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| Name | Class |
|---|---|
| Thrasher Research Fund | OTHER |
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Acute kidney injury (AKI) occurs in 40% of children following heart surgery. Serum creatinine (Scr) is a late biomarker of AKI, rising 24-48 hours after surgery. Thus, for medicines excreted in the urine, AKI could potentially lead to toxic levels in the blood. Urinary biomarkers have the ability to detect AKI earlier. Whether early detection of AKI through urinary biomarkers can predict altered drug levels is unknown.
Milrinone is used to improve heart function after surgery, but accumulates in AKI resulting in low blood pressure. Dose adjustments are not currently possible because of the late rise in SCr, and are based on clinical parameters that may lead to clinically relevant over or under-dosing. Thus, this study will address an important knowledge gap being the first to use elevations of AKI biomarker concentrations to anticipate increased milrinone levels.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Acute kidney injury | AKI defined by an elevation in urinary AKI biomarkers | ||
| No acute kidney injury | No AKI defined by normal urinary AKI biomarkers |
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| Measure | Description | Time Frame |
|---|---|---|
| Biomarker elevation and milrinone clearance | The primary outcome variables for Aim 1 are an elevation in urinary AKI biomarkers to predict a 25% reduction in milrinone clearance. | By 24 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Creatinine elevation and milrinone clearance | The secondary outcome variables for Aim 2 include a 50-75% increase in SCr to predict a 25% reduction in milrinone clearance | by 72 hours |
| Measure | Description | Time Frame |
|---|---|---|
| Hemodynamic parameters and AKI | Parameters of hemodynamic function defined by a decrease in central venous pressure of > 5cmH20, and/or a decrease in superior vena cava saturation by >10% at 12-36 hours after cardiopulmonary bypass. These surrogate markers of clinical outcome will be correlated with the following: operative mortality, longer time to achieve negative fluid balance, higher vasoactive inotrope score and longer intensive care and hospital length of stay. |
Inclusion Criteria:
Exclusion Criteria:
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All patients less than or equal to 1 year who present for cardiac surgery at Cincinnati Children's Hospital Medical Center who meet the eligibility criteria.
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| Name | Affiliation | Role |
|---|---|---|
| Katja M Gist, DO, MSCS | University of Colorado, Denver | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio | 45229 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30607889 | Derived | Mizuno T, Gist KM, Gao Z, Wempe MF, Alten J, Cooper DS, Goldstein SL, Vinks AA. Developmental Pharmacokinetics and Age-Appropriate Dosing Design of Milrinone in Neonates and Infants with Acute Kidney Injury Following Cardiac Surgery. Clin Pharmacokinet. 2019 Jun;58(6):793-803. doi: 10.1007/s40262-018-0729-3. | |
| 29529007 | Derived |
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| ID | Term |
|---|---|
| D006330 | Heart Defects, Congenital |
| D058186 | Acute Kidney Injury |
| ID | Term |
|---|---|
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D006331 | Heart Diseases |
| D000013 | Congenital Abnormalities |
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| by 72 hours |
| Gist KM, Cooper DS, Wrona J, Faubel S, Altmann C, Gao Z, Marino BS, Alten J, Hock KM, Mizuno T, Vinks AA, Joy MS, Wempe MF, Bennett MR, Goldstein SL. Acute Kidney Injury Biomarkers Predict an Increase in Serum Milrinone Concentration Earlier Than Serum Creatinine-Defined Acute Kidney Injury in Infants After Cardiac Surgery. Ther Drug Monit. 2018 Apr;40(2):186-194. doi: 10.1097/FTD.0000000000000496. |
| 28382566 | Derived | Gist KM, Goldstein SL, Wrona J, Alten JA, Basu RK, Cooper DS, Soranno DE, Duplantis J, Altmann C, Gao Z, Faubel S. Kinetics of the cell cycle arrest biomarkers (TIMP-2*IGFBP-7) for prediction of acute kidney injury in infants after cardiac surgery. Pediatr Nephrol. 2017 Sep;32(9):1611-1619. doi: 10.1007/s00467-017-3655-y. Epub 2017 Apr 5. |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |