Prevention of Post-Cardiac Surgery Acute Kidney Injury by Proton Pump Inhibitor
Study Details
Study Description
Brief Summary
The purpose of this study is to determine whether perioperative intravenous administration of pantoprazole will improve kidney function parameters following cardiac surgery with cardiopulmonary bypass compared to famotidine and to determine whether perioperative intravenous administration of pantoprazole will decrease the incidence of postoperative Acte Kidney Injury (AKI) and major adverse kidney events (MAKE)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Detailed Description
Each year more than 500,000 cardiac surgeries are performed in the USA alone. AKI is a common complication following cardiac surgery and is associated with poor patient outcomes and increased healthcare costs. Therefore, there is an urgent need to identify medical interventions and treatments that prevent AKI or mitigate its severity when it occurs after cardiac surgery.
One of the main causes of AKI following cardiac surgery involves renal hypoperfusion/ischemia and reperfusion injury. Hypoxia-inducible factors (HIFs) are key transcription factors responsible for tissue adaptation to low oxygen, which orchestrate the expression of a wide variety of genes including a set of microRNAs. MicroRNAs are endogenous single-stranded noncoding miRNAs of nucleotides that participate in physiological and pathological functions via regulating post-transcription of target genes. During ischemic injury, hypoxia upregulates endothelial MicroRNAs that has the potential in renal protection through vascular integrity and regeneration. Additionally, microRNAs exert protective effects via decreasing apoptosis and promoting tubular cell proliferation during ischemic AKI.
Moreover, decreased serum levels of MicroRNAs are highly correlated with AKI severity in the intensive care unit (ICU) patients. Our preliminary study identified ATP4A as the downstream target gene of MicroRNAs in the kidney. ATP4A (catalytic α subunit of H+/K+ ATPase) is located in intercalated cells in the distal tubules and cortical collecting ducts, which regulates urine acidification through secretion of hydrogen and reabsorption of potassium from urine. Proton pump inhibitors (PPIs) block the ATP hydrolysis of the H+/K+ ATPase via binding its active site of ATP4A and further enhance this endogenous kidney protection pathway. Despite robust animal model data, randomized controlled trial aiming to test the effectiveness of PPI in post-cardiac surgery AKI prevention is lacking. If proven to be effective, our studies could be easily implemented in clinical practice and serve as an effective treatment for perioperative AKI.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment group Pantoprazole (40 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. |
Drug: Pantoprazole
Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days.
|
| Active Comparator: Control Group Famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days. There will be no other modifications in patient care. |
Drug: Famotidine
Subjects will receive famotidine (20 mg iv q12H) for 2 days perioperatively (first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days.
|
Outcome Measures
Primary Outcome Measures
- The area under the curve (AUC) of urinary kidney injury biomarkers KIM-1 above baseline within 24 hours postoperatively [Baseline, post operative day 7 (POD 7)(or hospital discharge if earlier)]
Secondary Outcome Measures
- Number of subjects with incidence of any-stage postoperative AKI [Post Operative Day 7 (or hospital discharge if earlier).]
AKI will be defined using the 2012 Kidney Disease Improving Global Outcomes (KDIGO) criteria: serum creatinine (SCr) increase greater than 50% from baseline or ≥ 0.3 mg/dL increase within 48 hours after surgery.
- Number of subjects with incidence of MAKE [30 days after surgery]
MAKE is defined as the composite of death, dialysis, renal hospitalization or sustained kidney dysfunction (GFR decline of 25% or more from preoperative baseline)
- The area under the curve (AUC) of Urinary Kidney Injury Biomarkers (NGAL, TIMP-2, and IGFBP-7) [24 hours postoperatively]
Eligibility Criteria
Criteria
Inclusion Criteria:
- Scheduled for elective cardiac surgery with cardio pulmonary bypass (CPB) with a high risk of developing AKI (Cleveland risk score higher than 6, please see the appended table at end of the revised protocol)
Exclusion Criteria:
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Preoperative eGFR<30 ml/min per 1.73 m2
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Dialysis dependence
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Emergency surgery
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Interstitial nephritis
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Pregnancy
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Nursing Patients
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Proton pump inhibitors (PPIs) hypersensitivity
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Liver disease
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Vitamin B12 deficiency
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | The University of Texas Health Science Center at Houston | Houston | Texas | United States | 77030 |
Sponsors and Collaborators
- The University of Texas Health Science Center, Houston
- Society of Cardiovascular Anesthesiologists
Investigators
- Principal Investigator: Yafen Liang, MD, The University of Texas Health Science Center, Houston
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- HSC-MS-22-0502