長谷川 みどり

Background. Maxacalcitol (22-oxacalcitriol OCT) is a novel vitamin D analogue. In previous clinical studies, OCT was administered three times a week to hemodialysis patients with refractory secondary hyperparathyroidism (2HPT), in whom it acted by inhibiting parathyroid hormone secretion, as well as causing mildly elevated serum calcium. However, intravenous injection of OCT, which requires frequent visits to the outpatient clinic, degrades the quality of life of patients with continuous ambulatory peritoneal dialysis (CAPD) who otherwise visit the clinic only once or twice per month. In the present study, we investigated whether transperitoneal absorption of OCT inhibited intact parathyroid hormone (i-PTH) in CAPD patients when the OCT was added to the peritoneal dialysis fluid. Methods. Peritoneal dialysis fluid containing 20 μg of OCT was injected into the peritoneal cavity of five CAPD patients. The serum and peritoneal fluid levels of OCT, i-PTH, calcium, and phosphate were measured before and after treatment. Results. The mean concentration of OCT in peritoneal dialysis fluid rapidly decreased, from 25268.0 pg/ml at 0 h to 1694.0 pg/ml at 2 h and 44.9 pg/ml at 4 h. In contrast, the mean serum OCT level increased from the pretreatment level, which was below the detection limit of the assay, to 656.0 g/ml at 0.5 h and a peak of 759.0 pg/ml at 1 h, and thereafter gradually decreased, to 713.8 pg/ml at 2 h and 555.8 pg/ml at 4 h. Mean i-PTH significantly decreased, to 83.9% of the baseline level, at 1 h (P &lt 0.05) and thereafter stayed at around 90%. No consistent trends in calcium and phosphate levels were observed in the five patients. Conclusions. By injecting OCT into the peritoneal cavity, i-PTH levels could be significantly decreased. These findings indicate the therapeutic efficacy of intraperitoneal administration of OCT for CAPD patients.

Cholesterol embolic disease is a devastating complication of atherosclerosis. Universally recommended treatment is lacking thus far. Recent data suggest that a therapeutic protocol aimed at specifically combating three causes of mortality, recurrent bouts of cholesterol embolism, cardiac failure, and cahexia, were associated with a favorable clinical outcome. As for drug therapy, corticosteroid has been reported to be beneficial in reducing local and general inflammatory responses. Concerning apheresis, combined therapy consisting of plasma exchange and low to intermediate-dose corticosteroid therapy has been shown to be effective in multivisceral cholesterol embolism. Low density lipoprotein (LDL) apheresis has been reported to be beneficial for cholesterol embolism-induced damage to the skin and brain.

Mechanisms responsible for the development of focal segmental sclerotic lesions of the glomerulus (FSGS lesions) in transplanted kidneys were investigated by morphometric analysis. The mean glomerular area and the interstitial area were measured using computerized image analysis to compare implantation biopsies (so-called 1-h biopsies; 1Bx) with later biopsies (episode Bx; EBx) that had been taken for diagnostic purposes to identify the cause of deteriorating renal function. Groups of patients with (group A, n = 15) or without (group B, n = 10) FSGS lesions were compared. Twelve of 15 in group A and all in group B had lost graft function due to chronic allograft nephropathy. It was found that neither the mean glomerular area nor the interstitial area differed significantly between the two groups in either 1Bx or EBx. The interstitial area was significantly increased (P = 0.007) and the mean glomerular area tended to be increased (P = 0.085) in EBx compared with 1Bx in group A but not in group B. The serum creatinine level at the time of EBx in group A correlated with the interstitial area (P = 0.031) but not the mean glomerular area. However, there was no similar correlation in group B. In conclusion, factors for the development of FSGS lesions in transplanted kidneys may be the increase in interstitial area and possible glomerular hypertrophy following transplantation, rather than pre-existing reduced renal mass of the donor kidneys.

To minimize the adverse effects of high-dose administration of steroids and cyclophosphamide in patients with myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA), granulocytapheresis (GCAP) or leukocytapheresis (LCAP) was performed to reduce inflammation. Four patients with rapidly progressive glomerulonephritis (RPGN) and one patient with pulmonary hemorrhage due to MPO-ANCA-associated vasculitis were treated by cytapheresis. The prednisolone (PSL) dose was 0.28 +/- 0.15 mg/kg/day (mean +/- SD) (range 0.18-0.50 g/kg/day). In the 4 RPGN patients, the peak serum creatinine level was 3.7 +/- 1.9 mg/dl (range 1.7 to 5.6 mg/dl). GCAP was performed in 3 RPGN patients and in 1 pulmonary hemorrhage patient. LCAP was performed in 1 RPGN patient. In the 4 RPGN patients, renal function improved after combined therapy with cytapheresis and corticosteroids. In the pulmonary hemorrhage patient, evidence of pulmonary hemorrhage on chest computed tomography scanning diminished after combined therapy with cytapheresis and corticosteroids. Cytapheresis, when combined with a low-dose or intermediate-dose PSL regimen, is effective in the treatment of ANCA-associated vasculitis.

Reticulocyte hemoglobin content (CHr), percentage of hypochromic red blood cells (%HRC, level of serum transferrin receptor(sTfR), and sTfR/serum iron ratio (sTfR/Fe) were measured in 132 hemodialysis patients. On univariate analysis, CHr was positively correlated with serum amyloid A (SAA) and negatively correlated with Kt/V. %HRC showed a positive correlation with the recombinant human erythropoietin (rHuEPO) dosage. The dependency of each iron-status index on 5 variables, SAA, sFt, TS, KtN, and dose of rHuEPO administered, was determined by stepwise multiple regression analysis. CHr was influenced only by TS, while %HRC, sTfR and sTfR/Fe were influenced by both logrHuEPO dosage and TS. Patients whose hemoglobin concentration increased by more than 1 g/dl following iron supplementation were defined as Iron-Responders, and the remaining patients were defined as Iron-Nonresponders. Fifteen out of 20 patients responded to 10 consecutive intravenous administrations of 80 mg of saccharated ferric oxide at each dialysis session, while five did not. The baseline CHr was significantly lower in Iron-Responders than Iron-Nonresponders. The baseline %HRC, sTfR, and sTfR/Fe were significantly higher in Iron-Responders than Iron-Nonresponders. The baseline CHr, %HRC, and sTfR/Fe were correlated with the degree of change in Hb concentration at 4 weeks of iron supplementation. The absolute change in CHr at 2 weeks of iron supplementation was positively correlated with the absolute change in Hb concentration over the first 4 weeks. Conclusion: (1) In assessing the iron metabolic status of dialysis patients, CHr, %HRC, and sTfR/ Fe were unique indices compared with the ordinary indices, particularly in diagnosing the functional iron deficiency state. (2) CHr was a valuable marker of iron deficiency anemia and could predict the degree of increase in Hb level following iron supplementation. (3) The %HRC and sTfR/Fe seemed to reflect both erythropoiesis induced by rHuEPO and the iron supply to erythropoietic cells.

Objective The diagnosis of amyloidosis still relies on biopsy, but there has been a growing demand for the development of a specific noninvasive diagnostic technique, Hepatocyte growth factor (HGF) acts on a variety of epithelial cells in multiple ways and is predominantly produced by mesenchymal cells and macrophages, In the present study, me measured the serum HGF level in patients with amyloidosis and investigated its usefulness for the diagnosis of this disease. Methods The subjects were 18 patients diagnosed as having amyloidosis by biopsy. We also measured serum HGF in 47 patients with chronic glomerulonephritis, 32 patients on hemodialysis, and 24 healthy volunteers, The serum HGF level was measured using an HGF ELISA kit. Results The serum HGF level of patients with amyloidosis was significantly increased compared with that of healthy volunteers, patients with chronic glomerulonephritis, and hemodialysis patients (2.26+/-2.73 ng/ml versus 0.20+/-0.04 ng/ml, 0.23+/-0.08 ng/ml, and 0.18+/-0.07 ng/ml respectively, p<0.0001). There was no significant difference between amyloid light-chain and amyloid A amyloidosis, but the serum HGF level of amyloidosis patients who died within 1 year of measurement was significantly higher than that of patients who lived for more than 1 year (2.83+/-2.85 ng/ml versus 0.49+/-0.26 ng/ml, p<0.01). Conclusions The serum HGF level was significantly elevated in both amyloid light-chain and amyloid A amyloidosis and was a very useful indicator of suspected amyloidosis as well as a potential prognostic indicator. The serum HGF level may become a useful indicator for diagnosing amyloidosis.

In this report, we describe 5 patients with cholesterol atheroembolic renal failure. in 3 of the 5 patients, combined therapy with corticosteroids and plasma exchange was performed. These 3 patients survived, with 2 showing an improvement in renal function. The 2 remaining patients died of multifactorial causes, The literature on therapy for cholesterol atheroembolic renal failure is reviewed and the efficacy of combined therapy by use of corticosteroids and plasma exchange is evaluated. Copyright (C) 2000 S. Karger AG, Basel.

The levels of immune complex (IC) were studied by using two different methods in order to analyze the activation process of C 1 in IC diseases. In vitro, heat aggregated IgG (HAG) in various concentrations was added to normal sera, and was incuvated at 37°C for 48 hours. IC levels were determined both by the C 1 q solid phase assay (ELISA) and by the anti-C 1 q antibody assay (ELISA). Meanwhile, changes in the concentration of (C 1 r-C 1 s) C 1 inhibitor2 complex were also determined (ELISA) as the indications of the levels of activated C 1. The levels of IC obtained by the C 1 q solid phase assay decreased in the temporal course after adding HAG. On the other hand, a gradual increase in the temporal course after adding HAG was observed in the levels of IC determined by the anti-C 1 q antibody assay, and in those of (C 1 r-C 1 s) C 1 inhibitor2 complex. The larger the amounts of added HAG, the greater the increase in the levels of IC and (C 1 r-C 1 s) C 1 inhibitor2 complex. The activation of C 1 occurred after the connection of C 1 with HAG, which was demonstrated by the clear differences in the aspect of C 1 activity between the levels of IC measured by the C 1 q solid phase assay and by the anti-C 1 q antibody assay. These results suggest that the participation of C 1 in the development and progress of IC diseases can be examined more clearly by both assays. One ITP-patient was treated with steroid whose levels of IC determined by the anti-C 1 q antibody assay were continuously high and by the C 1 q solid phase assay were normal. During and after the treatment, his levels of IC, (C 1 r-C 1 s) C 1 inhibitor2 complex, and platelet-associated IgG were lowered, and the platelet counts and CH 50 levels were gradually improved. The results obtained by the in vitro study with HAG explain the discrepancies between the levels of IC determined by the C 1 q solid phase assay and by the anti-C 1 q antibody assay. © 1993, The Japan Society for Clinical Immunology. All rights reserved.

The requirements for a diagnosis of Goodpasture's syndrome (GPS) include: (1) the presence of glomerulonephritis, (2) alveolar bleeding, and (3) the presence of anti-glomerular basement membrane (anti-GBM antibody). Among Japanese case, the 2 patients reported here were rare in that they satisfied all of these requirements. In case 1 (a 40-year-old male), the disease developed with initial signs of proteinuria and hematuria. The patient developed hemoptysis after hospitalization. The interval from onset to hospitalization was 38 days. The serum creatinine (CRN) level was 3.6 mg/dl on admission. The pathological findings were rated as full-circumferential, cellular crescentic nephritis, and the patient did not display oliguria. The renal and pulmonary impairments in this case were markedly improved by glucocorticoid (prednisolone PSL, 60 mg/day), cyclophosphamide therapy (50 mg/day) and plasma exchange (PE 10 times). In case 2 (a 58-year-old male), the initial signs developed as proteinuria and hematuria, followed by rapidly progressive renal functional deterioration and hemoptysis occurred. Compared to Case 1, the interval from onset to hospitalization was longer in Case 2 (125 days) and the CRN level was also higher (10.7 mg/dl). Case 2 was rated as full-circumferential, fibrous crescentic nephritis, and the patient was oliguric. Although the pulmonary impairment was reduced by pulse therapy and 10 PES, recovery of renal function has not been achieved, still necessitating maintenance hemodialysis at present. In case 1, the disease relapsed at 4.5 years after remission, presenting with aggravated renal function and hemoptysis. In this case, low-dose PSL therapy had been discontinued at 3 months before the relapse. Following the relapse, the pulmonary impairment was reduced by hemodialysis, PE and pulse therapy, but recovery of renal function has not been achieved, so necessitating maintenance hemodialysis. In general, the percentage of complete remission is high for GPS, but some patients showing relapse have also been reported. The anti-GBM antibody titer, whose determination has become possible in recent years, is expected to represent a useful index in the prevention of relapse of GPS and in the management of patients during gluco-corticoid therapy. © 1993, Japanese Society of Nephrology. All rights reserved.

The patient was a 64-year-old female who had been treated by a local doctor for rheumatoid arthritis and hypertension for 10 years. Malaise and edema developed since July, 1990, and as proteinuria and renal dysfunction were noted, the patient was admitted to our hospital on November 2. On admission, BUN was 33mg/dl, creatinine was 2. 5mg/dl, and proteinuria was about 3g/day. Renal biopsy was performed after admission. Light microscopy revealed nodular lobulation of glomeruli and occlusion of loops. Dylon staining was negative. Immunofluorescent study showed granular deposition of IgG, IgM, C3, C4, Clq in the glomerular basement membrane and mesangial area. Electron microscopy showed a large amount of electron dense depositsin the subendthelium and mesangial area and dense aggregation of tubular structure in the deposit, part of which exhibited a profile of fingerprint deposit. The tubular structures were classified into three major types, which were 120, 100, and 50nm in diameter. From these findings, a diagnosis of immunotactoid glomerulopathy was made. After renal biopsy, plasmapheresis and prednisolone were administered, and the patient has been managed conservatively to date. © 1992, Japanese Society of Nephrology. All rights reserved.