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Updated: May 25, 2025
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion
Published on: February 2, 2021
Renal hypertrophy and hyperfiltration is enhanced in early acquired compared with a congenital solitary function
Zoe McArdle1, Reetu R Singh1, Sarah L Walton1
1Cardiovascular Disease Program, Monash Biomedicine Discovery Institute and Department of Physiology, Monash University, Melbourne, Australia.
Insights
Congenital solitary functioning kidney (C-SFK) sheep developed hypertension and reduced glomerular filtration rate (GFR). Early acquired solitary functioning kidney (EA-SFK) sheep showed attenuated nitric oxide response, suggesting potential long-term kidney disease risks.
Area of Science:
- Nephrology
- Developmental Biology
- Physiology
Background:
- Solitary functioning kidney (SFK) increases risks for hypertension and kidney disease.
- Early acquired SFK (EA-SFK) may pose a higher risk than congenital SFK (C-SFK).
- Mechanisms underlying EA-SFK risks require further investigation.
Purpose of the Study:
- To compare the long-term physiological consequences of C-SFK versus EA-SFK in a sheep model.
- To investigate the impact of SFK on blood pressure, kidney function, and renal hemodynamics.
- To explore potential differences in disease progression between C-SFK and EA-SFK.
Main Methods:
- C-SFK induced via fetal unilateral nephrectomy (UNX) at 100 days gestation in sheep.
- EA-SFK induced via neonatal UNX at approximately one month of age in lambs.
- Physiological parameters including blood pressure, glomerular filtration rate (GFR), albuminuria, and renal blood flow response to nitric oxide blockade were assessed at eight months of age.
Main Results:
- Both C-SFK and EA-SFK groups exhibited compensatory kidney hypertrophy.
- C-SFK sheep showed significantly higher blood pressure (~12 mmHg) and albuminuria (~67%) compared to sham controls.
- EA-SFK sheep had reduced GFR (~9%) and an attenuated renal blood flow response to nitric oxide blockade, similar to C-SFK sheep.
Conclusions:
- C-SFK is associated with hypertension and increased albuminuria in young sheep.
- EA-SFK sheep exhibit impaired vasodilator function, suggesting a potential for accelerated kidney disease progression.
- Long-term studies are necessary to confirm if hyperfiltration and disturbed vasodilator balance in EA-SFK lead to age-related renal decline.
Abstract:
A congenital solitary functioning kidney (C-SFK) or an early acquired SFK (EA-SFK), due to childhood unilateral nephrectomy (UNX), increases the risk of hypertension and kidney disease early in life. Evidence suggests that children with an EA-SFK may have a higher risk of future kidney disease compared with those with a C-SFK, but the precise underlying mechanisms need further investigation. C-SFK was induced by fetal UNX at 100 days gestation (term=150 days) in male sheep fetuses, and a sham procedure was performed. At approximately one month of age, EA-SFK was induced by UNX in male lambs. At eight months of age, total kidney weight was similar in all groups due to marked hypertrophy in the C-SFK and EA-SFK groups. Blood pressure was similar in EA-SFK and sham groups but ~12 mmHg higher in the C-SFK group compared with sham. Compared with the sham group, glomerular filtration rate (GFR) was ~9% less in the EA-SFK group and ~26% less in the C-SFK. GFR was ~23% higher in EA-SFK compared with the C-SFK group. Albuminuria was ~67% higher in C-SFK sheep but similar in the EA-SFK group compared with sham sheep. However, like the C-SFK group, the renal blood flow response to nitric oxide blockade was attenuated in the EA-SFK group compared with sham. In conclusion, long-term studies are needed to determine whether the higher hyperfiltration and disturbed vasodilator balance observed in EA-SFK sheep will cause an accelerated decline in renal function with aging.
