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Published on: May 26, 2022
Renoprotective effects of telmisartan after unilateral renal ablation in rats
Tomohiro Matsuo1, Yasuyoshi Miyata, Yuji Sagara
1Department of Nephro-Urology, Department of Investigative Pathology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Purpose:
The renoprotective function of the angiotensin II type 1 receptor blocker (ARB) is well-known in various studies, including the animal model of renal failure. However, detailed temporal changes of pathological and molecular findings after unilateral nephrectomy are not fully understood. The main purpose of this study was to clarify the renoprotective effects and pathological changes induced by the ARB in rat-remnant kidney (RK) tissues after unilateral nephrectomy, but not after a 5/6 nephrectomy.
Methods:
Telmisartan, which is structurally and functionally unique among ARB, was used in this study. Three rat groups were examined: A) no ARB administrated (RK, n=21); B) continuous subcutaneous infusion of an ARB administrated (RK-ARB, n=21); and C) a sham-operated group (Sham). Renal function was evaluated by blood urea nitrogen (BUN) levels and creatinine clearance (Ccr). Fibrosis was evaluated by hydroxyproline levels and Masson's trichrome staining. Expressions of angiotensin II type 1 receptor (AT1R) and transforming growth factor beta (TGF-β) were investigated by real-time polymerase chain reaction and Western blotting.
Results:
There was no significant difference regarding body and kidney weight or pathological features evaluated by hematoxylin and eosin staining between the RK and RK-ARB groups. The Ccr in the RK group was significantly lower than that in the Sham group (P<0.01), but no significant difference was found between the RK-ARB and Sham groups. The fibrotic area increased significantly with time after nephrectomy in the RK group. Although a similar trend was found in the RK-ARB group, the percentage of fibrous area in the RK-ARB group was significantly lower than that in the RK group at each time point (P<0.01). AT1R mRNA levels in the RK group were regulated immediately compared with those in the RK-ARB group. Although expressions of the AT1R and TGF-β were significantly higher in the RK-ARB group than in the Sham group, no significant differences were found between the RK-ARB and Sham group.
Conclusion:
The ARB had renoprotective effects after unilateral nephrectomy. The ARB effectively maintained Ccr. Our results also showed the possibility that fibrotic changes mediated by AT1R and TGF-β play an important role in renal protection. Moreover, this is the first report on changes of AT1R expression after using the ARB telmisartan in kidney tissues after unilateral nephrectomy. Finally, our results suggest that ARB may be useful to prevent renal failure in patients treated with nephrectomy.
Insights
Angiotensin II type 1 receptor blockers (ARBs) protect kidneys after unilateral nephrectomy by maintaining creatinine clearance and reducing fibrosis. This study clarifies ARB effects on remnant kidney tissues, suggesting their use in preventing renal failure post-nephrectomy.
Area of Science:
- Nephrology and Pharmacology
- Renal physiology and pathology
- Molecular mechanisms of kidney injury and protection
Background:
- The renoprotective role of angiotensin II type 1 receptor blockers (ARBs) is established, but detailed temporal pathological and molecular changes post-unilateral nephrectomy remain unclear.
- Understanding these changes is crucial for optimizing therapeutic strategies in patients with reduced renal mass.
Purpose of the Study:
- To investigate the renoprotective effects and pathological alterations induced by an ARB in rat remnant kidney (RK) tissues following unilateral nephrectomy.
- To elucidate the temporal changes in fibrosis, angiotensin II type 1 receptor (AT1R), and transforming growth factor beta (TGF-β) expression.
Main Methods:
- Telmisartan, a unique ARB, was administered to rats with unilateral nephrectomy (RK-ARB group, n=21) and compared to untreated RK rats (n=21) and sham-operated controls (n=21).
- Renal function assessed via blood urea nitrogen (BUN) and creatinine clearance (Ccr).
- Fibrosis quantified by hydroxyproline levels and Masson's trichrome staining. AT1R and TGF-β expression analyzed using real-time PCR and Western blotting.
Main Results:
- ARBs significantly maintained creatinine clearance (Ccr) in RK rats, comparable to sham controls, unlike untreated RK rats.
- Fibrotic area increased over time in RK rats; ARB treatment significantly reduced this fibrotic progression.
- AT1R mRNA levels were modulated by ARB treatment, and while AT1R and TGF-β expressions were elevated in RK-ARB versus Sham, the differences were not significant, suggesting a protective role.
Conclusions:
- ARBs demonstrate significant renoprotective effects after unilateral nephrectomy, primarily by maintaining renal function and mitigating fibrosis.
- Fibrotic changes mediated by AT1R and TGF-β are implicated in renal protection, with telmisartan showing efficacy.
- This study provides novel insights into ARB effects on AT1R expression post-unilateral nephrectomy, supporting ARB utility in preventing renal failure in nephrectomized patients.
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