Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney

Abstract Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic st...

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Autores principales:	Abhijit S. Naik, Su Q. Wang, Mahboob Chowdhury, Jawad Aqeel, Christopher L. O’Connor, Jocelyn E. Wiggins, Markus Bitzer, Roger C. Wiggins
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/64cee3c1b04e483891ea2275a2fe847c
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spelling	oai:doaj.org-article:64cee3c1b04e483891ea2275a2fe847c2021-12-02T19:16:54ZCritical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney10.1038/s41598-021-99124-z2045-2322https://doaj.org/article/64cee3c1b04e483891ea2275a2fe847c2021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99124-zhttps://doaj.org/toc/2045-2322Abstract Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic stress resulting in proteinuria and glomerulosclerosis, implying that GV increase could serve as a therapeutic target to prevent progression. In this report we examine how Angiotensin Converting Enzyme inhibition (ACEi), started before uninephrectomy can reduce compensatory GV increase in wild-type Fischer344 rats. An unbiased computer-assisted method was used for morphometric analysis. Urine Insulin-like growth factor-1 (IGF-1), the major diver of body and kidney growth, was used as a readout. In long-term (40-week) studies of uni-nephrectomized versus sham-nephrectomized rats a 2.2-fold increase in GV was associated with reduced podocyte density, increased proteinuria and glomerulosclerosis. Compensatory GV increase was largely prevented by ACEi started a week before but not after uni-nephrectomy with no measurable impact on long-term eGFR. Similarly, in short-term (14-day) studies, ACEi started a week before uni-nephrectomy reduced both GV increase and urine IGF-1 excretion. Thus, timing of ACEi in relation to uni-nephrectomy had significant impact on post-nephrectomy “compensatory” glomerular growth and outcomes that could potentially be used to improve kidney transplantation and live kidney donation outcomes.Abhijit S. NaikSu Q. WangMahboob ChowdhuryJawad AqeelChristopher L. O’ConnorJocelyn E. WigginsMarkus BitzerRoger C. WigginsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Abhijit S. Naik Su Q. Wang Mahboob Chowdhury Jawad Aqeel Christopher L. O’Connor Jocelyn E. Wiggins Markus Bitzer Roger C. Wiggins Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
description	Abstract Increasing evidence suggests that single in kidney states (e.g., kidney transplantation and living donation) progressive glomerulosclerosis limits kidney lifespan. Modeling shows that post-nephrectomy compensatory glomerular volume (GV) increase drives podocyte depletion and hypertrophic stress resulting in proteinuria and glomerulosclerosis, implying that GV increase could serve as a therapeutic target to prevent progression. In this report we examine how Angiotensin Converting Enzyme inhibition (ACEi), started before uninephrectomy can reduce compensatory GV increase in wild-type Fischer344 rats. An unbiased computer-assisted method was used for morphometric analysis. Urine Insulin-like growth factor-1 (IGF-1), the major diver of body and kidney growth, was used as a readout. In long-term (40-week) studies of uni-nephrectomized versus sham-nephrectomized rats a 2.2-fold increase in GV was associated with reduced podocyte density, increased proteinuria and glomerulosclerosis. Compensatory GV increase was largely prevented by ACEi started a week before but not after uni-nephrectomy with no measurable impact on long-term eGFR. Similarly, in short-term (14-day) studies, ACEi started a week before uni-nephrectomy reduced both GV increase and urine IGF-1 excretion. Thus, timing of ACEi in relation to uni-nephrectomy had significant impact on post-nephrectomy “compensatory” glomerular growth and outcomes that could potentially be used to improve kidney transplantation and live kidney donation outcomes.
format	article
author	Abhijit S. Naik Su Q. Wang Mahboob Chowdhury Jawad Aqeel Christopher L. O’Connor Jocelyn E. Wiggins Markus Bitzer Roger C. Wiggins
author_facet	Abhijit S. Naik Su Q. Wang Mahboob Chowdhury Jawad Aqeel Christopher L. O’Connor Jocelyn E. Wiggins Markus Bitzer Roger C. Wiggins
author_sort	Abhijit S. Naik
title	Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
title_short	Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
title_full	Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
title_fullStr	Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
title_full_unstemmed	Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
title_sort	critical timing of acei initiation prevents compensatory glomerular hypertrophy in the remaining single kidney
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/64cee3c1b04e483891ea2275a2fe847c
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Critical timing of ACEi initiation prevents compensatory glomerular hypertrophy in the remaining single kidney

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