부갑상선 절제술 후 골밀도의 증가를 보인 만성 신부전증에 병발된 신성 골 이영양증 1 예

채현기(Hyun Ki Chae),장대국(Dae Kuk Chang),강경원(Kyoung Won Kahng),안유헌(You Hern Ahn),김호중(Ho Jung Kim),박찬현(Chan Hyun Park),강종명(Chong Myung Kang),박한철(Han Chul Park),정파종(Pa Jong Jung),박문향(Moon Hyang Park) 대한내과학회 1995 대한내과학회지 Vol.48 No.4

Renal osteodystrophy, a term introduced over 51 years ago, is still used to describe any bone disease occuring in a patient with renal disease. In actually, a very wide spectrum of bone disease can occur in renal failure patients, ranging from states of makedly impaired bone formation and mineralization (such as low-turnover bone disease, osteomalacia) to states of markedly increased bone turnover (hyperparathyroidism). We had experienced one case of renal osteodystrophy and secondary hyperaparathyroidism, especially combined with advanced renal failure, who was admitted to Hayang University Hospital due to severe bone pain on both lowe extremites. Skull X-ray showed decreased bone density with so called salt and pepper appearance. Subperiosteal bone resorptions along the ribs and the proximal medial tibial metaphysis were noted on chest PA and both knee X-rays. Serum calcium level was 8.9mg/ dl, serum phosphorous level was 5.6mg/dl, serum alkaline phosphatase was 1872IU/L, serum parathyroid hormone level was 6.54ng/dl(normal; 0.22-0.66ng/dl). Dual photon bone densitometry showed marked decreased total body bone density. Renal osteodystrophy(osteitis fibrosa) was confirmed by bone biopsy stained with Haematoxylin & Eosin and double tetracycline labelling, and secondary hyperparathyroidism was confirmed by parathroid gland biopsies. She was treated with CaCO3, Al(OH)3, Cholecalcitriol after parathyroidectomy.

배양한 인체의 혈관간세포(Mesangial Cells)에서 활성화 산소종(Reactive Oxygen Species)의 발생과 이에 관련한 세포외 기질 증가에 있어서 Cyclosporine과 Tacrolimus의 차이점

이승구(Soong Ku Lee),이수진(Su Jeen Lee),김현준(Hyun Jun Kim),공구(Gu Kong),강경원(Kyoung Won Kahng),강종명(Chong Myung Kang) 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.2

신장이식에 사용하는 중요한 면역억제의 하나인 cyclosporine(CsA)과 tacrolimus(FK506)의 물질 구조는 완전히 다르나 면역억제의 기전은 유사하며 면역억제 효과는 tacrolimus가 CsA에 비해 더 강하다. 이 두 약제는 신장의 섬유모세포에서 collagen 발현의 정도, 혈관간세포(mesangial cell) 배양시 matrix metalloproteinases(MMPs)와 tissue inhibitors of matrix metalloproteinases(TIMPs)의 변화 등에서 차이가 있다고 보고된다. 한편 CsA은 배양세포에서 활성과 산소종(reactive oxygen species;ROS)을 발생시키며, 발생된 ROS는 세포외 기질의 축적에 영향을 미친다고 한다. 따라사ㅓ 저자들은 tacrolimus와 CsA가 ROS의 발생하는데 차이가 있는지 조사하고 이와 같은 차이가 세포외 기질의 축적에 어떤 영향을 미치는지 조사하고자 본 연구를 시행하였다. 방법 : 4대에서 8대 사이의 계대배양한 인간의 혈관간세포에 CsA을 각각 다른 농도(0, 2, 4, 8μg/mL)로 투여하였고, 또 다른 4μg/mL의 농도로 CsA를 투여한 세포군에 항산화제인 N-acetylcysteine(NAC)을 같이 투여하였다. Tacrolimus도 같은 방식으로 투여하였는데, 농도는 0, 0.1, 0.2, 0.4μg/mL으로 하였으며 NAC는 또 다른 0.2μg/mL의 dish에 투여하였다. 결과 : 실험한 세포들에서 생존율은 변화가 없었으나 CsA 투여군에서 tacrolimus 투여군에 비해 유의하게 세포 증식의 차이가 있었다. Flow cytometry에서 CsA 투여군은ROS의 생성을 확인할 수 있었으나 tacrolimus군은 확인할 수 없었고, CsA 군은 세포의 증식이 농도에 따라 감소하다가 다시 NAC에 의해 회복되는 것을 확인할 수 있었다. MMP2, TIMP2, MT1-MMP, Collagen III에 대한 RT-PCR 결과는 두 군 모두 변화가 없었으나 zymogram상에서 CsA 군은 MMP2의 활성도가 농도가 증가함에 따라 감소하였고 이는 다시 NAC에 의해 일부 회복되었으나 tacrolimus군은 이와 같은 변화가 없었다. 결론 : 저자들의 실험에서는 배양한 인체의 혈관간세포에서 일정 시간에서 CsA 투여에 따라 ROS가 발생함을 확인하였으나 tacrolimus에서는 ROS의 발생을 관찰하지 못하였다. CsA는 기질분해 효소인 MMP2의 활성도를 post-transcriptional level에서 tacrolimus에 비해 현저하게 감소시켰으며 이는 CsA에 의해 발생한 ROS와 연관되어 있었다. 하지만 tacrolimus도 더 높은 농도 (0.4μg/mL)에서는 MMP2의 활성도는 전사 후 과정 (post-transcriptional level)에서 감소시켰다. 따라서 tacrolimus와 CsA이 신독성이 유사한 점을 고려하면, 두 약제가 혈관간세포에 영향을 주는 작용기전은 서로 동일하지 않은 것으로 생각되며 이에 대한 더 많은 in Vitro 및 Objective: Cyclosporine(CsA) and tacrolimus, albeit different in structure, exert immunosuppressive effect by similar mechanism. Although most of clinical manifestations, including nephrotoxicity, are simi- lar in the patients using these drugs, there are some differences including gum hyperplasia, neurotoxicity, and hepatic fibrosis between two drugs. There are several reports about association between reactive oxygen species(ROS) and CsA. In contrast, tacrolimus is known to decrease ROS in central nervous system. Thus, we investigated the possibility of different effects of tacrolimus and CsA on the genera- tion of ROS, on the synthesis and degradation of collagen. Methods: Experiments were done in primary cultured mesangial cells between 4th and 8th passages. CsA was added to the culture dishes in different concentration(making final CsA concentration of 0, 2, 4, 8 μg/mL) and N-acetylcysteine(NAC) was also added in another mesangial cell culture at 4 μg/mL of CsA concentration; tacrolimus was added in similar pattern(making final tacrolimus concentration of 0, 0.1, 0.2, 0.4μg/mL, NAC in 0.2μg/mL of tacrolimus concentration). Results: No significant decrease in viability was noted in both cell groups, but growth retardation was weak in tacrolimus treated cells comparing with CsA treated cells. By flow cytometry, we could find the generation of ROS in CsA treated cells, but not in tacrolimus treated cells. In RT-PCR, there is no significant difference in m-RNA expression for a number of molecules including collagen III, MMP-2, TIMP-2, MT1-MMP in either CsA treated cells or tacrolimus cells. But in zymogram, MMP-2 activities were decreased at higher CsA concentration, then increased with addition of NAC. In tacrolimus cells, MMP2 activity was not changed at 0.1 and 0.2 μg/mL; but, at the concentration of 0.4 μg/mL, changed and not reversed by NAC. MMP-9 activity was similar in both cells. Conclusion: We could find ROS generation in CsA treated human mesangial cells, but not in tacrolimus treated cells. We think this difference resulted in the decrease of post-transcriptional MMP-2 activity in CsA treated cells and we also think tacrolimus cells in our experiments were not influenced by ROS. From these results, tacrolimus and CsA are different in the generation of ROS that have some effects in the matrix accumulation in mesangial cells. These result does not mean that tacrolimus is superior to CsA in nephrotoxicity, because nephrotoxicity is similar between two drugs. In conclusion, the mechanisms of nephrotoxicity are different between CsA and tacrolimus.

혈액투석 유지 요법 환자에서 하대정맥 직경과 좌심실 비대와의 관계

신진호(Jin Ho Shin),박찬현(Chan Hyun Park),최정혜(Jung Hye Choi),이창화(Chang Hwa Lee),강경원(Kyoung Won Kahng),김상목(Sang Mok Kim),강종명(Chong Myung Kang),박한철(Han Chul Park),장성렬(Sung Ryul Chang),이방헌(Bang Hun Lee) 대한내과학회 1998 대한내과학회지 Vol.55 No.5

Background: Volume overload is one of the most important, correctable factor far blood sure control in hemodialysis patient. But objective parameter for the ideal body weight is not available in clinical field yet. Recently inferior vena caval examination became a possible candidate for an objective parameter for intravascular volume status. Therefore we investigated how inferior vena cava changes during hemodialysis compared with total amount of ultrafiltration and ANP, and also the effect of changes of IVC diameter on LVK Methods: 43 patients on stable maintainance hemodialysis were enrolled. Among them, 21 patients were on antihypertensive medication. Just before and after the hemodialysis, inferior vena cava diameter, plasma atrial natriuretic peptide and left ventricular mass index were measured for each patient. Inferior vena cava was examined at the level just below the hepatic vein during quiet respiration and left ventricular mass index was calculated. Results- Inferior vena cava at expiration(IVCe) was significantly decreased during hemodialysis(before hemodialysis 21.9 4.9 mm, after hemodialysis 18.3 4.4 mm, p = 0.02). Collasibility index was significantly increased during hemodialysis (before hemodialysis 0.24 0.15, after hemodialysis 0.41 0.19, p< 0.001). Atrial natriuretic peptide(ANP) was significantly decreased during hemodialysis (before hemodialysis 252.3±119.0 pg/ml, after hemodialysis 185.6±93.2 pg/ml, p<0.001). Total ultrafiltration amount was significantly correlated with collapsibility change(r=-0.40) and change of ANP(r=-0.41). Left ventricular mass index was correlated with interdialysis weight gain(r=0.39, p<0.05), IVCe after hemodialysis(r=0.48, p<0.05) in univariate analysis but not in multivariate analysis. Conclusion: Collapsibility index of inferior vena cava, IVC diameter and ANP changes reflect the volume change during the hemodiaylsis. Therefore 1VC examination can be an objective parameter for volume change during hemodialysis. Postdialysis 1VCe correlates weakly with left ventricular mass index but it cannot be an independant risk factor for left ventricular hypertrophy in our study.

신 이식 후 Parvovirus B19 감염에 의한 적혈구무형성증 1 예

이정익(Jeong Ik Lee),강태영(Tae Young Kang),조한표(Han Pyo Cho),윤창옥(Chang Ok Yoon),정청일(Chung Il Jung),이숙진(Sook Jin Lee),강문수(Mun Su Kang),이창화(Chang Hwa Lee),강경원(Kyoung Won Kahng),박찬현(Chan Hyun Park),강종명(Chong M 대한신장학회 2001 Kidney Research and Clinical Practice Vol.20 No.4

Parvovirus B19 infection is known to cause chronic anemia in immunocompromised hosts, including organ transplant recipients. We report a case of pure red cell aplasia caused by parvovirus B19 in renal transplants. The patient was 16-year-old male who was diagnosed as chronic renal failure 7 years ago and had been on hemodialysis twice a week. He got renal transplantation in June 1999. But anemia was not improved in first postoperative period. On admission hemoglobin was 43.0 g/L, hematocrit was 12.7%. The bone marrow biopsy revealed severe erythroid hypoplasia with giant pronormoblasts. The pronormoblasts showed prominent intranuclear inclusions, characteristic of parvovirus B19 infection. The parvovirus H19 PCR and anti-parvovirus B19 IgM were positive. The patient was treated with intravenous immunoglobulin and then reticulocyte count was in- creased 5 days later. Hemoglobin level restored to 104 g/L two months later.

신이식환자에서 shell vial 배양을 이용한 cytomegalovirus 검사

강경원,강종명 한양대학교 의과대학 1996 한양의대 학술지 Vol.16 No.2

Cytomegalovirus(CMV) infection occurs more frequently in renal transplant recipients than in the normal population. We studied the difference and usefulness of various detection methods including IgM CMV antibody boy ELISA, shell vial culture. This study included 36 patients, 20 males and 16 females, who received renal transplantation at Hanyang University Hospital between July, 1995 and March, 1996. IgG and IgM CMV antibodies were detected and shell vial cultures were performed in recipient candidates and donor candidates preoperatively. Postoperatively, we checked IgM CMV and performred shell vial cultures in renal transplant recipients every month after the operation and at times in which CMV infections were suspected. Ten patients had CMV infection and three patients had CMV disease. IgM CMV was positive in 8 patients and shell vial cultures in 6 patients. In all patients with CMV disease, CMV positively appeared by all three detection methods. But detection time and duration of positivity were different. Symptomatic patients were positive in shell vial culture at the time of symptom, but negative in IgM CMV antibody. There was no significant difference in graft survival between CMV infected and non-infected patients. In conclusion, shell vial culture with blood sample is better to detect CMV infections than IgM CMV antibody when patients has the symptoms of CMV infection.

급성 피질괴사가 동반된 자궁근종 1예

박찬현,김상목,강경원,박한철,강종명,유영조,오석중,최일영 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.4

Uterine myoma is the most common neoplasm of women and occurs in up to 20% of reproductive women. Leiomyoma may undergo secondary degeneration such as hyaline degeneration, sarcomatous change, and necrosis. This report presents a case of acute cortical necrosis(ACN) and disseminated intravascular coagulation caused by a uterine myoma necrosis. The uterine myoma of this patient was diagnosed and observed 10 months ago at other hospital. She complained of low abdominal pain with vaginal bleeding and anuria from the previous day. The laboratory findings were as follows: platelets 49,000/ mm3; prothrombin time 38%(normal control, 12 seconds); aPTT 41seconds(normal control, 26seconds); fibrinogen 81mg/dL; FDP$lt;10?g/mL; BUN/sCr 23/ 2.9mg/dL. Acute cortical necrosis was diagnosed by radiologic grounds including abdominal computerized tomography(CT), which demonstrat ed decreased cortical contrast enhancement, normal medullary contrast enhancement, and preserved cortico-medullary differentiation. The patient was treatd conservatively and underwent a CAPD operation later in her hospital course. On the 135th day after diagnosis, the ultrasonography, done in outpatient department, revealed the decreased size of both kidneys, respectively 7.5cm and 7.8cm. Urine output was about 800cc/day and the creatinine clearance of this patient was 9.2mL/ min.

미분화 교원섬유질환에 동반된 microscopic polyangiitis 1 예

이창화,심종걸,강경원,강종명,박찬현,박문향 한양대학교 의과대학 2001 한양의대 학술지 Vol.21 No.1

Microscopic polyangiitis is a primary systemic vasculitis that involves small arterioles and capillaries. Clinical manifestations show generalized weakness, fever, myalgia, weight loss, oliguria, proteinuria, skin rash, neuromuscular symptoms. We describe a patient with unclassified connective tissue disease who developed microscopic polyangiitis. A 38 years-old woman admitted to our hospital due to hemoptysis. Laboratory results showed high creatinine, hematuria, proteinuria, positive p-ANCA(1:640), pulmonary fibrosis and hemorrhage on chest CT. Kidney biopsy showed focal segmental crescenteric necrotizing glomerulonephritis, foot process effacement on EM. Immunofluorescence study was negative. Her clinical feature, laboratory findings, and the kidney biopsy result were compatible with microscopic polyangiitis. The patient had been treated with prednisolne and cyclophosphomide. She was improved clinical sign and symptoms, decreased serum creatinine level.

사람의 혈관간세포에서 Cyclosporine이 반응성 산소종(Reactive Oxygen Species)과세포외 기질 축적에 미치는 영향

채현기,이수진,김현준,공구,강경원,강종명 대한신장학회 2000 대한신장학회잡지 Vol.19 No.6

한국인 신이식 환자에서의 Methylprednisolone의 약동학적 특성

신인철,안종훈,강주섭,곽진영,강경원,강종명 대한신장학회 1998 Kidney Research and Clinical Practice Vol.17 No.5

Glucocorticoids are usually given according to a standard dosing protocol regardless of individual difference. We evaluated the pharmacokinetic characteristics of methylprednisolone and the degree of interpatient variation in stable Korean renal transplant recipients during the period of 15-21 days after transplantation. This study included 23 renal transplant recipients, 13 males and 10 females, who received kidneys from living donors with stable graft function and without episode of acute rejection. On the study day at 8 A.M., 16.3mg of ethylprednisolone sodium succinate (i.v.) was administered to each patient instead of usual dose(20mg) of prednisolone(p.o.) after sampling of 7cc of baseline blood and additional blood samples were drawn after starting infusion. Plasma was separated and analyzed for methylprednisolone level using high performance liquid chromatography (HPLC) assay, and parameters for pharmacokinetics were calculated. There was significant interpatient variation in the pharmacokinetics of methylprednisolone in our patients group. There was no significant difference in the pharmacokinetic parameters between patients with and without side effects of steroid. Korean renal transplant recipients had higher volume of distribution than black renal transplant recipients; lower clearance than white renal transplant recipients; longer t1/2 than both black and white renal transplant recipients. Even if the number of patients included in this study was too small to reach conclusion, the differences in the pharmacokinetics of glucocorticoids do not seem to be a significant risk factor for side effects of steroid after transplantation. It may be necessary to individualize the dose of a glucocorticoid to achieve an optimal effect and also we need to establish a new steroid regimen protocol for Korean renal transplant recipients.

원발성 장관 악성 림프종에 동반된 AL형 신유전분증1예

이창화,이숭환,이재영,강경원,한동수,김상묵,김인순,박찬현,강종명,박한철,박문향 대한신장학회 1996 대한신장학회잡지 Vol.15 No.4