A design-based method for estimating glomerular number in the developing kidney

Luise A Cullen-McEwen, James A Armitage, Jens R Nyengaard, Karen M Moritz, John F Bertram

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Abstract

Low glomerular (nephron) endowment has been associated with increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 weeks gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was in part due to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here we describe a method that uses lectin histochemistry to identify developing glomeruli, and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number (N(glom)). We have characterized N(glom) throughout development in kidneys from 76 rats and model this development with a five parameter logistic equation to predict N(glom) from embryonic day 17.25 to adulthood (r2=0.98). This approach represents the first design-based method with which to estimate N(glom) in the developing kidney.
Original languageEnglish
Pages (from-to)F1448 - F1453
Number of pages6
JournalAmerican Journal of Physiology - Renal Physiology
Volume300
Issue number6
DOIs
Publication statusPublished - 2011

Cite this

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title = "A design-based method for estimating glomerular number in the developing kidney",
abstract = "Low glomerular (nephron) endowment has been associated with increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 weeks gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was in part due to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here we describe a method that uses lectin histochemistry to identify developing glomeruli, and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number (N(glom)). We have characterized N(glom) throughout development in kidneys from 76 rats and model this development with a five parameter logistic equation to predict N(glom) from embryonic day 17.25 to adulthood (r2=0.98). This approach represents the first design-based method with which to estimate N(glom) in the developing kidney.",
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A design-based method for estimating glomerular number in the developing kidney. / Cullen-McEwen, Luise A; Armitage, James A; Nyengaard, Jens R; Moritz, Karen M; Bertram, John F.

In: American Journal of Physiology - Renal Physiology, Vol. 300, No. 6, 2011, p. F1448 - F1453.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A design-based method for estimating glomerular number in the developing kidney

AU - Cullen-McEwen, Luise A

AU - Armitage, James A

AU - Nyengaard, Jens R

AU - Moritz, Karen M

AU - Bertram, John F

PY - 2011

Y1 - 2011

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AB - Low glomerular (nephron) endowment has been associated with increased risk of cardiovascular and renal disease in adulthood. Nephron endowment in humans is determined by 36 weeks gestation, while in rats and mice nephrogenesis ends several days after birth. Specific genes and environmental perturbations have been shown to regulate nephron endowment. Until now, design-based method for estimating nephron number in developing kidneys was unavailable. This was in part due to the difficulty associated with unambiguously identifying developing glomeruli in histological sections. Here we describe a method that uses lectin histochemistry to identify developing glomeruli, and the physical disector/fractionator principle to provide unbiased estimates of total glomerular number (N(glom)). We have characterized N(glom) throughout development in kidneys from 76 rats and model this development with a five parameter logistic equation to predict N(glom) from embryonic day 17.25 to adulthood (r2=0.98). This approach represents the first design-based method with which to estimate N(glom) in the developing kidney.

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JO - American Journal of Physiology - Renal Physiology

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