Neonatology pp 1018-1026 | Cite as

Pathophysiology of Fetal and Neonatal Kidneys

  • Farid Boubred
  • Isabelle Grandvuillemin
  • Umberto Simeoni


The definitive kidney, the methanephros, is formed by two processes, nephrogenesis (the formation of glomerulus and tubules) and branching morphogenesis (the formation of collecting ducts, calyces, pelvis and ureters). The metanephric kidney takes place after the formation and involution of two embryonic kidneys, the pronephros (non functional organ) and the mesonephros (first functional kidney), that in turn evolves into the ureteric bud (UB). The metanephros appears during the fifth gestational week, and develops from the specific interaction between the epithelial ureteric bud and the undifferentiated metanephric mesenchyme (MM). This interaction is crucial for the differentiation of the mesenchyme and the induction of UB branching division (Fig. 124.1). The UB arises in response to signals elaborated by the mesenchyme and then undergoes branching morphogenesis following the invasion of the MM by the UB. This process gives a 15 branch generation. At 20–22 weeks of gestation, branching morphogenesis is completed and results in the collecting system. Mesenchymal cells that are in close contact with the invading UB undergo an epithelial transformation. The induced metanephric mesenchyme (MM) gives the nephrons, through the consecutive stages of condensation, renal vesicule, vascular cleft, and S-shaped body. The glomerular capillary tuft is formed via recruitment and proliferation of endothelial and mesangial cells precursors. The nephrons develop in successive stages from the inner to the outer area of the fetal kidney in parallel with the vascular system. In the human, the primitive glomerulus appears at approximately 9–10 weeks of gestation. The nephrogenesis is completed by 34–36th weeks of gestation [1]. About 60% of the nephrons develop during the third trimester of gestation, while nephrogenesis may continue ex-utero in preterm infants [2]. Once nephrogenesis is complete, stroma cells differentiate into fibroblasts, pericytes and lymphocytes-like cells. At birth the final nephron number varies from 800,000 and 1 million per kidney. Such variation in nephron number is due to genetic factors and to the fetal environment [3]. Several genes and molecular pathways control the formation of the renal collecting system and nephrogenesis, such as transcriptional factors (PAX-2, WT1), growth factors (IGF, EGF, TGF), oncogenes, the extracellular matrix, and vascular factors (Table 124.1) [4]. These factors act at a specific time of kidney development especially when the UB interacts with the adjacent MM. Blockade of vascular endothelial growth factor receptor (VEGF-R), inhibition of the renin angiotensin system (RAS) and knock-out for cyclooxigenase (COX)-2 gene expression are associated with impaired nephrogenesis including glomerular cysts, dysplasic tubules and tubular dysgenesis [5, 6, 7].


Preterm Infant Renal Blood Flow Renin Angiotensin System Nephrogenic Diabetes Insipidus Fetal Kidney 
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  1. 1.
    Saxen L (1987) Organogenesis of the kidney. In: Barlow PW, Green PB, White CC (eds) Developmental and Cell Biology Series.Cambrige University Press, CambrigeGoogle Scholar
  2. 2.
    Merlet-Benichou C, Gilbert T, Vilar J et al (1999) Nephron number: variability is the rule. Causes andconsequences. Lab Invest 79: 515–526PubMedGoogle Scholar
  3. 3.
    Chevalier RL (1996) Developmental renal physiology of the low birth weight preterm newborn. J Urol 156: 714–719PubMedCrossRefGoogle Scholar
  4. 4.
    Burrow CR (2000) Regulatory molecules in kidney development. Pediatr Nephrol 14: 240–253PubMedCrossRefGoogle Scholar
  5. 5.
    Dinchuk JE, Car BD, Focht RJ et al (1995) Renal abnormalities and an altered inflammatory response in mice lacking cyclooxygenase 2. Nature 378: 406–409PubMedCrossRefGoogle Scholar
  6. 6.
    McGrath-Morrow S, Choc C, Molls R et al (2006) VEGF receptor 2 blockade leads to renal cyst formation in mice. Kidney Int 69: 1741–1748PubMedCrossRefGoogle Scholar
  7. 7.
    Pryde PG, Sedman AB, Nugent CE et al (1993) Angiotensin-converting enzyme inhibitor fetopathy. J Am Soc Nephrol 3: 1575–1582PubMedGoogle Scholar
  8. 8.
    Brophy PD, Robillard JE (2004) Functional development of the kidney in utero. In: Polin RA, Fox WW, Abman SW (eds) Fetal and neonatal physiology, 3th edn. W.B. Saunders, Philadelphia, pp 1229–1239Google Scholar
  9. 9.
    Khan KNM, Stanfield KM, Dannenberg A et al (2001) Cyclooxygenase- 2 expression in the developing human kidney. Pediatr Dev Pathol 4: 461–466PubMedCrossRefGoogle Scholar
  10. 10.
    Hoster M (2000) Embryonic epithelial membranes transporters. Am J Physiol 279: F74–F52Google Scholar
  11. 11.
    Nielsen S, Frokaier J, Marples D et al (2002) Aquaporins in the kidney:from molecule to medecine. Physiol Rev 82: 205–244PubMedGoogle Scholar
  12. 12.
    Solhaug MJ, Jose PA (2004) Postnatal maturation of renal blood flow. In: Polin RA, Fox WW, Abman SW (eds) Fetal and neonatal physiology, 3rd edn. W.B. Saunders, Philadephia, pp 1243–1249Google Scholar
  13. 13.
    Guignard JP (1975) Glomerular filtration rate in the first three weeks of life. J Pediatr 87: 268–272PubMedCrossRefGoogle Scholar
  14. 14.
    Rodriguez MM, Gomez AH, Abitbol CL (2004) Histomorphometric analysis of postnatal glomerulogenesis on extremely preterm infants. Pediatr Dev Pathol 7: 17–25PubMedCrossRefGoogle Scholar
  15. 15.
    Rodriguez MM, Gomez AH, Abitbol CL (2004) Histomorphometric analysis of postnatal glomerulogenesis on extremely preterm infants. Pediatr Dev Pathol 7: 17–25PubMedCrossRefGoogle Scholar
  16. 16.
    Bueva A, Guignard JP (1994) Renal function in preterm neonates. Pediatr Res 36: 572–577PubMedCrossRefGoogle Scholar
  17. 17.
    Giniger RP, Buffat C, Millet V et al (2007) Adrenal effects of ibuprofen for the treatment of patent ductus arteriosus in premature infants. J Matern Fetal Neonatal Med 20: 275–283PubMedCrossRefGoogle Scholar
  18. 18.
    Sweet D, Working Group on Prematurity (2007) European consensus guidelines on the management of neonatal respiratory distress syndrome. J Perinat Med 35: 175–186PubMedCrossRefGoogle Scholar
  19. 19.
    Catarelli D, Chirico G, Simoni U (2002) Renal effects of antenally and postnatally administered steroids. Pediatr Med Chir 24: 157–162Google Scholar
  20. 20.
    Rodriguez-Soriano J (2000) New insight into the pathogenesis of renal tubular acidosis-from functional to molecular studies. Pediatr Nephrol 14: 1121–1136PubMedCrossRefGoogle Scholar
  21. 21.
    Peters CA, Carr MC, Lais A et al (1992) The response of the fetal kidney to obstruction. J Urol 148: 503–509PubMedGoogle Scholar
  22. 22.
    Boubred F, Vendemia M, Garcia-Meric P et al (2006) Effects of maternally administered drugs on the fetal and neonatal kidney. Drug Saf 29: 397–419PubMedCrossRefGoogle Scholar
  23. 23.
    Brenner BM, Garcia DL, Anderson S (1988) Glomeruli and blood pressure. Less of one, more the other. Am J Hypertens 1: 335–347Google Scholar
  24. 24.
    Keller G, Zimmer G, Gerhard M et al (2003) Nephron number in patients with primary hypertension. N Engl J Med 348: 101–108PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2012

Authors and Affiliations

  • Farid Boubred
  • Isabelle Grandvuillemin
  • Umberto Simeoni
    • 1
  1. 1.Division of NeonatologyLa Conception HospitalMarseilleFrance

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