Use of Biomarkers to Optimize Fluid Dosing,CRRT Initiation and Discontinuation in Pediatric ICU Patients With AKI
| Status: | Terminated |
|---|---|
| Conditions: | Renal Impairment / Chronic Kidney Disease, Hospital |
| Therapuetic Areas: | Nephrology / Urology, Other |
| Healthy: | No |
| Age Range: | 1 - 25 |
| Updated: | 9/22/2018 |
| Start Date: | August 2011 |
| End Date: | December 2015 |
Use of Neutrophil Gelatinase-Associated Lipocalin (NGAL) to Optimize Fluid Dosing, Continuous Renal Replacement Therapy (CRRT) Initiation and Discontinuation in Critically Ill Children With Acute Kidney Injury (AKI)
Acute Kidney Injury (AKI) is a common clinical problem defined by an abrupt (< 48 hour)
increase in serum creatinine (SCr) resulting from an injury or insult that causes a
functional or structural change in the kidney. Despite significant advancements in the care
of the critically ill child, mortality rates observed in critically ill children who develop
AKI have not improved. The investigators have shown even "small" increases in SCr, which is
the standard kidney function marker, are associated with increased child mortality, even when
outcome was controlled for significant patient co-morbidity. Furthermore, the investigators
have also shown that the amount of fluid accumulation observed in critically ill children
with AKI is independently associated with mortality suggesting that earlier dialysis may
improve survival. However, the investigators also do not want to dialyze patients who don't
ultimately need dialysis, as it is an invasive procedure. The data cited above highlight the
need not only to detect AKI early, but also predict it severity in order to optimize clinical
decision making with respect to fluid administration and dialysis initiation. While
substantial research has been expended to validate NGAL as an early marker of AKI, it has not
been studied in the context of clinical decision support to guide a therapeutic intervention.
The investigators hypothesize that NGAL levels can be used to determine predict which
critically ill children will develop severe and prolonged AKI with substantial volume
overload, thereby providing the clinician with a diagnostic tool to guide CRRT initiation.
increase in serum creatinine (SCr) resulting from an injury or insult that causes a
functional or structural change in the kidney. Despite significant advancements in the care
of the critically ill child, mortality rates observed in critically ill children who develop
AKI have not improved. The investigators have shown even "small" increases in SCr, which is
the standard kidney function marker, are associated with increased child mortality, even when
outcome was controlled for significant patient co-morbidity. Furthermore, the investigators
have also shown that the amount of fluid accumulation observed in critically ill children
with AKI is independently associated with mortality suggesting that earlier dialysis may
improve survival. However, the investigators also do not want to dialyze patients who don't
ultimately need dialysis, as it is an invasive procedure. The data cited above highlight the
need not only to detect AKI early, but also predict it severity in order to optimize clinical
decision making with respect to fluid administration and dialysis initiation. While
substantial research has been expended to validate NGAL as an early marker of AKI, it has not
been studied in the context of clinical decision support to guide a therapeutic intervention.
The investigators hypothesize that NGAL levels can be used to determine predict which
critically ill children will develop severe and prolonged AKI with substantial volume
overload, thereby providing the clinician with a diagnostic tool to guide CRRT initiation.
The specific aims of this proposal are:
1. Determine if NGAL (POC plasma and confirmatory urine) concentrations can predict which
critically ill children will ultimately develop significant (>10%) positive ICU fluid
accumulation Hypothesis to be tested: Elevated plasma NGAL concentrations (initial
plasma threshold > 250 ng/ml) will predict which critically ill children will develop a
positive ICU net fluid accumulation of > 10% of ICU admission weight
2. Determine if NGAL (POC plasma and confirmatory urine) concentrations can predict which
critically ill children who develop >10-20% ICU fluid overload will recover urine output
and kidney function rapidly Hypothesis to be tested: Elevated plasma NGAL concentrations
(initial urinary threshold >1 ng/mg Cr ) will predict which critically ill children who
develop >10-20% FO will not have an improvement in AKI as determined by an improvement
of at least one pRIFLE strata within 24-48 hours of developing pRIFLE-I or pRIFLE-F
3. Determine if NGAL (POC plasma and confirmatory urine) concentrations can predict kidney
function recovery in critically ill children develop >10-20% ICU fluid overload who
receive continuous renal replacement therapy Hypothesis to be tested: Decreasing NGAL
concentrations will be associated with improvement in urine output and initial
resolution of AKI in < 72 hours
This pilot study will be novel in that the investigators will evaluate NGAL levels in near
real-time, twice daily to guide clinical decision support in terms of fluid administration
effect assessment and CRRT provision in this critically ill pediatric population.
Specifically, the investigators will use the NGAL data daily to 1) drive initiation of CRRT
in children with elevated NGAL and > 10-20% fluid overload and 2) drive CRRT discontinuation
in patients with decreasing NGAL concentrations. In addition, the investigators will employ
an adaptive study design to readjust the threshold NGAL during the time course of the study
if the data suggest adjustment will enrich the data pool.
1. Determine if NGAL (POC plasma and confirmatory urine) concentrations can predict which
critically ill children will ultimately develop significant (>10%) positive ICU fluid
accumulation Hypothesis to be tested: Elevated plasma NGAL concentrations (initial
plasma threshold > 250 ng/ml) will predict which critically ill children will develop a
positive ICU net fluid accumulation of > 10% of ICU admission weight
2. Determine if NGAL (POC plasma and confirmatory urine) concentrations can predict which
critically ill children who develop >10-20% ICU fluid overload will recover urine output
and kidney function rapidly Hypothesis to be tested: Elevated plasma NGAL concentrations
(initial urinary threshold >1 ng/mg Cr ) will predict which critically ill children who
develop >10-20% FO will not have an improvement in AKI as determined by an improvement
of at least one pRIFLE strata within 24-48 hours of developing pRIFLE-I or pRIFLE-F
3. Determine if NGAL (POC plasma and confirmatory urine) concentrations can predict kidney
function recovery in critically ill children develop >10-20% ICU fluid overload who
receive continuous renal replacement therapy Hypothesis to be tested: Decreasing NGAL
concentrations will be associated with improvement in urine output and initial
resolution of AKI in < 72 hours
This pilot study will be novel in that the investigators will evaluate NGAL levels in near
real-time, twice daily to guide clinical decision support in terms of fluid administration
effect assessment and CRRT provision in this critically ill pediatric population.
Specifically, the investigators will use the NGAL data daily to 1) drive initiation of CRRT
in children with elevated NGAL and > 10-20% fluid overload and 2) drive CRRT discontinuation
in patients with decreasing NGAL concentrations. In addition, the investigators will employ
an adaptive study design to readjust the threshold NGAL during the time course of the study
if the data suggest adjustment will enrich the data pool.
Inclusion Criteria:
1. Age 1-25 years old
2. Must weigh at least 20kg
3. Receiving mechanical ventilation
4. Receiving at least 1 vasoactive medication: dopamine (dose greater then 5
micrograms/kg/min), Dobutamine, Epinephrine, Norepinephrine or Vasopressin
Exclusion Criteria:
1. History of End Stage Renal Disease, on Dialysis
2. Immediately post renal transplant
3. Within 96 hours of Cardiopulmonary Bypass Surgery
4. Weight less than 20 kg Patient with a DNR order, "do not escalate care" order, or life
expectancy of less than 1 week.
We found this trial at
2
sites
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
Click here to add this to my saved trials
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
Click here to add this to my saved trials