephrectomy. Histological examination of the permanent specimen revealed renal cell carcinoma. Renal cyst associated with renal cell carcinoma was regarded as rare clinical entity, but such cases are reported in increasing number in recent years. We report such cases and review the pertinent literature in this paper.

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Endothelium-derived relaxing factor (EDRF) is a substance that is released by the vascular endothelium and mediates vasodilator responses induced by various substances including acetylcholine (AC). Superoxide anion (O₂-) inactivates EDRF. It is well known that the endothelium-dependent vascular relaxations to AC are depressed in the aorta of spontaneously hypertensive rats (SHR). We studied the role of O₂ on onset and maintenance of hypertension in SHR. Male 4- and 17-week old SHR (4SHR, 17SHR), and enalapril treated 17-week old SHR (5 mg/kg/day for 4 weeks: ETSHR), and age-matched normotensive Wistar-Kyoto rats (WKY; 4WKY, 17WKY) were used. Relaxation responses to AC or superoxide dismutase (SOD) were measured in isolated aortae from rats. Mean arterial pressure (MAP) was measured after injection of SOD in rats under conscious state. Systolic blood pressure of 4SHR, 17SHR, ETSHR, 4WKY, and 17WKY were 129± 2 mmHg, 203±3 mmHg, 158±3 mmHg, 97±1 mmHg, and 138±2 mmHg, respectively. Although relaxation responses to AC were decreased in aortae from 4SHR, 17SHR, and ETSHR compared with those from age-matched WKY, relaxation responses to SOD dit not differ between SHR and corresponding WKY. Whereas the injection of SOD(10000 U/kg) elicited a significant reduction of MAP in 4SHR (-11±3 mmHg) and 17SHR (-24±5 mmHg), it has no effect in WKY. These data suggest that AC mediated endothelium-dependent relaxation is attenuated in SHR and that excessive O₂ in the endothelium resulted from hypertension may conributes the decreased response in SHR.

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A 28-year old male was admitted to our hospital because of heart tallure, cnronlc renal failure and nephrotic syndrome. Light microscopic findings of his kidney biopsy showed proliferation of mesangial cell and marked narrowing the lumina of small arteries and arterioles. The changes of these small vessels were not those of typical vasculitis, when we considered his age and his past history. The diagnosis of dilated cardiomyopathy was made by the findings in echocardiography and cardiac catheterization. Since the heart failure and renal disease seemed to be simultaneous initated, it was supposed that the diseases in two organs were caused by a common pathogenesis related to that of vasculitis. When steroid pulse therapy was adopted, both of cardiac and renal function responded to this treatment (ejection fraction from 26% to 52%, creatinine clearance from 48 to 62 ml/ min). Increase of CD56 positive cells ( natural killer cells) in peripheral blood was ameliorated after the treatment. These findings suggest that cellular immunity may be concerned with the pathogenesis of the combination of dilated cardiomyopathy and renal disease in this case.

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We report a case of microscopic polyarteritis nodosa associated with myeloperoxldaseantineutrophil cytoplasmic autoantibodies( MPO-ANCA) . A 38 year-old female was admitted to our hospital, because of proteinuia, reccurent pyrexia, polyarthralgia, abdominal pain and purpura. She had a history of severe pulmonary hemorrhage and 4 kg weight loss for 8 months. On admission perinuclear ANCA without cytoplasmic ANCA was detected by indirect immunofluorescence assay and MPO-ANCA was detected by emzyme linked immunosorbent assay. But anti-nuclear antibodies, immune complexes and anti-glomerular basement mambrane antibodies were not detected. Renal biopsy showed necrotizing crescentic glomerulonephritis without immune deposits. Skin biopsy revealed leukocytoclastic vascu-litis. Diagnosis of microscopic polyarteritis nodosa was made by these clinical and histological evidence of vasculitis. As renal failure progressed after admission, corticosteroid and cyclophosphamide administration were started. Renal function and other symptomes improved paralleled with decreased MPO-ANCA titer to normal values. It is suggested that MPO-ANCA may be closely related to the pathogenesis of microscopic polyarteritis nodosa and it may be a good serological marker for diagnosis and disease activity of this disease.

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A 67-year-old man was hospitalized with a diagnosis of nephrotic syndrome. Physical findings at admission were generalized edema and macroglossia. Urinalysis showed massive proteinuria, + + occult blood, and granular and broad casts. Ig A λ monoclonal gammopathy was noted in the serum. There was no evidence of myeloma in the bone marrow aspirate, scintigram or X-ray of the bone. A biopsy specimen of the kidney showed massive deposits of structureless material in the glomeruli. Marked cell infiltration was also observed in the interstitium. Multinucleated giant cells were occasionally seen in the Bowman's capsules and the interstitium. There were reactive changes in the Bowman's capsule adjacent to the giant cell. The deposits were proved to be amyloid by positive staining with Congo red and apple-green birefringence by polarized light. In addition, microfibrills seen on electron microscopy displayed deposits. Amyloid depositions were observed in other tissues such as gingiva, skin and tongue. Staining of amyloid with Congo red was resistant to potassium permanganate, and amyloid was posi-tively stained with λ-light chain of immunoglobulin. These findings indicated that the patient had primary amyloidosis. Infiltration of the multinucleated giant cell has been reported only in patients wlth familial amyloidosis and secondary amyloidosis associated with rheumatoid arthritis. To our knowledge the present case is a first report of the giant cell infiltration in a Bowman's capsule in primary amyloidosis.

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This study aimed to elucidate the effects of intravenously infused magnesium on renal calcium and sodium metabolism in patients with essential hypertension. Mean arterial pressure (MAP), heart rate (HR), urine volume (UV), endogenous creatinine clearance (Ccr), urinary excretion of calcium (U_CaV) and sodium (U_NaV), fractional excretion of calcium (FE_Ca) and sodium (FE_NaV), plasma ionized calcium (pCa²⁺) and parathyroid hormone(PTH) were measured before and after intravenous infusion of 10% magnesium sulfate (initial dose: Mg 13.5mg/m²BSA/15 min.: maintenance dose: Mg 2.7mg/m² ·BSA/105min) in 6 normotensive subjects (NT) and 13 mild-to-moderate essential hypertensives (EHT). After the magnesium infusion, significant increases of UV, U_CaV, U_NaV, FEca and FE_Na, and a significant decrease of PTH were observed in both NT and EHT while MAP and HR did not change in either group. PCa²⁺ significantly decreased and Ccr tended to increase only in EHT. Although no significant difference was found in the change in Ccr (ACcr) or PTH (Z PTH) between NT and EHT, the changes of U_CaV (Δ_CaV), U_NaV (ΔU_CaV), FE_Ca (ΔFE_Ca) and FE_Na (ΔFE_Na) were greater in EHT than each in NT. A positive correlation was found between ΔU_CaV and ΔFE_Ca, as well as ΔU_CaV and ΔC_Cr, but the former was more remarkable in both groups. In addition, ΔU_CaV was positively correlated with ΔFE_Na in EHT, but not in NT. No significant relationship was observed between ΔU_CaV and ΔPTH in either group. Thus, it is concluded that in EHT, the i. v. infusion of magnesium produces the enhanced calciuresis and natriuresis which might result from suppression of renal tubular reabsorption of calcium and sodium, and this suppression is partly related to the attenuation of plasma PTH. Furthermore, a possibility should be considered that the enhanced calciuretic response might contribute to the hypotensive mechanism of long-term magnesium loading in EHT.

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