4.7 Article

Brief Early Life Angiotensin-Converting Enzyme Inhibition Offers Renoprotection in Sheep with a Solitary Functioning Kidney at 8 Months of Age

期刊

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
卷 33, 期 7, 页码 1341-1356

出版社

AMER SOC NEPHROLOGY
DOI: 10.1681/ASN.2021111534

关键词

solitary functioning kidney; angiotensin converting enzyme inhibition; glomerular hyperfiltration; renal functional reserve; nitric oxide bioavailability; kidney disease

资金

  1. ZonMw (The Netherlands Organization for Health Research and Development) [ZonMw 016.156.454]
  2. National Health and Medical Research Council of Australia [APP1041844, APP1078164]
  3. Australian Government PhD Research Training Program stipend

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Brief and early ACEi treatment in SFK is associated with reduced glomerular hyperfiltration-mediated kidney disease up to 8 months of age in a sheep model.
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.& nbsp;Methods SFK was induced in male sheep fetuses at 100 days gestation (term5150 days). Between 4 and8 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]).& nbsp;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.& nbsp;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.

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