Kidney Week

Abstract: SA-PO1187

Genetic Atypical Hemolytic Uremic Syndrome Causing Kidney Transplant Failure

Session Information

• Transplantation: Clinical - Complications, Pediatrics, and Multi-Organ Considerations
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

• 2002 Transplantation: Clinical

Authors

• Taylor, Joseph, University of Southern California, Los Angeles, California, United States

Joseph Taylor, DO

• Tawadrous, Marina Magdy, University of Southern California, Los Angeles, California, United States

Marina Magdy Tawadrous, MD

• Kaur, Rupinder, University of Southern California, Los Angeles, California, United States

Rupinder Kaur, MD

• Su, Lauren, University of Southern California, Los Angeles, California, United States

Lauren Su, MD

• Shah, Sapna, University of Southern California, Los Angeles, California, United States

Sapna Shah, MD

Introduction

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) that can cause multiorgan failure through small vessel thrombosis. Genetic mutations in complement regulatory pathways are a known etiology and may complicate renal transplantation.

Case Description

We present a 49-year-old female with end stage renal disease (ESRD) secondary to systemic lupus erythematosus (SLE) with lupus nephritis (LN, diagnosed 1995). She underwent a living unrelated renal transplant from husband in 2007, followed by recurrent renal failure requiring dialysis in 2015 after development of atypical HUS diagnosed 2014. She later presented for a second renal transplantation at our medical center.
In 2014, she developed allograft dysfunction at an outside hospital. Transplant renal biopsy demonstrated chronic thrombotic microangiopathy (TMA), antibody mediated rejection (AMR), and membranous LN. She was treated with eculizumab, pulse steroids, rituximab, and IVIg; however, graft function declined and dialysis was restarted. Subsequent evaluation at our institution identified a heterozygous thrombomodulin mutation, c.127G>A (p.Ala43Thr) on exon 1. She was transitioned to ravalizumab, which was interrupted for two years prior to her second transplant due to insurance barriers.
Following her second transplantation, delayed graft function was attributed to recurrent TMA. Eculizumab was restarted on postoperative day four. Her course was complicated by a mycotic aneurysm with hematoma requiring evacuation, followed by cardiac arrest due to significant intracardiac clot burden with suspected pulmonary emboli, and she unfortunately expired intraoperatively. Autopsy revealed recurrent TMA in the new allograft.

Discussion

Atypical HUS has multiple etiologies, with inherited complement regulatory mutations representing a less common cause. In this case, the thrombomodulin mutation likely predisposed the patient to develop aHUS either from SLE flare and/or AMR, as incomplete penetrance of the heterozygous gene requires a “two-hit” mechanism. After the second transplant, likely triggers for recurrent aHUS include ischemia-reperfusion injury, calcineurin inhibitors, or graft infection. This case highlights the risk of recurrent TMA in patients with complement-mediated HUS and the importance of sustained complement inhibition therapy in the peri-transplant setting.