Plasma resistant atypical hemolytic uremic syndrome associated with a CFH mutation treated with eculizumab: a case report.
BACKGROUND
Thrombotic microangiopathies are a group of diseases presenting as microangiopathic hemolytic anemia, thrombocytopenia and end-organ dysfunction. As the role of the complement system was elucidated in atypical hemolytic uremic syndrome pathogenesis, eculizumab was successfully introduced into clinical practice. We present a large pedigree with multiple individuals carrying a functionally significant novel factor H mutation. We describe the proband's presentation following a presumed infectious trigger requiring plasma exchange and hemodialysis.


METHODS
A 32-year-old Caucasian woman presented with pyrexia and headache lasting one week to our Emergency Department. She gave no history of diarrhea or other symptoms to account for her high temperature. She was not taking any medication. She was pyrexial (38°C), tachycardic (110 bpm) and hypertensive (160/110 mmHg). Her fundoscopy revealed grade IV hypertensive retinopathy. She had mild pretibial and periorbital edema, with oliguria (450 mL/day). She had a pregnancy one year previously, during which she had hypertension, proteinuria and edema, with successful delivery at term. Her mother had died in her early 30s with a clinical picture consistent with thrombotic microangiopathy. Her laboratory evaluation showed microangiopathic hemolytic anemia. After 22 sessions of plasma exchange, her lactate dehydrogenase levels started to climb. As a result, she was classified as plasma resistant and eculizumab therapy was instituted. Her lactate dehydrogenase level and platelet count normalized, and her renal function recovered after three months of dialysis.


CONCLUSIONS
We demonstrate that, even in patients with atypical hemolytic uremic syndrome and prolonged dialysis dependence, recovery of renal function can be seen with eculizumab treatment. We suggest a treatment regime of at least three months prior to evaluation of efficacy.
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. musevinc@hotmail.com.
Mustafa
M
Sevinc
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. tanerbast@yahoo.com.
Taner
T
Basturk
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. tu_cay83@yahoo.com.
Tuncay
T
Sahutoglu
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. sakacitamer@hotmail.com.
Tamer
T
Sakaci
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. dryenerkoc@mynet.com.
Yener
Y
Koc
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. elbis.ahbap@sislietfal.gov.tr.
Elbis
E
Ahbap
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. cakgol2001@yahoo.com.
Cuneyt
C
Akgol
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. karaekrem79@hotmail.com.
Ekrem
E
Kara
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. vickybrocklebank@doctors.org.uk.
Vicky
V
Brocklebank
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. tim.goodship@newcastle.ac.uk.
Tim H J
TH
Goodship
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK. davidkavanagh@doctors.org.uk.
David
D
Kavanagh
Department of Nephrology, Sisli Hamidiye Etfal Training and Education Hospital, Halaskargazi Cad. Etfal Sok, 34371, Şişli, Istanbul, Turkey. abdulkadir.unsal@sislietfal.gov.tr.
Abdulkadir
A
Unsal
D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome / Q000188:drug therapy* / Q000235:genetics / Q000628:therapy; D017242:Complement Factor H / Q000235:genetics*; D051056:Complement Inactivating Agents / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D010951:Plasma Exchange; D006435:Renal Dialysis; D057049:Thrombotic Microangiopathies / Q000188:drug therapy
D061067:Antibodies, Monoclonal, Humanized; D051056:Complement Inactivating Agents; D017242:Complement Factor H; C481642:eculizumab