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Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants

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Pediatric and Developmental Pathology

Abstract

Until now oligonephropathy to indicate “too few nephrons” has been associated with intrauterine growth restriction and experimentally induced abnormalities of renal development. The purpose of this study was to determine whether there is evidence of abnormal postnatal glomerulogenesis in extremely low birth weight preterm infants. Renal autopsy tissue was studied by computer-assisted morphometry from 56 extremely premature infants (birth weight ≤ 1000 g) and 10 fullterm infants as controls. Preterm infants were divided into two groups (short survival < 40 days vs. long survival ≥40 days). Each group was subdivided into those with renal failure (RF) and those with normal renal function. Forty-two of 56 preterm infants (75%) were adequate for gestational age. Glomerulogenesis as measured by radial glomerular counts (RGC) was markedly decreased in all preterm infants as compared to term controls and correlated significantly with gestational age (r = 0.87; P < 0.001). Active glomerulogenesis with “basophilic S-shaped bodies” was absent in longer surviving preterm and all term infants. RGC of preterm infants surviving ≥40 days with RF were significantly less than RGC of those with long survival and no RF (P < 0.001). Only this latter group demonstrated increased glomerular size as measured by mesangial tuft area and Bowman’s capsule area compared to all other groups (P < 0.001). The kidney continues to form postnatally in preterm neonates, but glomerulogenesis ceases after 40 days. Moreover, it is further inhibited by RF. Compensatory mechanisms in longer surviving preterm infants include glomerular hypertrophy and mesangial proliferation that could lead to hyperfiltration.

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References

  1. LL Woods JR Ingelfinger JR Nyengaard R Rasch (2001) ArticleTitleMaternal protein restriction suppresses the newborn renin-angiotensin system and programs adult hypertension in rats. Pediatr Res 49 460–467 Occurrence Handle1:CAS:528:DC%2BD3MXjtVyitb4%3D Occurrence Handle11264427

    CAS  PubMed  Google Scholar 

  2. JR Ingelfinger LL Woods (2002) ArticleTitlePerinatal programming, renal development, and adult renal function. Am J Hypertens 15 (Suppl 1) 46S–49S Occurrence Handle10.1016/S0895-7061(01)02302-0

    Article  Google Scholar 

  3. VM Vehaskari DH Aviles J Manning (2001) ArticleTitleFetal programming of adult hypertension in the rat. Kidney Int 59 238–245 Occurrence Handle10.1046/j.1523-1755.2001.00484.x Occurrence Handle1:STN:280:DC%2BD3M7jtFWrtA%3D%3D Occurrence Handle11135076

    Article  CAS  PubMed  Google Scholar 

  4. CM Law AW Shiell CA Newsome et al. (2002) ArticleTitleFetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age. Circulation 105 1088–1092 Occurrence Handle10.1161/hc0902.104677 Occurrence Handle1:STN:280:DC%2BD387ksFeqsw%3D%3D Occurrence Handle11877360

    Article  CAS  PubMed  Google Scholar 

  5. WE Hoy M Rees E Kile et al. (1999) ArticleTitleA new dimension to the Barker hypothesis: low birth weight and susceptibility to renal disease. Kidney Int 56 1072–1077 Occurrence Handle10.1046/j.1523-1755.1999.00633.x Occurrence Handle1:STN:280:DyaK1MzpvVGgtQ%3D%3D Occurrence Handle10469376

    Article  CAS  PubMed  Google Scholar 

  6. C Merlet-Bénichou T Gilbert J Vilar et al. (1999) ArticleTitleNephron number: variability is the rule. Causes and consequences. Lab Invest 79 515–527 Occurrence Handle10334563

    PubMed  Google Scholar 

  7. M Lelievre-Pegorier J Vilar ML Ferrier et al. (1998) ArticleTitleMild vitamin A deficiency leads to nephron deficit in the rat. Kidney Int 54 1455–462 Occurrence Handle10.1046/j.1523-1755.1998.00151.x Occurrence Handle1:CAS:528:DyaK1cXnsVeqt7w%3D Occurrence Handle9844121

    Article  CAS  PubMed  Google Scholar 

  8. C Merlet-Bénichou T Gilbert M Muffat-Joly et al. (1994) ArticleTitleIntrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol 8 175–180 Occurrence Handle8018495

    PubMed  Google Scholar 

  9. T Gilbert M Lelievre-Pegorier R Malienou et al. (1987) ArticleTitleEffects of prenatal and postnatal exposure to gentamicin on renal differentiation in the rat. Toxicology 43 301–313 Occurrence Handle10.1016/0300-483X(87)90089-8 Occurrence Handle1:CAS:528:DyaL2sXhvVymsL0%3D Occurrence Handle3824397

    Article  CAS  PubMed  Google Scholar 

  10. R Mañalich L Reyes M Herrera et al. (2000) ArticleTitleRelationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58 770–773 Occurrence Handle10.1046/j.1523-1755.2000.00225.x Occurrence Handle10916101

    Article  PubMed  Google Scholar 

  11. G Keller G Zimmer G Mall et al. (2003) ArticleTitleNephron number in patients with primary hypertension. N Engl J Med 348 101–108 Occurrence Handle10.1056/NEJMoa020549 Occurrence Handle12519920

    Article  PubMed  Google Scholar 

  12. E Donovan J Tyson R Ebrenkranz et al. (1999) ArticleTitleInaccuracy of Ballard scores before 28 weeks’ gestation. J Pediatr 135 147–152 Occurrence Handle1:STN:280:DyaK1Mzmt1Ghuw%3D%3D Occurrence Handle10431107

    CAS  PubMed  Google Scholar 

  13. A Drukker JP Guignard (2002) ArticleTitleRenal aspects of the term and preterm infant: a selective update. Curr Opin Pediatr 14 175–182 Occurrence Handle10.1097/00008480-200204000-00006 Occurrence Handle11981287

    Article  PubMed  Google Scholar 

  14. J Bernstein RA Risdon (1997) Renal system. E Gilbert-Barness (Eds) Potter’s Pathology of the Fetus and Infant. Mosby St Louis 863–866

    Google Scholar 

  15. H Motulsky (1995) Intuitive Biostatistics. Oxford University Press New York 207–262

    Google Scholar 

  16. R Resnik (2002) ArticleTitleIntrauterine growth restriction. Obstet Gynecol 99 490–496 Occurrence Handle10.1016/S0029-7844(01)01780-X Occurrence Handle11864679

    Article  PubMed  Google Scholar 

  17. JC Kleinman LA Fingerhut K Prager (1991) ArticleTitleDifferences in infant mortality by race, nativity status and other maternal characteristics. Am J Dis Child 145 194–199 Occurrence Handle1:STN:280:By6C3srmvVA%3D Occurrence Handle1994686

    CAS  PubMed  Google Scholar 

  18. A Kempe P Wise S Barkan et al. (1992) ArticleTitleClinical determinants of the racial disparity in very low birth weight. N Engl J Med 327 969–973 Occurrence Handle1:STN:280:By2A1M%2FgtFY%3D Occurrence Handle1518548

    CAS  PubMed  Google Scholar 

  19. MA Valdés-Dapena (1979) Kidney. . . (Eds) Histology of the Fetus and Newborn, 1st ed. W.B. Saunders Philadelphia 345–359

    Google Scholar 

  20. NY Boo SS Zulkifli MS Lye (1999) ArticleTitleRisk factors associated with umbilical vascular catheter-associated thrombosis in newborn infants. J Paediatr Child Health 35 460–465 Occurrence Handle10.1046/j.1440-1754.1999.355392.x Occurrence Handle1:STN:280:DC%2BD3c%2FjvF2qug%3D%3D Occurrence Handle10571759

    Article  CAS  PubMed  Google Scholar 

  21. SB Schwedler T Gilbert E Moreau et al. (1999) ArticleTitleNephrotoxic exposure in utero reduces glomerular number in sclerosis-prone but not sclerosis-resistant mice. Kidney Int 56 1683–1690 Occurrence Handle10.1046/j.1523-1755.1999.00749.x Occurrence Handle1:CAS:528:DyaK1MXnslWqu74%3D Occurrence Handle10571776

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Dr. Liliane J. Striker and Anna R. Plati from the Laboratory of Renal Cell Biology, Division of Nephrology, Department of Medicine, University of Miami, for allowing us to use the morphometric analysis system. We also thank Carmen Duboue, HT, ASCP, and Bonnie Cohen, HT, ASCP, for their assistance cutting histologic renal preparations and performing PAS stains.

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Correspondence to Maria M. Rodríguez.

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Rodríguez, M., Gómez, A., Abitbol, C. et al. Histomorphometric Analysis of Postnatal Glomerulogenesis in Extremely Preterm Infants. Pediatr. Dev. Pathol. 7, 17–25 (2004). https://doi.org/10.1007/s10024-003-3029-2

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  • DOI: https://doi.org/10.1007/s10024-003-3029-2

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