Assessment of Worldwide Acute Kidney Injury Epidemiology in Neonates: Design of a Retrospective Cohort Study

Abstract

Introduction: Acute kidney injury (AKI) affects ~30% of hospitalized neonates. Critical to advancing our understanding of neonatal AKI is collaborative research among neonatologists and nephrologists. The Neonatal Kidney Collaborative (NKC) is an international, multidisciplinary group dedicated to investigating neonatal AKI. The AWAKEN study (Assessment of Worldwide Acute Kidney injury Epidemiology in Neonates) was designed to describe the epidemiology of neonatal AKI, validate the definition of neonatal AKI, identify primary risk factors for neonatal AKI, and investigate the contribution of fluid management to AKI events and short-term outcomes.

Methods and analysis: The NKC was established with at least one pediatric nephrologist and neonatologist from 24 institutions in 4 countries (USA, Canada, Australia, and India). A Steering Committee and four subcommittees were created. The database subcommittee oversaw the development of the web-based database (MediData Rave™) that captured all NICU admissions from 1/1/14 to 3/31/14. Inclusion and exclusion criteria were applied to eliminate neonates with a low likelihood of AKI. Data collection included: (1) baseline demographic information; (2) daily physiologic parameters and care received during the first week of life; (3) weekly "snapshots"; (4) discharge information including growth parameters, final diagnoses, discharge medications, and need for renal replacement therapy; and (5) all serum creatinine values.

Ethics and dissemination: AWAKEN was proposed as human subjects research. The study design allowed for a waiver of informed consent/parental permission. NKC investigators will disseminate data through peer-reviewed publications and educational conferences.

Discussion: The purpose of this publication is to describe the formation of the NKC, the establishment of the AWAKEN cohort and database, future directions, and a few "lessons learned." The AWAKEN database includes ~325 unique variables and >4 million discrete data points. AWAKEN will be the largest, most inclusive neonatal AKI study to date. In addition to validating the neonatal AKI definition and identifying risk factors for AKI, this study will uncover variations in practice patterns related to fluid provision, renal function monitoring, and involvement of pediatric nephrologists during hospitalization. The AWAKEN study will position the NKC to achieve the long-term goal of improving the lives, health, and well-being of newborns at risk for kidney disease.

Keywords: AWAKEN; KDIGO; NKC; acute renal failure; database; neonate.

Figures

Figure 1

The Steering committee is composed of the director and the co-chairs of each of the sub-committees. The Protocol Committee was tasked to provide oversight and critique of the protocols submitted to the committee, both for the initial retrospective study (AWAKEN) and any future studies. It will also be charged with creating and submitting protocols to funding agencies and Institutional Review Boards. Other responsibilities include establishing rules for Primary Investigator designation and a system for group involvement for the establishment of future protocols. The Database Committee was charged with the development of the database, including the Manual of Procedures and Case Report Forms. Input was solicited from the NKC membership as to the data needed to answer the specific questions of interest for the AWAKEN study. These suggestions were collated and presented to the Steering Committee for final review. The myriad of data potentially available and the number of questions to be answered had the potential for an unwieldy and overwhelming amount of information. Data points that were included were thoroughly vetted by both nephrologists and neonatologists to balance the time of data collection with quality of the data elements. Once agreement was reached, in concert with the Data Management Center at Cincinnati Children’s Hospital Medical Center, electronic data forms were developed, tested, and finalized. The Manuscript Committee is responsible for initiating and developing abstracts for national and international meetings and manuscripts for submission to peer-reviewed journals. This committee will also review these abstracts and manuscripts prior to submission and provide the authors suggestions, as well as determine their suitability. The Ancillary Studies Committee will be responsible for developing rules on requesting use of data for ancillary studies and in developing these ideas into abstracts and manuscripts.

Figure 2

Of the 4273 NICU admissions at the 24 participating institutions during the period 1/1/14–3/31/14, 2162 patients were enrolled. The majority of those not included did not receive at least 48 h of IV hydration and/or nutrition. The second most common reason for exclusion was admission to the NICU at greater than 14 days of age. Subjects may have been excluded for more than one reason and may be counted more than once in the “not enrolled” numbers.