Cholestasis in pregnancy associated with ciclosporin therapy in renal transplant recipients.
Obstetric cholestasis (OC) presents with pruritus in the second half of pregnancy and is associated with increased risk of foetal distress, intra-uterine death and premature delivery. From a tertiary referral, renal-obstetric clinic, we report the occurrence of OC in 5/23 pregnancies of women with renal transplants maintained on ciclosporin treatment (European incidence 0.1-1.5% of pregnancies). All required premature delivery for foetal reasons at 33-37/40 (median 34/40). Ciclosporin, at therapeutic concentrations, inhibits bile salt excretion pump (BSEP) function in rats and humans. We propose that OC developed in our patients because the mild inhibition of the canalicular pumps by ciclosporin was only revealed in pregnancy when increases in progesterone metabolites overwhelmed pump function. We suggest that all pregnant women receiving ciclosporin should be closely monitored from the second trimester for the development of OC. If detected, enhanced foetal and maternal monitoring to optimize time of delivery and pregnancy outcome is required.
Day
Clara
C
Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham, UK.
Hewins
Peter
P
Sheikh
Lumaan
L
Kilby
Mark
M
McPake
Dawn
D
Lipkin
Graham
G
D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters / Q000037:antagonists & inhibitors; D000328:Adult; D001648:Bile Canaliculi / Q000187:drug effects / Q000378:metabolism; D002779:Cholestasis / Q000209:etiology*; D016572:Cyclosporine / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects*; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology*
C093491:ABCB11 protein, human; D000074020:ATP Binding Cassette Transporter, Subfamily B, Member 11; D018528:ATP-Binding Cassette Transporters; D007166:Immunosuppressive Agents; D016572:Cyclosporine