Pathogenesis of Twin-Twin Transfusion Syndrome: The Renin-Angiotensin System HypothesisMahieu-Caputo D.a · Muller F.e · Joly D.b · Gubler M.-C.c · Lebidois J.d · Fermont L.d · Dumez Y.a · Dommergues M.a
Departments of aObstetrics, bNephrology and cINSERM U423, dPaediatric Cardiology, Hôpital Necker-Enfants Malades, AP-HP and University Paris V, and eBiochemistry Laboratory, Hôpital Ambroise Paré, Boulogne, AP-HP and University Paris V, Paris, France
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In spite of active perinatal management, twin-twin transfusion syndrome (TTTS) remains a severe disease with a high risk of neonatal mortality and morbidity. TTTS initially results from an unbalanced blood flow from a donor to a recipient twin. However, its pathogenesis remains unclear, although cardiovascular disturbances and regulation of fetal volemia and diuresis seem central in this syndrome. Previously, we demonstrated that the renin-angiotensin system (RAS) was up-regulated in donor twins as a consequence of hypovolemia, and down-regulated in recipients. This was the first evidence of the implication of the RAS in TTTS. We hypothesize that the RAS plays a key role in the pathogenesis of TTTS. In the donor, RAS up-regulation aggravates oligohydramnios and may increase arterial resistance, which could contribute to placental dysfunction leading to intrauterine growth restriction. In the recipient, paradoxical RAS activation, due to transfer of effectors such as angiotensin II through placental shunts, could explain fetal vascular disturbances and cardiomyopathy. According to our hypothesis, TTTS would appear similar to the classical model of hypertension referred to as ‘2 kidneys-1 clip’ with a donor twin, comparable to the clipped kidney, intoxicating its cotwin, comparable to the normal kidney.
© 2001 S. Karger AG, Basel
- Gaziano EP, De Lia JE, Kuhlmann RS: Diamnionic monochorionic twin gestations: An overview. J Matern Fetal Med 2000;9:89–96.
- Hecher K, Plath H, Bregenzer T, Hansmann M, Hackeloer BJ: Endoscopic laser surgery versus serial amniocentesis in the treatment of twin-twin transfusion syndrome. Am J Obstet Gynecol 1999;180:717–724.
- Ville Y, Hecher K, Gagnon A, Sebire N, Nicolaides K: Endoscopic laser coagulation in the management of severe twin-twin transfusion syndrome. Br J Obstet Gynaecol 1998;105:446–453.
- Machin G, Still K, Lalani T: Correlations of placental vascular anatomy and clinical outcomes in 69 monochorionic twin pregnancies. Am J Med Genet 1996;61:229–236.
- Bajoria R, Wigglesworth J, Fisk NM: Angioarchitecture of monochorionic placentas in relation to the twin-twin transfusion syndrome. Am J Obstet Gynecol 1995;172:856–863.
- Denbow ML, Cox P, Taylor M, Hammal DM, Fisk NM: Placental angioarchitecture in monochorionic twin pregnancies: Relationship to fetal growth, fetofetal transfusion syndrome, and pregnancy outcome. Am J Obstet Gynecol 2000;182:417–426.
- Denbow M, Fogliani R, Kyle P, Letsky E, Nicolini U, Fisk N: Haematological indices at fetal blood sampling in monochorionic pregnancies complicated by feto-fetal transfusion syndrome. Prenat Diagn 1998;18:941–946.
- Saunders NJ, Snijders RJ, Nicolaides KH: Twin-twin transfusion syndrome during the 2nd trimester is associated with small intertwin hemoglobin differences. Fetal Diagn Ther 1991;6:34–36.
- Mahieu-Caputo D, Dommergues M, Delezoide AL, Lacoste M, Cai Y, Narcy F, Jolly D, Gonzales M, Dumez Y, Gubler MC: Twin-to-twin transfusion syndrome. Role of the fetal renin-angiotensin system. Am J Pathol 2000;156:629–636.
- Baud O, Lebidois J, Van Peborgh P, Ville Y: Fetal and neonatal hypertension in twin-twin transfusion syndrome: A case report. Fetal Diagn Ther 1998;13:223–226.
- Cheung YF, Taylor MJ, Fisk NM, Redington AN, Gardiner HM: Fetal origins of reduced arterial distensibility in the donor twin in twin-twin transfusion syndrome. Lancet 2000;355:1157–1158.
- Hecher K, Ville Y, Nicolaides KH: Fetal arterial Doppler studies in twin-twin transfusion syndrome. J Ultrasound Med 1995;14:101–108.
- Taylor M, Peart S, Porter K, Zondek L, Zondek T: Concentration and molecular forms of active and inactive renin in human fetal kidney, amniotic fluid and adrenal gland: Evidence for renin-angiotensin system hyperactivity in second trimester of pregnancy. J Hypertens 1986;4:121–129.
Gomez RA, El-Dahr S, Chevalier RL: Vasoactive hormones; in Barratt TM, Avner ED, Harmon WE (eds): Pediatric Nephrology, ed 4. Baltimore, Lippincott-Williams & Wilkins, 1999, pp 83–99.
- Ratajska A, Campbell SE, Cleutjens JPM, Weber KT: Angiotensin II and structural remodeling of coronary vessels in rats. J Lab Clin Med 1994;124:408–415.
- Silvestre JS, Robert V, Heymes C, Aupetit-Faisant B, Mouas C, Moalic JM, Swynghedauw B, Delcayre C: Myocardial production of aldosterone and corticosterone in the rat. Physiological Regulations. J Biol Chem 1998;273:4883–4891.
- Barr M, Sedman AB, Heidelberger KP: Renal tubular dysgenesis in twins. Pediatr Nephrol 1998;12:408–413.
Gubler MC, Sarrut S, Imbert MC, Narcy F, Lacost M, Guicharnaud L, Gasc JM, Mounier F: Renal tubular dysgenesis (RTD), an autosomal recessive disorder and the renin-angiotensin system. J Am Soc Nephrol 1993;4:263.
- Zosmer N, Bajoria R, Weiner E, Rigby M, Vaughan J, Fisk NM: Clinical and echographic features of in utero cardiac dysfunction in the recipient twin in twin-twin transfusion syndrome. Br Heart J 1994;72:74–79.
- Fesslova V, Villa L, Nava S, Mosca F, Nicolini U: Fetal and neonatal echocardiographic findings in twin-twin transfusion syndrome. Am J Obstet Gynecol 1998;179:1056–1062.
- Johnson RJ, Alpers CE, Yoshimura A, Lombardi D, Pritzl P, Floege J, Schwatz SM: Renal injury from angiotensin II-mediated hypertension. Hypertension 1992;19:464–474.
- Navar LG, Rosivall L: Contribution of the renin-angiotensin system to the control of intrarenal hemodynamics. Kidney Int 1984;25:857–868.
- Wiecaker P, Wilhelm C, Prompeler H, Petersen KG, Schillinger H, Breckwoldt M: Pathophysiology of polyhydramnios in twin transfusion syndrome. Fetal Diagn Ther 1992;7:87–92.
- Baker KM, Booz GW, Dostal DE: Cardiac actions of angiotensin II: Role of an intracardiac renin-angiotensin system (review). Annu Rev Physiol 1992;54:227–241.
- Akishita M, Ito M, Lehtonen JY, Daviet L, Dzau VJ, Horiuchi M: Expression of the AT2 receptor developmentally programs extracellular signal-regulated kinase activity and influences fetal vascular growth. J Clin Invest 1999;103:63–71.
- Bower SJ, Flack NJ, Sepulveda W, Talbert DG, Fisk NM: Uterine artery blood flow response to correction of amniotic fluid volume. Am J Obstet Gynecol 1995;173:502–507.
- Machin GA: Velamentous cord insetion in monochorionic twin gestation. An added risk factor. J Reprod Med 1997;42:785–789.
- Wood JM, Gulati N, Michel JB, Hofbauer KG: Two-kidney, one clip renal hypertension in the marmoset. J Hypertens 1986;4:251–254.
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