Study of the Prediction of Acute Kidney Injury in Children Using Risk Stratification and Biomarkers (AKI-CHERUB)

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: NCT01735162
Recruitment Status : Completed
First Posted : November 28, 2012
Last Update Posted : February 3, 2015
Information provided by (Responsible Party):
Rajit Basu, MD, F.A.A.P., Children's Hospital Medical Center, Cincinnati

Brief Summary:
Acute kidney injury (AKI) is a common clinical event with severe consequences. In the pediatric intensive care unit (PICU), AKI occurs in almost 10% of all patients and evidence suggests that children are dying not just with AKI, but from AKI. Unfortunately, the treatment for AKI is limited to a great extent by delayed diagnosis. Reliance on markers of kidney injury that change only when significant damage has already occurred has rendered potential therapies ineffective. For this reason, identification of new markers of AKI that change early in the course of injury is paramount. While new AKI biomarkers have been identified, their performance in the general PICU population is variable. The investigators recently proposed the concept of 'renal angina' as a way to risk stratify patients in the ICU for AKI risk. In the AKI-CHERUB study, the investigators propose to study renal angina in PICU patients alone and in combination with urinary biomarkers for AKI prediction. The investigators hypothesize that renal angina will increase the predictive precision of urinary biomarkers for AKI.

Condition or disease
Renal Angina Acute Kidney Injury

Detailed Description:
Reliance on serum creatinine and urine output for diagnosis of acute kidney injury (AKI) has limited the ability of potential therapeutic measures to be effective. The investigators' recent proposition of the renal angina construct aims to improve and expedite AKI diagnosis through use of risk stratification. An apt parallel is the profound outcome change that has been effected in acute coronary syndrome through targeted troponin measurements in patients with both risk factors and clinical symptoms of coronary ischemia. Novel AKI biomarkers will struggle to gain widespread use until their performance in patients of varying degrees of AKI risk can be balanced with their cost and availability. The investigators hypothesize risk stratification using renal angina (ANG) identifies children at-risk vs. not at-risk for AKI, focusing subsequent biomarker measurement to "rule out" AKI only in children with ANG, increasing biomarker predictive precision. This study is significant because it represents the next step in the vertical integration of AKI biomarkers into routine clinical practice to guide their use rationally. The identification of at-risk patients to guide appropriate biomarker use is high-impact because it will make implementation of preventive and supportive therapies for AKI more effective; data from this study would serve to provide the indications to the Food and Drug Administration (FDA) for biomarker use in critically ill children. The study is innovative because it is the first prospective attempt to study the predictive performance of biomarkers AKI in the PICU population using ANG stratification. The investigators will observe all children admitted to the PICU with an expected length of stay > 48 hours. Urine will be collected from these children and levels of neutrophil gelatinase associated lipocalin (NGAL), interleukin-18 (IL-18), liver-fatty acid binding protein (l-FABP), and kidney injury molecule-1 (KIM-1) will be measured. Renal angina will be assessed at time of admission. Primary outcome will be presence of AKI (as measured by Kidney Diseases Improving Global Outcome (KDIGO) Class 2 or greater) at hospital day 3.

Study Type : Observational
Actual Enrollment : 184 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Prospective Study of Acute Kidney Injury in Critically Ill Children Predicted by Renal Angina and Urinary Biomarkers
Study Start Date : October 2012
Actual Primary Completion Date : May 2013
Actual Study Completion Date : October 2014

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Angina
U.S. FDA Resources

Very high risk
Very high risk PICU patients are on mechanical ventilation and at least one inotrope or vasopressor at time of admission
High Risk
High risk PICU patients have a history of transplantation (solid organ or bone marrow)
Moderate risk
Moderate risk PICU patients are all other admissions to the ICU (may have either mechanical ventilation or inotropy/vasopressor use but not both). Cannot have a history of transplant. Minimum expected stay 48 hours.

Primary Outcome Measures :
  1. Acute kidney injury [ Time Frame: At day 3 of PICU admission ]
    Development of AKI by KDIGO Stage 2 criteria (Creatinine > 200% baseline)

Secondary Outcome Measures :
  1. PICU length of stay [ Time Frame: 60 days ]
    Observational assessment of duration of length of stay in PICU from time of renal angina assessment

Other Outcome Measures:
  1. Mortality [ Time Frame: 60 day ]
    Incidence of death within 60 days of ICU admission

  2. Renal replacement therapy [ Time Frame: During ICU stay ]
    We will use a dichotomization (yes/no) of whether renal replacement therapy was used in each patient until ICU discharge or death, whichever came first, followed up to 60 days

Biospecimen Retention:   Samples Without DNA
Urinary samples, intended for discard so waiver of consent obtained. Urine samples spun and frozen at -80C. Samples to be run for biomarker ELISA kits.

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Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
All children admitted to a tertiary children's hospital pediatric intensive care unit with an expected length of stay > 48 hours.

Inclusion Criteria:

  • Minimum stay 48 hours
  • Indwelling urinary catheter

Exclusion Criteria:

  • History of renal disease

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): NCT01735162

United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Principal Investigator: Stuart Goldstein, MD Children's Hospital Medical Center, Cincinnati

Additional Information:
Responsible Party: Rajit Basu, MD, F.A.A.P., Director, Center for Acute Care Nephrology, Children's Hospital Medical Center, Cincinnati Identifier: NCT01735162     History of Changes
Other Study ID Numbers: CIN001-AKI-CHERUB
First Posted: November 28, 2012    Key Record Dates
Last Update Posted: February 3, 2015
Last Verified: February 2015

Keywords provided by Rajit Basu, MD, F.A.A.P., Children's Hospital Medical Center, Cincinnati:
Renal angina
Pediatric Intensive Care

Additional relevant MeSH terms:
Wounds and Injuries
Angina Pectoris
Acute Kidney Injury
Chest Pain
Neurologic Manifestations
Nervous System Diseases
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Signs and Symptoms
Renal Insufficiency
Kidney Diseases
Urologic Diseases