Yasuhiro Shinkai

Planned Genetic Diagnosis of Atypical Hemolytic Uremic Syndrome and Successful Preemptive Treatment with Eculizumab for Recurrence after Cadaveric Kidney Transplantation: Case Report

Introduction Atypical hemolytic uremic syndrome (aHUS) is rare and patient prognosis is poor following recurrence after kidney transplantation (KTX). Previously, diagnosis and treatment were difficult, while recent progress in genetic diagnosis techniques and use of eculizumab have contributed to effective treatment strategies. Although the number of reports of eculizumab treatment for recurrent aHUS after KTX has increased, in most of those genetic diagnosis of aHUS was not done before KTX and eculizumab was administered for recurrent aHUS after transplantation. We present a case of recurrent aHUS after cadaveric KTX treated with planned eculizumab because of genetic diagnosis obtained prior to transplantation. Case Report The patient was a 45-year-old man. He had cold symptoms and hematuria at 10 years of age, and was diagnosed with HUS, after which multiple HUS attacks occurred and renal function gradually declined. At the age of 18 years, the hemodialysis was begun and he was enrolled on the national kidney transplantation waiting list in Japan. After 24 years of waiting, a genetic examination was performed to prepare for selection as a recipient candidate and the diagnosis was confirmed as aHUS with C3 mutation. Subsequently, the patient underwent cadaveric KTX from a non-heart beating donor. Serum creatinine was decreased to 2.0 mg/dl at 10 days after surgery, then increased to 3.0 mg/dl on day 21. Although graft biopsy findings revealed no obvious thrombotic microangiopathy, LDH elevation and decreased platelets in addition to renal dysfunction were observed. A minor attack due to aHUS recurrence was diagnosed and administration of eculizumab started. Thereafter, creatinine decreased to 1.5 mg/dl, and LDH and platelet count also recovered, with eculizumab continued. Discussion Genetic diagnosis of aHUS requires time, whereas recurrence following KTX rapidly develops, thus it is preferred to genetically examine patients on the waiting list with a history of HUS to determine the presence of aHUS prior to transplantation for prediction and preparation for possible recurrence. In the present case, recurrent aHUS diagnosis and treatment with eculizumab were accurately performed without delay on the basis of pre-confirmed gene diagnosis despite no obvious thrombotic microangiopathy in biopsy pathology findings, and the graft was rescued. An aHUS attack shows various clinical conditions according to the type of complement-related factor gene mutation, thus cases such as the present with a C3 mutation might develop even with only minor pathological factors Conclusion Our experience with this case suggests that pre-transplant gene diagnosis before KTX is useful for rapid diagnosis and effective treatment of recurrent aHUS. Eculizumab was shown to be safe and useful even for a minor attack because of prior gene diagnosis.