Renin gene expression in fetal kidneys of pregnancies complicated by twin-twin transfusion syndrome

Twin-twin transfusion syndrome (TTTS) complicates one in five monochorionic pregnancies and is generally associated with high mortality and morbidity. One twin (the recipient) grows appropriately and has polyhydramnios while the other (the donor) may have a reduced growth velocity and severe oligohy dramnios. The disparities in amniotic fluid volumes represent differences i n fetal urine output. These differences occur secondary to hemodynamic chan ges, in which the vascular arrangement of placental anastomoses in TTTS lea ds to unidirectional flow from the donor to the recipient twin. A better un derstanding of the pathophysiology may contribute to improved management of this morbid condition. We studied three consecutive prospectively diagnosed stillborn twin pairs a ffected by early-onset TTTS. Renin gene expression was studied in sections of fetal kidneys with immunocytochemistry using a renin antiserum and with in situ hybridization using riboprobes complementary to renin mRNA, and ren in-secreting cells (RCC) were counted. The overall maturation of the renal cortex was assessed by the percentage of immature glomeruli. The donor twin kidneys were smaller than those of the recipients, but the maturation of t he renal cortex was not significantly different (28.2% immature glomeruli i n the donor and 24.4% in the recipient kidney). The donor kidney showed increased renin gene expression with hyperplastic j uxtaglomerular apparatuses (JGAs) that contained excess RCCs (median 20.02 [E25th-75th centiles, 5.4, 25.1 RCCs per 100 glomeruli]). In contrast, the recipient kidney was virtually devoid of these cells (0.04 [0, 0.36] RCCs p er 100 glomeruli; P < 0.05). In the donor kidney, increased renin release may, by a local action, contri bute to renal vasoconstriction and oliguria. Increased renin and/or angiote nsin IT in the blood passing through the placental anastomoses may, by an e ndocrine action, suppress renin synthesis in the recipient kidney, thereby increasing renal blood now and causing polyuria and polyhydramnios. These c hanges in the renal RAS could thus contribute to the pathogenesis of TTTS. The renal renin changes noted here may represent a contributory or compensa ting mechanism, the success of which may dictate the overall survival of th e twin pregnancy and allow better understanding of the pathophysiology and perhaps therapy that may be employed in this condition.