Abstract: FR-PO805
Clinical and Genetic Characteristics of Pregnancy-Associated aHUS in Japan
Session Information
- Genetic Diseases of the Kidney - II
November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1002 Genetic Diseases of the Kidneys: Non-Cystic
Authors
- Ikeda, Yoichiro, The University of Tokyo School of Medicine, Tokyo, Japan
- Yoshida, Yoko, The University of Tokyo School of Medicine, Tokyo, Japan
- Sugawara, Yuka, The University of Tokyo School of Medicine, Tokyo, Japan
- Nangaku, Masaomi, The University of Tokyo School of Medicine, Tokyo, Japan
Background
Complement dysregulations mostly by the genetic alterations of the complement related factors are involved in the pathogenesis of atypical hemolytic uremic syndrome (aHUS). Pregnancy can impact on the onset of aHUS. Clinical courses and pathogenesis of pregnancy-associated aHUS is not yet fully clarified.
Methods
Blood samples of aHUS patients were analyzed by hemolytic assay, anti-CFH antibody test and whole exome sequences. Pregnancy-associated aHUS was defined as aHUS that occurs during pregnancy or perinatal period. TMA cases with active underlying diseases were excluded.
Results
Out of 264 cases consulted to our division, 6 cases were associated to the pregnancy. All the cases developed TMA immediately after delivery within 12 hours, and no TMA events during pregnancy were observed. The ages of the patients ranged from 25 to 33 years old, and all the cases were primipara. 2 cases underwent Caesarean sections. 5 cases showed both liver and kidney dysfunctions, leading to the diagnoses of aHUS and HELLP syndrome. Hemolytic assays were negative to weak positive, and anti-CFH antibody tests were all negative. Whole exome sequencing detected diverse mutations in complement related factors (C3 V555I, C3 S562L, CFH R1215G, CFI R201S, CFB K533R, MCP S13F). Each mutation corresponds to each case, and there are no common mutations to them. 4 mutations are found in the idiopathic aHUS patients in our cohort, one (CFB K533R) is previously described as an aHUS causing mutation and one (C3 V555I) is novel. One case (CFI R201S) required temporary hemodialysis for severe acute kidney injury. 5 cases recovered the kidney function, while one case (CFB K533R) reached to the end stage kidney disease 1.5 years after the onset of the disease. One case (CFH R1215G) continued eculizumab therapy every two weeks until now. All the cases were followed up for up to 5 years and one case had the second pregnancy with successful delivery. No recurrence of TMA was observed during follow-up period.
Conclusion
The clinical and genetic characteristics of pregnancy-associated aHUS in our cohort are; 1) postpartum TMA with HELLP syndrome is typical, 2) the recurrence rate of aHUS is low, 3) the recovery of kidney and liver functions is generally good, 4) diverse mutations in complement related factors were detected, but they might not be the sole factors responsible for the onset of the disease.
Funding
- Government Support - Non-U.S.