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최규헌(Kyu Hun Choi),이호영(Ho Yung Lee),한대석(Dae Suk Han),하성규(Sung Kyu Ha),류동렬(Dong Ryeol Ryu),송현용(Hyun Yong Song),신석균(Suk Kyun Shin),황재하(Jae Ha Hwang),노현정(Hyun Jung Roh),유태현(Tae Hyun Yoo),김주성(Joo Seong Kim 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1
N/A Lupus nephritis is a major cause of morbidity and mortality arising from systemic lupus erythematous. It is generally acknowledged that the presence of diffuse proliferative lupus nephritis(DPLN) is highly predictive of a poor prognosis in terms of renal and patient out- come on survival. The objective of this study was to evaluate the clinicopathologic characteristics, renal out- come according to therapeutic regimen, and prognostic factors of biopsy-proven diffuse proliferative lupus nephritis. Among the biopsy-proven lupus nephritis patients who were admitted to Yonsei University Medical Center from January 1986 to June 1997, 36 patents who were diagnosed DPLN by renal biopsy and treated for at least 6 months and regularly followed-up for at least 12 months were included. We retrospec-tively reviewed the medical recorders. Patients were treated with steroid regimen with or without cyclo-phosphamide. According to the therapeutic response, patients were divided into two groups : a therapeutic response group(n=24), and a therapeutic non-response group<n=12). The mean age of the patients was 27.4 years and the mean follow-up duration was 51 months. Lupus nephritis developed at a mean 9.7 months after SLE diagnosis and mean duration of nephritis was 39.2 months. Mean serum creatinine was 1.6mg/ dL, 24 hour proteinuria was 4,873mg, and anti-DNA antibody was positive in 8196 of patients at the time of renal biopsy. Activity index and chronicity index were 10.4 and 2.8, respectively. Overall 5 year renal survival rate was 7596 and no difference between steroid single therapy and cyclophosphamide combination therapy was observed. Factors affecting therapeutic response included delayed development of nephritis(3.1 vs 13.8 months, p<0.05) and elevated serum creatinine level(0.9 vs 1.9mg/dL, p<0.05), which were associated with poor therapeutic response. Other clinicopathologic, biochemical and immunologic parameters were not different between the therapeutic response group and the therapeutic non-response group. In conclusion, delayed development of lupus nephritis and elevated serum creatinine at nephritis presentation are poor prognostic factors of DPLN, but further randomized prospective study{including divided cytoxan intravenous pulse therapy and oral therapy, with long-term follow-up) is necessary.
최규헌 ( Kyu Hun Choi ) 대한내과학회 2007 대한내과학회지 Vol.73 No.2
Leptin, the product of the adipose-specific ob gene, regulates food intake and energy expenditure in animal models. It is well known that serum leptin levels are increased in patients with chronic renal failure before start of dialysis or even after dialysis. This disorder is basically mediated by a decrease in the renal clearance of leptin, whereas the potential role of an increased secretion of this hormone awaits further confirmation. In this issue of the Journal, Park and Do investigate the longitudinal changes in body composition, serum(S) and dialysate(D) leptin levels in CAPD patients with time. There are significant increases in fat mass, S and D leptin at the 12th month after initiation of PD, especially in diabetes. Factors associated with the changes of fat mass during the first 1 year are D/Plasma 4-hour creatinine, glucose absorption via peritoneal cavity, and duration of dialysis. The correlation between changes of S or D leptin and %fat mass is significant. Consequently, they conclude that increased leptin levels of serum and dialysate may be associated with fat mass in PD patients with time. They found much further increase of D leptin concentration than S leptin, suggesting the possibility of intraperitoneal production of leptin. The molecular weight of leptin is small enough to pass through the peritoneum. Therefore, the extent of S leptin cleared by PD and/or whether a significant intraperitoneal leptin production occurs during PD with glucose-rich solution should be studied. It is well documented that the continuous glucose load during PD will result in chronic hyperinsulinemia which has been shown to increase leptin level by about 40%. Increased generation of proinflammatory cytokines, which is a common feature of PD, may also be a factor stimulating leptin gene expression. The relationship between insulin or proinflammatory cytokine and leptin concentration in PD patients is worthy of further study. In addition, the finding that the dialysate concentration of vascular endothelial growth factor potentially mediating neovascularization in the peritoneal cavity positively correlate with the increase of D/S leptin during the 1st year deserve consideration.(Korean J Med 73:119-122, 2007)
고 농도의 당 존재하에서 신 세뇨관 상피 세포의 세포외 기질 생성 조절 기전에 관한 연구
강신욱(Shin Wook Kang),최규헌(Kyu Hun Choi),이호영(Ho Yung Lee),한대석(Dae Suk Han),송현용(Hyun Yong Song),유태현(Tae Hyun Yoo),황재하(Jae Ha Hwang),김주성(Joo Seong Kim),송영수(Young Su Song),정득림(Deug Lim Chong),김경섭(Kyung Sup 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.1
N/A Thickening of tubular basement membrane and progressive tubulointerstitial fibrosis has been reported as important components of diabetic nephropathy, In order to investigate the mechanisms of tubulinterstitial changes in diabetic nephropathy, we evaluated the effects of a high concentration of glucose(25mM; 450mg/dL) on glucose transporter GLUT1 level, fibronectin production and tissue inhibitors of metalloproteinases (TIMP)-1 concentration in renal tubular(LLC-PK₁) cells. As the effect of high glucose-induced alteration in LLC-PK< cells, the expression of facilitative glueose transporter, GLUT1 was decreased after longer than 24-hours exposure to 25mM glucose, compared to control(5.6mM). The administration of protein kinase C (PKC) inhibitor GF109203X(10μM) did not show significant effect on high glucose-induced decrease of GLUT1 level. On western blot analysis of fibronectin production, The exposure of LLC-PK cells to 25mM glucose for 48 hours significantly increasc4 fibro- nectin production, dose-dependently. The addition of GF102903X at the concentration of 10pM induced the significant increase of fibronectin level in LLC-PK₁cells under glucose-free condition, whereas there was no significant effect on the high glucose-induced increase of fibronectin production. The addition of anti-TGF-βantibody at 30μg/mL partly inhibited the high glucose-induced increase of fibronectin production. Concerning the changes of tissue inhibitor of metallo-proteinase(TIMP)-1 levels in the presence of high glucose, the exposure to high glucose for 24 and 43 hours increased TIMP-1 levels in culture supernatant of LLC-PK₁ cells, dose-dependently. The TIMP-1 levels of 48-hour exposure to 15 and 25mM glucose were also significantly higher than those of 24-hourexposure. The treatment with 10μM GF102903X or 30μg/mL anti-TGF-βantibody had no significant effects on TIMP-1 levels measured under the high glucose culture condition. In conclusion, the expression of facilitative glucose transporter, GLUT1 is inhibited and the production of fibronectin is increased in renal tubular cells cultured in the presence of high concentration of glucose, which is partly mediated by TGF-β. The TIMP-1 level is also increased under high glucose culture condition. The enhanced productions of fibronectin and TIMP-1 of renal tubular cells under high glucose concentration may contribute to tubulointerstitial fibrosis that occurs in diabetic nephropathy.
이차성 부갑상선 기능 항진증이 있는 지속성 외래 복막투석(CAPD) 환자에서 칼시트리올(칼시오) 경구 충격요법과 저용량 매일요법의 비교 연구
강신욱(Shin Wook Kang),최규헌(Kyu Hun Choi),이호영(Ho Yung Lee),한대석(Dae Suk Han),유태현(Tae Hyeon Yoo),신석균(Sug Kyun Shin),하성규(Sung Kyu Ha),노현진(Hyun Jin Noh),류동렬(Dong Ryeol Ryu),송현용(Hyun Yong Song),황재하(Jae Ha Hwan 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.3
N/A The most widely used method for treatment of secondary hyperparathyroidism(SH) in CAPD patients has been the administration of calcitriol by oral route. In this study, we compared the efficacy and safety of daily low dose calcitriol therapy with those of intermittent high dose pulse therapy. The study group consisted of 38 patients undergoing CAPD with serum intact PTH level of more than 200pg/ mL. Twenty patients were randomly administered daily low dose calcitriol(0.25μg/day for 1 month followed by 0.5μg daily dose for the next 3 mon-ths) while 18 patients were given intermittent pulse therapy(0.5μg-0.5μg-0.75μg 3 times a week for 1 month, increased to 1.0μg-1.25μg-1.25μg 3 times a week for the next 3 months). Thirty five patients completed the study : 17 on daily oral calcitriol (M: F=0.7:1, mean age=47.3±10.6 years, mean duration of CAPD=48.9±41.1 months), and 18 on oral pulse calcitriol(M: F=1.6: 1, mean age=41.5±12.7 years, mean duration of CAPD=49.2±41.6 months). The baseline serum levels of calcium, phosphorus, i-PTH, alkaline phosphatase, and total CO₂were not different be- tween daily and pulse group(9.5±0.8 vs 9.3±0.9mg/ dL, 5.8±1.3 vs 5.1±1.2mg/dL, 443.1±162.5 vs 546±385.9pg/mL, 91.8±47.7 vs 108.9±66.5IU/L, 23.7±1.9 vs 25.5±2.0mEq/L, p>0.05, respectively). The i-PTH level decreased significantly in daily calcitriol group after 1 month(332.8±214.8pg/mL, p<0.01), and at final evaluation(180.4±254.8pg/mL, p<0.01). In pulse calcitriol group, i-PTH level also decreased signi-ficantly to 400,4±225.8pg/mL(p<0.05), 89.4±122.6 pg/mL(p<0.01), respectively. The rate of decline in i-PTH level from baseline were similar(daily=25.4±22.7 vs pulse=19.5±12.6%decline/month, p>0.05). The serum calcium increased similarly in both groups after treatment(daily=10.6±0.8 vs pulse=l0.1±1.0mg/ dL, p>0.05). Hypercalcemia(>11.0mg/dL) was rarely observed in all patients(daily=5, pulse=8 episodes). In conclusion, both daily and pulse calcitriol therapy were similarly effective and safe in control of SH.