Abstract: PO0416
Effects of Proton Pump Inhibitors (PPIs) on Renal Vascular Reactivity in Cirrhotic Rats
Session Information
- AKI: Repair and Progression
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Author
- Chuang, Chiao-Lin, Taipei Veterans General Hospital, Taipei, Taiwan
Background
Hepatorenal syndrome is, a lethal complication of cirrhosis, defined as renal hypoperfusion resulting from intense renal vasoconstriction. Vascular dysregulation such as ET-1 and nitric oxide (NO) might be the contributing factor.
Proton pump inhibitors (PPIs) are widely used for peptic ulcer. Although generally safe, recent studies reported that PPIs decreased NO production, leading to reduction of arterial relaxation. The prevalence of gastric ulcer in cirrhotic patients is higher than healthy controls. The impact of PPIs on renal vascular responsiveness in cirrhosis is worth to be studied.
Methods
Liver cirrhosis was induced in S-D rats by common bile duct ligation (CBDL). Sham-operated (SHAM) rats were surgical controls. On the 29th day after surgery, in-situ renal perfusion was performed. In acute treatment study, rats were randomized to receive Krebs solution or Esomeprazole (30 mM) incubation for 1h before renal perfusion. In chronic treatment study, rats were randomly received oral distill water or Esomeprazole (3.6 mg/kg/d) for 28 days.
Results
The were no significant changes in renal vascular reactivity to ET-1 after acute (Fig. A) and chronic (Fig. B) PPIs treatment in CBDL rats . Chronic PPIs treatment had no significant effects on systemic hemodynamics and renal function but decreased hemoglobin in both SHAM and CBDL rats (Table).
Conclusion
In conclusion, PPIs showed no renal vascular effects. The mechanisms of lower hemoglobin following PPIs treatment need further analysis.
Table. Hemodynamic and biochemistry data
| SHAM-DW | SHAM-PPIs | CBDL-DW | CBDL-PPIs | |
| Mean arterial pressure (mmHg) | 146±4 | 155±3 | 117±4§ | 123±6 |
| Portal pressure (mmHg) | 8.7±0.3 | 8.0±0.3 | 15.4±0.5§ | 15.2±0.9 |
| Superior mesentery artery flow (ml/min/100g) | 4.0±0.2 | 4.1±0.2 | 5.5±0.4§ | 6.2±0.5 |
| Renal artery flow (ml/min/100g) | 2.7±0.2 | 2.6±0.2 | 3.3±0.3 | 3.6±0.2 |
| ALT (IU/L) | 49±4 | 58±4 | 139±12§ | 146±10 |
| Creatinine (mg/dL) | 0.47±0.02 | 0.45±0.03 | 0.53±0.03 | 0.52±0.02 |
| Hemoglobin (g/dL) | 16.6±0.3 | 15.8±0.2¶ | 14.6±0.3§ | 13.5±0.3¶ |
Expressed as mean ± SEM §, P < 0.01 vs DW-treated SHAM group ¶, P < 0.01 vs corresponding DW-treated group
Fig. Concentration-response curves in perfuse kidneys of CBDL rats following (A) acute and (B) chronic PPIs treatment.