Acute Kidney Injury
Conditions
Keywords
cardiac surgery
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).
Detailed description
Each year more than 500,000 cardiac surgeries are performed in the United States of America (USA) alone. Acute kidney injury (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 micro-ribonucleic acid (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. Adenosine triphosphate (ATP)4A (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.
Interventions
DRUGPantoprazole
Subjects will receive pantoprazole (40 mg iv q12H) for 2 days perioperatively \[first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on post operative day 1 (POD 1) for a total of 4 doses over 2 days\].
DRUGFamotidine
Subjects will receive famotidine (20 mg iv q12H) for 2 days perioperatively \[first dose after anesthesia induction and before surgical incision, second dose at chest closure, then followed by 2 doses daily (Q12hr dosing) on POD 1 for a total of 4 doses over 2 days\].
Sponsors
The University of Texas Health Science Center, Houston
Society of Cardiovascular Anesthesiologists
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Outcomes Assessor)
Masking description
The outcome assessor who tests the urinary kidney injury biomarkers is blinded.
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Scheduled for elective cardiac surgery with cardio pulmonary bypass (CPB) with a moderate to high risk of developing AKI (Cleveland risk score equal or higher than 3)
Exclusion criteria
* Preoperative eGFR\<30 ml/min per 1.73 m2 * Dialysis dependence * Emergency surgery * Pregnancy * Nursing Patients * Interstitial nephritis * Proton pump inhibitors (PPIs) hypersensitivity * Liver disease * Vitamin B12 deficiency
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Kidney Injury Molecule-1 (KIM-1) Above Baseline Within 24 Hours Postoperatively | from baseline (time 0) to 24 hours postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng\*h/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Neutrophil Gelatinase-associated Lipocalin (NGAL) Above Baseline Within 24 Hours Postoperatively | from baseline (time 0) to 24 hours postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng\*h/mL). |
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Tissue Inhibitor of Metalloproteinases 2 (TIMP-2) Above Baseline Within 24 Hours Postoperatively | from baseline (time 0) to 24 hours postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng\*h/mL). |
| Area Under the Curve (AUC) of Urinary Kidney Injury Biomarker Insulin-like Growth Factor-binding Protein 7 (IGFBP-7) Above Baseline Within 24 Hours Postoperatively | from baseline (time 0) to 24 hours postoperatively | The area under the curve (AUC) is a summary measure of the concentration of the biomarker over time and is expressed as (ng\*h/mL). |
| Number of Participants With Any-stage Postoperative Acute Kidney Injury (AKI) | from baseline to postoperative day 7 (or hospital discharge if earlier) | Acute kidney injury (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 Participants With Major Adverse Kidney Events (MAKE) | from baseline to 30 days after surgery | MAKE is defined as the composite of death, dialysis, renal hospitalization or sustained kidney dysfunction defined as glomerular filtration rate (GFR) decline of 25% or more from preoperative baseline. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORYafen Liang, MD
The University of Texas Health Science Center, Houston
Participant flow
Pre-assignment details
All 100 participants completed the study; however, upon further verification before analysis, 2 participants who completed (1 per arm) were deemed to not meet the inclusion criteria; therefore, these 2 participants (1 per arm) were excluded from the analysis.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 65 years |
| Race and Ethnicity Not Collected | 0 Participants |
| Region of Enrollment United States | 49 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 50 | 1 / 50 |
| other Total, other adverse events | 3 / 50 | 5 / 50 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 |
Outcome results
None listed