말기신부전 환자의 조기 사망에 대한 연구

송현용,박영수,류동렬,유태현,노현정,황재하,노현진,신석균,강신욱,최규헌,하성규,한대석,이호영 대한내과학회 1999 대한내과학회 추계학술대회 Vol.57 No.-

지속성 외래 복막투석 환자에서 염증 지표와 고해상도 B 모드 경동맥 초음파 소견의 연관성에 관한 연구

송현용,송영수,안철우,강신욱,최규헌,하성규,이현철,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

배 경 : 저알부민혈증 및 C-반응 단백(C-reactive protein, CRP)이 증가된 지속성 외래 복막투석 환자의 사망률이 높은 정확한 이유는 밝혀져 않다. 혈액투석 환자에서처럼 복막투석 환자에서 저알부민혈증 및 염증반응이 심혈관계 질환 위험인자 인지 알아보고자 하였다. 방 법: 비당뇨병성 말기 신부전, 지속성 외래 복막투석 환자 93명의 심혈관계 질환 위험인자들과 복막 투과 특성 및 알부민, CRP 등의 염증지표에 따라 고해상도 초음파를 이용한 경동맥내막-중간막 두께, 내막-중간막 면적, 플라크의 유무 등을 단면적으로 비교하였다. 결 과: 복막 투과 특성은 고투과막군 14명, 중간 고투과막군 38명, 중간 저투과막군 31명, 저투과막군 10명으로 각 군간의 경동맥 내막-중간막 두께, 플라크 유무 및 내막-중간막 면적의 차이는 없었다. 기존 관상동맥 질환 환자는 8예(8.6%)로 내막-중간막 두께는 관상동맥 질환이 없는 환자보다 증가되었고(0.79±0.21 vs 0.60±0.11 mm, p<0.05) 플라크 형성은 더 많이 보이나 통계적 유의성은 없었다(75.0 vs 63.5%, p>0.05). 혈청 알부민치와 경동맥 내막-중간막 면적은 역상관관계를 보였다(r=-0.27, p<0.05). 저알부민혈증 환자(혈청 알부민 <3.5 g/dL)는 정상 알부민혈증 환자보다 내막-중간막 두께가 증가되었고(0.67±0.15 vs 0.61±0.12 mm, p<0.05), 플라크도 유의하게 많았다(68.0 vs 55.8%, p<0.05). 혈청 CRP치와 경동맥 내막-중간막 면적은 양의 상관관계가 있었으며(r=0.21, p<0.05) CRP가 높은 환자(≥0.8 mg/dL, n=18)에서플라크가 많이 관찰되었으나(65.8 vs 50.0%, p<0.05) 경동맥 내막-중간막 두께 및 내막-중간막면적은 양군간에 차이가 없었다. 다변량 회귀 분석상 경동맥 내막-중간막 두께에 영향을 미치는 인자는 고령, 높은 CRP, 기존 심혈관계질환, 낮은 혈청 알부민 순이였다. 결 론 : 복막투석 환자에서 고해상도 초음파를 이용한 경동맥 내막-중간막 두께 측정은 심혈관계 질환 유무 예측의 비침습적 검사가 될 수 있고 저알부민혈증 및 높은 CRP과 같은 만성염증 지속상태가 복막투석 환자에서 죽상 동맥 경화증의 발생을 증가시킨다고 가정할 수 있다. Background : Continuous ambulatory peritoneal dialysis(CAPD) patients with low albumin(LA) and signs of inflammation reflected by increased C-reactive protein(CRP) level have an increased mortality, but the mechanism of this phenomenon is not clear yet. Methods : To answer whether LA and inflammation also enhance cardiovascular risk in CAPD patients, we performed cross sectional study measuring carotid artery intima-media thickness(IMT), calculated intima-media area(cIM area) and the presence of plaque by high-resolution B-mode ultrasonography in 93 non-diabetic CAPD patients. Results : Patients with coronary artery disease (CAD, n=8) had significantly increased IMT(0.79± 0.21 mm vs. 0.60±0.11 mm, p<0.05) and higher prevalence of carotid plaques(75.0% vs. 63.5%) compared to the non-CAD patients. Significant inverse correlation was observed between serum albumin (SA) level and cIM area(r=-0.27, p<0.05). Those patients with LA(SA <3.5 g/dL) had significantly increased IMT compared to non-LA patients(0.67±0.15 mm vs 0.61±0.12 mm, p<0.05). Prevalence of carotid plaques was also significantly higher in LA patients (68.0% vs. 55.8%, p<0.05). CRP level revealed a significant positive correlation with cIM area(r=0.21, p< 0.05). Patients with high CRP(≥0.8 mg/dL, n=18) had higher prevalence of carotid plaques (65.8% vs. 50.0%, p<0.05) compared to those patients with CRP <0.8 mg/dL, but IMT and cIMT area were not different. By multivariate logistic regression analysis, old age, high CRP, history of CAD and low SA were the independent risk factors affecting IMT. Conclusion : Our study strongly suggests that low albumin and chronic inflammatory state of CAPD patients could be associated with increasing atherosclerotic cardiovascular disease. (Korean J Nephrol 2002;21(2):285-294)

B형 간염과 연관된 신증후군 치료에 Lamivudine 단독요법과 Lamivudine 및 Steroid 병합요법의 비교

송현용,류동렬,이호영,신석균,황재하,강신욱,최규헌,한광협,하성규,한대석,노현진 대한신장학회 1999 Kidney Research and Clinical Practice Vol.18 No.4

Treatment of nephrotic syndrome associated with hepatitis B are controversial, but some patients may respond to interferon therapy. Steroid therapy in these patients could be limited, because it may aggravate hepatitis with the acute viral replication. Lamivudine may also be effective in reducing viral burden and may convert patients from HBsAg and HBeAg positive to negative. But there was no report for the usefulness of lamivudine in treatment of these patients. We performed a randomized comparative study to assess the usefulness of lamivudine and the effect of steroid in the use of lamivudine in treatment of B-viral associated nephrotic syndrome. Twelve patients(M:F=1:0.2, mean age 34.3 years, MCD 1, MPGN 5, MGN 6 patients) suspected to have the acute viral replication with nephrotic syndrome were included. They were randomly assigned to receive lamivudine and steroid combination therapy(group I, 150mg of lamivudine with high-dose steroid, 1mg/kg/day, orally once daily in 6 patients) or lamivudine alone therapy(group II, 150 mg of lamivudine orally once daily alone in 6 patients). The duration of lamivudine use was 6 months in both groups, and that of steroid use was 6 weeks in group I. Then, lamivudine and steroid were tapered according to the amount of proteinuria and serum HBV-DNA titer. All patients were closely monitored every 2 months with clinical, bioche mical, and serological parameters for 10 months. The rate of negative sero-conversion of HBV- DNA were 91.7%(11/12) at 2 months of lamivudine therapy in all patients, and there was no difference between group I and II(83.3% vs. 100%, p$gt;0.05). In group I, there were a significant decreases of mean serum HBV-DNA values(899.2±711.9 vs. 31.4±32.7, 12.7±27.6, and 137.2±278.1pg/ml, p$lt;0.05, respectively), proteinuria(11.0±3.6 vs. 3.9±2.3, 2.1±2.3, and 2.5±3.1g/d, p$lt;0.05, respectively), and SGPT (57.7±18.9 vs. 30.5±12.4, 23.8±10.2, and 26.0±10.4 IU/L, p$lt;0.05, respectively) measured at 2, 6, and 10months compared to before therapy, and serum albumin levels were significantly increased at 2, 6, and 10months compared to before therapy(2.2±0.5 vs. 3.1±0.5, 3.9±0.8, and 3.9±0.9g/dL, p$lt;0.05, respectively). In group II, serum HBV-DNA was significantly decreased at 2, 6, and 10 months compared to before therapy(358.8±369.3 vs. 19.1±27.0, 0.0±0.0, and 0.0±0.0pg/ml, p$lt;0.05, respectively), and proteinuria and SGPT were significantly decreased at 6 and 10 months compared to before therapy(8.5±5.5 vs. 2.6±1.3 and 2.1±2.3g/d, p$lt;0.05; 67.5±43.0 vs. 25.3±11.6 and 31.5±9.2IU/L, p$lt;0.05, respectively). Serum albumin levels were significantly increased at 10 months compared to before therapy(2.8±0.8 vs. 4.3±0.1g/dL, p$lt;0.05). Serum HBV-DNA levels rebounded in two patients of group I, but none was observed in group II. No serious adverse events were observed in all the patients. In conclusion, lamivudine and steroid combination therapy may more rapidly decrease proteinuria than lamivudine alone in B-viral associated nephrotic syndrome, but may induce the rebound of serum HBV-DNA.

집먼지 진드기(Dermatophagoides farinae) 흡입 유발 검사에서 기관지 반응 예측에 영향을 끼치는 인자에 대한 연구

송현용,라선영,박중원,남동호,홍천수 대한천식알레르기학회 1994 천식 및 알레르기 Vol.14 No.1

The most importan method in detecting the causative allergens in bronchial asthma is bronchoprovocation test. However, problems in implementation and patients discomfort make us wonder if general parameters alone could predict the results of specific bronchial provocation test. In this study we compared the results of Dermatophagoides farinae-bronchial provo- cation test with skin prick test, RAST, serum total IgE level, total eosinophil count (TEC), PC20 of methacholine, age, sex and duration of disease in 177 asthma patients for evaluation of predictive values. The results were followed.: (1) Early response(GE I) with inhalation of 1:10000 w/v solution of whole body extract of D.farinae was in 12.4%, isolated late re- sponse(GL) in 7.9%, dual response(GD) in 12.4% and 1:2500 response(GR) within 10 minutes on inhalation of 1:2500 w/v solution of whole body extract of D. farinae followed 7 hours after challenge with 1:10000 w/v solution was in 11.2% 1:1000 response(GE io) within 10 minutes on inhalation of 1:1000 w /v solution was in 45% of 177 cases. (2) The mean age in the dual response and 1:2500 response group were lower than that of other groups. The mean age of the positive and negative response groups were 29. 28+-10.9 years and 33.25+-9.8 years respectively. The average of negative response rate was 45.8% in each age groups. The negative response rates was 12.5% in the second decade and 25% in the six decade, which was significantly lower than that of the other age group. (3) The positive rate of skin prick test of D. farinae(A/H ratiol) did not differ sig- nificantly among the response groups, but were in the following descending order 1:2500 response(G R), dual response(GD), early re- sponse(GE I), 1:1000 response(GE p), isolated late response(GL >) and negative response group(GN io). The mean A/H ratio of D.far- inae skin prick test was higher in the chal- lenge positive group than of challenge nega- tive group. (4) The PC20M of the challenge positive and negative response group were 0.365 mg /ml and 0.631 mg/ml, indicating that the nonspecific bronchial reactivity appeared to be at lower level in the challenge positive group. The PC20M did not show any signifi- cant difference among the response groups but it did appear the lowest PC2QM in the dual response group. (5) The serum IgE levels of the challenge negative and positive groups were 224.39 IU/ml and 491.473 IU/ml respectively, The serum IgE level was the highest in the dual response group but there was no significant difference among others response groups. (6) The total eosinophil count(TEC) of the challenge positive group was 504+354/mm', which was significantly higher than that of the challenge negative group(366+299/mm). TEC was highest in the dual response group with significant difference among the other response groups. (7) The negative response rate of challenge test was 62% in patients with duration of less than 1 year and 34% in patients with longer disease duration. The negative response rate to the bronchoprovocation test was statistically signficantly lower in patients with longer duration of disease. (8) The positive predictive value for discriminant analysis between the challenge positive and negative groups was 75.14% with A/H ratio, age, PC20M, serum total IgE, and duration of disease in contributing order. The positive predictive value for discriminant analysis among the challenge response groups was 38.65% with A/H ratio, serum total IgE, duration of disease and age in contributing order.

제 20 차 대한신장학회 춘계학술대회 : 말기 신부전환자에서 투여경로에 따른 유전자 재조합 Erythropoietin(Epokine)의 효과와 안정성에 대한 연구

송현용,윤향숙,강신욱,최규헌,이호영,한대석 대한신장학회 2000 춘계학술대회 초록집 Vol.2000 No.-

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말기 신부전 환자에서 투여 경로에 따른 유전자 재조합 인 Erythropoietin(Epokine^(�))의 효과와 안정성에 대한 연구 : 제 4상 연구 A Phase 4 Single Center Study

송현용,윤향숙,강신욱,최규헌,하성규,이호영,한대석 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.2

목 적 : 국내 독자적 기술로 첫 개발된 유전자 재조합 인 에리트로포에틴(Epokineⓡ)의 투여방법에 따른 유효성과 안정성을 알아보고자 하였다. 방 법 : Epokineⓡ을 주당 100-150 U/kg, 주 2회, 12주간 피하 주사하여 목표 또는 안정된 혈색소치 유지 후 무작위로 피하 및 정맥 주사군으로 나누어 12주간 혈액투석 및 복막투석 환자13명, 28명에서 유효성, 안정성을 분석하였다. 결 과 : 양군에서 혈색소치와 헤마토크릿은 Epokineⓡ 투여 2주 후부터 증가, 혈색소치가 혈액투석 환자는 투여 전 7.3 g/dL, 투여 12주 9.5 g/dL, 24주 10.6 g/dL로, 복막투석 환자는 6.8g/dL에서 12주 10.2 g/dL, 24주 10.8 g/dL로 증가하였다. 양군에서 교정 망상적혈구수(%)는투여 1주 후부터 전 기간동안 증가하였다. 혈청 내 철분, ferritin치는 양군에서 투여 2주 후부터감소, 총 철분 결합능은 투여 2주 후부터 증가하였다. 12주째 혈액투석 환자에서 많은 Epokineⓡ용량이 필요했으나(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001) 24주 후 양군의 용량차이는 없었다(123.6±41.5 vs 99.2±49.3 U/kg/wk, p>0.05). 혈액투석 환자에서 피하 주사가Epokineⓡ 투여용량이 더 적었으나(97.4±15.4 vs 145.4±2.9 U/kg/wk, p<0.002) 복막투석 환자는 차이가 없었다(93.0±60.2 vs 105.4±9.7 U/kg/wk, p>0.05) 연구기간 중 9명(18.8%)에서혈압강하제 추가가 필요한 혈압상승, 근육통 동반 상기도 감염 유사증상 및 두통 등의 부작용이 있었다. 대부분 자연소실 혹은 대증요법으로 치유되었고 2명이 부작용으로 탈락하였다. 결 론 : 말기 신부전 환자의 빈혈 개선에 사용하는 Epokineⓡ의 효과는 복막투석 환자에서 더 좋았으며 투여 경로는 정맥주사보다 피하주사가 높음을 알 수 있었다. Background : We evaluated the clinical efficacy and safety of recombinant human erythropoietin(Epokine^(ⓡ)). Methods : A comparative prospective study of intravenously and subcutaneously administrated Epokine^(ⓡ) conducted 13 patients performing hemodialysis and 28 patients performing continuous ambulatory peritoneal dialysis with end-stage renal disease. Epokine^(ⓡ) was given initially at a dosage of 100 unit/kg, subcutaneously, two times a week. The patients had achieved stable or more than 10 g/dL of hemoglobin level for 12 weeks and then we randomized switching intravenously or subcutaneously administrated Epokine^(ⓡ) for another 12 weeks. Results : Hemoglobin(g/dL) and hematocrit(%) increased significantly from baseline levels beginning from 2 weeks after Epokine^(ⓡ) administration. In HD patients, hemoglobin increased significantly from 7.3 to 9.5 after 12 weeks and to 10.6 after 24 weeks. In CAPD patients, hemoglobin increased significantly from 6.8 to 10.2 after 12 weeks and then 10.8 after 24 weeks(p<0.05). Corrected reticulocyte count(%) was significantly increased from baseline levels beginning from 1 week after Epokine^(ⓡ) administration and continuously increased during study period in both group. Serum ferritin and serum iron decreased significantly and total iron binding capacity increased significantly after 2 weeks. At 12 weeks, HD patients were significantly needed more dosage of Epokine^(ⓡ) than CAPD patients(142.2±20.5 vs 117.3±33.6 U/kg/wk, p<0.001), but at 24 weeks, the dosage was not different(123.6±41.5 vs 99.2±49.3 U/kg/wk, p> 0.05). In HD patients, intravenously administrated Epokine^(ⓡ) group was more dosage than subcutaneously group(97.4±15.4 vs 145.4±2.9 U/kg/wk, p< 0.002), but CAPD patients were not different by administration method(93.0±60.2 vs 105.4±9.7 U/kg/ wk, p>0.05). The 9 cases(18.8%) were suffered from headache and flu-like syndrome, but these side effects were not severe and disappeared from conventional therapy. Conclusion : Epokine^(ⓡ) administration is safe and effective in treating anemia of ESRD patients and subcutaneously administration is significantly more effective than intravenously. (Korean J Nephrol 2002;21(2):190-198)

말기신부전 환자의 조기 사망에 대한 연구

송현용(Hyun Yong Song),박영수(Young Soo Park),강신욱(Shin Wook Kang),최규헌(Kyu Hun Choi),하성규(Sung Kyu Ha),한대석(Dae Suk Han),이호영(Ho Yung Lee) 대한신장학회 2002 Kidney Research and Clinical Practice Vol.21 No.4

목 적 : 의학의 발달과 노인 인구의 증가 등으로 말기신부전 환자의 수는 계속 증가하고 있으며 신대체 요법의 발달에 따른 환자의 삶의 질과 생존율은 계속 향상되고 있으나 말기신부전 환자의 사망률은 아직도 여전히 높은 편이다. 말기신부전 환자의 투석 방법에 따른 생존율의 차이에 대한 비교 연구와 장기간 투석을 시행받고 있는 환자의 예후에 대한 연구는 많으나 투석 개시 후 3개월 이내 사망한 조기 사망군에 대한 연구는 별로 없는 실정이다. 따라서 이들 조기 사망군의 특성을 이해하고 사망률을 낮춘다면 전체 말기신부전 환자의 생존율의 향상을 기대할 수 있다. 방 법 : 1994년 1월 1일부터 1999년 6월 30일까지 말기 신부전증으로 진단받고 처음 신대체 요법을 시행받은 환자 986명 중 투석 개시 후 90일 이내에 사망한 환자 66명과 투석 개시 후 1년 이상 생존한 환자 920명을 대상으로 하여 두 군간의 투석 개시시의 임상상, 동반질환, 생화학적 지표 및 사망 원인에 차이가 있는지 후향적으로 조사하였다. 결 과 : 전체 환자의 1년내 사망률은 10.4%였고 이중 조기 사망군의 사망률은 6.9%(1년내 사망 환자의 64.1%)였으며 평균 생존 기간은 28.9±23.0일이었다. 대상 환자의 평균 연령은 조기 사망군이 생존군에 비해 많았으며(47.6±15.1세 vs 64.7±13.8세, p<0.001) 남녀비는 조기 사망군 30 : 36, 생존 환자군 506 : 414로 조기 사망군에서 여성이 많았으나 통계적 유의성은 없었고 조기 사망군에서 신장내과 의사에게 투석전 적절한 전치료를 받은 조기의뢰군의 비율이 낮은 경향을 보였으나 통계적 유의성은 없었다. 투석 시작시 심전도 변화는 생존군의 경우 좌심실 비대 396예(43.0%), 허혈성변화 86예(9.3%), 부정맥 67예(7.3%), 정상 506예(55.0%)였으며 조기 사망군의 경우 좌심실 비대 24예(36.4%), 허혈성 변화 12예(18.2%), 부정맥 12예(18.2%), 정상 32예(48.5%)로 조기사망군의 경우 허혈성 변화와 부정맥의 빈도가 많았다(p<0.05). 조기 사망군의 동반 질환이 생존군에 비해 많았으며(2.7±1.4 vs 1.6±1.1, p<0.001) 특히 심혈관계 질환 및 악성종양의 동반이 통계적으로 유의하게 많았으나 당뇨 동반여부는 통계적 유의성이 없었다. 혈청 생화학적 검사상 조기 사망군의 경우 투석 전 백혈구의 증가와 림파구의 감소, 혈청 크레아티닌의 감소, 혈청 알부민의 감소, 총 콜레스테롤의 감소와 혈청 C-reactive protein(CRP)의 증가가 생존군에 비해 통계학적으로 유의한 차이를 보였다. 조기 사망군의 위험인자로 나이가 많을수록, 동반질환이 많을수록 특히 악성종양과 심부전이 동반되어 있는 경우, 혈청알부민이 저하 되어있는 경우 및 CRP가 증가되어있는 경우의 순으로 나타났으며 성별, 고혈압, 당뇨의 유무와는 상관관계가 없었다. 조기 사망군의 사망원인은 감염 32예(48.5%), 심혈관계 질환 28예(42.4%), 악성종양 4예(6.1%), 영양실조 2예(3.0%)였다. 결 론: 말기신부전 환자의 조기 사망은 투석 개시 전 감염증의 동반, 심혈관계 질환 및 악성 종양의 동반과 혈청 알부민의 저하, 총 콜레스테롤의 감소, 크레아티닌의 저하 등 영양 상태 불량과 심한 대사성 산증 및 고칼륨혈증 등 전신 상태가 나빠 응급 투석이 요하는 경우가 많으므 Background : Despite improvements in dialysis care, the mortality of patients with end-stage renal disease(ESRD) remains high. Patients who die within the first 90 days after beginning dialysis are not included in mortality rates and may be absent from incidence count. Therefore, the identification of modifiable characteristics associated with the risk of death during the first 90 days of treatment could lead to improved survival during this interval. Methods : We performed a retrospective analysis in 986 patients(at least 1 year survival from initiating dialysis were 920 patients, and 66 patients died within 90 days after dialysis) who were initiated renal replacement therapy first at Yonsei Medical Center from Jan 1994 to Jun 1999. Results : The 1 year mortality rate of total patients was 10.4%, and early death rate was 6.9%. The mean survival duration was 28.9±23.0 days. Characteristics independently associated with increased risk of early death included older age, inflammation, nutritional impairment, more comorbid condition and previous history of cardiovascular disease at starting dialysis. But Diabetes was not increased early death rate. By multivariate logistic regression analysis, old age, combined comorbid conditions, especially malignancy and congestive heart failure, low serum album and elevated C-reactive protein level were the independent risk factors affecting early death. Other variables such as sex, dyslipidemia, hypertension and diabetes mellitus were not significant risk factors. The leading cause of death in early death group was infection rather than cardiovascular accidents. Conclusion : Proper treatment of infection and improved nutritional status by adequate predialytic managements may contribute to their prolonged survival on dialysis patients.

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