A250
EFFECTS OF AN INFUSION OF IGF-I ON THE FETAL KIDNEY AND ON FETAL SURVIVAL
Marsh A.C.1 Gibson K.J. 1 Lumbers E.R. 1 and Thomas D2
1
School of Physiology and Pharmacology, The University of New South Wales, Sydney, NSW, 2052. 2Clinical
Chemistry, Prince of Wales Hospital, Sydney, NSW.
A prolonged infusion of insulin-like growth factor-I (IGF-I) to the ovine fetus in late gestation substantially
promotes the growth of the fetal kidney (Lok et al., 1996). This study aimed to determine whether similar
treatment with IGF-I affects the function of the fetal kidney in addition to growth. 12 chronically catheterised
fetal sheep (120 ± 1 days gestation) were infused i.v. for 10 days with 80 g/h IGF-I. 7 control fetuses received
the vehicle (0.1% BSA in 0.15 M saline) over the same period. Fetal renal and cardiovascular function, and
blood gases, were measured during the first 4h of infusion, and after 4 and 10 days of treatment.
Fetal kidney growth was accelerated by 29.8% by 8 ± 1 days of IGF-I infusion (n=7; P<0.05), compared with
non-treated fetuses (10 d vehicle infusion or no infusion; n=7). Kidney weight relative to body weight was
39.8% greater (P<0.005).
During the first 4h of infusion, glomerular filtration rate (GFR) did not change from control, and renal blood
flow fell (P<0.05-0.01). There was a marked increase in fractional phosphate reabsorption, from 91.9 ± 2.9%
during control, to 97.9 ± 0.8 after 4h (P<0.05). Fractional reabsorption of sodium, chloride and bicarbonate
also rose acutely (P<0.05-0.01). These changes in reabsorption may be due to a direct action of IGF-I on the
renal tubules. Arterial Po2 fell during the first 4h, resulting in a lactic acidaemia. The kidney responded by
increasing fractional bicarbonate reabsorption (P<0.01), and excreting more acid (P<0.01). Arginine
vasopressin (AVP) was probably released in response to the hypoxaemia, as an antidiuresis, fall in free water
clearance, and rise in urinary osmolality were also seen acutely (P<0.05-0.01).
After 4 days of infusion, GFR was increased to 1.76 ± 0.14 mL/min/kg fetal body weight, compared with 1.34 ±
0.15 mL/min/kg pre-infusion (P<0.05; n=5). Fractional reabsorption of sodium, both by the entire nephron,
and the proximal tubule, were not reduced despite the elevated GFR. Fractional reabsorption of chloride,
bicarbonate and phosphate were also similar to control. Fetal Po2 had fallen by 4 days (P<0.05; n=5), but
plasma lactate, arterial pH and renal acid-base parameters were not significantly affected. Urine flow rate, free
water clearance and urinary osmolality were also similar to baseline values.
7 of 12 fetuses infused with IGF-I died within the first 4 days of infusion, compared with only 1 of 7
vehicle-infused fetuses. Before the IGF-I infusion, these 7 ‘non-survivors’ had a higher urinary osmolality
(288 ± 31 mOsm/kg) than the 5 fetuses that survived the IGF-I infusion (128 ± 6; P<0.005). The non-survivors
also had lower arterial Po2 and pH, and higher plasma lactate levels prior to the infusion, compared with the
surviving fetuses (P<0.05), and tended to be excreting more acid. It is likely that these fetuses, because of their
condition prior to infusion, were unable to tolerate the metabolic changes rapidly induced by IGF-I.
Fetal renal function was therefore affected in a number of ways by an infusion of IGF-I in late gestation.
Atypically for the fetus, when GFR was elevated at day 4, glomerulotubular balance was maintained primarily
by the proximal tubule. This is an adult characteristic, and together with the rise in GFR and the acute
stimulatory effect on tubular reabsorption, it suggests that the maturation of renal function in treated fetuses was
accelerated by IGF-I. This action may be partly related to renal growth, as many of the effects on renal
function were only apparent after chronic treatment.
Lok F. Owens J.A. Mundy L. Robinson J.S. and Owens P.C. (1996). Am J Physiol, 270, R1148-R1155.