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Kidney Week

Abstract: TH-PO102

Cytokines and Urinary Biomarkers Predict Adverse Renal Impacts of Propranolol in Biliary Cirrhotic Rats

Session Information

  • AKI: Mechanisms - I
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Chuang, Chiao-Lin, Taipei Veterans General Hospital, Taipei, Taiwan
  • Huang, Hui-Chun, Taipei Veterans General Hospital, Taipei, Taiwan
Background

Non-selective beta-blockers (NSBBs) are the mainstay of treatment for variceal bleeding in cirrhotic patients. However, the advantage of NSBBs must be weighed against the potential risk of acute kidney injury (AKI).

Methods

Secondary biliary cirrhosis was induced by common bile duct ligation (CBDL). We used propranolol-treated CBDL rats to delineate the thorough hemodynamics, urinary biomarkers, and inflammatory cytokines.

Results

Propranolol treatment led to significant decreases in mean arterial pressure (MAP), portal pressure (PP), and renal blood flow (RBF) in CBDL rats (p < 0.05). Both MAP and PP significantly correlated with RBF, while RBF inversely correlated with urinary liver-type fatty acid-binding protein (L-FABP) and the combination of tissue inhibitor of metalloproteinase-2 and insulin-like growth factor binding protein-7 ([TIMP-2]x[IGFBP7]) levels in propranolol-treated CBDL rats (p < 0.05). Propranolol-treated CBDL rats with severe hypotension (MAP < 65 mmHg) showed higher IL-1β, but lower IL-6 levels than those with MAP ≥ 65 mmHg (p < 0.05).

Conclusion

NSBBs treatment in cirrhosis may need to be individualized accompanied by careful monitoring of blood pressure and inflammatory condition. Urinary L-FABP and [TIMP-2]x[IGFBP7] serve as promising candidates for detecting renal hypoperfusion following NSBBs. The changes in serum IL-1β and IL-6 over time might allow physicians to predict the possibility of NSBBs-induced AKI in cirrhosis.

Hemodynamic and biochemistry data of CBDL rats
 Control (n = 10)Propranolol + MAP ≥ 65 mmHg (n = 13)Propranolol + MAP < 65 mmHg (n=6)
Portal pressure (mmHg)13.1±0.511.5±0.96.3±0.5a,b
Renal blood flow (ml/min 100 g)2.4±0.21.9±0.20.8±0.1a,b
Serum creatinine (mg/dl)0.55±0.050.49±0.030.52±0.05
Urine L-FABP (pg/ml)0.7±0.10.7±0.12.7±0.7a,b
Urine [TIMP-2]x[IGFBP7](ng/ml)20.05±0.010.09±0.020.47±0.12a,b

Data expressed as mean ± SEM. aP<0.05 vs. control, bP < 0.05 vs. MAP ≥ 65 mmHg following propranolol

Correlation between RBF with PP(A), MAP(B), and urinary biomarkers(C&D) in propranolol-treated CBDL rats.

Serum inflammatory markers in propranolol-treated CBDL rats.