Pathogenesis of twin-twin transfusion syndrome: The renin-angiotensin system hypothesis

In spite of active perinatal management, twin-twin transfusion syndrome (TT TS) remains a severe disease with a high risk of neonatal mortality and mor bidity. TTTS initially results from an unbalanced blood flow from a donor t o a recipient twin. However, its pathogenesis remains unclear, although car diovascular disturbances and regulation of fetal volemia and diuresis seem central in this syndrome. Previously, we demonstrated that the renin-angiot ensin system (RAS) was up-regulated in donor twins as a consequence of hypo volemia, and downregulated in recipients. This was the first evidence of th e implication of the RAS in TTTS. We hypothesize that the RAS plays a key r ole in the pathogenesis of TTTS. In the donor, RAS up-regulation aggravates oligohydramnios and may increase arterial resistance, which could contribu te to placental dysfunction leading to intrauterine growth restriction. In the recipient, paradoxical RAS activation, due to transfer of effecters suc h as angiotensin II through placental shunts, could explain fetal vascular disturbances and cardiomyopathy. According to our hypothesis, TTTS would ap pear similar to the classical model of hypertension referred to as '2 kidne ys - 1 clip' with a donor twin, comparable to the clipped kidney, intoxicat ing its cotwin, comparable to the normal kidney. Copyright (C) 2001 S. Karg erAG, Basel.