Normal foetal kidney volume in offspring of women treated for gestational diabetes.

AIMS: The worldwide prevalence of gestational diabetes mellitus (GDM) is increasing. Studies in rodent models indicate that hyperglycaemia during pregnancy alters kidney development, yet few studies have examined if this is so in humans. The objective of this study was to evaluate the association of treated GDM with foetal kidney size. MATERIALS AND METHODS: Participants were recruited from an Australian tertiary hospital, and clinical data were collected from women without GDM and women diagnosed and treated for GDM and their offspring. Participants underwent an obstetric ultrasound at 32-34 weeks gestation for foetal biometry and foetal kidney volume measurement. RESULTS: Sixty-four non-GDM and 64 GDM women participated in the study. Thirty percent of GDM women were diagnosed with fasting hyperglycaemia, while 89% had an elevated 2-hour glucose level. Maternal age, weight and body mass index were similar in women with and without GDM. Estimated foetal weight, foetal kidney dimensions, total foetal kidney volume and birth weight were similar in offspring of women with and without GDM. CONCLUSIONS: We conclude that a period of mild hyperglycaemia prior to diagnosis of GDM and treatment initiation, which coincides with a period of rapid nephron formation and kidney growth, does not alter kidney size at 32-34 weeks gestation.

Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants.

BACKGROUND: During normal human kidney development, nephrogenesis (the formation of nephrons) is complete by term birth, with the majority of nephrons formed late in gestation. The aim of this study was to morphologically examine nephrogenesis in fetal human kidneys from 20 to 41weeks of gestation. METHODS: Kidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24h after birth. Using image analysis, nephrogenic zone width, the number of glomerular generations, renal corpuscle cross-sectional area and the cellular composition of glomeruli were examined. Kidneys from female and male infants were analysed separately. FINDINGS: The number of glomerular generations formed within the fetal kidneys was directly proportional to gestational age, body weight and kidney weight, with variability between individuals in the ultimate number of generations (8 to 12) and in the timing of the cessation of nephrogenesis (still ongoing at 37weeks gestation in one infant). There was a slight but significant (r2=0.30, P=0.001) increase in renal corpuscle cross-sectional area from mid gestation to term in females, but this was not evident in males. The proportions of podocytes, endothelial and non-epithelial cells within mature glomeruli were stable throughout gestation. INTERPRETATION: These findings highlight spatial and temporal variability in nephrogenesis in the developing human kidney, whereas the relative cellular composition of glomeruli does not appear to be influenced by gestational age.

Effects of preterm birth and ventilation on glomerular capillary growth in the neonatal lamb kidney.

OBJECTIVES: Preterm birth is linked to the development of hypertension later in life. This may relate to impaired glomerular capillary growth following preterm birth. The aim of this study was to determine the effects of preterm birth, and/or ventilation, on glomerular capillary growth in the neonatal lamb kidney. METHODS: Four experimental groups were analysed: preterm lambs delivered at 130 days gestation (term = 147 days) and mechanically ventilated for 3 days (preterm ventilated: n = 9), 133 days gestational controls (gestational control: n = 5), term controls, unassisted breathing for 3 days (term control: n = 8), and term lambs ventilated for 3 days (term ventilated: n = 5). In perfusion-fixed kidneys, total nephron number, average total capillary length, and surface area per renal corpuscle were stereologically assessed, and total renal filtration surface area (TRFSA) was calculated. RESULTS: In comparison with term controls, preterm lambs had significantly reduced glomerular capillary length, surface area, and TRFSA, indicative of a low renal functional capacity. Term-ventilated lambs exhibited significantly reduced glomerular capillary length and surface area compared with term controls, indicating that ventilation impairs glomerular capillary growth independently of preterm birth. CONCLUSION: Impaired glomerular capillary growth and subsequent reduced TRFSA following preterm birth may mediate the increased predisposition to hypertension later in life.

Chronic intrauterine exposure to endotoxin does not alter fetal nephron number or glomerular size.

A reduced nephron endowment early in life adversely impacts on long-term functional reserve in the kidney. A recent study has shown that acute exposure to chorioamnionitis during late gestation can adversely impact on nephrogenesis. The present study aimed to examine the effects of chronic, low-dose endotoxin exposure in utero, during the period of nephrogenesis, on nephron number and glomerular size in preterm lambs. Ewes were administered either endotoxin (lipopolysaccharide; 1 mg/day) or saline at 110-133 days of gestation (term approximately 147 days) via surgically implanted osmotic minipumps within the amniotic cavity. The ewes were induced to deliver preterm at 133 days gestation and the kidneys of the lambs were analysed at 8 weeks after term-equivalent age. Nephron number per kidney was determined using a combined optical disector and fractionator stereological approach; renal corpuscle size was also measured stereologically. At 8 weeks after term-equivalent age there was no significant effect of in utero exposure to endotoxin on bodyweight or kidney weight and there were no significant differences in nephron number, nephron density or renal corpuscle volume between groups. We conclude that chronic intrauterine inflammation during the period of nephrogenesis may not adversely impact on the number of nephrons formed within the kidney or on the volume of the renal corpuscle.