THE ROLE OF THE KIDNEY IN CHRONIC FETAL ANEMIA

In acute fetal anemia there is redistribution of blood flow toward
the brain and heart with no change in blood pressure or cardiac
output. Urine flow, glomerular filtration and sodium excretion
decrease. In contrast, in chronic fetal anemia we have found
generalized vasodilation with an increase in blood flow to all
tissues except the placenta. Despite an increase in cardiac
output, mean arterial pressure falls. Notably, renal blood flow
nearly doubles. In the proposed studies we plan to determine the
role of the kidney in the fetal adaptation to chronic anemia. The
purpose is to understand the hemodynamic mechanisms of adaptation
to chronic fetal anemia and to relate these to the mechanisms which
generate extravascular fluid accumulation. Furthermore, we hope
these studies will provide insight into disease processes in human
fetuses in which chronic anemia is part of the pathophysiology.
Specifically, we will test the following hypotheses: (1) In the
anemic fetus, the kidneys, by releasing renin, contribute
significantly to the maintenance of mean arterial pressure and
thereby placental blood flow. We will determine the temporal
activation of renin-angiotensin, arginine vasopressin, and
catecholamines in response to chronic fetal anemia and evaluate
with selective blockade of these systems their individual roles in
controlling blood pressure and regional blood flow. (2) The
increase in renal blood flow is accompanied by an increase in urine
flow, glomerular filtration rate, and sodium excretion. In turn,
the increase in urine flow results in polyhydramnios. (3) Renal
tubular reabsorption of salt and water in chronic anemia is limited
by oxygen availability. If this is the case, relative to controls,
the kidneys of anemic fetuses will have reduced oxygen uptake, and
decreased ATP levels, and will shift from lactate uptake towards
lactate production. (4) In chronic fetal anemia renal osmotic
clearance is increased. The fetus that is chronically anemic and
nephrectomized will increase plasma osmolality as well as
extravascular fluid when compared to anemic fetuses with intact
kidneys.