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Fluid Chloride and AKI in Cardiopulmonary Bypass

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02668952
Recruitment Status : Completed
First Posted : January 29, 2016
Results First Posted : March 19, 2018
Last Update Posted : May 14, 2018
Information provided by (Responsible Party):
Neal Gerstein, University of New Mexico

Brief Summary:
Acute kidney injury (AKI) is a potential complication of cardiac surgery. In animal models, excess exogenous Cl- ion in the bloodstream is associated with AKI. Normal saline IV fluid has higher levels of Cl- ion than the blood usually carries. An alternative IV fluid sold under the name Isolyte has lower Cl- ion levels. There is no literature comparing AKI outcomes in cardiac patients between patients receiving normal saline vs. Isolyte. The investigators propose to recruit and randomize 30 trial-completing cardiac surgery patients (up to 40 enrolled) into 2 study arms and compare renal outcomes.

Condition or disease Intervention/treatment Phase
Acute Kidney Injury Drug: 0.9% Normal Saline (0.9% Sodium Chloride) injection Drug: Isolyte S injection Phase 2

Detailed Description:

Acute kidney injury (AKI) is a potential complication for patients undergoing cardiac surgery. AKI in post-cardiac surgery patients is associated with adverse outcomes, such as prolonged intensive care and hospital stay, diminished quality of life, increased long-term mortality, and an increased risk of chronic kidney disease requiring dialysis. The mortality in cardiac surgery patients with AKI severe enough to require renal replacement therapy (RRT) can be as high as 60%. One of the putative agents associated with AKI in animal models receiving crystalloid fluids for resuscitative interventions is excess exogenous chloride ion (Cl-). As compared to non-Cl- containing solutions in animal models, excess Cl- appears to lead to a hyperchloremic metabolic acidosis, increased renal vascular resistance, reduced renal blood flow, and reduced glomerular filtration rate - all of which are injurious to kidney function.

Historically, one of the most common balanced salt-solutions used in adult cardiac surgery has been 0.9% normal saline (NS), a crystalloid solution with 154 mmol/L of Cl-. This is much higher than physiologic plasma levels of 103 mmol/L. Isolyte, a less commonly used crystalloid solution, is much closer to physiologic levels at 98 mmol/L Cl-. In the context of cardiac surgery, there is no literature expressly comparing the effects of balanced crystalloid solution such as Isolyte versus NS on AKI incidence. There is a single trial examining a low-Cl- containing colloid solution in cardiac surgery that found less metabolic acidosis; however, AKI or markers of AKI were not measured outcomes in that lone trial, so it is not known whether low Cl- solution will have any effect on AKI risk in humans.

AKI results from a series of extremely complex cellular and molecular pathways involving endothelial, epithelial, inflammatory, and interstitial cells. The gold standard for identification and classification of AKI is dependent on serial serum creatinine (Scr) measurements, but this measurement can be unreliable during acute changes in kidney function. Recent studies have shown that tissue inhibitor of metalloproteinase (TIMP-2) performs better than existing markers for predicting the development of moderate or severe AKI (Kidney Disease: Improving Global Outcomes [KDIGO] stage 2 or 3) within 12 hours of sample collection. To further enhance the sensitivity of utilizing TIMP-2, the investigators plan on also measuring urinary insulin-like growth factor-binding protein 7 (IGFBP7). Along with TIMP-2, IGFBP7 is also an inducer of G1 cell cycle arrest, a key mechanism implicated in AKI.

This study will utilize the urinary [TIMP-2]*[IGFBP7] multiplicative product as a composite biomarker index to investigate the impact of intraoperative infusion of NS versus Isolyte on post-cardiac surgery renal function. This biomarker should identify patients at risk of imminent (within 12 hours) AKI KDIGO criteria.

Patients presenting for cardiac surgery are already quite ill often with multiple comorbidities. Acute kidney injury in this population is associated with significant morbidity and mortality. The available literature indicates that a fairly simple intervention could plausibly reduce the incidence of AKI, but it has not yet been examined in humans. Generating an evidence basis for it will substantially improve the safety of patients who need cardiac surgery. This intervention to reduce AKI may also then be applied to the broader non-cardiac surgery population as well.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: The Impact of Low Chloride Containing Fluids on Acute Kidney Injury After Cardiopulmonary Bypass as Assayed by Urinary [TIMP2*IGFBP7]
Actual Study Start Date : January 2016
Actual Primary Completion Date : February 4, 2017
Actual Study Completion Date : February 2018

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: Normal Saline group
0.9% Normal Saline (0.9% Sodium Chloride) injection intravenously as needed. The amount administered (dosage, frequency, and duration) will be left to the clinical judgment of the attending physicians, and will follow usual patterns of use in cardiac surgery patients.
Drug: 0.9% Normal Saline (0.9% Sodium Chloride) injection
Experimental: Isolyte group
Isolyte S (B Braun, Irvine CA) injection intravenously as needed. The amount administered (dosage, frequency, and duration) will be left to the clinical judgment of the attending physicians, and will follow usual patterns of use in cardiac surgery patients. Isolyte S is a prepackaged solution containing sodium chloride 0.53%, sodium gluconate 0.5%, sodium acetate trihydrate 0.37%, potassium chloride 0.037%, and magnesium chloride hexahydrate 0.03% w/v.
Drug: Isolyte S injection

Primary Outcome Measures :
  1. Change in [TIMP2]*[IGFBP7] Biomarker [ Time Frame: Baseline and postoperatively at 24 hours ]
    The difference in the [TIMP2]*[IGFBP7] biomarker between the preoperative value and a repeated measurement at 24 hours postoperatively. Positive values represent increase; negative values represent decrease

Secondary Outcome Measures :
  1. Serum Creatinine Level at 24 Hours [ Time Frame: 1 day ]
    Serum creatinine measurement at 24 hours

  2. Serum Chloride Level at 24 Hours [ Time Frame: 1 day ]
    Serum chloride ion measurement at 24 hours postoperatively

  3. Proportion of Patients With Need for Dialysis [ Time Frame: One week ]
    Clinically-determined need for dialysis prior to discharge from hospital

  4. Postoperative Arterial pH [ Time Frame: One day ]
    Arterial pH, measured 24 hours after surgery

  5. Serum Creatinine Level at 48 Hours [ Time Frame: 2 days ]
    Serum creatinine level 48 hours postoperatively

  6. Serum Chloride at 48 Hours [ Time Frame: 2 days ]
    Serum chloride measurement at 48 hours postoperatively

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Planned on- or off-pump cardiac surgery including: bypass grafting, valvular procedures, congenital defect correction, and thoracic aortic procedures or a combination of these procedures

Exclusion Criteria:

  • Emergency surgery
  • Pregnancy
  • Previous renal transplantation
  • Documented moderate to severe acute kidney injury prior to enrollment (e.g. RIFLE-I or RIFLE-F/KDIGO stage 2 or 3)
  • Patients already receiving dialysis (acute or chronic) or in imminent need of dialysis at time of enrollment
  • Chronic kidney disease without baseline serum creatinine value obtained within 6 months of enrollment

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02668952

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United States, New Mexico
University of New Mexico Hospital
Albuquerque, New Mexico, United States, 87106
Sponsors and Collaborators
University of New Mexico
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Principal Investigator: Neal S Gerstein, MD University of New Mexico
  Study Documents (Full-Text)

Documents provided by Neal Gerstein, University of New Mexico:
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Responsible Party: Neal Gerstein, Associate Professor, University of New Mexico Identifier: NCT02668952    
Other Study ID Numbers: 15-572
First Posted: January 29, 2016    Key Record Dates
Results First Posted: March 19, 2018
Last Update Posted: May 14, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Upon publication of study results, qualified researchers may contact the PI for the deidentified dataset.
Additional relevant MeSH terms:
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Acute Kidney Injury
Renal Insufficiency
Kidney Diseases
Urologic Diseases