• Clinical and Experimental Pediatrics
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• v.61 no.2
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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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• v.24 no.2
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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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• v.21 no.2
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• pp.160-164
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• 2017

C3 glomerulopathy (C3G) is a recently defined pathological entity characterized by C3 accumulation with absent or scant immunoglobulin deposition, leading to variable glomerular inflammation. The clinical presentation of patients with C3G is highly variable, as they may present with symptoms ranging from microscopic or mild proteinuria to full-blown nephrotic syndrome, with or without renal impairment. However, there is no consensus recommendation for specific treatment in children with C3G. Recently, new therapies have been suggested to target complement pathways, owing to an improvement in the understanding of the pathogenesis of C3G. C3G complement blockade with eculizumab, a monoclonal antibody targeted against complement C5, inhibits activation of the alternative complement pathway. We could not use eculizumab owing to its high price; thus, we administered oral prednisolone and mycophenolate mofetil (MMF). MMF was replaced with cyclosporine because proteinuria persisted, with a consistently low serum C3 level; we tapered off the prednisolone because of a Cushingoid appearance and amenorrhea. Thereafter, proteinuria improved, and the serum C3 level returned to normal. Thus, we report the effectiveness of cyclosporine in a patient with C3G and an inadequate response to prednisolone and MMF, who was detected via school urinary screening.

• Childhood Kidney Diseases
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• v.26 no.1
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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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• v.17 no.1
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• pp.6-12
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• 2013

Thrombotic microangiopathy (TMA) is a microvascular thrombotic lesion caused by endothelial injury and subsequent formation of platelet rich thrombus. TMA is first described as a classical pathologic feature of HUS/TTP. Renal biopsy finding of TMA represents kidney involvement of HUS/TTP as well as other diseases such as malignant hypertension, drug toxicity, eclampsia, pre-eclampsia, and several systemic infections. Autoimmune diseases and transplant kidney sometime also have TMA. It is needed to consider a complete autoimmune work-up of patients presenting with TMA including tests for ANA, ANCA, and ADAMTS13 inhibitory antibodies, because there are several reports of association with TMA in patients of SLE, anti-phospholipid syndrome, and ANCA-associated vasculitis.

• Childhood Kidney Diseases
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• v.17 no.1
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• pp.1-5
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• 2013

C3 glomerulonephritis (C3GN) is a recently described entity that shows a glomerulonephritis on light microscopy, bright C3 staining and the absence of C1q, C4, and immunoglobulins on immunofluorescence microscopy and mesangial and/or subendothelial electron-dense deposits on electron microscopy. The term 'C3 glomerulopathy' is often used to include C3GN and dense deposit disease (DDD), CFHR5 nephropathy, those of which result from dysregulation of the alternative pathway of complement. C3GN shares some aspects of atypical hemolytic uremic syndrome, MPGN, late stage of post infectious glomerulonephritis and other glomerulonephrtis. When C3GN is considered, measurement of serum complement proteins including C3, CFH, CFI, CFB and testing for the presence of C3 nephritic factor, anti-factor H autoantibodies are necessary. To screening for mutations, genes that encode complement regulators should be evaluated. This disorder equally affected all ages, both genders, and typically presented with hematuria and proteinuria. In both the short and long term, renal function remained stable in the majority of patients.

• Childhood Kidney Diseases
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• v.24 no.1
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• pp.1-13
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• 2020

Immunoglobulin (Ig)A vasculitis nephritis (IgAVN), also referred to as Henoch-Schönlein purpura nephritis, is a relatively benign disease in children. However, two 24-year European cohort studies have reported high sustained rates of hypertension, severe proteinuria, and renal dysfunction in patients with IgAVN. Notably, the incidence and exacerbation rates of proteinuria, hypertension, and renal dysfunction during pregnancy were high even in women who recovered from IgAVN before pregnancy. Patients with IgAVN need lifelong care. Trials have been performed to investigate early biomarkers and genes associated with poor prognosis to identify high-risk patients in whom IgAVN may progress to severe renal disease. Urinary IgA/cr, IgM/cr levels, and HLAB35 and angiotensinogen gene expression were shown to be predictors of progression of IgAVN to severe renal dysfunction. The 2019 Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative group published guidelines for pediatric IgAVN, following the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines established in 2012. Compared with the KDIGO guidelines, the SHARE guidelines recommend earlier corticosteroid administration in cases of mild proteinuria (>0.5 g/d). Clinical trials of targeted budesonide delivery to the distal ileum, monoclonal antibody targeting C5, eculizumab and anti-CD20 monoclonal antibody administration, among others are currently underway in patients with IgA nephropathy. It is expected that newer therapeutic agents would become available for IgAVN in the near future. This review summarizes IgAVN with emphasis on recently published literature, including possible preventive strategies, predictive biomarkers for progression of IgAVN, and various treatments.