Use of Eculizumab During Pregnancy in Kidney Transplant Recipients With Atypical HUS.

To the Editor:

Duval et al. recently described a kidney transplant recipient who developed atypical hemolytic uremic syndrome, and was treated with eculizumab during pregnancy with a successful outcome. We described a similar case recently (Cheung CK, Evans K, Williams M, et al. A successful pregnancy in a patient following renal transplantation for atypical HUS managed with eculizumab. UK Kidney Week; June 2018. Available at: https://britishrenal.org/ukkw2018-2/abstracts-2/. Accessed September 29, 2019).

Our case was a 24-year-old woman, with end-stage renal disease of uncertain etiology who underwent a live kidney transplant. Subsequently, a transplant biopsy for graft deterioration showed recurrent atypical hemolytic uremic syndrome. She was commenced on eculizumab 1200 mg every 2 weeks, and her graft function stabilized (estimated glomerular filtration rate 45 ml/min per 1.73 m2). She later expressed a desire to become pregnant, did not have significant proteinuria, and was taking tacrolimus and azathioprine. After becoming pregnant, her eculizumab dose was increased at 16 weeks (Table 1), with monitoring for hemolysis and complement activity (C3, C4, C5, CH50, AH50 assays) every 2 weeks. At 29+5/40, she developed edema, hypertension, increased proteinuria, decline in renal function and platelets, and increased lactate dehydrogenase. An emergency cesarean delivery was performed, and placental histopathology later confirmed preeclampsia. A female infant weighing 950 g was delivered, with patent ductus arteriosus (which subsequently closed), and was fed with expressed breastmilk. The patient was given two 900-mg eculizumab infusions in the first postnatal week, which was later reduced. Hemoglobin and platelets stabilized, and kidney function returned to prepregnancy levels. Total complement activity remained suppressed throughout pregnancy. Both mother and child are currently well.

Table 1

Eculizumab dosing during the pregnancy

Gestational age	Eculizumab dosage, mg	Infusion frequency
Booking	1200	Every 2 wk
16 wk	1500	Every 2 wk
28 wk	900	Weekly
Within 24 h of delivery	900	Additional infusion
7 d postnatal	1200	Weekly
14 d postnatal	1200	Every 2 wk

These reports suggest that preemptive increased dosing of eculizumab to prevent breakthrough haemolysis, with close monitoring for hemolysis and complement activity, represents a safe and viable strategy during pregnancy in kidney transplant recipients with atypical hemolytic uremic syndrome.