사이클로포스파마이드 충격요법 후 증식성 루푸스 신염의 임상경과와 관해 및 재발의 예측인자

박민찬 ( Min Chan Park ),이상원 ( Sang Won Lee ),박용범 ( Yong Beom Park ),최규헌 ( Kyu Hun Choi ),이수곤 ( Soo Kon Lee ) 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.2

Objective: This study was designed to investigate the clinical outcomes of proliferative lupus nephritis and to identify the predictive factors of remission and relapse of proliferative lupus nephritis after intravenous cyclophosphamide (IVCYC) pulse therapy. Methods: Seventy-four patients with proliferative lupus nephritis that had been diagnosed by renal biopsy and treated with IVCYC pulse therapy were studied. Their demographic data, clinical manifestations, laboratory findings, disease activity index, damage index, activity and chronicity indices of renal pathology, and treatment modalities were evaluated. Clinical outcomes of lupus nephritis were assessed by defined criteria. Results: Remission or response were achieved in 79.7% of patients with proliferative lupus nephritis (remission in 32.4% and response in 47.3%, respectively), and 30.5% of those with remission or response experienced relapse or flare of lupus nephritis (relapse in 20.8% of those with remission and flare in 37.1% of those with response) after IVCYC pulse therapy. High creatinine clearance at diagnosis of lupus nephritis, short lag time from diagnosis of lupus nephritis to initiation of immunosuppressive treatment, and long-term cyclophosphamide pulse therapy were the independent predictive factors for remission or response. Long lag time from completion of immunosuppressive treatment to onset of remission or response, and incomplete cyclophosphamide were the independent risk factors for relapse or flare of lupus nephritis. Conclusion: Good renal function and early initiation of long-term IVCYC pulse therapy are important in induction of remission or response, while delayed remission or response and incomplete immunosuppressive treatment is strongly associated with poor outcome.

미만성 증식성 낭창성 신염의 임상상 및 예후인자

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.

전신성 홍반성 루푸스 신염 활성도와 소변 Transforming Growth Factor-β Induced Gene-h3 (βig-h3)의 연관성

김일 ( Il Kim ),홍철호 ( Cheol Ho Hong ),조현석 ( Hyun Seok Cho ),유선진 ( Sun Jin You ),백창희 ( Chang Hee Paik ),이혜순 ( Hye Soon Lee ),엄완식 ( Wan Sik Uhm ),김태환 ( Tae Hwan Kim ),전재범 ( Jae Bum Jun ),유대현 ( Dae Hyun Yo 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.4

Background: TGF-β-induced gene-h3 (βig-h3) is a novel gene induced by active TGF-β and the association with other renal disease is reported. Lupus nephritis is characterized by excessive extracelluar matrix accumulation and the implication that TGF-β is increased in lupus nephritis is known. We measured the urinary βig-h3 in lupus nephritis and sought its association with the activity of lupus nephritis through renal biopsy. The objective of this study was to examine urinary βig-h3 excretion in lupus nephritis and the association with activity of lupus nephritis. Methods: Fifteen patients (median age 32.6±2.9 years, range 18∼64) who developed lupus nephritis underwent renal biopsy. At the time of biopsy, they showed significant proteinuria. Total urinary βig-h3 concentration was assayed by enzyme-linked immunoabsorbent assay and expressed as a ratio to urinary creatinine concentration. Results: There were correlations between urinary βig-h3 and the reduction of C3 (r=-0.566, p=0.028<0.05), the magnitude of proteinuria (r=0.531, p=0.042<0.05). The Activity Index, Chronicity Index in the renal biopsy, C4, anti-dsDNA Ab titer were not significantly correlated with urinary βig-h3 excretion, but the patients with high Activity Index had the increased level of urinary βig-h3. Five patients who had fibrinoid necrosis in renal biopsy showed higher level of urinary βig-h3 than the others (107.78±43.02 vs. 50.21±10.12 ng/ml, p=0.061) Conclusion: In this study, There is some correlation between urinary βig-h3 and the activity of lupus nephritis. Urinary βig-h3 may play a role in predicting the active lupus nephritis. A further study is needed in large population and in situ expression of βig-h3.

루푸스 신염의 활동성 예측 척도로서 혈청 C1q-Circulating Immune Complexes의 유용성

박성환 ( Sung Hwan Park ),김상현 ( Sang Hyon Kim ),김주연 ( Ju Youn Kim ),김해림 ( Hae Rim Kim ) 대한류마티스학회 2010 대한류마티스학회지 Vol.17 No.4

Objective: The purpose of this study was to evaluate whether serum C1q-circulating immune complexes (C1q-CIC) serve as a predictive marker for renal flares in patients with lupus nephritis. Methods: Twenty-five patients with lupus nephritis and 24 healthy controls were enrolled. Patients with lupus nephritis had their serum C1q-CIC titers and other serologic parameters such as serum C3, C4, anti-dsDNA antibody, and erythrocyte sedimentation rate measured simultaneously. The systemic lupus erythematosus disease activity index (SLEDAI) was also checked. Results: Serum C1q-CIC titers were higher in patients with lupus nephritis than in healthy controls (109.33±53.79 μg/mL vs. 75.28±22.91 μg/mL, p=0.008). A statistically significant association was found between serum C1q-CIC titers and C3 (p=0.011), C4 (p=0.027), and anti-dsDNA antibody (p=0.014). SLEDAI was also correlated with serum C1q-CIC titers (p=0.022). Conclusion: Serum C1q-CIC appears to be related to renal disease activity in patients with lupus nephritis. These results suggest that serum C1q-CIC is a predictive marker for renal flares in patients with lupus nephritis.

신조직 검사로 입증된 루푸스 신염에 대한 치료 효과 및 예후 인자에 대한 후향적 연구

이찬희 ( Chan Hee Lee ),서창희 ( Chang Hee Suh ),이충원 ( Choong Won Lee ),이원기 ( Won Ki Lee ),이지수 ( Ji Soo Lee ),박용범 ( Yong Beom Park ),송정식 ( Jung Sik Song ),송창호 ( Chang Ho Song ),정현주 ( Hyeon Joo Jeong ),최규헌 ( 대한류마티스학회 1999 대한류마티스학회지 Vol.6 No.1

Objectives: To evaluate the clinicopathologic character, therapeutic outcome, and prognostic factor of biopsy-proven lupus nephritis. Methods: Biopsy proven lupus nephritis patients who were admitted at Yonsei Medical Center from January 1986 to June 1997 were included in this study. We retrospectively reviewed the medical records. Patients were treated with steroid regimen with or without cyclophosphamide. According to the therapeutic response, patients were divided into two groups: therapeutic response group and therapeutic nonresponse group. Results: The results are as follows; 1. Among 68 biopsy-proven lupus nephritis cases, 54 patients who were treated at least 6 months were included in this study. 2. The mean follow up duration was 51 months. Mean serum creatinine was 1.4mg/dl, 24-hour proteinuria was 4,868mg, and anti-DNA antibody was positive in 76% at the time of renal biopsy. 3. Diffuse proliferative nephritis was the most common pathologic findings(32 cases, 59%). Activity index was highest in diffuse proliferative nephritis. 4. Overall 5-year renal survival rate was 25% and there was no difference between steroid single therapy and cyclophosphamide combination therapy. In diffuse proliferative nephritis, 5-year renal survival rate was 18% and there was no difference according to treatment. 5. Factor affecting therapeutic response was pathologic classification; diffuse proliferative nephritis was associated with poor therapeutic response(p=0.032). 6. Six patients(11%) progressed to end stage renal disease. 7. Major complications with treatment were infections including herpes zoster. Conclusion: In our series of lupus nephritis, diffuse proliferative nephritis was poor prognostic factor.

신침범의 임상증상이 없는 낭창성 신염의 임상 및 병리소견 분석

박수길(Soo Kil Park),이종호(Jong Ho Lee),한진석(Jin Suk Han),김성권(Suhng Gwon Kim),최성재(Sung Jae Choi),이정상(Jung Sang Lee),이현순(Hyun Soon Lee),김용일(Yong Il Kim) 대한내과학회 1988 대한내과학회지 Vol.34 No.5

N/A Because of the limited validity of serologic tests, there has been interest in alternative ways of assessing prognosis and disease severity in systemic lupus erythematosus(SLE), espec ally in direct histopathologic evaluation of affected tissue. Since the renal disease is still a major cause of morbidity and mortality in SLE and the kidney is the most accessible organ by biopsy, the role of renal biopsy in the management of SLE has been discussed frequently. It is known that despite of the absence of clinical abnormalities of urine, histological examination of renal tissue has been shown variable morphological changes including diffuse proliferative type that has the worst prognosis in lupus nephritis. To investigate the usefullness of renal biopsy and the treatment modalities we performed the analysis of clinical and pathological findings in lupus nephritis without clinical renal involvement. Among the 95 patients of SLE, the number of silent lupus nephritis was 23, who were less hypertensive and clinically more favorable. The decrease of C3 and C4 was more marked in the patients who had the renal symptoms clinically. The severity of extrarenal symptoms was not correlated with whether the patient had the renal symptoms or not. The pathologic classification in silent lupus nephritis was as followings; WHO class IIa;8, IIb;7, class IIl;4, class IV;3, class V;1 respectively. Thus we concluded that the diffuse lupus glomer-ulonephritis could be clinically silent and the type of morphologic lesion in lupus nephritis cannot be deduced from the clinical criteria alone. It may be necessary to perform the biopsy in any SLE patient, regardless of the clinical renal involvement.

Response to Intravenous Cyclophosphamide Treatment for Lupus Nephritis Associated with Polymorphisms in the <i>FCGR2B-FCRLA</i> Locus

Kim, Kwangwoo,Bang, So-Young,Joo, Young Bin,Kim, Taehyeung,Lee, Hye-Soon,Kang, Changwon,Bae, Sang-Cheol Journal of Rheumatology Pub. Co 2016 The Journal of rheumatology Vol.43 No.6

<P>Objective. Cyclophosphamide (CYC) is an immunosuppressant drug widely used to treat various diseases including lupus nephritis, but its efficacy highly varies from individual to individual. This pharmacogenomics association study searched for genetic variations associated with CYC efficacy. Methods. Genome-wide association scan was performed for 109 Korean patients with systemic lupus erythematosus with lupus nephritis (classes III-V) who received intravenous CYC induction therapy. Genetic differences between responders and nonresponders were examined using Cochran-Armitage trend tests, and genotype imputation was used for defining the association locus. Results. Genetic polymorphisms in the Fc gamma receptor gene (FCGR) cluster at human chromosome 1q23, previously associated with lupus nephritis susceptibility, were associated with the response to CYC treatment for lupus nephritis. Significant response association was found for 3 perfectly correlated (r(2) = 1) single-nucleotide polymorphisms (SNP): rs6697139, rs10917686, and rs10917688, located between the FCGR2B and FCRLA genes (p = 3.4 x 10(-8)). Carriage of the minor alleles in these SNP was found only in nonresponders (31%) and none in responders (0%). Conclusion. This first genome-wide association approach for CYC response yielded a robust profile of genetic associations including large-effect SNP in the FCGR2B-FCRLA locus, which may provide better insights to CYC metabolism and efficacy.</P>

루푸스 신염 관해 유도 치료로서 Mycophenolate Mofetil과 Cyclophosphamide 치료 효과

김용균 ( Yong Kyun Kim ),도연실 ( Yeon Sil Do ),최소연 ( So Yeon Choi ),장은희 ( Eun Hee Jang ),이정은 ( Jung Eun Lee ),차훈석 ( Hoon Suk Cha ),허우성 ( Woo Seong Huh ),김대중 ( Dae Joong Kim ),오하영 ( Ha Young Oh ),권기영 ( Ghee 대한신장학회 2007 Kidney Research and Clinical Practice Vol.26 No.2

목적: 사이클로포스파마이드 (CYC)정맥투여는 활동성 루푸스 신염에서 표준적 치료이나 심각한 독성이 발생할 위험이 높다. 저자들은 활동성 루푸스 신염 환자에서 관해 유도치료로 선택적으로 림프구 증식을 억제하고 독성이 적은 마이코페놀레이트 모페틸 (MMF)치료를 시행하여 CYC 치료와 비교하였다. 방법: 2000년 8월부터 2005년 8월까지 신조직 검사로 활동성 루푸스 신염으로 진단 받고 초기 관해 유도치료로 MMF 치료를 받은 환자 22명과 CYC 정맥투여 치료 받은 환자 28명들을 대상으로 6개월 치료 후 관해율과 부작용을 조사하였다. 완전 관해는 소변 단백 대 크레아티닌 비 (Up/Cr)가 0.3 이하이고 정상 요 침사 소견과 정상 혈청 알부민 수치를 보이며 혈청 크레아티닌이 기저 수치 보다 15% 이상 높지 않는 경우로 정의하였다. 불완전 관해는 Up/Cr가 0.3에서 2.9 사이에 해당되고 혈청 알부민 수치가 적어도 3 g/dL 이상이며 안정된 신기능을 보이는 경우로 정의하였다. 결과: MMF 군은 22명, CYC 군은 28명이었다. 신조직 검사상 class Ⅲ 8명 중 7명은 MMF로, class IV 27명 중 19명은 CYC 정맥투여 치료 했다. MMF 군에서 완전 관해는 7명, 불완전 관해는 10명, 치료 실패는 5명이였으며 CYC 군에서 완전 관해는 11명, 불완전 관해는 11명, 치료 실패는 6명으로 양 치료군 간 차이는 없었다. 4주 간격으로 3회의 CYC 정맥투여 후 MMF 치료로 전환하여 3개월간 관해 유도 치료한 환자는 4명이었으며 치료 후 완전 관해가 2명, 불완전 관해가 1명, 치료 실패가 1명이었다. 부작용은 MMF 군과 CYC 군 사이에 유의한 차이가 없었다. 결론: 활동성 루푸스 신염 환자 초기 관해 유도 치료로서 MMF는 CYC 정맥투여와 비교하여 치료 6개월 후 관해율에 차이가 없었다. 그러나 두 치료군 대상 환자들의 중증도에 차이가 있어 향후 잘 대조된 다수 환자를 대상으로 전향적인 연구가 필요 할 것이다. Purpose: The combination of intravenous cyclophosphamide (CYC) and prednisolone is effective for the treatment of severe lupus nephritis but has serious adverse effects. Mycophenolate mofetil (MMF) Is a new immunosuppressive agent that selectively inhibits activated lymphocytes. This study reports on the clinical experiences at our clinic with MMF and intravenous CYC for the initial induction treatment in patients with lupus nephritis. Methods: 50 patients with lupus nephritis received induction therapy consisting of MMF and prednisolone (n=22) or intravenous CYC and prednisolone (n=28), and followed up for six months. Complete remission was defined as a value for urinary protein: urinary creatinine ratio (Up/Cr) that was less than 0.3, with normal urinary sediment, a normal serum albumin concentration and values for serum creatinine that were no more than 15 percent above the base-line values. Partial remission was defined as a value for Up/Cr that was between 0.3 and 2.9, with a serum albumin concentration of at least 3.0 g/dL. Results: 22 patients treated with MMF and 28 patients with intravenous CYC resulted in complete remission (31.8% vs 39.3%), partial remission (45.5% vs 39.3%) and treatment failure (22.7% vs 21.4 %). Fewer severe infections occurred among patients treated with MMF and prednisolone. Conclusion: As for the induction therapy of lupus nephritis, the combination of MMF and prednisolone may be an effective regimen. However, further randomized, prospective studies are needed to prove the effectiveness of MMF therapy in lupus nephritis.

루푸스 신염의 치료에 있어 Mycophenolate Mofetil의 효과와 안전성

김해림 ( Hae Rim Kim ),김상현 ( Sang Hyon Kim ),김성동 ( Sung Dong Kim ),박경수 ( Kyung Soo Park ),윤종현 ( Chong Hyeon Yoon ),김완욱 ( Wan Uk Kim ),홍연식 ( Youn Sik Hong ),이상헌 ( Sang Heon Lee ),박성환 ( Sung Hwan Park ),조철 대한류마티스학회 2004 대한류마티스학회지 Vol.11 No.3

Objective: To determine the therapeutic effect of mycophenolate mofetil (MMF) and the adverse effects associated with MMF in patients with lupus nephritis. Methods: We studied 51 patients with lupus nephritis, who had received MMF for more than 3 months. The efficacy was assessed as renal profiles, SLE disease activity index (SLEDAI), serum cytokine levels and oral corticosteroid dose. The adverse effects were evaluated by medical records and interview of each patient. Serum cytokine levels of IL-10, IFN-α and IFN-γ were determined by sandwich ELISA at starting MMF and at 12 months after MMF therapy. Results: MMF treatment resulted in complete remission 52.9%, partial remission 25.5% and treatment failure 21.6%. There was no difference of MMF efficacy between WHO class IV and V in 32 patients with biopsy-proven nephritis. The renal profiles and parameters for disease activity were improved, as assessed by increased serum albumin and C3 level, decreased proteinuria, cyturia, ESR, SLEDAI and oral corticosteroid doses. Serum IL-10 decreased after MMF therapy in class IV group, but not in class V group. Serum IFN-α, IFN-γ level and IFN-γ/IL-10 ratio also tended to decrease after MMF therapy. GI troubles including dyspepsia, nausea, vomiting and diarrhea were the most common adverse effects of MMF as 54.9%, followed by hair loss, leukopenia, anemia, infection, but there was no serious adverse effect. Conclusion: MMF is an effective and well tolerable immunosuppressant for both class IV and V lupus nephritis, even not responding or intolerable to conventional immunosuppressive therapy.

Renal expression of galectin-3 in systemic lupus erythematosus patients with nephritis

Kang, EH,Moon, KC,Lee, EY,Lee, YJ,Lee, EB,Ahn, C,Song, YW SAGE Publications 2009 Lupus Vol.18 No.1

<P>The aim of the study is to characterize the expression pattern of galectin-3 (Gal-3) in renal tissues of patients with systemic lupus erythematosus (SLE) nephritis and to determine whether tissue and serum Gal-3 are associated with SLE nephritis. Gal-3 expressions were examined with immunohistochemistry in renal biopsy specimens of 88 patients with SLE nephritis and in five normal specimens. Activity and chronicity indexes and glomerular Gal-3 expressions were analysed in each specimen. Serum Gal-3 levels were measured using enzyme-linked immunosorbent assays in 20 patients with SLE, including 11 with nephritis, and in 50 healthy controls. Glomerular Gal-3 expression was observed in 81.8% (72/88) of patients with SLE nephritis but not in 5 controls. Gal-3 staining was attributed mainly to its cellular expression rather than its deposition, and Gal-3 expression levels were correlated with histologic activity indexes, anti-dsDNA titers, and complement 3 and 4 levels. Serum Gal-3 levels were higher in patients with SLE, particularly in those with nephritis, than in healthy controls, and correlated with anti-dsDNA titers. In conclusion, glomerular Gal-3 expression in renal tissue and serum Gal-3 levels were elevated in patients with SLE nephritis versus healthy controls; moreover, they reflected disease activity. These findings suggest that Gal-3 might contribute to the inflammatory process in SLE.</P>