Pregnancy in a Kidney Transplant Woman Under Treatment With Eculizumab for Atypical Hemolytic Uremic Syndrome: Is It Safe?

Duval, Anna; Olagne, Jérôme; Cognard, Noëlle; Gautier-Vargas, Gabriela; Joly, Mélanie; Perrin, Peggy; Fritz, G.; Fourtage, Marion; Moulin, Anne‐Marie; Caillard, Sophie

doi:10.1016/j.ekir.2018.12.014

Cited by 10 publications

(11 citation statements)

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“…Eculizumab was not detected in umbilical cords or neonate plasma samples in 2 of the patients described in their study [8]. Recently, a successful pregnancy in a kidney transplantation patient who was receiving maintenance Eculizumab for aHUS has been reported [15]. In that case, moderate pre-eclampsia and fetal growth faltering were present from week 28 of gestation, and a cesarean delivery was scheduled at week 32 of gestation.…”

Section: Discussionmentioning

confidence: 98%

Relapse of Atypical Hemolytic Uremic Syndrome During Pregnancy in a Patient on Eculizumab Maintenance Treatment: A Case Report

et al. 2019

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Rare disease Background: Atypical hemolytic uremic syndrome (aHUS) is a genetic disorder with uncontrolled complement activation leading to systemic thrombotic microangiopathy; kidneys are almost invariably involved. Eculizumab has dramatically improved the prognosis of aHUS and affected women in the childbearing age are more likely to consider pregnancy, even if this could represent a risk for disease reactivation. Pregnancies in women with aHUS during Eculizumab treatment have been reported, with no cases of aHUS relapse. Case Report: We report the case of a female patient affected by aHUS with no specific gene mutations who had a pregnancyassociated aHUS relapse at 26-weeks of gestation during maintenance Eculizumab treatment. The patient developed stage II acute kidney injury and microangiopathic hemolytic anemia. Delivery by cesarean section at week 27, plasma exchange sessions and several supplemental Eculizumab administrations were required. After appropriate treatment, the patient partially recovered kidney function; the baby had a prolonged stay in the intensive care unit and showed no signs of neurologic damage. Conclusions: Previous reports indicated that pregnancy-related aHUS relapses were unlikely in women undergoing Eculizumab treatment. Based on our case, we suggest caution in counselling pregnancy in women with aHUS treated with Eculizumab, especially in the absence of pathogenic mutations in complement-regulating genes. Clinicians should be aware of possible aHUS relapse in pregnancy during Eculizumab treatment.

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Section: Discussionmentioning

confidence: 98%

Relapse of Atypical Hemolytic Uremic Syndrome During Pregnancy in a Patient on Eculizumab Maintenance Treatment: A Case Report

et al. 2019

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“…These 2 reports 2 show the relevance of the issue of conception in transplanted women with atypical hemolytic uremic syndrome while undergoing C5-inhibitor therapy. Moreover, it gives guidelines on the management of these high-risk pregnancies.…”

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confidence: 86%

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Duval

Moulin

Caillard

2019

Kidney International Reports

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1 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/ukkw 2018-2/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 m 2 ). 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 29þ5/40, 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.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. 1. Duval A, Olagne J, Cognard N, et al. Pregnancy in a kidney transplant woman under treatment with eculizumab for atypical hemolytic uremic syndrome: is it safe? Kidney Int Rep.

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“…More recently, eculizumab was used to treat cTMA flares during pregnancy ( Table S1 ) and after delivery ( Table S2 ), but also in a preventive setting, in which patients with cTMA became pregnant during ongoing eculizumab therapy. 6 , 7 Servais et al 6 reported 5 pregnancies in 3 women during ongoing eculizumab therapy and showed rather poor pregnancy and delivery outcomes. Complications included 1 abortion and 2 growth retardations, and all 4 neonates were small for gestational age.…”

Section: Introductionmentioning

confidence: 99%

“…Each of the reported women experienced either HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome or, in 2 cases, preeclampsia. 6 Duval et al 7 recently reported another pregnancy during ongoing eculizumab treatment in a patient who delivered a preterm child by caesarean section that was performed due to signs of moderate eclampsia and fetal distress at week 32 of gestation. Furthermore, Fontana et al 8 described a patient with cTMA who presented with severe preeclampsia as of week 26 of gestation during ongoing eculizumab therapy (low dose with 900 mg fortnightly) that resulted in a caesarian section at gestational week 27 with plasma and higher dose eculizumab rescue therapy.…”

Section: Introductionmentioning

confidence: 99%

Successful Pregnancies During Ongoing Eculizumab Therapy in Two Patients With Complement-Mediated Thrombotic Microangiopathy

et al. 2020

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In patients with pregnancy-associated complement gene variant–mediated thrombotic microangiopathy (cTMA), terminal complement blockade is used for treatment of cTMA flares during pregnancy or following delivery. We report pregnancy and delivery outcomes of 2 genetically high-risk patients with cTMA, including 1 kidney transplant recipient, during ongoing eculizumab therapy. In both patients, the first manifestation of cTMA occurred independent from pregnancy. One patient has a history of 2 uneventful pregnancies with prophylactic plasma infusions, and the other has a history of early abortion during long-term eculizumab therapy following kidney transplantation. Overall, pregnancy and delivery outcomes under ongoing eculizumab therapy in our 2 patients with preserved kidney function were excellent as compared with other patients reported in the literature. Eculizumab plasma concentrations were maintained in the therapeutic range during pregnancy and were also detectable in cord blood. Results of cord blood analysis showed deficient complement activity, with low factor and regulator levels, most likely reflecting the age of the neonates and presence of eculizumab in cord blood. In conclusion, pregnancy during ongoing eculizumab treatment appeared to be safe in 2 women with a history of high-risk genetic cTMA and excellent kidney function, even following kidney transplantation.

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Pregnancy in a Kidney Transplant Woman Under Treatment With Eculizumab for Atypical Hemolytic Uremic Syndrome: Is It Safe?

Cited by 10 publications

References 9 publications

Relapse of Atypical Hemolytic Uremic Syndrome During Pregnancy in a Patient on Eculizumab Maintenance Treatment: A Case Report

Relapse of Atypical Hemolytic Uremic Syndrome During Pregnancy in a Patient on Eculizumab Maintenance Treatment: A Case Report

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Successful Pregnancies During Ongoing Eculizumab Therapy in Two Patients With Complement-Mediated Thrombotic Microangiopathy

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