Twin-to-Twin Transfusion Syndrome: Role of the Fetal Renin-Angiotensin System

Abstract

An unbalanced blood supply to monochorionic twins, based on placental anastomotic shunting, is the cause of twin-to-twin transfusion syndrome (TTS), which may lead to restricted growth and renal tubular dysgenesis in the donor twin and visceromegaly in the recipient. About 5 percent of these pregnancies are affected. Survival has improved in recent years, but perinatal mortality rates as high as 50 percent are still reported, and some survivors have neurological morbidity. The facts that the donor twin typically is oliguric and the recipient polyuric, possibly because of hypervolemia secondary to increased production of atrial natriuretic factor, suggest that activation of the renin-angiotensin system in the donor twin might be an adverse adaptive change in TTS. This idea was tested in a retrospective autopsy study of 21 monochorionic twin pairs dying of TTS and 39 control subjects. Renal morphology was compared in the two groups, and renin expression was examined immunohistochemically and by in situ hybridization using a renin cDNA clone. Ten of the 21 donor twins, studied at a gestational age of 18 to 30 weeks, exhibited renal tubular dysgenesis affecting the deep cortex; distal tubules and collecting ducts were comparatively spared. Renin protein was overexpressed, and there frequently was evidence of renin production by mesangial cells. The kidneys of recipient twins were enlarged and congested and almost always exhibited hemorrhagic infarction. The glomeruli were very enlarged and focal mesangiolysis was sometimes observed. Preglomerular and interlobular arteries were thickened in about half of the recipient twins. No renin-positive cells were detected in 19 of these 21 infants. Renin expression was lacking or at most very limited in six of the seven recipient fetuses tested. The renal lesions seen in these TTS fetuses are ascribed in part to hemodynamic changes: hypovolemia in the donor and both hypervolemia and polycythemia in the recipient. Hypovolemia activates renin synthesis in the donor, possibly harming both fetuses by promoting hypoperfusion in the donor infant and raising blood pressure in the recipient. Am J Pathol 2000;156:629–636