Effects of a reduction in maternal renal mass on pregnancy and cardiovascular and renal function of the pregnant ewe

Abstract

Maternal renal disease is associated with high maternal and fetal morbidity. To establish an animal model to study renal dysfunction in pregnancy and its potential role in programming for renal disease and hypertension in adult life, a kidney was removed from each of 16 nonpregnant ewes, and a branch of the renal artery of the remaining kidney was ligated (STNx ewes). The 16 STNx and 15 intact ewes were time mated 2.5–17 mo later and studied at 119–132 days of gestation. STNx ewes demonstrated renal hypertrophy and glomerular hyperfiltration. They had higher diastolic arterial pressures ( P < 0.05) and larger left ventricles ( P < 0.0005), drank more water ( P < 0.01), were hypochloremic ( P < 0.01) and hyperglycemic ( P < 0.0005), and had higher plasma creatinine levels ( P < 0.0005) than intact ewes. Effective renal plasma flows and glomerular filtration rates were lower ( P < 0.01) and protein excretion was greater ( P < 0.05) in STNx than in intact ewes. Glomerulotubular balance was impaired in STNx ewes. Proximal tubular Na+reabsorption was reduced ( P < 0.05), so Na+excretion was increased ( P < 0.05). In STNx ewes, filtered K+loads were reduced ( P < 0.005), but K+excretion was the same as in intact ewes. There was net K+secretion in STNx ewes; in intact ewes, there was net reabsorption. Plasma renin and angiotensinogen concentrations in STNx and intact ewes were similar, so the hypertension in STNx ewes was not renin dependent. STNx fetuses grew normally, and their blood gases, blood pressure, and heart rates were normal. These alterations in maternal fluid and electrolyte balance and the potential risk of maternal salt depletion or hyperkalemia may adversely affect the fetus.