BackgroundDuring 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 41 weeks of gestation.MethodsKidney samples were obtained at autopsy from 71 infants that died acutely in utero or within 24 h 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.FindingsThe 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 37 weeks 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.InterpretationThese 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.

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: 1) Preterm lambs delivered at 130d gestation (term=147d) and mechanically ventilated for 3 days (Preterm ventilated: n=9); 2) 133d gestational controls (Gestational control: n=5); 3) Term controls, unassisted breathing for 3 days (Term control: n=8); and 4) Term lambs ventilated for 3 days (Term ventilated: n=5). In perfusion-fixed kidneys, total nephron number and average total capillary length and surface area per renal corpuscle were stereologically assessed and total renal filtration surface area (TRFSA) calculated. Results In comparison to 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 to 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.