• Clinical and Experimental Pediatrics
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• 제61권2호
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• pp.37-42
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• 2018

Hemolytic uremic syndrome (HUS) is often encountered in children with acute kidney injury. Besides the well-known shiga toxin-producing Escherichia coli-associated HUS, atypical HUS (aHUS) caused by genetic complement dysregulation has been studied recently. aHUS is a rare, chronic, and devastating disorder that progressively damages systemic organs, resulting in stroke, end-stage renal disease, and death. The traditional treatment for aHUS is mainly plasmapheresis or plasma infusion; however, many children with aHUS will progress to chronic kidney disease despite plasma therapy. Eculizumab is a newly developed biologic that blocks the terminal complement pathway and has been successfully used in the treatment of aHUS. Currently, several guidelines for aHUS, including the Korean guideline, recommend eculizumab as the first-line therapy in children with aHUS. Moreover, life-long eculizumab therapy is generally recommended. Further studies on discontinuation of eculizumab are needed.

• Childhood Kidney Diseases
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• 제10권2호
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• pp.109-118
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• 2006

Purpose : HUS usually occurs in children after infection with shiga toxin-producing microorganism(D＋HUS). In contrast, non-postdiarrheal(D-) HUS occurs at any age and has a high rate of relapse and a poor prognosis. The clinical presentation of D-HUS is similar to that of thrombotic thrombocytopenic purpura(TTP). Recently severe deficiencies of ADAMTS13 were reported not only in TTP and D- HUS but also in D+ HUS during their acute phase. The purpose of the study is to evaluate the plasma ADAMTS13 activity in D＋ and D-HUS. Methods : Nineteen children with HUS(D＋ HUS 12 and D- HUS 7) were enrolled. The assays of plasma ADAMTS13 activity were performed during the acute stage in the D＋ HUS and at various stages of relapsing courses in the D- HUS patients by multimer assay, based on electrophoresis. Results : The median plasma activity of ADAMTS13 in D＋ HUS and D- HUS were 80.9%(37.8-132.4%) and 53.9%(1.0-94.1%), respectively, which were not statistically significantly different from control(86.4%, 34.2-112.3%)(P>0.05). One boy with D- HUS had severe deficiency of ADAMTS13(1.0%). His platelet count was normalized temporarily by fresh frozen plasma infusion. Conclusion : We have demonstrated that there is no significant difference of the plasma ADAMTS13 activity between D＋ HUS, D- HUS and control. We detected severe deficiency of ADAMTS13 in one boy who presented with relapsing episodes of D- HUS. ADAMTS13 deficiency should be considered in the subgroup of D- HUS especially with early onset and recurrent courses. Plasma therapy can be beneficial in this subgroup.

• Childhood Kidney Diseases
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• 제26권1호
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• pp.58-62
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• 2022

Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury without any association with preceding diarrhea. Dysregulation of the complement system is the most common cause of aHUS, and monoclonal humanized anti-C5 antibodies are now recommended as the first-line treatment for aHUS. However, if the complement pathway is not the cause of aHUS, C5 inhibitors are ineffective. In this study, we report the second reported case of aHUS caused by DGKE mutations in Republic of Korea. The patient was an 11-month-old infant who presented with prodromal diarrhea similar to typical HUS, self-remitted with conservative management unlike complement-mediated aHUS but recurred with fever. While infantile aHUS often implies genetic dysregulation of the complement system, other rare genetic causes, such as DGKE mutation, need to be considered before deciding long-term treatment with C5 inhibitors.

• Childhood Kidney Diseases
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• 제23권1호
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• pp.43-47
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• 2019

Atypical hemolytic uremic syndrome (aHUS), a rare form of thrombotic microangiopathy, is distinguished from the typical form by the absence of a preceding verotoxin-producing Escherichia coli infection. Notably, aHUS occurs in association with genetic or acquired disorders causing dysregulation of the alternative complement pathway. Patients with aHUS may show the presence of anti-complement factor H (CFH) autoantibodies. This acquired form of aHUS (antiCFH-aHUS) primarily affects children aged 9-13 years. We report a case of a 13-year-old Lao girl with clinical features of aHUS (most likely anti-CFH-aHUS). The initial presentation of the patient met the classical clinical triad of thrombotic microangiopathy (microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury) without preceding diarrheal illness. Low serum levels of complement 3 and normal levels of complement 4 indicated abnormal activation of the alternative complement pathway. Plasma infusion and high-dose corticosteroid therapy resulted in improvement of the renal function and hematological profile, although the patient subsequently died of infectious complications. This is the first case report that describes aHUS (possibly anti-CFH-aHUS) in Laos.

• Clinical and Experimental Pediatrics
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• 제50권10호
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• pp.931-937
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• 2007

The hemolytic uremic syndrome (HUS) is a rare disease of microangiopathic hemolytic anemia, low platelet count and renal impairment. HUS usually occurs in young children after hemorrhagic colitis by shigatoxin-producing enterohemorrhagic E. coli (D+HUS). HUS is the most common cause of acute renal failure in infants and young children, and is a substantial cause of acute mortality and morbidity; however, renal function recovers in most of them. About 10% of children with HUS do not reveal preceding diarrheal illness, and is referred to as D- HUS or atypical HUS. Atypical HUS comprises a heterogeneous group of thrombomicroangiopathy (TMA) triggered by non-enteric infection, virus, drug, malignancies, transplantation, and other underlying medical condition. Emerging data indicate dysregulation of alternative complement pathway in atypical HUS, and genetic analyses have identified mutations of several regulatory genes; i.e. the fluid phase complement regulator Factor H (CFH), the integral membrane regulator membrane cofactor protein (MCP; CD46) and the serine protease Factor I (IF). The uncontrolled activation of the complement alternative pathway results in the excessive consumption of C3. Plasma exchange or plasma infusion is recommended for treatment of, and has dropped the mortality rate. However, overall prognosis is poor, and many patients succumb to end-stage renal disease. Clinical presentations, response to plasma therapy, and outcome after renal transplantation are influenced by the genotype of the complement regulators. Thrombotic thrombocytopenic purpura (TTP), another type of TMA, occurs mainly in adults as an acquired disease accompanied by fever, neurologic deficits and renal abnormalities. However, less frequent cases of congenital or hereditary TTP associated with ADAMTS-13 (a disintegrin and metalloprotease, with thrombospondin 1-like domains 13) gene mutations have been reported, also. Recent advances in molecular genetics better allow various HUS to be distinguished on the basis of their pathogenesis. The genetic analysis of HUS is important in defining the underlying etiology, predicting the genotype-related outcome and optimizing the management of the patients.

• Journal of Microbiology and Biotechnology
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• 제28권9호
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• pp.1413-1425
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• 2018

Shiga toxins (Stxs) are the main virulence factors expressed by the pathogenic Stx-producing bacteria, namely, Shigella dysenteriae serotype 1 and certain Escherichia coli strains. These bacteria cause widespread outbreaks of bloody diarrhea (hemorrhagic colitis) that in severe cases can progress to life-threatening systemic complications, including hemolytic uremic syndrome (HUS) characterized by the acute onset of microangiopathic hemolytic anemia and kidney dysfunction. Shiga toxicosis has a distinct pathogenesis and animal models of Stx-associated HUS have allowed us to investigate this. Since these models will also be useful for developing effective countermeasures to Stx-associated HUS, it is important to have clinically relevant animal models of this disease. Multiple studies over the last few decades have shown that mice injected with purified Stxs develop some of the pathophysiological features seen in HUS patients infected with the Stx-producing bacteria. These features are also efficiently recapitulated in a non-human primate model (baboons). In addition, rats, calves, chicks, piglets, and rabbits have been used as models to study symptoms of HUS that are characteristic of each animal. These models have been very useful for testing hypotheses about how Stx induces HUS and its neurological sequelae. In this review, we describe in detail the current knowledge about the most well-studied in vivo models of Stx-induced HUS; namely, those in mice, piglets, non-human primates, and rabbits. The aim of this review is to show how each human clinical outcome-mimicking animal model can serve as an experimental tool to promote our understanding of Stx-induced pathogenesis.

• Childhood Kidney Diseases
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• 제24권2호
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• pp.138-142
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• 2020

Atypical hemolytic uremic syndrome (aHUS) is an extremely rare and life-threatening disorder. Typical HUS is often caused by Shiga toxin-positive Escherichia coli, while aHUS is caused by dysregulation of the alternative pathway of the complement system in association with genetic abnormalities or development of autoantibodies. Eculizumab, a humanized anti-complement 5 monoclonal antibody, is recommended for the treatment of aHUS, but its long-term safety and efficacy in pediatric patients remain under review. In this paper, we report a pediatric case of aHUS with anti-complement factor H autoantibodies, who was treated successfully with eculizumab.

• Childhood Kidney Diseases
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• 제6권2호
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• pp.237-242
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• 2002

용혈성 요독 증후군은 용혈성 빈혈, 혈소판 감소증, 급성신부전의 임상양상을 보이는 질환으로서 전형적인 경우 EHEC에 의해 유발되며, 설사(특히 혈변) 등의 전구증상과 연관된다. 비전형적으로 드물게 폐구균 감염으로도 유발되며, 이 경우 매우 불량한 예후를 보이는 것으로 알려져 있고, 아직 국내엔 폐구균 감염과 연관된 HUS에 대해 보고된 바가 없다. 저자들은 폐구균 감염이 진단된 후 급격히 심한 비전형적 용혈성 요독 증후군이 진행되었으나 성공적으로 치료한 1례를 경험하였기에 보고하는 바이다.

• Childhood Kidney Diseases
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• 제19권1호
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• pp.48-52
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• 2015

Streptococcus pneumoniae associated hemolytic uremic syndrome (SpHUS) is one of the causes of atypical hemolytic uremic syndrome, and increasingly reported. They are more severe and leave more long-term sequelae than more prevalent, typical hemolytic uremic syndrome. But it is not so easy to diagnose SpHUS for several reasons (below), and there was no diagnostic criteria of consensus. A 18 month-old-girl with sudden onset of oliguria and generalized edema was admitted through the emergency room. She had pneumonia with pleural effusion and laboratory findings of HUS, DIC, and positive direct Coombs' test. As DIC or SpHUS was suspected, we started to treat her with broad spectrum antibiotics, transfusion of washed RBC and replacement of antithrombin III. On the $3^{rd}$ day, due to severe hyperkalemia and metabolic acidosis, continuous renal replacement therapy (CRRT) was started. She showed gradual improvement in 4 days on CRRT and discharged in 16 days of hospital care. At the follow up to one year, she has maintained normal renal function without proteinuria and hypertension. We report this case with review of articles including recently suggested diagnostic criteria of SpHUS.

• Clinical and Experimental Pediatrics
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• 제57권2호
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• pp.96-99
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• 2014

Hemolytic uremic syndrome (HUS) is one of the most common causes of acute renal failure in childhood and is primarily diagnosed in up to 4.5% of children who undergo chronic renal replacement therapy. Escherichia coli serotype O157:H7 is the predominant bacterial strain identified in patients with HUS; more than 100 types of Shiga toxin-producing enterohemorrhagic E. coli (EHEC) subtypes have also been isolated. The typical HUS manifestations are microangiopathic hemolytic anemia, thrombocytopenia, and renal insufficiency. In typical HUS cases, more serious EHEC manifestations include severe hemorrhagic colitis, bowel necrosis and perforation, rectal prolapse, peritonitis, and intussusceptions. Colonic perforation, which has an incidence of 1%-2%, can be a fatal complication. In this study, we report a typical Shiga toxin-associated HUS case complicated by small intestinal perforation with refractory peritonitis that was possibly because of ischemic enteritis. Although the degree of renal damage is the main concern in HUS, extrarenal complications should also be considered in severe cases, as presented in our case.