• Clinical and Experimental Pediatrics
• /
• 제61권2호
• /
• pp.37-42
• /
• 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
• /
• 제24권2호
• /
• pp.138-142
• /
• 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
• /
• 제21권2호
• /
• pp.160-164
• /
• 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
• /
• 제26권1호
• /
• pp.58-62
• /
• 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
• /
• 제17권1호
• /
• pp.6-12
• /
• 2013

사구체에 면역글로불린은 음성이면서 C3 만 침착되는 경우, 다른 원인이 없는 경우 C3GN을 의심하여야 한다. 광학현미경으로는 세포의 증식이 있는 경우와 없는 경우가 있지만, 전자현미경으로는 EDD가 내피세포 밑으로 혹은 메산지움 등에 침착함을 확인하여야 한다. 대체보체경로의 조절이상이 원인임으로 혈청 C3 치를 비롯하여 CFH, CFI, CFB 등을 측정하여야 하며, C3 nephritic factor, antifactor H 자가항체 등을 조사하는 것이 필요하다. 보체 조절이상을 일으키는 유전자 돌연변이를 조사해 보아야 한다. 예후는 안정적이지만, 치료는 대증적이다. 이론적으로 보체의 활성화를 저지하는 약으로 가능할 것으로 생각되며, C5 항체인 eculizumab으로 치유된 보고도 있다.

• Childhood Kidney Diseases
• /
• 제17권1호
• /
• pp.1-5
• /
• 2013

사구체에 면역글로불린은 음성이면서 C3 만 침착되는 경우, 다른 원인이 없는 경우 C3GN을 의심하여야 한다. 광학현미경으로는 세포의 증식이 있는 경우와 없는 경우가 있지만, 전자현미경으로는 EDD가 내피세포 밑으로 혹은 메산지움 등에 침착함을 확인하여야 한다. 대체보체경로의 조절이상이 원인임으로 혈청 C3 치를 비롯하여 CFH, CFI, CFB 등을 측정하여야 하며, C3 nephritic factor, anti-factor H 자가항체 등을 조사하는 것이 필요하다. 보체 조절이상을 일으키는 유전자 돌연변이를 조사해 보아야 한다. 예후는 안정적이지만, 치료는 대증적이다. 이론적으로 보체의 활성화를 저지하는 약으로 가능할 것으로 생각되며, C5 항체인 eculizumab으로 치유된 보고도 있다.

• Childhood Kidney Diseases
• /
• 제24권1호
• /
• pp.1-13
• /
• 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.