Abstract: TH-PO176

Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation: First Case Report on a Patient with IgA Nephropathy

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Iimura, Yukiya, Shinonoi General Hospital, Nagano, Japan
  • Nakamura, Hironori, Shinonoi General Hospital, Nagano, Japan
  • Mariko, Anayama, Shinonoi General Hospital, Nagano, Japan
  • Makino, Yasushi, Shinonoi General Hospital, Nagano, Japan
  • Nagasawa, Masaki, Shinonoi General Hospital, Nagano, Japan
Background

Several types of glomerulopathy, including focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, C3 glomerulonephritis, and Henoch–Schönlein purpura, can be complicated by atypical hemolytic uremic syndrome (aHUS). Although immunoglobulin (Ig) A nephropathy (IgAN) has been associated with HUS or thrombotic microangiopathy, no report on its association with aHUS has been published. A recent study has found that rare variants of complement factor H (CFH)-related protein 5 may contribute to the genetic susceptibility to IgAN.

Methods

Here we present the first case of a 76-year-old man with IgAN who developed aHUS and was confirmed of harboring a CFH gene mutation.

Results

This patient was admitted with thrombotic microangiopathy findings. On admission, he was afebrile without diarrhea. His blood pressure was 178/109 mmHg. Blood analysis data demonstrated platelets counts of 1.1 × 104/µL; hemoglobin level, 9.6 g/dL; lactate dehydrogenase level, 3270 IU/L; and creatinine level, 4.2 mg/dL. Schistocytes were detected on blood smears. The patient was suspected of having thrombotic thrombocytopenic purpura or aHUS and was treated with plasma exchange, hemodialysis, and methylprednisolone. The level of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, was not decreased. The patient was definitively diagnosed with aHUS, and subsequently, plasma exchange and hemodialysis were discontinued. Eculizumab (900 mg/week) was initiated on day 18. Light microscopy findings were consistent with those of HUS, and an immunofluorescence analysis revealed IgA and C3 in the mesangial area. A hemolytic assay using sheep red blood cells revealed increased hemolytic activity. A genetic analysis revealed a p.Arg1215Gln mutation in CFH. Eculizumab therapy was effective for 5 months. The serum creatinine level was approximately 2 mg/dL without hemodialysis, and the hemoglobin level was 9 g/dL without proteinuria or hematuria.

Conclusion

We report the first case of a patient with IgAN who developed aHUS and was confirmed of harboring a CFH gene mutation. Both IgAN and aHUS activate the alternate pathway. Accordingly, this chronic trigger, namely IgAN, might have facilitated aHUS development in our genetically predisposed patient.