Fluid Chloride and AKI in Cardiopulmonary Bypass
| Status: | Completed |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease |
| Therapuetic Areas: | Nephrology / Urology |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 5/16/2018 |
| Start Date: | January 2016 |
| End Date: | February 2018 |
The Impact of Low Chloride Containing Fluids on Acute Kidney Injury After Cardiopulmonary Bypass as Assayed by Urinary [TIMP2*IGFBP7]
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.
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.
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.
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.
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
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