Date: Tuesday, June 14, 2016
Session Time: 2:30pm-4:00pm
Presentation Time: 3:30pm-3:42pm
Location: Ballroom A
Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease with a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. Subjects homozygous for the CFHR3-CFHR1 deletion are at increased risk for aHUS which often leads to ESRD. These subjects continue to manifest a greater risk for aHUS after renal transplantation. We report that heterozygosity for this genotype also confers increased risk for aHUS post-transplant.
Methods: We report three subjects, of whom two developed ESRD secondary to presumed hypertension and a third due to congenital nephrotic syndrome. None had a diagnosis of aHUS before renal transplant. All patients had tacrolimus (FK), mycophenolic acid and prednisone for maintenance immunosuppression. All 3 patients developed aHUS within 1-2 weeks of transplant, with thrombocytopenia, hemolytic anemia, and graft dysfunction. Biopsy demonstrated thrombotic microangiopathy (TMA), no DSAs and negative C4d staining in 2 patients who were biopsied.
FK was stopped immediately after the TMA diagnosis and alternate medications were used. One patient is maintained on belatacept and eculizumab. The other two were started on everolimus; one remains stable on it.
Genetic analysis revealed heterozygous CFHR3-CFHR1 deletions in all three patients. In two patients, a heterozygous CFH H402Y variant was also identified. The third patient was heterozygous for CFHR3 deletion and homozygous for CFHR1 deletion.
Conclusion: Heterozygous CFHR3-CFHR1 deletions in combination with a second heterozygous variant in a complement gene may be pathogenic in the setting of transplantation or tacrolimus exposure, while each variant in isolation may be benign. The use of perioperative eculizumab may help minimize this risk.
|Age Gender||65 M||44 F||35 F|
|TMA on biopsy||Y||—||Y|
|Associated variant||Homozygous CFHR1 deletion||Heterozygous CFH H402Y||Heterozygous CFH H402Y|
|Factor H autoantibody||N||—||N|
|Immunosuppression change/treatment||Eculizumab, Belatacept||Everolimus,1 dose eculizumab||Everolimus, then belatacept/eculizumab|
|Current Cr (mg/dL)||1.3||1.6||Nephrectomy|
CITATION INFORMATION: Rhazouani S, Malone A, Alhamad T, Maw T, Brennan D, Delos Santos R. Early Post Renal Transplant aHUS in Patients with Heterozygous CFHR3-CFHR1 Deletion. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Rhazouani S, Malone A, Alhamad T, Maw T, Brennan D, Santos RDelos. Early Post Renal Transplant aHUS in Patients with Heterozygous CFHR3-CFHR1 Deletion. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/early-post-renal-transplant-ahus-in-patients-with-heterozygous-cfhr3-cfhr1-deletion/. Accessed February 26, 2021.
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