혈액투석 환자에서 Erythropoietin 저항성에 영향을 미치는 인자 -혈액투석 환자에서 EPO 저항성-

권건호(Kun Ho Kwon),황경화(Kyung Hwa Hwang),김경수(Kyung Soo Kim) 대한내과학회 2000 대한내과학회지 Vol.58 No.5

N/A Background : More than 90% of dialysis patients respond in a dose-dependent manner to erythropoietin(EPO) administration and the others are resistant. The causes of EPO resistance are iron deficiency, vitamin deficiency, severe hyperparathyroidism, aluminum toxicity, and inflammation. Much literature has been published concerning iron deficiency and its role in EPO resistance. However little attention has been given to the contribution of inflammation to the EPO-resistant anemia observed in hemodialysis patients. Methods : In the present study, we examined the contribution of parathyroid hormone levels, iron idices, normalized protein catabolic rate(nPCR), Kt/Vurea, albumin, and C-reactive protein(CRP) to erythropoietin resistance index(weekly rhEPO dose/body weight/hematocrit; ERI) in clinically stable 48 hemodialysis patients. Results : The factors correlated with ERI were CRP(R=0.608, p<0.01), ferritin(R=0.460, p<0.01) and serum albumin(R=-0.359, p<0.05). In stepwise multiple regression analysis, the independent factor affecting on ERI was CRP(β=0.620, p<0.01). Comparing high CRP group(≥0.4 mg/dL) with normal CRP group(<0.4 mg/dL), there were significant differences in serum albumin, creatinine, ferritin, and ERI. Conclusion : Acute-phase response, assessed by the level of CRP, was the most important predictor or EPO resistance in stable hemodialysis patients.(Korean J Med 58:510-515, 2000)

혈액투석 환자에서 혈청 C-reactive Protein 농도에 따른 영양상태의 비교

권건호(Kun Ho Kwon),김경수(Kyoung Soo Kim),김준영(Joon Young Kim),최홍엽(Hong Youp Choi),양윤경(Yuun Kyoung Yang) 대한신장학회 2000 Kidney Research and Clinical Practice Vol.19 No.3

N/A Serum C-reactive protein(sCRP) is an acute-phase reactant that exhibiting negative correlation with serum albumin concentration. It was reported that sCRP is an independent predictor of survival in both hemodialysis and peritoneal dialysis patients, and an acute phase inflammation could be preceded by protein catabolism, hypoalbuminemia, anorexia and even atherosclerotic cardiovascular disease. We have evaluated serum biochemical parameters including albumin and prealbumin, Kt/Vurea, nPCR, SGA score, anthropometric parameters and diet history in 30 ESRD patients maintained on chronic hemodialysis subdivided by sCRP concentration. Upon comparing the two subgroups[high CRP group(sCRP>0.4mg/dL), n=15 vs. normal CRP group (sCRP<0.4mg/dL), n=15], high CRP group showed significantly lower levels of hemoglobin(9.3±0.7 vs. 9.8±0.6g/L, p<0.05), hematocrit(28.3±2.3 vs 29.8± 1.696, p<0.05), creatinine(9.6±3.1 vs. 12.2±2.5mg/dL, p<0.05), prealbumin(20.9±5.0 vs. 25.8±6.4mg/dL, p< 0.05), SGA score(5.0±1.2 vs. 5.9±0.7, p<0.05), and percent of patients who have higher nPCR than protein intake(85.7 vs. 28.6%, p<0.05). Ferritin was significantly higher in high CRP group(503.1±205.7 vs. 323.3±186.6, p<0.05). There were no differences in age, sex, duration of hemodialysis, prevalence of diabetic nephropathy and cardiovascular disease, Kt/Vurea, nPCR, residual renal function, amount of protein intake and other nutritional parameters. In conclusion, there was higher probability of mal- nutrition, anemia and protein catabolism in hemo-dialysis patients with elevated sCRP concentration.

복합 항암 화학요법 후 HBsAg 양성 악성림프종환자의 임상경과

구본권(Bon Kwon Ku),한지숙(Jee Sook Hahn),한광협(Kwang Hyub Hahn),이승태(Seung Tae Lee),서형찬(Hyung Chan Suh),권건호(Kun Ho Kwon),이진헌(Jin Hun Lee),민유홍(Yoo Hong Min),고윤웅(Yun Woong Ko) 대한내과학회 1997 대한내과학회지 Vol.52 No.4

N/A Objectives: Infection and replication of the hepatitis B virus are closely related to the host imm- unity. Anticancer chemotherapy decreases the immune response of the host, Especially, glucocorticoid can activate the replication of hepatitis B virus directly. It is well known that hepatitis B virus infection and hepatic complications are more common in patients with hematologic malignancies like malignant lymphoma. We studied the incidence of hepatitis B virus infection and hepatic complications following anti- cancer chemotherapy in patients with malignant lymphoma. Methods: Among 224 cases diagnosed as malignant lymphoma from January 1989 to December 1993 at Yonsei University Medical Center, 77 cases tested for hepatitis B virus serology was studied. Results: 1) Eighteen cases (23%) was HBsAg positive. 2) The results of hepatitis C virus serology in six cases were all negative. 3) Eight (57%) of 14 follow-up cases had hepatic complications, Two patients had fulminant hepatitis, two nonicteric hepatitis and four icteric hepatitis. 4) Interferon-alpha was administered in three cases among the patients with hepatic complications. Loss of HBeAg was observed in one case and loss of HBsAg in another case. Conclusion: Serious hepatic complications can be occurred following anticancer chemotherapy in HBsAg-positive patients with malignant lymphoma. Therefore, we recommend that patients being considered as candidates for anticancer chemotherapy should routinely undergo serologic test for Hepatitis B virus. In addition HBsAg-positive patients with anticancer chemotherapy should be regularly monitored for hepatic injury. And with the careful use of steroid and interferon, prolongation of survival might be searched for these patients.

저칼륨혈증성 주기성 마비로 발현한 원발성 쇼그렌 증후군

정은미 ( Eun Mi Jeong ),권건호 ( Kun Ho Kwon ),홍창권 ( Chang Kwon Hong ),김형태 ( Hyung Tae Kim ),김경수 ( Kyung Soo Kim ) 대한류마티스학회 2000 대한류마티스학회지 Vol.7 No.2

We describe a 46-year-old woman with hypokalemic paralysis as the initial manifestation of Sjogren`s syndrome. Sjogren`s syndrome is an autoimmune exocrinopathy, characterized by keratoconjuntivitis sicca and xerostomia. Among the extraglandular manifestations of Sjogren`s syndrome, renal tubular involvement, especially renal tubular acidosis, is the most often latent or minimally symptomatic. Renal tubular acidosis is estimated to be present in 25~30 percent of the cases. Hypokalemic paralysis may serve as a clinical marker for more severe renal disease in patient who has primary Sjogren`s syndrome with renal tubular acidosis, even though it is a rare manifestation of Sjogren`s syndrome.

Lovastatin 및 Isoprenylation 억제제에 의한 배양한 백서 사구체 혈관간세포의 사멸과 세포골격 변형

박형천(Hyeong Cheon Park),권건호(Kun Ho Kwon),노현정(Hyun Jung Roh),강신욱(Shin Wook Kang),최규헌(Kyu Hun Choi),이호영(Ho Yung Lee),한대석(Dae Suk Han) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.2

Lovastatin은 세포내 cholesterol 합성에 관여하는 3-hydroxy-3methylglutaryl coenzyme A(HMG CoA) reductase를 경쟁적으로 억제하는 약제로 HMG CoA로부터 mevalonate 생성을 억제한다. 최근 mevalonate와 중간 대산 산물의 생성을 억제시킬 경우 Rho 단백질을 포함한 저분자 guanosine triphosphate(GTP) 결합 단백질의 isoprenylation 억제 과정을 통해 세포골격 변형과 세포 사멸을 유발할 수 있을 것으로 보고되어 종양 세포를 포함한 여러 종류의 세포를 대상으로 활발한 연구가 진행되어 왔다. 그러나 lovastatin에 의한 백서 사구체 혈관간세포(mesangial cell)의 사멸과 세포 형태 변형에 대한 연구는 거의 없고, geranylgeranyltransferase I과 farnesyltransferase를 각각 선택적으로 억제하는 GGTI-286과 L-744,832에 의한 백서 사구체 혈관간세포 사멸과 세포골격 변형에 관한 연구는 아직까지 없는 실정이다. 이에 저자 등은 백서에서 추출한 사구체 혈관간세포를 배양하여 lovastatin, GGTI-286, 그리고 L-744,832에 각각 노출하여 혈관간세포에 대한 이들 약물의 직접적인 사멸 유발 효과를 Hoechst 33258 염색, DNA 분절, 그리고 유세포분석으로 알아보았다. 또한 이들 약물 투여에 따른 혈관간세포내 actin 스트레스 섬유의 변화를 형광현미경으로 관찰하고, 동시에 세포외적으로 투여한 GGPP와 FPP로 인한 lovastatin에 의한 세포골격 변형과 사멸의 가역성 여부를 실험하여 다음의 결과를 얻었다. 1) Lovastatin은 배양 시간과 약물 농도에 비례하여 혈관간세포 사멸을 유발하였다. Isoprenoid인 GGPP의 세포외적 투여는 lovastatin에 의한 혈관간세포 사멸을 완전히 가역화였고, FPP의 세포외적 투여는 부분적인 사멸 억제 효과를 나타내었다. 2) 선택적인 isoprenylation 억제제인 GGTI-286은 lovastatin과 같이 배양 시간과 약물농도에 비례하여 혈관간세포 사멸을 유발하였다. 그러나 L-744,832는 대조군에 비행 유의하게 혈관간세포 사멸을 유발하는 효과가 없었다. 3)Lovastatin에 의해 유발된 혈관간세포 사멸에서 사멸 억제와 관련이 있는 Bcl-2 발현의 변화를 관찰할 수 없었다. 4) Lovastatin과 GGTI-286은 혈관간세포의 세포골격 변형과 세포골력을 이루는 actin 스트레스 섬유의 파괴를 유발하였으며, GGPP 또는 FPP의 세포외적 투여는 세포 형태 변형과 actin스트레스 섬유의 파괴를 완전히 가역화 하였다. 5)Lovastatin과 GGTI-286은 저분자 GTP결합 단백질 중 세포골격 구서오가 사멸 조절에 관여하는 RhoA 단백질의 isoprenylation을 억제하였고, GGPP의 세포외적 투여는 lovastatin의 효과를 가역화 하였다. Products of mevalonate pathway, such as farnesyl pyrophosphate(FPP) and geranylgeranyl pyrophospha- te(GGPP) play a critical role in protein isoprenylation. Lovastatin, which blocks mevalonate production is an isoprenylation inhibitor reported to alter cytoskeletal architecture and induce apoptosis in a variety of cell lines. Exogenous isoprenoids reversed the effects of lovastatin, suggesting the importance of isop- renoid products for cytoskeletal organization and apoptosis. The aim of this study was to define the effects of lovastatin and isoprenylation inhibitors on induction of apoptosis and cytoskeletal changes in cultured rat glomerular mesangial cells. In addition, GGPP and FPP were added exogenously with lovastatin to determine which metabolite played a more important role in apoptosis and cytoskeletal changes, respectively. Lovastatin and GGTI-286 induced changes in the degree of RhoA isoprenylation was assessed to further support the role of protein isoprenylation in apoptosis and cytoskeletal changes. The results obtained were as follows; 1) Lovastatin induced apoptosis of cultured glomerular mesangial cells in a time and dose-dependent manner independent of bcl-2. The GGPP completely reversed the proapoptotic effects of lovastatin, while FPP partially reversed it. 2) GGTI-286, a specific inhibitor of protein geranylgeranyltransferase, induced apoptosis of cultured glomerular mesangial cells in a time and dose-dependent manner similar to lovastatin. But L-744,832, a specific inhibitor of protein farnesyltransferase, did not induce apoptosis compared to control group. 3) Lovastatin and GGTI-286 induced actin stress fiber disruption, but L-744,832 failed to induce actin stress fiber disruption in cultured glomerular mesangial cells. Both GGPP and FPP completely reversed the cytoskeletal changes induced by lovastatin. 4) Cultured glomerular mesangial cells treated with lovastatin or GGTI-286 were associated with decreased isoprenylation of RhoA, a protein reported to be involved in actin cytoskeletal organization and cell survival. Such finding further supports the role of protein isoprenylation inhibition in mesangial cell apoptosis and cytoskeletal change induced by isoprenylation inhibitors. In conclusion, lovastatin and GGTI-286 induced apoptosis in cultured glomerular mesangial cells. The effect of lovastatin was completely reversed by addition of GGPP and only partially by FPP, suggesting a critical role for geranylgeranylated proteins in cultured glomerular mesangial cell apoptosis. The actin cytoskeletal change induced by lovastatin was completely reversed by addition of GGPP or FPP, sug- gesting both geranylgeranylated and farnesylated proteins are involved in actin cytoskeletal change.

한국인에서 Human T - cell Lymphotropic Virus Type 1 ( HTLV - 1 ) 에 대한 항체보유

김준명(June Myung Kim),오영철(Young Chul Oho),박형천(Hyeong Cheon Park),권건호(Kun Ho Kwon),김응(Eung Kim),이선호(Seon Ho Lee),김기홍(Ki Hong Kim) 대한내과학회 1996 대한내과학회지 Vol.51 No.1

N/A Objectives: HTLV-I infections are newly recognized disease entity which are common in some tropical and subtropical areas including southwestern district of Japan. Inspite of geographical adjacency and frequent cultural exchanges between Korea and Japan, it has been known that Korea is not an endemic area and HTLV-I associated illnesses are very rare in Korea. Our study was designed to reevaluate the prevalence of anti-HTLV-I antibodies in Korea and its regional distributions. Methods: Sera were obtained from blood donors from various districts of Korea. Anti-HTLV-I anti- bodies were detected using microtiter particle agglutination test kit( Fujirebio Inc. Japan) employing an indirect agglutination technique. Results: The results were as follows 1) Total 9,281 donors were tested and 12 donors were anti-HTLV-I positive(positive rate = 0.13%) 2) Positive rate was 0.11% in male and 0.46% in female, with relative female sex predominence. 3) Frequency of seropositive donors had tendency to increase gradually with age. 4) Relatively high incidence of anti-HTLV-I positive donors were observed in Jonnam(0.15%), Kyung-nam(0.31%), and Chejue(0.80%) which showed increasing incidence as the district got closer to Japan. Conclusion : In conclusion the prevalence rate of anti-HTLV-I seemed to be very low in Korea. But districts close to endemic areas of Japan showed relatively high incidence of anti-HTLV-I positive donors. Surprisingly high incidence of of anti- HTLV-I positive donors were noticed in Chejue warranting further research on HTLV-I associated illnesses and prevention programs.

만성 신부전 환자에게서 발생한 괴사성 근막염 1예

홍창권,권건호,정은미,김형태,박진찬,김경수,안창수,하두희 대한신장학회 2000 대한신장학회잡지 Vol.19 No.5

비장결핵 1례

윤명호,권건호,김응,김준명 대한감염학회 1995 감염 Vol.27 No.3

저자들은 최근 비장결핵 1예를 경험하였는바, 비장적출술 전에 세침흡인술로 비장결핵을 진단하고 항결핵제 투여를 계속하였으나 치료 효과가 없어, 결국 비장적출술을 시행후 항결핵제를 투여하면서 유의할 만한 호전을 보여 문헌 고찰과 함께 보고하는 바이다. Splenic tuberculosis is an uncommonly considered diagnosis in clinical practice. We report a patient with splenic tuberculosis who was admitted to the hospital because of fever, anorexia and weight loss. Abdominal sonography and computerized tomography revealed the presence of multiple hypoechoic and hypodense splenic lesions. A diagnostic needle aspiration under the sonographic guidance was performed. Seven weeks later Mycobacteium tuberculosis was cultured from aspirated fluid. Despite antituberculous therapy with isoniazid, rifampicin, ethambutol and pyrazinamide for one month, the patient became worse. So splenectomy was done. Antituberculous therapy was continued after splenectomy, and the clinical condition of the patient was improved.

혈액투석 후 요소 반등이 투석 적절도에 미치는 영향

김문재,이승우,권건호 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.6

Urea reduction ratio(URR) and Kt/Vurea are objective parameters of dialysis delivery in hemodialysis patients and correlate with nutritional status and patient outcome. URR and Kt/Vurea depend on postdialysis blood urea nitrogen(BUN). In patients with severe postdialysis urea rebound(PDUR), these parameters do not accurately reflect dialysis adequacy. We measured PDUR 30 minutes after dialysis in 26 chronic stable hemodialysis patients. The impact of PDUR on dialysis delivery assessed by URR and Kt/Vurea and the independent factors affecting on PDUR were evaluated. All patients had been dialyzed for 4 hours thrice a week using hemophan membrane. 1) The mean age of patients was 48.6±14.8 years and sex ratio was 1:2.3. The mean duration of hemodialysis was 42.7±45.0 months. Primary renal diseases were chronic glomerulonephritis 11(42.3%), diabetic nephropathy 7(26.9%), and hypertension 4 (15.4%). 2) The mean blood flow was 209.2±17.4ml/min. URR, Kt/Vurea, and nPCR using immediate postdialysis BUN were 60±1.13?0.21, 1.09±0.28g/kg/ day, respectively. The mean recirculation rate was 4.4±2.3%. 3)The mean PDUR was 12.2±4.6%(range:6-22 %). URR, Kt/Vurea, and nPCR using BUN 30 minutes after dialysis were 55±7%, 0.99?0.18, and 1.02±0.25 g/kg/day, respectively and were significantly lower than those using immediate postdialysis BUN(P$lt;0.05). 4) When the patients were divided according to the degree of PDUR(low PDUR group:$lt;12%, high PDUR group:≥12%), high PDUR group was significantly higher than low PDUR group in hematocrit (27.0±2.6 vs. 23.5±3.6%, P=0.008), URR(64.3±5.4 vs. 55.8±6.8%, P=0.002), Kt/Vurea(1.26±0.17 vs. 1.03±0.18, P=0.002), and total recirculation rate(5.6±2.7 vs. 3.6±1.7%, P=0.05). There were no differences in age, sex, postdialysis body weight, ultrafiltration rate, blood flow, serum albumin, predialysis BUN, creatinine, and nPCR. 5) In multiple regression analysis, the independent factors affecting on PDUR were Kt/Vurea(β=0.546, P$lt;0.001), recirculation rate(β=0.422, P$lt;0.001), and h P=0.0017). In conclusion, we think that PDUR should be considered in hemodialysis patients when estimating dialysis delivery, especially if they had high Kt/ Vurea, recirculation rate, and hematocrit.

미만성 경피증에 발생한 신발증 1예

이승우,박원,권건호,김문재,전정배,김화숙 대한내과학회 1999 대한내과학회지 Vol.56 No.5

Scleroderma renal crisis is defined as the new onset of accelerated arterial hypertension and/or rapidly progressive oliguric renal failure. The pathogenesis is not well understood but there is increasing evidence that renin- angiotensin system is involved. We report an one female patient with diffuse scleroderma and renal crisis. Initial treatment with ACE inhibitor was not effective in controlling blood pressure until the temporal initiation of hemodialysis. Predialysis serum creatinine level was 8.4 mg/dL, but after initiation of hemodialysis, adequate control of blood pressure was achieved with ACE inhibitor alone. This case illustrated many features of the syndrome of scleroderma renal crisis and supported the early use of captopril and emergency hemodialysis if indicated.