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Updated: Oct 31, 2025

5/6th Nephrectomy in Combination with High Salt Diet and Nitric Oxide Synthase Inhibition to Induce Chronic Kidney Disease in the Lewis Rat
Published on: July 3, 2013
Hypertension and the Kidney: Reduced Kidney Mass Is Bad for Both Normotensive and Hypertensive Rats
Kyle Ware1, Vedat Yildiz2, Min Xiao1
1Department of Pathology, The Ohio State University, Columbus, Ohio, USA.
Background:
Hypertension is a leading cause of chronic kidney disease worldwide. Early studies demonstrated the short-term effects of hypertension on kidney function and morphology in ablative nephropathy. The aim of this study was to investigate the long-term consequences of hypertension in 5/6 nephrectomy (5/6NE) model.
Methods:
Reduction of the kidney mass by 5/6NE was created in spontaneous hypertensive rats (SHR) and genetically similar normotensive Wistar Kyoto (WKY) rats. Blood pressure, serum creatinine (SCr), hematuria, and proteinuria were monitored weekly for 23 weeks. Kidney morphology was assessed at the end of the study. Sham-operated rats from both strains were used as controls.
Results:
Rats with 5/6NE had increased SCr, blood pressure, hematuria, and proteinuria in both SHR and WKY. Even though the SCr levels and blood pressure were greater in 5/6NE SHR as compared with 5/6NE WKY rats, absolute changes from sham-operated rats were not statistically significant between these 2 groups. 5/6NE SHR had earlier onset and higher proteinuria than 5/6NE WKY rats. Hematuria was similar in 5/6NE SHR and 5/6NE WKY rats. However, 5/6NE SHR had enlarged glomeruli, increased interstitial fibrosis, and prominent intimal thickening in the small arteries/arterioles as compared with 5/6NE WKY rats.
Conclusions:
The long-term severity of kidney injury correlated with higher blood pressure. Reduction of the kidney mass increases SCr, hematuria, proteinuria, and blood pressure in both normotensive and hypertensive rats. Histological assessment provides better information about underlying chronic kidney injury than actual changes in SCr and urinalysis.
Insights
Hypertension exacerbates kidney injury after 5/6 nephrectomy, leading to worse outcomes in hypertensive rats. Histology reveals more severe damage than blood markers alone.
Area of Science:
- Nephrology
- Cardiovascular Research
- Experimental Pathology
Background:
- Hypertension is a primary driver of chronic kidney disease globally.
- Previous research focused on short-term hypertension effects on kidney function post-nephrectomy.
- This study examines the long-term impact of hypertension on kidney injury in a 5/6 nephrectomy model.
Purpose of the Study:
- To investigate the long-term consequences of hypertension in rats undergoing 5/6 nephrectomy.
- To compare kidney injury progression in hypertensive versus normotensive rats post-nephrectomy.
Main Methods:
- Created 5/6 nephrectomy in Spontaneous Hypertensive Rats (SHR) and Wistar Kyoto (WKY) rats.
- Monitored blood pressure, serum creatinine, hematuria, and proteinuria weekly for 23 weeks.
- Assessed kidney morphology at study completion; used sham-operated rats as controls.
Main Results:
- 5/6 nephrectomy increased serum creatinine, blood pressure, hematuria, and proteinuria in both SHR and WKY rats.
- 5/6 nephrectomy SHR showed earlier onset and higher proteinuria than WKY rats.
- Histological analysis revealed enlarged glomeruli, interstitial fibrosis, and intimal thickening in 5/6 nephrectomy SHR compared to WKY rats.
Conclusions:
- Long-term kidney injury severity correlated with elevated blood pressure.
- Kidney mass reduction worsens kidney function and elevates blood pressure in both normotensive and hypertensive rats.
- Histological assessment offers superior insight into chronic kidney injury compared to serum creatinine and urinalysis alone.
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