糖尿病性腎症の早期診断には微量アルブミン尿の検出が標準的であるが,腎組織の変化をより早く捕らえる目的で尿中IV型コラーゲン濃度の測定も広く行われている。そこで糖尿病性腎症合同委員会では,健康診断施設受診者から健常者390人を選択し,健常者における随時尿の尿中IV型コラーゲンと尿中クレアチンの比を測定した。健常者の正常上限値は,両側5%検定(平均値+2S.D.)では8.17μg/g・Cr以下,片側5%検定(平均値+1.645S.D.)では7.26μg/g・Cr以下であった。今回は健常者の正常値の検討であり,この数値がそのまま糖尿病患者に対して有用であるかについては新たな検討が必要である。

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The major metabolic change that characterizes nephrotic syndrome (NS) is hypoalbuminemia. Edema, which is a well-recognized clinical feature, often results in disorder of peripheral circulation and congestive heart failure. We previously reported that the albumin content of kidney lysosomal proteins was increased more than ten-fold in nephrotic rats compared to control rats, suggesting that kidney lysosomes play an important role in protein degradation in NS . The present study was carried out to elucidate the role of catabolism of BNP, which is one of the functional protein-natriuretic peptides. We injected puromysin aminonucleoside (PAN) to induce the nephrotic rat state and isolated kidney lysosomes from normal and nephrotic rat kidney cortex by our methods. Immunoblot analysis of tricine-SDS polyacrylamide gel electrophoresis of rat kidney lysosomal proteins revealed the presence of an immuno-reactive peptide band, corresponding to the endogenous BNP. In addition, this was reduced as compared with the normal control . These results suggest that kidney lysosomes play an important role in BNP metabolism to maintain body fluid homeostasis and regulate blood pressure levels.

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Low-dose cyclosporin (CsA) therapy combined with prednisolone was performed in 10 adult patients with frequently relapsing minimal change nephrotic syndrome (MCNS) . Oral CsA was administered at the dose of 1-3 mg/kg/day (50-150 mg/day) in combination with preceding prednisolone (32.5±13.1 mg/day). The whole blood traugh concentration of CsA was maintained at the level of 50-100 ng/ml (ranging in 35-160 ng/ml, mean : 68.0±42.8 ng/ml), and the therapy was continued for 31.7±12.7 months. The urinary protein excretion, serum total protein, albumin and total cholesterol significantly improved after treatment. The serum creatinine increased slightly at 3-6 months after treatment, but decreased to within the normal range thereafter. The frequency of relapse and the ratio of the complete remission period to the total observed period were compared between the pre-treatment period (36.6±42 .5 months) and post-treatment period (31.7±12.7 months). The frequency of relapse was significantly de creased after CsA treatment (2.3±1.5 times/year→0.7±0.7 times/year, p=0.02). The ratio of the com plete remission period to the total observed period was increased significantly after CsA therapy (61.7±24.3%→88.6±14.5 %, p=0.01). Thus, the low dose cyclosporin (CsA) therapy combined with prednisolone was an effective treatment for adult MCNS patients who relapsed frequently under conventional prednisolone therapy.

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Reticulocyte hemoglobin content (CHr), percentage of hypochromic red blood cells (%HRC, level of serum transferrin receptor (sTfR), and STIR/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 supplementa-tion 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 sTIR/Fe were correlated with the degree of change in Hb concentra-tion 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.

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The spectrum of bone disease in end-stage renal failure is changing, but secondary hyperparathyroidism is still a troublesome complication. The vitamin D3 analog, maxacalcitol, has reduced calcemic action compared to vitamin D3, but show equivalent suppression of parathyroid hormone (PTH) secretion. In the first step of the study, we investigated the severity of secondary hyperparathyroidism in 670 chronic hemodialysis patients, whose age, sex (male/female), and duration on dialysis were 63.5±12.4 years, 383/287, and 7.3±6.0 years, respectively. The number of patients with serum intact-PTH concentrations over 300pg/ml was 118. Most patients in this group (87.3 %) were already being prescribed oral vitamin D₃ analog. In the second step, maxacalcitol was administered intravenously, instead of the oral vitamin D₃ analog, to 92 patients selected from the above-described group. The age, sex (male/female), and duration of dialysis were 59.4±11.5 years, 56/36, and 7.3±6.0 years, respectively. Serum intact-PTH concentration and alkaline phosphatase activity decreased significantly, from 612.3±32.7 to 414.2±26.8 pg/ml, and from 329.3±17.3 to 277.0±12.5 IU/l, respectively. Serum calcium phosphorous concentration increased signifi-cantly, and maxacalcitol administration was interrupted because of hypercalcemia in 17 patients (18.5 %). Serum intact-PTH concentration did not decrease in patients with serum Ca concentrations of 10.5 mg/dl or more before maxacalcitol therapy. In conclusion, maxacalcitol suppressed PTH secretion more effectively in hemodialysis patients with secondary hyperparathyroidism than did oral active vitamin D3 therapy, especially in patients with serum Ca concentrations lower than 10.5 mg/dl

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The direct effect of vitamin D on osteoblasts in secondary hyperparathyroidism (2°HPT) is not necessarily obvious. We found an unusual hemodialyzed patient without any response to oral calcitriol pulse therapy (4μg×2/week), and who was administrated maxacalcitol at a dose of up to 15μg×3/week for 28 months. Plasma intact parathyroid hormone (PTH) was not suppressed from the initial level of 1, 773 pg/ml to 2, 100 pg/ml. However, on the contrary, alkaline phosphatase (ALP) was successively suppressed from 2 weeks from the initial level of 1, 261 IU/l to 276IU/l.

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A 51-year-old woman with systematic lupus erythematosus (SLE) associated with minimal change nephrotic syndrome (MCNS) is described. The patient was diagnosed as SLE at 33 years of age. After steroid therapy for two years, the patient's course was uneventful without therapy until June 2000, when facial erythema and facial, pretibial edema developed. On admission, proteinuria and renal dysfunction were detected. Subsequently, oliguric acute renal failure developed and hemodialysis was started. Laboratory examination showed no significant change in complements and anti ds-DNA antibody levels. Renal biopsy revealed minor glomerular abnormalities without the deposition of immune complexes. Electron microscopic examination showed foot process fusion and a vacuolar change in glomerular epithelial cells. The diagnosis of MCNS was made and administration of steroid (40mg/day) was started. Urine volume and renal function improved after 2 weeks, and nephrotic syndrome remitted completely after 5 weeks. Although the association of SLE and MCNS is rare, the findings suggest that in the course of SLE manifesting acute ranal failure, not only lupus nephritis, but also the complication of MCNS should be considered.

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A Japanese girl aged 13 years with myeloperoxidase anti-neutrophil cytoplasmic antibodies (MPO-ANCA) -associated glomerulonephritis (GN) progressed to end stage renal failure after 7 years' clinical observation. She had been suffering from recurrent disease flare associated with serum MPO-ANCA elevation (i. e. 153EU/ml, 208EU/ml and 358EU/ml, maximum at each of the episodes, normal<10EU/ml). Each flare was treated successfully with prednisolone combined with cyclophosphamide and azathioprine. However, her renal function gradually deteriorated, and peritoneal dialysis (PD) was initiated 7 years after the onset of the disease. During the clinical course, no extrarenal manifestations were observed. Due to subsidence of the serum MPO-ANCA titer (10EU/ml) after starting PD, prednisolone and azathioprine were tapered thereafter. Her daily urine volume was preserved at approximately 600 ml at that time. She suddenly developed fatigue with severe anemia, oliguria and hypertension 4 months after discontinuation of immunosuppressive therapy. The serum titer of MPO-ANCA increased to 100 EU/ml. These clinical observation suggests that disease flare may occur in selected patients with MPO-ANCA-associated GN, who develop end-stage renal failure requiring PD. Although recurrent flare associated with an increased serological activity in a proportion of patients with lupus nephritis who have received dialysis has been reported to date, to our knowledge, a similar clinical observation in the MPO-ANCA-associated GN has not been reported. Selected patients with the disease should be followed with close observation after undergoing dialysis.

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