Combining new tools to assess renal function and morphology

A holistic approach to study the effects of aging and a congenital nephron deficit

Stefania Geraci, Jorge Chacon-Caldera, Luise Cullen-McEwen, Lothar R Schad, Carsten Sticht, Victor G. Puelles, John F. Bertram, Norbert Gretz

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life (t1/2) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes.

Original languageEnglish
Pages (from-to)F576-F584
Number of pages9
JournalAmerican Journal of Physiology - Renal Physiology
Volume313
Issue number3
DOIs
Publication statusPublished - 1 Sep 2017

Keywords

  • Glomerular number
  • Glomerular volume
  • MRI
  • Renal function

Cite this

@article{77eca849fd9046048a96dd08b4bc1d47,
title = "Combining new tools to assess renal function and morphology: A holistic approach to study the effects of aging and a congenital nephron deficit",
abstract = "Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life (t1/2) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes.",
keywords = "Glomerular number, Glomerular volume, MRI, Renal function",
author = "Stefania Geraci and Jorge Chacon-Caldera and Luise Cullen-McEwen and Schad, {Lothar R} and Carsten Sticht and Puelles, {Victor G.} and Bertram, {John F.} and Norbert Gretz",
year = "2017",
month = "9",
day = "1",
doi = "10.1152/ajprenal.00329.2015",
language = "English",
volume = "313",
pages = "F576--F584",
journal = "American Journal of Physiology - Renal Physiology",
issn = "1522-1466",
publisher = "American Physiological Society",
number = "3",

}

Combining new tools to assess renal function and morphology : A holistic approach to study the effects of aging and a congenital nephron deficit. / Geraci, Stefania; Chacon-Caldera, Jorge; Cullen-McEwen, Luise; Schad, Lothar R; Sticht, Carsten; Puelles, Victor G.; Bertram, John F.; Gretz, Norbert.

In: American Journal of Physiology - Renal Physiology, Vol. 313, No. 3, 01.09.2017, p. F576-F584.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Combining new tools to assess renal function and morphology

T2 - A holistic approach to study the effects of aging and a congenital nephron deficit

AU - Geraci, Stefania

AU - Chacon-Caldera, Jorge

AU - Cullen-McEwen, Luise

AU - Schad, Lothar R

AU - Sticht, Carsten

AU - Puelles, Victor G.

AU - Bertram, John F.

AU - Gretz, Norbert

PY - 2017/9/1

Y1 - 2017/9/1

N2 - Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life (t1/2) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes.

AB - Recently, new methods for assessing renal function in conscious mice (transcutaneous assessment) and for counting and sizing all glomeruli in whole kidneys (MRI) have been described. In the present study, these methods were used to assess renal structure and function in aging mice, and in mice born with a congenital low-nephron endowment. Age-related nephron loss was analyzed in adult C57BL/6 mice (10-50 wk of age), and congenital nephron deficit was assessed in glial cell line-derived neurotrophic factor heterozygous (GDNF HET)-null mutant mice. Renal function was measured through the transcutaneous quantitation of fluorescein isothiocyanate-sinistrin half-life (t1/2) in conscious mice. MRI was used to image, count, and size cationic-ferritin labeled glomeruli in whole kidneys ex vivo. Design-based stereology was used to validate the MRI measurements of glomerular number and mean volume. In adult C57BL/6 mice, older age was associated with fewer and larger glomeruli, and a rightward shift in the glomerular size distribution. These changes coincided with a decrease in renal function. GNDF HET mice had a congenital nephron deficit that was associated with glomerular hypertrophy and exacerbated by aging. These findings suggest that glomerular hypertrophy and hyperfiltration are compensatory processes that can occur in conjunction with both age-related nephron loss and congenital nephron deficiency. The combination of measurement of renal function in conscious animals and quantitation of glomerular number, volume, and volume distribution provides a powerful new tool for investigating aspects of renal aging and functional changes.

KW - Glomerular number

KW - Glomerular volume

KW - MRI

KW - Renal function

UR - http://www.scopus.com/inward/record.url?scp=85028945421&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00329.2015

DO - 10.1152/ajprenal.00329.2015

M3 - Article

VL - 313

SP - F576-F584

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 1522-1466

IS - 3

ER -