title: Paradoxic activation of the renin-angiotensin system in twin-twin transfusion syndrome: an explanation for cardiovascular disturbances in the recipient.
abstract: Despite advances in treatment, twin-to-twin transfusion syndrome (TTTS) still carries a high risk for perinatal mortality and morbidity. Simple blood transfer from the donor to the recipient twin cannot explain all of the features of this disease, in particular the recipient's hypertensive cardiomyopathy. We report a case in which TTTS resulted in preterm delivery with early neonatal death of both twins, allowing assessment of the renin angiotensin system (RAS) status of each fetus, both by cord blood renin and aldosterone assay and by renal immunohistochemistry. The donor had severe oliguria/oligohydramnios, whereas the recipient, in addition to severe polyuria/polyhydramnios, had cardiomyopathy, atrioventricular regurgitation, and ascites. Although immunohistochemistry demonstrated that renal secretion of renin was up-regulated in the donor and down-regulated in the recipient, cord blood levels of renin and aldosterone were similar, with high renin levels in both twins. This observation supports the hypothesis that despite renal RAS down-regulation, the recipient is exposed to RAS effectors elaborated in the donor and transferred via placental shunts. This may contribute to cardiomyopathy and hypertension in the recipient, which cannot be accounted for by hypervolemia alone. We thus hypothesized that in TTTS, the recipient's hypertensive cardiomyopathy could be due to a mechanism similar to the classical model of hypertension referred to as "2 kidneys-1 clip." Thus the hypovolemic donor twin, comparable to the clipped kidney, produces vasoactive hormones that compromise the recipient, comparable to the normal kidney, causing hypertension and cardiomyopathy.
authors.affiliation: Department of Obstetrics, Hôpital Bichat-Claude Bernard AP-HP and Université Paris, France. dominique.mahieu-caputo@bch.ap-hop-paris.fr
authors.forename: Dominique
authors.initials: D
authors.lastname: Mahieu-Caputo
authors.forename: Alain
authors.initials: A
authors.lastname: Meulemans
authors.forename: Jelena
authors.initials: J
authors.lastname: Martinovic
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Delezoide
authors.forename: Françoise
authors.initials: F
authors.lastname: Muller
authors.forename: Patrick
authors.initials: P
authors.lastname: Madelenat
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Fisk
authors.forename: Marc
authors.initials: M
authors.lastname: Dommergues
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood; D009202:Cardiomyopathies / Q000209:etiology*; D002319:Cardiovascular System / Q000473:pathology*; D015536:Down-Regulation; D017809:Fatal Outcome; D005260:Female; D005312:Fetal Blood / Q000378:metabolism; D005330:Fetofetal Transfusion / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007668:Kidney / Q000473:pathology; D008297:Male; D016104:Oligohydramnios / Q000378:metabolism; D009846:Oliguria / Q000473:pathology; D011247:Pregnancy; D047928:Premature Birth; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000450:Aldosterone; D012083:Renin