Twin-to-twin transfusion syndrome - Role of the fetal renin-angiotensin system

The twin-to-twin transfusion syndrome (TTS) results from an unbalanced bloo d supply through placental anastomoses in monochorionic twins, It induces g rowth restriction, renal tubular dysgenesis, and oliguria in the donor and visceromegaly and polyuria in the recipient, A better understanding of its pathophysiology could contribute to improving the management of TTS, which still carries a high perinatal mortality in both twins, As well as several other candidates, the renin-angiotensin system might be involved in TTS, To evaluate its role in the pathogenesis of the syndrome, we studied the kidn eys of 21 twin pairs who died from TTS at 19 to 30 weeks, compared with 39 individuals in a control group, using light microscopy, immunohistochemistr y, and in situ hybridization. The overexpression of the renin protein and t ranscript with frequent evidence of renin synthesis by mesangial cells was observed in the donor kidneys, presumably as a consequence of chronic renal hypoperfusion, This upregulation of renin syn thesis might be beneficial t o restore euvolemia. In severe cases of TTS, however, angiotensin-II-induce d vasoconstriction acts as an additional deleterious factor by further redu cing the renal blood flow in donors. In recipients, renin expression was vi rtually absent, possibly because it was down-regulated by hypervolemia. How ever, in addition to congestion and hemorrhagic infarction, there were seve re glomerular and arterial lesions resembling those observed in polycythemi a- or hypertension-induced microangiopathy, We speculate that fetal hyperte nsion in the recipient might be partly mediated by the transfer of circulat ing renin produced by the donor, through the placental vascular shunts.