Ontogeny of single glomerular perfusion rate in fetal and newborn lambs.

Abstract

Summary: The developmental pattern of regional glomerular density and glomerular perfusion rate (GPR) was studied in 20 chronically catheterized fetal lambs between 106 and 140 days of gestation (term, 145 days) and in six newborn lambs between 3 and 19 days of age. The present study demonstrates for the first time in lambs that the nephrogenic zone disappears around 130 days of gestation and that the total glomerular counts per kidney in fetuses over 130 days (468296 ± 41173 glomeruli per kidney) is not significantly different than in newborn lambs (433704 ± 21553). Glomerular density, determined in four cortical zones (zone I being the outermost portion of the cortex) did not show any significant changes during fetal life; however, significant decreases in glomerular density were observed in each cortical zone after birth. The relative distribution of glomeruli during fetal life decreased in the outer portion (zones I and II) and increased in the inner portion (zones III and IV) of the cortex as fetuses matured and approached term. After birth, this difference became even more prominent; the outer cortical fraction (zone I) decreased from 49.6 ± 2.9% in fetuses of less than 120 days to 37.8 ± 1.5% (P < 0.05) in newborn lambs, whereas the fraction found in zone III increased from 14.9 ± 1.3% to 20.8 ± 0.7% (P < 0.05). Small but significant increases in glomerular filtration rate (GFR) (P < 0.01) and total renal blood flow (P < 0.05) were observed during fetal life: GFR and total renal blood flow increased, respectively, from 1.84 ± 0.11 and 37 ± 2 ml/min in fetuses <120 days to 3.05 ± 0.2 and 46 ± 4 ml/min in fetuses >130 days gestation. During the same period, filtration fraction (FF) did not increase significantly whereas a significant (P < 0.01) 58% increase in FF was observed after birth: FF increased from 10.16 ± 0.74% in fetuses >130 days gestation to 16.12 ± 1.66% in newborn lambs. Renal vascular resistance decreased from 1.03 ± 0.08 mm Hgml-1 min-1 in fetuses >130 days to 0.51 ± 0.05 mm Hgml-1min-1 (P < 0.01) in newborn lambs. Glomerular perfusion rate (GPR), computed for each cortical zone did not change significantly during the last trimester of gestation. After birth, GPR increased almost three times in zones I and II (from 69.2 ± 8.9 and 53.6 ± 4.2 nl/min in fetuses >130 days to 206.9 ± 16.8 and 161.3 ± 20.7 nl/min in newborn lambs, respectively), doubled in zone III (from 55.6 ± 10 nl/min in fetuses >130 days to 119.5 ± 8.9 nl/min in newborn lambs) and remained unchanged in zone IV when compared to fetal GPR values. After birth, the increase in GFR correlated closely with the GPR increase in zone I (r = 0.87) and zone II (r = 0.87), suggesting that the developmental pattern of GFR after birth may depend on the increase in GPR in the outer zones of the renal cortex.Speculation: The addition of new nephron units may be an important determinant of glomerular filtration rate (GFR) in fetuses of less than 130 days of gestation. In fetuses over 130 days of gestation, the addition of new nephron units is no longer a factor to explain the increase in fetal GFR but other factors such as increases in surface area for filtration, effective filtration pressure and capillar filtration coefficient may then play an important role. After birth, one can speculate that a decrease in glomerular vascular resistance is a major determinant in the postnatal increase in glomerular perfusion rate and GFR.