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Updated: Jul 18, 2026
08:35
Improved Renal Denervation Mitigated Hypertension Induced by Angiotensin II Infusion
Published on: May 26, 2022
TNF-alpha neutralization ameliorates obstruction-induced renal fibrosis and dysfunction
K K Meldrum1, R Misseri, P Metcalfe
1Department of Urology, Indiana University, Indianapolis, IN 46202, USA. kmeldrum@iupui.edu
Summary
Tumor necrosis factor-alpha (TNF-alpha) drives kidney fibrosis and dysfunction following upper urinary tract obstruction. Neutralizing TNF-alpha with PEG-sTNFR1 effectively reduced these detrimental effects in a rat model.
Area of Science:
- Nephrology
- Immunology
- Pathophysiology
Background:
- Upper urinary tract obstruction causes tubulointerstitial fibrosis and renal dysfunction.
- The role of Tumor Necrosis Factor-alpha (TNF-alpha) in this process is not fully understood.
Purpose of the Study:
- To investigate the contribution of TNF-alpha to obstruction-induced renal fibrosis and dysfunction.
- To evaluate the therapeutic potential of TNF-alpha neutralization.
Main Methods:
- Male Sprague-Dawley rats underwent unilateral ureteral obstruction or sham surgery.
- Rats received either vehicle or a pegylated form of soluble TNF receptor type 1 (PEG-sTNFR1).
- Kidney tissues and glomerular filtration rate were analyzed for markers of fibrosis and renal function.
Main Results:
- Renal obstruction increased TNF-alpha, TGF-beta1, collagen deposition, alpha-SMA, angiotensinogen, and interstitial volume, leading to renal dysfunction.
- PEG-sTNFR1 treatment significantly attenuated these obstruction-induced changes.
- Glomerular filtration rate was preserved in rats treated with PEG-sTNFR1.
Conclusions:
- TNF-alpha plays a critical role in mediating renal fibrosis and dysfunction following upper urinary tract obstruction.
- Neutralization of TNF-alpha represents a promising therapeutic strategy for obstructive nephropathy.
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