PMID- 35351818
OWN - NLM
STAT- MEDLINE
DCOM- 20220704
LR  - 20230703
IS  - 1533-3450 (Electronic)
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 33
IP  - 7
DP  - 2022 Jul
TI  - Brief Early Life Angiotensin-Converting Enzyme Inhibition Offers Renoprotection 
      in Sheep with a Solitary Functioning Kidney at 8 Months of Age.
PG  - 1341-1356
LID - 10.1681/ASN.2021111534 [doi]
AB  - BACKGROUND: Children born with a solitary functioning kidney (SFK) are 
      predisposed to develop hypertension and kidney injury. Glomerular hyperfiltration 
      and hypertrophy contribute to the pathophysiology of kidney injury. 
      Angiotensin-converting enzyme inhibition (ACEi) can mitigate hyperfiltration and 
      may be therapeutically beneficial in reducing progression of kidney injury in 
      those with an SFK. METHODS: SFK was induced in male sheep fetuses at 100 days 
      gestation (term=150 days). Between 4 and 8 weeks of age, SFK lambs received 
      enalapril (SFK+ACEi; 0.5mg/kg per day, once daily, orally) or vehicle (SFK). At 8 
      months, we examined BP, basal kidney function, renal functional reserve (RFR; GFR 
      response to combined amino acid and dopamine infusion), GFR response to nitric 
      oxide synthase (NOS) inhibition, and basal nitric oxide (NO) bioavailability 
      (basal urinary total nitrate and nitrite [NOx]). RESULTS: SFK+ACEi prevented 
      albuminuria and resulted in lower basal GFR (16%), higher renal blood flow 
      (approximately 22%), and lower filtration fraction (approximately 35%), but 
      similar BP, compared with vehicle-treated SFK sheep. Together with greater 
      recruitment of RFR (approximately 14%) in SFK+ACEi than SFK animals, this 
      indicates a reduction in glomerular hyperfiltration-mediated kidney dysfunction. 
      During NOS inhibition, the decrease in GFR (approximately 14%) was greater among 
      SFK+ACEi than among SFK animals. Increased (approximately 85%) basal urinary 
      total NOx in SFK+ACEi compared with SFK animals indicates elevated NO 
      bioavailability likely contributed to improvements in kidney function and 
      prevention of albuminuria. CONCLUSIONS: Brief and early ACEi in SFK is associated 
      with reduced glomerular hyperfiltration-mediated kidney disease up to 8 months of 
      age in a sheep model.
CI  - Copyright (c) 2022 by the American Society of Nephrology.
FAU - McArdle, Zoe
AU  - McArdle Z
AD  - Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of 
      Physiology, Monash University, Melbourne, Victoria, Australia.
FAU - Singh, Reetu R
AU  - Singh RR
AD  - Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of 
      Physiology, Monash University, Melbourne, Victoria, Australia.
FAU - Bielefeldt-Ohmann, Helle
AU  - Bielefeldt-Ohmann H
AD  - School of Veterinary Science, The University of Queensland, Gatton, Queensland, 
      Australia.
AD  - School of Chemistry and Molecular Biosciences, The University of Queensland, St 
      Lucia, Queensland, Australia.
FAU - Moritz, Karen M
AU  - Moritz KM
AD  - Child Health Research Centre and School of Biomedical Sciences, University of 
      Queensland, Brisbane, Queensland, Australia.
FAU - Schreuder, Michiel F
AU  - Schreuder MF
AD  - Department of Pediatric Nephrology, Amalia Children's Hospital, Radboud 
      University Medical Center, Nijmegen, The Netherlands.
FAU - Denton, Kate M
AU  - Denton KM
AUID- ORCID: 0000-0002-5929-4387
AD  - Cardiovascular Program, Monash Biomedicine Discovery Institute and Department of 
      Physiology, Monash University, Melbourne, Victoria, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220329
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Angiotensins)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Albuminuria
MH  - Angiotensins
MH  - Animals
MH  - Glomerular Filtration Rate
MH  - Kidney
MH  - *Kidney Diseases/etiology/prevention & control
MH  - Male
MH  - Nitric Oxide
MH  - Sheep
MH  - *Solitary Kidney
PMC - PMC9257814
OTO - NOTNLM
OT  - angiotensin converting enzyme inhibition
OT  - glomerular hyperfiltration
OT  - kidney disease
OT  - nitric oxide bioavailability
OT  - renal functional reserve
OT  - solitary functioning kidney
EDAT- 2022/03/31 06:00
MHDA- 2022/07/06 06:00
PMCR- 2023/07/01
CRDT- 2022/03/30 05:40
PHST- 2021/11/30 00:00 [received]
PHST- 2022/03/18 00:00 [accepted]
PHST- 2022/03/31 06:00 [pubmed]
PHST- 2022/07/06 06:00 [medline]
PHST- 2022/03/30 05:40 [entrez]
PHST- 2023/07/01 00:00 [pmc-release]
AID - 00001751-202207000-00019 [pii]
AID - 2021111534 [pii]
AID - 10.1681/ASN.2021111534 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2022 Jul;33(7):1341-1356. doi: 10.1681/ASN.2021111534. Epub 
      2022 Mar 29.