Foetal Fluid Balance and Hormone Status Following Nephrectomy in the Foetal Sheep

Abstract

1. The role of the kidneys in the maintenance of normal foetal plasma (FP) composition and hormone concentrations was examined in the present study. Five ovine foetuses were chronically cannulated and nephrectomized (nephx) at 100 +/- 1 days of gestation and maintained for 14 days. These were compared to five intact control foetuses. 2. Four hours after nephx, FP renin concentrations were significantly lower than in control foetuses. By 48 h, renin concentrations in nephx foetuses were below the level of detectability of the assay. Foetal plasma aldosterone concentrations declined in nephx foetuses, but were not significantly different to those in control foetuses (P = 0.08). 3. During the second week, the nephx foetuses were significantly hypoxic, but FP erythropoietin concentrations were not increased. Adrenocorticotropic hormone (ACTH) and cortisol concentrations, when measured on day 14, were not different between the two groups. Adrenocorticotropic hormone levels were correlated with adrenal weight at post-mortem. 4. Foetal plasma creatinine, magnesium and phosphate concentrations in nephx foetuses increased, eventually reaching values approximately twice that in controls. Foetal plasma chloride levels decreased continuously in nephx foetuses, eventually being 23 mmol/L lower than controls. Maternal plasma composition was unchanged. 5. Total foetal fluid (amniotic + allantoic) volumes were reduced when measured at post-mortem on day 14 after nephx. The composition of both fluids was significantly altered in the nephx foetuses compared with controls. 6. Fetuses can survive in utero for 2 weeks after bilateral nephrectomy. However, there are multiple changes in plasma composition that may compromise foetal survival in the long term.

Bone Development and Mineral Homeostasis in the Fetus and Neonate: Roles of the Calciotropic and Phosphotropic Hormones

“…Data have already been cited about how circulating calcitriol levels are low in fetal rats but increased in fetal sheep. As already noted, fetal nephrectomy in lambs reduced the serum calcitriol level by 60% and was accompanied by a fall in serum calcium and an increase in serum phosphorus in one study (455), but serum calcium remained normal in another study of nephrectomized fetal lambs (459), and serum calcium and phosphorus were normal in nephrectomized fetal rats (105). The investigators in the first study assumed that loss of renal production of calcitriol caused the hypocalcemia and hyperphosphatemia and were able to show that pharmacological treatment with calcitriol reversed these abnormalities (455).…”

“…The investigators concluded that loss of renal 1␣-hydroxylase and production of calcitriol resulted in altered fetal mineral homeostasis, rather than the loss of renal function to reabsorb and excrete minerals. However, other investigators performed bilateral nephrectomy in fetal lambs and observed an increase in serum phosphorus, no change in serum calcium, and a nonsignificant reduction in the excretion of calcium into the amniotic fluid and allantois (459). Bilateral nephrectomy in fetal rats did not alter the serum calcium or phosphorus either; calcitriol and PTH were not measured in those experiments (105).…”

Impaired ability to modulate glomerular filtration rate in aged female sheep following fetal uninephrectomy

“…Merino ewes carrying fetuses of known gestational age underwent uni‐x or sham surgery at 100 days postconception, as previously described (uni‐x, n = 7; sham n = 7) (Moritz et al. ). Only female fetuses were selected for use in this study.…”

Blunted Sodium Excretion in Response to a Saline Load in 5 Year Old Female Sheep Following Fetal Uninephrectomy

“…Merino ewes carrying female fetuses of known gestational age underwent surgery at 100 days post-conception, as described previously [20], [27]. The left renal artery, vein and ureter were ligated and the kidney was cleared from the surrounding fat (uni-x group, n = 7).…”