Clinical trial NCT01735162: Study of the Prediction of Acute Kidney Injury in Children Using Risk Stratification and Biomarkers
Official title: Prospective Study of Acute Kidney Injury in Critically Ill Children Predicted by Renal Angina and Urinary Biomarkers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Renal Angina
Acute Kidney Injury
Keywords: Renal angina
AKI
Pediatric Intensive Care
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
First posted: 2012-11-28
Enrollment: 184
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Eligibility criteria: Inclusion Criteria:

* Minimum stay 48 hours
* Indwelling urinary catheter

Exclusion Criteria:

* History of renal disease

Primary outcomes:
measure: Acute kidney injury
timeFrame: At day 3 of PICU admission
Secondary outcomes:
measure: PICU length of stay
timeFrame: 60 days
Other outcomes:
measure: Mortality
timeFrame: 60 day
measure: Renal replacement therapy
timeFrame: During ICU stay
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Children's Hospital Medical Center, Cincinnati
name: Stuart Goldstein, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Goldstein SL. Acute kidney injury biomarkers: renal angina and the need for a renal troponin I. BMC Med. 2011 Dec 21;9:135. doi: 10.1186/1741-7015-9-135.
citation: Basu RK, Chawla LS, Wheeler DS, Goldstein SL. Renal angina: an emerging paradigm to identify children at risk for acute kidney injury. Pediatr Nephrol. 2012 Jul;27(7):1067-78. doi: 10.1007/s00467-011-2024-5. Epub 2011 Oct 20.
citation: Goldstein SL, Chawla LS. Renal angina. Clin J Am Soc Nephrol. 2010 May;5(5):943-9. doi: 10.2215/CJN.07201009. Epub 2010 Mar 18.
citation: Gist KM, Selewski DT, Brinton J, Menon S, Goldstein SL, Basu RK. Assessment of the Independent and Synergistic Effects of Fluid Overload and Acute Kidney Injury on Outcomes of Critically Ill Children. Pediatr Crit Care Med. 2020 Feb;21(2):170-177. doi: 10.1097/PCC.0000000000002107.