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.

Diagnosis and Treatment of Monogenic Hypertension in Children

신재일,박세진 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.

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.

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

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.

소아 루프스 신염의 임상양상 및 치료결과

박지민,신재일,김병길,이재승,Park Jee-Min,Shin Jae-Il,Kim Pyung-Kil,Lee Jae-Seung 대한소아신장학회 2002 Childhood kidney diseases Vol.6 No.2

목적 : 전신성 홍반성 낭창(Systemic lupus erythematosus, SLE)은 여러장기를 침범하는 자가면역성 질환으로 신장의 손상이 본 질환의 예후를 좌우하는 주요원인이다. 특히 소아에서 루프스 신염은 성인보다 그 빈도가 높고, 증상이 심하므로, 신생검은 효과적인 치료의 계획을 위해서 중요한 수기이다. 이에 저자는 소아연령에서 루프스 신염의 임상적 병리학적 특성 및 치료방법에 대해 전반적으로 고찰하여 예후의 향상을 기대하고자 한다. 방법 : 1990년 1월부터 2002년 9월까지 소아과에서 전신성 홍반성 낭창으로 진단받은 63례의 환아중 신생검을 시행하여 루프스 신염으로 진단되었던 40례를 대상으로 의무 기록을 후향적으로 고찰하였다. 결과 : 환아의 남녀비는 1:3이었고 진단당시 평균발병 연령은 12.1(2-18)세였다. ARA 기준중에서는 형광 항핵항체(95.0%), 항dsDNA항체(87.5%), 나비모양 홍반(80.0%)의 순이었다. 가장 흔한 신장증상은 단백뇨와 현미경적 혈뇨(75.0%), 신증후군(55.0%), 현미경적 혈뇨 단독(15.0%)의 순이었고, 신생검상 27례(67.5%)에서 WHO Class IV 병변이 관찰되었고 3례에서 추적 관찰 신생검에서 조직소견이 바뀌었다. 치료는 prednisolone 단독 5례, prednisolone+azathioprine 9례, prednisolone+azathioprine+정맥cyclophosphamide 14례, prednisolone+cyclosporineA+정맥 cyclophosphamide 12례였고, 9례에서 혈장 교환술을 시행하였다. 환아들의 평균 추적관찰은 $51.8{\pm}40.5$개월이었고 사망은 4례에서 있었다. 사망과 관련된 위험인자로는 진단당시 성별이 남아일 때, WHO class IV의 조직소견, 급성 신부전을 동반할 때 의미있는 것으로 나타났다. 결론 : SLE 환아 중 루프스 신염의 빈도는 63.5%였으며 그중 67.5%가 예후가 불량한 WHO Class IV로 확인되었다. 따라서 신염의 초기에 적극적인 면역억제제 사용이 장기 예후 향상에 도움을 주리라고 생각된다. 하지만 소아기에 성장, 정신 사회적 발달, 생식기의 독성 등도 중요한 문제이므로 항상 적절한 치료를 위해 세심한 관심을 쏟아야 할 것이다. Purpose; Systemic lupus erythematosus(SLE) is an autoimmune disease with multi-system involvement and renal damage is a major cause of morbidity and mortality in children. Renal involvement is more common and severe in children than in adults. Therefore, renal biopsy plays a crucial role in planning effective therapy. In this study, we investigated the clinical and pathological findings of lupus nephritis in children to aid clinical care of the disease. Methods: The clinical and pathological data of 40 patients who were diagnosed as SLE with renal involvement in Shinchon Severance Hospital from Jan. 1990 to Sep. 2002 were analyzed retrospectively. Results: The ratio of male to female patients was 1:3 and the median age at diagnosis was 12.1(2-18) years old. FANA(95.0%), anti-ds DNA antibody(87.5%), malar rash(80.0%) were the most common findings among the classification criteria by ARA. Microscopic hematuria with proteinuria(75.0%), nephrotic syndrome(55.0%), and microscopic hematuria alone(15.0%) were the most common renal presentations in the respective order at diagnosis. There were 27 cases with WHO class IV lupus nephritis confirmed by renal biopsy and 3 cases with pathological changes of WHO class type. Different treatment modalities were carried out : prednisolone only in 5 cases, prednisol-one+azat-hioprine in 9 cases, prednisolone+azathioprine+intravenous cyclophosphamide in 14 cases, prednisolone+cyclosporine A+intravenous cyclophosphamide in 12 cases, plasma exchange in 9 cases and intravenous gamma-globulin in 2 cases. The average follow-up period was $51.8{\pm}40.5$ months. During $51.8{\pm}40.5$ months. During follow-up, 4 patients expired. The risk factors associated with mortality were male, WHO class IV and acute renal failure at diagnosis. Conclusion: Renal involvement was noted in 63.5% of childhood SLE, and 67.5% of renal lesion was WHO class IV lupus nephritis which is known to be associated with a poor prognosis. Therefore aggressive treatment employing immunosuppressant during the early stages of disease could be helpful in improving long-term prognosis. But careful attention should be given to optimize the treatment due to unique problems associated with growth, psychosocial development and gonadal toxicity, especially in children.

신생아와 영아의 지속적 신대체 요법

김성헌,신재일,Kim, Seong Heon,Shin, Jae Il 대한소아신장학회 2014 Childhood kidney diseases Vol.18 No.1

지속적 신 대체 요법(CRRT)은 급성 신손상이 있는 중증 소아의 치료로 점차 사용이 늘어나고 있으며 CRRT의 기술과 실제 사용법이 발달하면서 작은 영아나 신생아에서도 그 사용이 조금씩 늘어나고 있다. 고암모니아혈증이나 체외막산소화 장치(ECMO) 치료 중에 발생한 급성 신손상 등의 경우 CRRT가 안전하고 효과적인 치료가 될 수 있으나, 혈관 접근이나 출혈 그리고 신생아 전용 CRRT device의 부재로 인한 여러 가지 제한점이 있다. 이 종설에서는 기본적인 CRRT의 원리를 알아보고 신생아와 영아에서 특별히 고려해야 할 사항들에 대해 알아보고자 한다. Continuous renal replacement therapy (CRRT) has become the preferred dialysis modality to support critically ill children with acute kidney injury. As CRRT technology and clinical practice advances, experiences using CRRT on small infants and neonates have increased. In neonates with hyperammonemia or acute kidney injury during extracorporeal membrane oxygenation (ECMO) therapy, CRRT can be a safe and effective technique. However, there are many limitations of CRRT in neonates, including vascular access, bleeding complications, and lack of neonatespecific devices. This review discusses the basic principles of CRRT and the special considerations when using this technique in neonates and infants.

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.

급성 신손상을 가진 소아의 지속적 신대체 요법

박세진,신재일,Park, Se-Jin,Shin, Jae-Il 대한소아신장학회 2011 Childhood kidney diseases Vol.15 No.2

Acute kidney injury (AKI) is associated with mortality and may lead to increased medical expense. A modified criteria (pediatric RIFLE [pRIFLE]: Risk, Injury, Failure, Loss, and End-stage renal disease) has been proposed to standardize the definition of AKI. The common causes of AKI are renal ischemia, nephrotoxic medications, and sepsis. A majority of critically ill children develop AKI by the pRIFLE criteria and need to receive intensive care early in the course of AKI. Factors influencing patient survival (pediatric intensive care unit discharge) are known to be low blood pressure at the onset of renal replacement therapy (RRT), the use of vasoactive pressors during RRT, and the degrees of fluid overload at the initiation of RRT. Early intervention of continuous RRT (CRRT) has been introduced to reduce mortality and fluid overload that affects poor prognosis in patients with AKI. Here, we briefly review the practical prescription of pediatric CRRT and literatures on the outcomes of patients with AKI receiving CRRT and associations among AKI, fluid overload, and CRRT. In conclusion, we suggest that an increased emphasis should be placed on the early initiation of CRRT and fluid overload in the management of pediatric AKI. 소아에서 급성 신손상의 흔한 원인들로는 신허혈, 신독성 약물들, 그리고 패혈증 등이 있으며, 신대체요법 시작시의 저혈압, 신대체 요법 동안 승압제의 사용, 그리고 신대체 요법 시작시의 수액 과부하 정도가 환자의 생존(소아 중환자실 퇴원)에 영향을 미치는 요인들로 알려져 있다. 지속적 신대체 요법의 빠른 시작은 급성 신손상을 가진 환자들에게서 사망률과 예후에 나쁜 영향을 미치는 수액 과부하를 감소시키는 것으로 보고되었다. 이에 저자들은 소아 환자에게서 지속적 신대체 요법의 실제 처방과 급성 신손상, 수액 과부하, 그리고 지속적 신대체 요법간의 연관성 및 치료결과를 살펴보고자 한다. 결론적으로, 급성 신손상을 가진 소아의 치료에 있어서 과도한 수액 과부하가 발생하기 전에 빠른 지속적 신대체 요법의 시작이 필요하다고 제시하는 바이다.

Complications of nephrotic syndrome

박세진,신재일 대한소아청소년과학회 2011 Clinical and Experimental Pediatrics (CEP) Vol.54 No.8

Nephrotic syndrome (NS) is one of the most common glomerular diseases that affect children. Renal histology reveals the presence of minimal change nephrotic syndrome (MCNS) in more than 80% of these patients. Most patients with MCNS have favorable outcomes without complications. However, a few of these children have lesions of focal segmental glomerulosclerosis, suffer from severe and prolonged proteinuria, and are at high risk for complications. Complications of NS are divided into two categories: disease-associated and drug-related complications. Disease-associated complications include infections (e.g., peritonitis, sepsis, cellulitis, and chicken pox),thromboembolism (e.g., venous thromboembolism and pulmonary embolism), hypovolemic crisis (e.g., abdominal pain, tachycardia, and hypotension), cardiovascular problems (e.g., hyperlipidemia), acute renal failure, anemia, and others (e.g., hypothyroidism, hypocalcemia,bone disease, and intussusception). The main pathomechanism of disease-associated complications originates from the large loss of plasma proteins in the urine of nephrotic children. The majority of children with MCNS who respond to treatment with corticosteroids or cytotoxic agents have smaller and milder complications than those with steroid-resistant NS. Corticosteroids, alkylating agents, cyclosporin A, and mycophenolate mofetil have often been used to treat NS, and these drugs have treatment-related complications. Early detection and appropriate treatment of these complications will improve outcomes for patients with NS.