Altered primate glomerular development due to in utero urinary tract obstruction

Douglas G. Matsell, Amy Mok, Alice F Tarantal

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Background. In utero urinary tract obstruction is an important cause of newborn and childhood renal failure. Ureteric obstruction during active nephrogenesis results in cystic renal dysplasia; the earlier and longer the obstruction the more severe the histopathological changes of dysplasia. We have reported on a non-human primate model of non-surgical in utero fetal ureteric obstruction that accurately reflects the human equivalent of obstructive renal dysplasia. A striking feature of this model is the effect of obstruction on normal glomerular development and podocyte survival. Methods. To study the effect of urinary obstruction on glomerular development, kidneys were studied from fetuses undergoing unilateral ureteric obstruction by ultrasound guided injection of alginate beads as early as 75 days gestation (term gestation = 165 ± 10 days). These kidneys displayed all the features of human obstructive cystic dysplasia, had reduced weights, and significant deficiencies in terminal ureteric duct branching. Results. A combination of histochemistry, histomorphometry, and immunocytochemistry was used to demonstrate deficient cortical ureteric duct development and branching, reduced glomerular number, and altered glomerular basement membrane formation with in utero urinary tract obstruction. Conclusions. These data suggest that urinary tract obstruction during active nephrogenesis results in a defect in ureteric duct branching morphogenesis, and altered vascularization of the glomerulus with consequent podocyte dropout and decreased glomerular number. These abnormalities reflect human renal dysplasia, which is associated with compromised postnatal renal function and, thus, should be predictive of postnatal outcome.

Original languageEnglish (US)
Pages (from-to)1263-1269
Number of pages7
JournalKidney International
Volume61
Issue number4
DOIs
StatePublished - 2002

Fingerprint

Urinary Tract
Primates
Kidney
Podocytes
Anatomic Models
Pregnancy
Glomerular Basement Membrane
Morphogenesis
Renal Insufficiency
Fetus
Immunohistochemistry
Weights and Measures
Injections

Keywords

  • Branching morphogenesis
  • Fetal kidney
  • Monkey
  • Nephrogenesis
  • Urinary obstruction

ASJC Scopus subject areas

  • Nephrology

Cite this

Altered primate glomerular development due to in utero urinary tract obstruction. / Matsell, Douglas G.; Mok, Amy; Tarantal, Alice F.

In: Kidney International, Vol. 61, No. 4, 2002, p. 1263-1269.

Research output: Contribution to journalArticle

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