Effects of Bilateral Nephrectomy and Angiotensin Ii Replacement on Body Fluids in Foetal Sheep

Abstract

1. To determine the importance of the kidneys in maintaining the normal volume and composition of foetal body fluids, measurements were made in 11 chronically catheterized foetuses (123-136 days) that had been bilaterally nephrectomized at least 5 days previously and compared with 10 intact foetuses (121-133 days). 2. The nephrectomized foetuses had reduced extracellular (ECV), blood, plasma and interstitial volumes per kg foetal weight (P < 0.005), reduced plasma chloride levels (P < 0.001) and were acidaemic, hypoxaemic and hypercapnaemic (P < 0.05) compared with intact foetuses. They also had reduced lung liquid production (P < 0.05) and reduced lung liquid sodium and osmolality levels (P < 0.05). Their arterial pressure was more variable between foetuses (P < 0.005) and was directly related to ECV/kg (P = 0.013). 3. To determine which of these changes were due to absence of the foetal renin-angiotensin system, seven chronically catheterized nephrectomized foetal sheep (124-132 days) were infused with replacement doses of angiotensin (Ang)II (1.5 micrograms/kg per h) for 3 days. Six nephrectomized foetuses were infused with 0.15 mol/L saline. 4. The AngII infusion was non-pressor. It prevented the fall in ECV that occurred in the control group (P < 0.05) and foetal plasma chloride concentration rose (P < 0.05). Blood gas status and lung liquid production rate did not change, but lung liquid sodium concentration fell (P < 0.05) and potassium concentration rose (P < 0.05). 5. Bolus injections of AngII (0.3-5 micrograms) were given to assess vascular sensitivity to AngII. This was not altered by either nephrectomy or AngII replacement. 6. It is concluded that the foetal kidneys are important for the maintenance of the normal volume and composition of foetal body fluids. Angiotensin II, perhaps because it promotes fluid transfer across the placenta, helps maintain foetal ECV and plasma chloride levels.

Increased Cardiovascular and Renal Risk Is Associated with Low Nephron Endowment in Aged Females: An Ovine Model of Fetal Unilateral Nephrectomy

“…The timing at which uni-x is performed in our model coincides with the commencement of rapid maturation of cardiac myocytes in sheep [65]. While we found no information available on the effects of fetal uni-x on extracellular fluid status, bilateral nephrectomy has been shown to decrease extracellular fluid, plasma and blood volumes in the fetal sheep [66]. Furthermore, Dalshaug and colleagues have reported that 100d ovine fetal hearts have reduced ability to increase blood flow in response to a pressure overload challenge [67].…”

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

“…This is also true when haemorrhage is the stimulus. 8 Plasma aldosterone concentrations tended to decline in nephx foetuses, but there was great variation between animals, particularly within the control group. Although there is evidence that inhibition of the RAS can decrease foetal blood pressure, in the short or long term 31 bilateral nephrectomy leads to greater decreases than obtained by inhibition of the RAS.…”

“…The fact that the plasma Epo concentrations were not significantly different in control and nephx foetuses, even after the nephx foetuses became hypoxic, suggests that increased liver production of Epo is not able to compensate for loss of kidney Epo production. 8 Of interest, replacing AngII increases the extracellular fluid volume, but does not fully restore plasma Cl. 6 Plasma renin concentrations decreased in nephx foetuses very rapidly.…”

“…5 The kidney is an important site of erythropoietin (Epo) production and bilateral nephrectomy of the ovine foetus reduces the ability of the foetus to increase plasma Epo in response to a standard haemorrhage. 8 Extracellular volume could be restored by 3 days infusion with angiotensin (Ang)II, 8 indicating the importance of an intact renin-angiotensin system (RAS) for fluid regulation. 3,4,7 However, the effect of lack of renal function on overall fluid balance and maintenance of plasma composition in the foetus has received rather less attention.…”

Cardiorenal Syndrome is Present in Human Fetuses with Severe, Isolated Urinary Tract Malformations

“…In fetal lambs, intra- and extracellular volume is reduced after second-trimester nephrectomy [32]; the same, however, may not apply for nephropathies and urinary tract malformations during fetal life. Postnatally, end-stage renal disease is associated with volume retention which correlates with increasing BNP-levels [33].…”