Effects of Cyclosporin A Therapy Combined with Steroids and Angiotensin Converting Enzyme Inhibitors on Childhood IgA Nephropathy

신재일,임범진,김평길,이재승,정현주,김지홍 대한의학회 2010 Journal of Korean medical science Vol.25 No.5

To evaluate the effects of cyclosporin A (CyA) on clinical outcome and pathologic changes in children with IgA nephropathy (IgAN), we retrospectively evaluated 14children (mean age 8.9±2.9 yr; eight males, six females) who were treated with CyA and steroids. The starting dose of CyA was 5 mg/kg per day, and the drug level was maintained at 100-200 ng/mL. The mean CyA level was 183.8±48.3 ng/mL (range 120.7-276.0 ng/mL) and the mean duration of CyA therapy was 10.9±1.9months (range 8-12 months). After CyA therapy the mean 24 hr urinary protein excretion declined from 107.1±35.1 mg/m2/hr to 7.4±2.4 mg/m2/hr (P<0.001) and serum albumin increased from 3.3±0.6 g/dL to 4.3±0.3 g/dL (P<0.001). At a follow-up biopsy the histological grade of IgAN was improved in seven (50%) of the 14 patients,remained the same in three (21%), and was aggravated in four (29%). Serum creatinine,creatinine clearance, and blood pressure did not differ before and after CyA therapy. Two patients (14%) showed CyA-induced nephrotoxicity at the second biopsy. Our findings indicate that CyA therapy may be effective in reducing proteinuria and regressing renal pathology in a subset of children with IgAN.

Comment on: A Case of Post-streptococcal Glomerulonephritis with Diffuse Alveolar Hemorrhage

신재일,이재승 대한의학회 2008 Journal of Korean medical science Vol.23 No.2

Treatment of Severe Henoch-Schoenlein Purpura Nephritis in Children

신재일,이재승,Shin, Jae-Il,Lee, Jae-Seung Korean Society of Pediatric Nephrology 2010 Childhood kidney diseases Vol.14 No.1

헤노흐-쇤라인 자반증의 전반적인 예후는 양호하나 심한 신염의 경우 말기신부전으로 진행될 위험이 높다. 최근 연구는 심한 헤노흐-쇤라인 자반증 신염을 가진 소아에서 조기 치료의 중요성을 강조하고 있으나 심한 자반증 신염의 치료는 맹검 대조 연구가 드물어 여전히 논쟁의 여지가 있다. 그럼에도, 정맥 고용량 메틸프레드니솔론 충격요법, 면역억제/세포독성 약제, 섬유소용해 치료, 항응고제, 항혈소판제, 혈장교환술같은 여러 강력한 치료가 심한 자반증 신염을 가진 소아에서 사용되어 왔다. 이 종설에서는 심한 자반증 신염을 가진 소아의 치료를 중점적으로 기술하였다. The overall prognosis of Henoch-Schoenlein purpura (HSP) is favorable, but severe nephritis has a high risk of progression to end stage renal failure. Recent studies emphasize the importance of early treatment in children with severe HSP nephritis, but the treatment of severe HSP nephritis still remains controversial due to the rarity of randomized controlled studies in this field. Nevertheless, several intensive therapies, such as intravenous high-dose methylprednisolone pulse, immunosuppressive/cytotoxic drugs, fibrinolytic therapy, anticoagulants, antiplatelet agent and plasma exchange, have been used in children with severe HSP nephritis. In this review, we focus on the treatment of severe HSP nephritis in children.

소아기 류마티스 관절염의 경과 및 예후 인자

신재일 ( Jae Il Shin ),김동수 ( Dong Soo Kim ),이수곤 ( Soo Kon Lee ),김현우 ( Hyun Woo Kim ) 대한류마티스학회 2003 대한류마티스학회지 Vol.10 No.4

Objective: To assess the disease course and prognostic factors in juvenile idiopathic arthritis (JIA). Methods: We performed a retrospective study of 136 patients between 1990 and 2000. Patients were classified with respect to the International League of Associations for Rheumatology (ILAR) criteria and prognostic factors were evaluated according to the different subtypes. Poor outcome measures were persistent disease, joint destruction and physical disability. Results: There were 73 males and 63 females and the mean follow up period was 5 years (range 2∼25). Predictors of persistent disease in the systemic onset type were polyarticular involvement, symmetric arthritis, and the presence of active systemic disease at 6 months. A poor outcome in the oligoarticular onset type correlated with polyarticular extension, joint erosion, chronic arthritis (duration>6 months), relapse, high antinuclear antibody (ANA) titers (>1:160), persistently high erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). Polyarticular extension was associated with chronic arthritis, involvement of small joints at disease onset, and positive HLA-B27. Predictors of persistent disease in the polyarticular type were chronic arthritis, relapse, and the presence of anemia at disease onset. The risk of joint destruction correlated with sex (female>male), polyarticular involvement, polyarticular extension, chronic arthritis, persistently high ESR or CRP, high ANA titers (>1:160), relapse, and positive rheumatoid factor. Conclusion: Factors predictive of severity in JIA were identified and prognosis was related more to the disease course than the onset type of JIA. So early diagnosis and more aggressive treatment of patients with poor prognostic features could improve functional outcome.

Urinary N-Acetyl-beta-D-Glucosaminidase and beta 2-Microglobulin in Children with Various Renal Diseases

윤소진,신재일,이재승,김현숙,Yoon, So-Jin,Shin, Jae-Il,Lee, Jae-Seung,Kim, Hyon-Suk Korean Society of Pediatric Nephrology 2008 Childhood kidney diseases Vol.12 No.2

목 적 : 요 중 N-acetyl-beta-D-glucosaminidase(NAG) 와 beta 2-microglobulin(B2M) 은 신세뇨관 간질 손상의 표적으로 생각된다. 이 연구의 목적은 다양한 신장 질환 환아 에서 요 중 NAG 와 B2M 수치를 검사해 보는 것이다. 방 법: 우리는 21명의 환아(8.9$\pm$4.5세, 남:녀=14:7)를 조사해서 세 군으로 분류하였다: I군(스테로이드에 반응하는 신증후군 환아-4명), II군(다양한 종류의 사구체 신염 환아-4명), III군(정상뇨 또는 비사구체성 신장 질환 환아-13명). 결 과: I군과 II군에서의 요 중 NAG 수치는 III군에서보다 유의하게 높았다.(19.4$\pm$11.5와 30.0$\pm$30.1 vs. 4.7$\pm$3.9, P=0.01) 반면에 요 중 NAG 수치와 B2M 수치가 양의 상관 관계에 있음에도(r=0.49, P=0.03), 요 중 B2M 수치는 세 군에서 차이가 없었다. 요 중 NAG 와 B2M 수치는 모두 단백뇨, 혈중 알부민, 콜레스테롤과 상관관례를 보였다. 결 론: NAG 와 B2M 의 배설량은 스테로이드에 반응하는 신증후군 환아와 다양한 종류의 사구체 신염 환아에서 증가되어 있었다. 이는 이런 질환들에서 세뇨관 기능저하를 의미하는 것으로 보인다. Purpose : Urinary N-acetyl-beta-D-glucosaminidase(NAG) and beta 2-microglobulin(B2M) is considered to be a marker of tubulointerstitial injury. The aim of this study was to examine the urinary levels of NAG and B2M in children with various renal diseases. Methods : We studied 21 children(8.9$\pm$4.5 years, Male:Female=14:7) and they were divided into three groups: group I(steroid-sensitive nephrotic syndrome-4 patients), group II(various kinds of glomerulonephritis-4 patients), and group III(normal urinalysis or non-glomerular renal diseases-13 patients). Results : Urinary NAG levels in groups I and II were significantly higher than those in group III(19.4$\pm$11.5 and 30.0$\pm$30.1 vs. 4.7$\pm$3.9, P=0.01), while urinary B2M levels did not differ among the 3 groups, although urinary NAG levels were positively correlated with urinary B2M levels(r=0.49, P=0.03). Urinary NAG and B2M levels were all correlated with proteinuria(r=0.79, P<0.001 and r=0.68, respectively, P=0.001) serum albumin(r=-0.72, P<0.001 and r=-0.57, respectively, P=0.01) and cholesterol(r=0.58, P=0.006 and r=0.56, respectively, P=0.013) levels. Conclusions : Urinary excretions of NAG and B2M are increased in children with steroidsensitive nephrotic syndrome and various kinds of glomerulonephritis, suggesting tubular dysfunction might be present in these diseases.

Inflammation and hyponatremia: an underrecognized condition?

박세진,신재일 대한소아청소년과학회 2013 Clinical and Experimental Pediatrics (CEP) Vol.56 No.12

Timely diagnosis of hyponatremia is important for preventing potential morbidity and mortality as it is often an indicator of underlying disease. The most common cause of eurvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. Recent studies have demonstrated that proinflammatory cytokines such as interleukin (IL) 1β and IL-6 are involved in the development of hyponatremia, a condition that is associated with severe inflammation and is related to antidiuretic hormone (ADH) secretion. Serum sodium levels in hyponatremia are inversely correlated with the percentage of neutrophils, C-reactive protein, and N-terminal-pro brain type natriuretic peptide. Additionally, elevated levels of serum IL-6 and IL-1β are found in inflammatory diseases, and their levels are higher in patients with hyponatremia. Because it is significantly correlated with the degree of inflammation in children, hyponatremia could be used as a diagnostic marker of pediatric inflammatory diseases. Based on available evidence, we hypothesize that hyponatremia may be associated with inflammatory diseases in general. Understanding the mechanisms responsible for augmented ADH secretion during inflammation, monitoring patient sodium levels, and selecting the appropriate intravenous fluid treatment are important components that may lower the morbidity and mortality of patients in a critical condition.

소아 Henoch-$Sch{\ddot{o}}nlein$ 자반증에서의 항호중구 항체

최지나,신재일,이재승,김현숙,Choi, Ji-Na,Shin, Jae-Il,Lee, Jae-Seung,Kim, Hyon-Suk 대한소아신장학회 2008 Childhood kidney diseases Vol.12 No.2

목 적 : Henoch-$Sch{\ddot{o}}nlein$ 자반증에서 항호중구 항체에 대한 외국의 여러 논문이 있었으나 이들은 대조적인 연구결과를 보였고, 국내에서는 Henoch-$Sch{\ddot{o}}nlein$ 자반증 환아를 대상으로 한 항호중구 항체의 연구가 없었다. 따라서 한국 소아 Henoch-$Sch{\ddot{o}}nlein$ 자반증에서 항호중구 항체의 임상적인 의의를 알아보고자 본 연구를 시행하였다. 방 법 : 2007년 5월부터 2008년 8월까지 신촌 세브란스병원 소아과에 내원하여 Henoch-$Sch{\ddot{o}}nlein$ 자반증으로 진단받은 30명의 환아들을 대상으로 의무기록을 후향적으로 조사하여 분석하였고, 일반적인 특징으로 나이, 성별, 자반증 등의 증상등을 조사하였다. 검사 소견으로는 백혈구수, 혈소판수, 혈침 속도, Anti-streptolysin O titer, 대변 잠혈 검사, 혈청 면역 글로불린(IgG, IgA, IgM), 혈청 보체(C3, C4), 항핵 항체, 항호중구 항체(c-ANCA, p-ANCA)를 조사하였다. 결 과 : 총 30명의 환아중 남자가 13명, 여자가 17명이었고 평균 연령은 6.0${\pm}$1.9세(범위: 5-12세)였다. 자반은 모든 환아(100%)에서 관찰되었고, 복통은 20 명(67%), 관절통은 17명(57%), 신침범은 11명(37%)에서 관찰되었다. Anti-streptolysin O titer는 검사한 환아 15명 중 1명(7%)에서 증가된 소견을 보었고, 혈청 IgA 수치는 모든 환아에서 증가되지 않았다. 간접면역형광법으로 시행한 항호중구 항체 검사에는 오직 한 명(3%)에서만 p-ANCA가 약양성 소견을 보였으나 이는 추적 검사시 음성으로 전환되었고 나머지 환아에서는 c-ANCA, p-ANCA가 모두 음성 소견을 보였다. 결 론 : 항호중구 항체는 소아 Henoch-$Sch{\ddot{o}}nlein$ 자반증에서 진단적 혹은 면역학적으로 특이한 검사소견은 아닌 것으로 보이며, 이는 항호중구 항체가 소아 Henoch-$Sch{\ddot{o}}nlein$ 자반증의 병인과 연관성이 없음을 암시한다. Purpose : There have been some reports on the prevalence of positive antineutrophil cytoplasmic antibody(ANCA) in Henoch-$Sch{\ddot{o}}nlein$ purpura(HSP), but the results were conflicting. We performed this study to evaluate the clinical significance of ANCA(c-ANCA and p-ANCA) in Korean children with HSP. Methods : The medical records of 30 patients(13 boys and 17 girls) aged 6.0$\pm$1.9(5-12) years with a clinical diagnosis of HSP based on the EULAR/PReS criteria were reviewed retrospectively. From the years 2007 to 2008, the sera from children with acute HSP were tested for antineutrophil cytoplasmic antibodies(ANCA). The target antigens of these autoantibodies are proteinase 3(c-ANCA) or myeloperoxidase(p-ANCA). Results : Palpable purpura was seen in all 30 patients(100%), abdominal pain in 20(67%), arthralgia in 17(57%), and renal involvement in 11(37%). Laboratory findings showed leukocytosis in 4 patients(13%), thrombocytosis 18 in(60%), and elevated erythrocyte sedimentation rate in 18(60%). Anti-streptolysin O titers were elevated in 7% of the patients and no patient showed elevation of serum IgA level. The sera from 29 patients were negative for c-ANCA and p-ANCA by indirect immunofluorescence, but only one patient had weakly positive results, which became negative at follow-up. Conclusions : We conclude that c-ANCA or p-ANCA is not an important serologic marker in children with HSP, because it was neither diagnostically nor immunologically specific in children with HSP. These results suggest that ANCA are not involved in the pathogenesis of HSP in children.

Diagnosis and Treatment of Monogenic Hypertension in Children

박세진,신재일 연세대학교의과대학 2023 Yonsei medical journal Vol.64 No.2

Although the majority of individuals with hypertension (HTN) have primary and polygenic HTN, monogenic HTN is a secondary type that is widely thought to play a key role in pediatric HTN, which has the characteristics of early onset, refractory HTN with a positive family history, and electrolyte disorders. Monogenic HTN results from single genetic mutations that contribute to the dys regulation of blood pressure (BP) in the kidneys and adrenal glands. It is pathophysiologically associated with increased sodium reabsorption in the distal tubule, intravascular volume expansion, and HTN, as well as low renin and varying aldosterone levels. Si multaneously increased or decreased potassium levels also provide clues for the diagnosis of monogenic HTN. Discovering the ge netic factors that cause an increase in BP has been shown to be related to the choice of and responses to antihypertensive medica tions. Therefore, early and precise diagnosis with genetic sequencing and effective treatment with accurate antihypertensive agents are critical in the management of monogenic HTN. In addition, understanding the genetic architecture of BP, causative molecular pathways perturbing BP regulation, and pharmacogenomics can help with the selection of precision and personalized medicine, as well as improve morbidity and mortality in adulthood.

봄베이 O형

권대혁,신재일 한국생물공학회 2007 BT NEWS Vol.14 No.1

소아 $Henoch-Sch\"{o}nlein$ 자반병 신염의 임상양상 및 병리소견과 임상경과

허윤정,신재일,박지민,정현주,이재승,Huh Yun-Jung,Shin Jae-Il,Park Jee-Min,Jeong Hyeon-Joo,Lee Jae-Seung 대한소아신장학회 2003 Childhood kidney diseases Vol.7 No.1

목적 : $Henoch-Sch\"{o}nlein$ 자반병은 자연 관해 질환으로 예후는 대체로 양호하나, 신장침범 유무가 장기적 예후의 중요한 인자로 알려져 있다. 이에 저자들은 $Henoch-Sch\"{o}nlein$ 자반병 신염을 진단받은 환아를 대상으로 임상양상 및 병리학적 소견과 그에 따른 임상결과를 알아보고자 본 연구를 시행하였다. 방법 : 1990년부터 2002년까지 연세대학교병원 소아과에서 $Henoch-Sch\"{o}nlein$ 자반병으로 진단받은 260명 중 $Henoch-Sch\"{o}nlein$ 자반병 신염이 100명이었으며 그 중 신장 조직검사를 한 60명을 대상으로 임상양상 및 병리학적 소견과 임상결과와의 관련성을 후향적으로 조사하였다. 결과 : 1) 남녀 비는 1.2 : 1이었다. 2) $Henoch-Sch\"{o}nlein$ 자반병 신염 환아 60명 중 81%에서 질병발병 후 3개월 이내 신장을 침범한 것으로 나타났다. 3) 현미경적 혈뇨를 동반한 경우는 100%, 단독 혈뇨 15%, 신염 증후군 7%, 신증후군을 동반한 경우는 22%였으며 임상양상과 임상결과 간에 관련성이 있었다. 4) 혈청 IgA의 증가는 60%에서 보였으며 임상결과와 관련성이 없었다. 5) 임상양상은 병리학적 소견과 연관성이 없었다. 6) 신조직 병리소견의 ISKDC의 분류에 따른 빈도는 G I 5.0%, G II 30.0%, G III 58.3%, G IV 5.0%, G V는 1.7%로 G II와 G III가 가장 많았다. 7) G I, G II는 비교적 양성 경과를 보였고, G IV는 임상결과 B를 G V는 임상결과 D를 보여 병리학적 소견은 임상결과와 관련성이 있었다. 결론 : $Henoch-Sch\"{o}nlein$ 자반병 신염에서, 신장 침범의 임상양상은 임상결과와 관련성이 있었고 병리학적 소견도 임상결과와 관련성이 있었다. 조직학적 변화가 심할수록 예후가 불량한 것으로 나왔으며 향후 병리학적 소견에 따른 치료에 대한 적극적인 연구 및 추적관찰이 필요하다고 사료된다. Purpose : $Henoch-Sch\"{o}nlein$ purpura(HSP) is usually a self-limited disease with a good eventual outcome. The prognosis of HSP is mainly determined by the renal involvement. In this study, We evaluated children with biopsy-proven $Henoch-Sch\"{o}nlein$ purpura nephritis about the clinical outcome correlated with renal manifestation and morphologic findings. Methods : The clinical features, initial laboratory and pathologic findings, and clinical out-come were evaluated in 60 children with biopsy-proven $Henoch-Sch\"{o}nlein$ purpura nephritis at Yonsei University Severance Hospital during the period from Jan. 1990 to Dec. 2002. Results : The ratio of male to female patients was 1.2:1. The interval between the onset of $Henoch-Sch\"{o}nlein$ purpura and renal manifestation was less than 3 months in 81% of the patients. Initial renal manifestation was microscopic hematuria in 100% of patients, isolated hematuria in 15%, acute nephritic syndrome in 7%, nephrotic syndrome In 22% of patients. Renal manifestation correlated with clinical outcome. Grade II and III were the most common in histologic grades of ISKDC. Renal pathologic finding correlated with clinical outcome. Conclusion : Renal manifestation and pathologic findings correlated with the clinical out-come. It is necessary to evaluate the correlation between pathologic findings and treatment.