Kidney Week

Abstract: FR-PO1009

Recurrence of Atypical Hemolytic Uremic Syndrome (HUS) after Kidney Transplantation in Patients with the Complement C3 p.Arg161Trp Variant

Session Information

• Transplantation: Basic
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2101 Transplantation: Basic

Authors

• ter Steeg, Lieke, Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Nijmegen, Netherlands

Lieke ter Steeg, MD

• Bouwmeester, Romy N., Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Nijmegen, Netherlands

Romy N. Bouwmeester, MD

• Duineveld, Caroline, Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, Netherlands

Caroline Duineveld, MD

• van de Logt, Anne-Els, Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, Netherlands

Anne-Els van de Logt, MD, PhD

• van der Meijden, W.A.G., Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, Netherlands

W.A.G. van der Meijden, MD

• Van den Heuvel, Lambertus P.W.J., Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Nijmegen, Netherlands

Lambertus P.W.J. Van den Heuvel, PhD

• Wijnsma, Kioa L., Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Nijmegen, Netherlands

Kioa L. Wijnsma, MD, PhD

• Wetzels, Jack F., Radboud University Medical Center, Radboud Institute for Health Sciences, Department of Nephrology, Nijmegen, Netherlands

Jack F. Wetzels, MD, PhD

• Van De Kar, Nicole, Radboud University Medical Center, Amalia Children's Hospital, Radboud Institute for Molecular Life Sciences, Department of Pediatric Nephrology, Nijmegen, Netherlands

Nicole Van De Kar, MD, PhD

Background

Graft loss due to disease recurrence is a major concern in kidney transplant (KTx) recipients with complement-mediated atypical hemolytic uremic syndrome (CaHUS). Gain-of-function mutations have been identified by KDIGO as a high risk factor for recurrent CaHUS. We describe a large cohort of transplant recipients with the common Dutch variant C3 p.Arg161Trp.

Methods

We retrospectively analyzed the outcome after first KTx in CaHUS patients with this variant. None of the patients received eculizumab prophylaxis, according to the Dutch guideline. Relapses were defined as restart of treatment (eculizumab or plasmapheresis) by treating physician.

Results

This study included 15 CaHUS patients with the C3 p.Arg161Trp variant. Median (range) time between first presentation of CaHUS and KTx was 6 (1-23) years, and median (range) follow up time after KTx was 6 (0-12) years. Treatment for suspected CaHUS recurrence was initiated in 5 (33%) patients. Median (range) time between KTx and recurrence was 10 (4-46) months. A trigger was identified in all patients with recurrence and included rejection (n=3) and infection (n=2). Two relapses, occurring at 4 and 10 months, were characterized by acute kidney disease and systemic thrombotic microangiopathy (TMA). Notably, one relapse, occurring after 4 years, presented only with slow eGFR loss and signs of chronic TMA in kidney biopsy. Laboratory data was missing for two relapses. Recurrence was treated with eculizumab (n=2) or plasmapheresis (n=3). Graft loss occurred in two patients, both treated with plasmapheresis. In patients treated with eculizumab, kidney function improved to baseline or stabilized. One patient experienced two more relapses, after eculizumab discontinuation, in subsequent years without graft loss.

Conclusion

CaHUS patients with the C3 p.Arg161Trp variant show low risk of early recurrence after kidney transplantation. Post-transplant recurrence may present solely with gradual loss of kidney function.