Eculizumab therapy in a child with hemolytic uremic syndrome and CFI mutation

Çaycı, Fatma Şemsa; Çakar, Nilgün; Hancer, Veysel Sabri; Uncu, Nermin; Acar, Banu

doi:10.1007/s00467-012-2283-9

Cited by 36 publications

(16 citation statements)

References 14 publications

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“…[8][9][10] The resulting lack of inhibition leads to uncontrolled complement activation, TMA, endothelial lesions, and platelet aggregation leading to the typical triad of HUS symptoms: hemolytic anemia, thrombocytopenia, and renal insufficiency. 5 Distinguishing aHUS from STEC-HUS, particularly in infants, is often difficult and may take several days, which may be detrimental to outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Several case studies have also been published in older children, revealing the benefits of eculizumab after unsuccessful PE/PI. 8,[15][16][17][18] Because our patient had a very high probability of aHUS, even without having results of genetic testing, and given these positive reports of eculizumab, we decided to use eculizumab as first-line therapy without previous plasmapheresis. Our decision was also encouraged by the need to initiate treatment quickly to avoid TMA progression and permanent organ damage, because other studies have shown a negative effect of treatment delay to recovery of renal function.…”

Section: Discussionmentioning

confidence: 99%

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Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

Christmann

Hansen

Bergmann³

et al. 2014

Pediatrics

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Atypical hemolytic uremic syndrome (aHUS) is a genetic, life-threatening, chronic disease that can affect patients of all ages. aHUS is caused by uncontrolled complement activation due to genetic defects of complement regulation. Plasma exchange or infusion has been used to manage aHUS and may transiently maintain hematologic variables in some patients, but as the underlying complement dysregulation persists, end-stage renal disease or death occurs in 33% to 40% of patients during the first clinical manifestation. Here we present a pediatric case showing that first-line eculizumab treatment successfully blocked the progression of thrombotic microangiopathy in aHUS.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

Christmann

Hansen

Bergmann³

et al. 2014

Pediatrics

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“…Three CFI variants seen in our study have previously been reported in acute hemolytic-uremic syndrome (aHUS) and 2 ADAMTS13 variants were reported in TTP; 1 CFHR5 variant is known to cause CFH-related protein deficiency. [21][22][23][24][25] A CFD variant (c.357116C.A) was detected only in African American patients with TMA. The median number of gene variants seen in transplant recipients with TMA was 1 (range, 0-7) and 0 (range, 0-2) in those without TMA (P , .0001).…”

Section: Gene Variants Identifiedmentioning

confidence: 99%

The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy

Jodele

Zhang

Zou

et al. 2016

Blood

163

147

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“…Özellikle uluslarası konsensüs raporlarında, a HÜS hastalarında eculizumab kullanımı tedavinin erken basamaklarında önerilmektedir. Bununla beraber, bazı yazarlar, eculizumab plazma tedavilerine yanıt-sız olan aHÜS'lü olgularda önerilmiştir (2,12,13) . Bu öneriler güçlü çocuk tabanlı klinik araştırmalara dayanmasa da, genelde ergen ve yetişkinlerdeki olgu sunumlarına dayanmaktadır (8) .…”

Section: Discussionunclassified

“…Klinik hastalar; coombs negatif mikroanjiopatik hemolitik anemi, trombositopeni ve böbrek yetmezliği tablosu ile başvururlar (1)(2)(3) . Çocuklarda atipik HÜS (aHÜS), %10 sıklıkta görülür (1) .…”

Section: Introductionunclassified

The case with atypical hemolytic uremic syndrome presented with nose-bleeding

Yılmaz¹,

İlgün²,

Sönmez³

et al. 2017

Terh

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ÖZAtipik hemolitik üremik sendrom (aHÜS), mortalitesi ve morbiditesi yüksek olan bir hastalıktır. Erken dönemde eculizimab tedavisinin aHÜS'lü çocuklarda kullanımıyla ilgili, literatürdeki kısıtlı sayıda makalede net bir görüş bildirilmemiştir. Sunduğumuz aHÜS'lü olgumuz ile literatüre bu konuda katkıda bulunmak istedik. Üç yaşında erkek olgu, burun kanaması ile başvurduğunda kliniği ve laboratuvarı ile aHÜS tanısı düşünüldü. Plazma infüzyon tedavisi ile yanıt alınamayan olguya, tedavinin 2. gününde eculizimab tedavisi başlandı. Hızla böbrek fonksiyonlarının bozulması ve kan basıncı yüksekliği nedeniyle periton diyalizi (PD) başlandı. Olguda kompleman sistemi genetik mutasyonlarından, kompleman faktör I (KFI) geninde p.Thr300Ala aminoasit değişikliği homozigot varyasyon olarak saptandı. Eculizimab tedavisinin 14. gününde hemoglobin, trombosit sayısı normale dönen olgunun ödemleri kaybolup, kan basıncı normale geldi. Başlanmış olan PD tedavisi, GFH 85 ml/1,73 m 2 /dk. olunca 14. gününde sonlandırıldı. Ancak, nefrotik düzeyde proteinürisi devam ettiği için taburculuk sırasında anjiyotensin dönüştürücü enzim (ACE) inhibitör tedavisine devam edildi. Halen izlemde olan olgu, 2 haftada bir 300 mg eculizimab tedavisini almakta ve tedavinin 3. ayında C3 (67 mg/dl) düzeyi halen düşük devam etmektedir. Atipik HÜS'lü olgumuzda, erken dönemde başlanan eculizimab tedavisinin klinikte ve böbrek fonksiyonlarında tam bir düzelme sağladığını düşünüyoruz.Anahtar kelimeler: Atipik hemolitik üremik sendrom, çocuk, eculizimab, böbrek ABSTRACT Atypical hemolytic uremic syndrome (aHUS) is a disease with a high mortality and morbidity. Any clear-cut opinion about the use of eculizumab treatment during the early phase of the disease in children with aHUS has not been expressed in limited number of articles in the literature. We wanted to contribute to the literature with our aHUS case we presented. As the 3-year-old boy presented with nose-bleeding, clinical, and laboratory analyses suggested the diagnosis of aHUS. Eculizumab treatment was started on the second day of treatment because he was unresponsive to plasma infusion therapy. Due to increasing blood pressure and rapid deterioration of kidney functions peritoneal dialysis was started. In the case the aminoasid change p. Thr300Ala in gene complement factor I (CFI) which is one of the genetic mutations of the complement system, was detected as a homozygous variant. On the 14 th day of eculizimab treatment, hemoglobin and thrombocyte count returned to normal, his edematous lesions disappeared and his high blood pressure was normalized. Peritoneal dialysis was terminated once glomerular filtration rate (GFR) reached to 85 ml/1.73 m 2 /min on the 14 th day. However, since his proteinuria persisted at nephrotic level during the discharge, his angiotensin converting enzyme inhibitor therapy was maintained. The case that has been still under our surveillance is receiving 300 mg eculizimab therapy biweekly, and on the third month of the therapy the level of C3 (63 mg/dl) has still remained...

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Eculizumab therapy in a child with hemolytic uremic syndrome and CFI mutation

Abstract: It is our belief that eculizumab can be the treatment of choice in children who have plasma exchange-refractory HUS with defective regulation of the alternative complement pathway.

Cited by 36 publications

References 14 publications

Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

The genetic fingerprint of susceptibility for transplant-associated thrombotic microangiopathy

The case with atypical hemolytic uremic syndrome presented with nose-bleeding

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