Histological evidence

TTTS. Histological evidence

An interesting study on placental histology was performed in 1998.17 Tertiary villi were studied and the number of muscular arteries was counted in a subset of 9 consecutive TTTS diagnosed by ultrasound, with 20% growth discordance and oligo–polyhydramnios sequence. The placenta near the cord insertion of the donor and the recipient was studied blinded for the pathologist. They found significantly less muscular arteries in the donors (5.81 ± 0.55 vs 6.66 ± 0.24; p = 0.017). 

Concomittantly, the umbilical artery S/D Doppler index was higher in the donors than in the recipients. In a previous publication of the same cases, they found that 66% of the pairs had feto–fetal transfusion, and only 25% of them had anemia/ polycythemia. 

The authors sustain the hypothesis that the primary factor is the vascular resistance in the donor’s placenta, which increases until a threshold at which it becomes higher than the pressure in the anastomoses and provokes the perfusion of the recipient.18 This interesting theory supposes that fetal hypertension in the donor is a condition for the feto–fetal transfusion. An interesting study was performed in 21 TTTS cases with death of both twins, with striking differences in kidney changes between the donors and recipients.

Most donors had renal tubular dysgenesis, characterized by nearly complete absence of identifiable proximal tubules and the ischemic appearance of the glomeruli. Donor twins are thought to suffer from chronic hypovolemia, so it may be assumed that the renal tubular disgenesis (RTD) lesions of these fetuses result from chronic hypoperfusion of the kidney, as it has also been observed as a congenital autosomal, recessive disorder responsible for oligohydramnios and in fetuses exposed in utero to angiotensin-converting enzyme inhibitors. 

This hypothesis is also supported by the observation of similar tubular changes in children with postnatal renal ischemia. Up-regulation of renin synthesis was also demonstrated using immunohistochemistry and in-situ hybridization, with a strong increase in renin protein and mRNA content in the donor kidneys. The recipient kidneys were large and congested, showing various degrees of hemorrhagic infarction and glomeruli. Renin was not detected in 20/21 recipient fetuses. 

Plasma renin concentration or activity was not measured in this series. However, it was speculated that circulating renin from the donor is transferred to the recipient through placental vascular anastomoses. Indeed, renin activity was previously detected in both twins in three cases of TTTS.20 

This inappropriate presence of renin in hypervolemic fetuses, with the eventual increase of angiotensin II generation and aldosterone synthesis, represents a potential factor in aggravating hypervolemia and its renal and extrarenal consequences for the recipient, including systemic hypertension. The hypothesis of the investigators was that adaptation of the donor by renin– angiotensin up-regulation may finally become deleterious to both twins, because in donors it may aggravate renal vasoconstriction and perfusion, and in recipients it may increase diuresis.