A Single Center Experience of Atypical Hemolytic Uremic Syndrome Post Solid Organ Transplantation – “Benign Genetic Variants: Perhaps No More”
University of Cincinnati, Cincinnati, OH
Meeting: 2020 American Transplant Congress
Abstract number: D-261
Keywords: Heart, Kidney transplantation, Outcome
Session Information
Session Name: Poster Session D: Biomarkers, Immune Assessment and Clinical Outcomes
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*Purpose: Atypical hemolytic uremic syndrome (aHUS) is a genetic-based thrombotic microangiopathy (TMA) that is mediated by the activation of the alternative complement pathway. Heterozygous deletion in CFHR3-CFHR1 occurs in 30% of the general population and contrary to homozygous deletion associated with auto-antibody to factor H (CFH-Ab), it hasn’t been classically linked to aHUS. Post-transplant de-novo and recurrent aHUS have been associated with a high rate of graft dysfunction and loss. Here, we report our case series of patients who developed aHUS after solid organ transplantation.
*Methods: Five cases of post-transplant aHUS were identified at our center since 2012. Genetic testing was performed in all but one. All patients received anti-C5 monoclonal antibody, eculizumab.
*Results: One patient had a presumed TMA diagnosis before transplant. One heart and four kidney (KTx) transplant recipients were diagnosed with aHUS based on the clinical picture of TMA, acute kidney injury and normal ADAMTS13 activity. Genetic mutation testing revealed heterozygous deletion in CFHR3-CFHR1 without a CFH-Ab in two patients and a heterozygous complement factor- I (CFI) variant of uncertain clinical significance (Ile416Leu) in a third. Four patients were on a calcineurin inhibitor (tacrolimus), one had an anti-HLA-A68 donor specific antibody (DSA) (5800 MFI), and another had borderline acute cellular rejection at the time of aHUS diagnosis. Four responded to eculizumab and one out of two patients came off renal replacement therapy. One KTx recipient died from severe bowel necrosis in setting of early aHUS post transplantation (Table 1).
*Conclusions: Calcineurin inhibitors, rejection, DSA, infections, surgery and ischemia-reperfusion injury are common triggers that could unmask aHUS in solid organ transplant recipients. Therefore, aHUS should be recognized in this patient population and treated with anti-C5 therapy promptly. Heterozygous deletion in CFHR3-CFHR1 and CFI variants of uncertain clinical significance may be important susceptibility factors acting as the first hit for alternative complement pathway dysregulation.
To cite this abstract in AMA style:
Khan M, Anand M, Kaur T, Bumb S, Shah S, Govil A, Jawdeh BGAbu. A Single Center Experience of Atypical Hemolytic Uremic Syndrome Post Solid Organ Transplantation – “Benign Genetic Variants: Perhaps No More” [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/a-single-center-experience-of-atypical-hemolytic-uremic-syndrome-post-solid-organ-transplantation-benign-genetic-variants-perhaps-no-more/. Accessed May 11, 2025.« Back to 2020 American Transplant Congress