Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study

Rajit K Basu, Ahmad Kaddourah, Stuart L Goldstein, AWARE Study Investigators, Ayse Akcan-Arikan, Megan Arnold, Cody Cruz, Michele Goldsworthy, Nancy Jaimon, Stephen Alexander, Marino Festa, Deirdre Hahn, Lauren Brown, Ari Jeon, Akash Deep, David Askenazi, Sean Bagshaw, Catherine Morgan, Rashid Alobaidi, Rajit Basu, David Cooper, Stuart Goldstein, Ahmad Kaddourah, Theresa Mottes, Tara Terrell, Patricia Arnold, Christina Metcalf, Shalayna Woodley, Radovan Bogdanović, Natasa Stajić, Branko Kovacevic, Amira Peco-Antic, Aleksandra Paripovic, Patrick Brophy, Timothy Bunchman, Duane Williams, Michelle Hoot, Vimal Chadha, Keefe Davis, Vikas Dharnidharka, Leslie Walther, Vincent Faustino, Janet Taft, Joana Tala, Katja Gist, Danielle Soranno, Soo Ha Il, Gyung Kang Hee, Richard Hackbarth, Mary Avendt-Reeber, Chloe Butler, Doug DeGraaf, Dawn Eding, Nathalie Hautala, Akunne Ndika, Eka Laksmi Hidayati, Songming Huang, Sean Kennedy, Madeleine Didsbury, Hari Kushartono, Risky Prasetyo, Cherry Mammen, Matthew Paden, Cheryl Stone, Stefano Picca, Federica Connola, James Schneider, Todd Sweberg, Aaron Kessel, David Selewski, Susan Hieber, Brankica Spasojević-Dimitrijeva, Ivana Ivanisevic, Jovana Putnik, Snezana Ristic, Scott Sutherland, Amy Staples, Craig Wong, Senan Hadid, Catherine Joseph, Robert Woroniecki, Michael Zappitelli, Noha Elsaerafy, Joshua Zaritsky, Rajit K Basu, Ahmad Kaddourah, Stuart L Goldstein, AWARE Study Investigators, Ayse Akcan-Arikan, Megan Arnold, Cody Cruz, Michele Goldsworthy, Nancy Jaimon, Stephen Alexander, Marino Festa, Deirdre Hahn, Lauren Brown, Ari Jeon, Akash Deep, David Askenazi, Sean Bagshaw, Catherine Morgan, Rashid Alobaidi, Rajit Basu, David Cooper, Stuart Goldstein, Ahmad Kaddourah, Theresa Mottes, Tara Terrell, Patricia Arnold, Christina Metcalf, Shalayna Woodley, Radovan Bogdanović, Natasa Stajić, Branko Kovacevic, Amira Peco-Antic, Aleksandra Paripovic, Patrick Brophy, Timothy Bunchman, Duane Williams, Michelle Hoot, Vimal Chadha, Keefe Davis, Vikas Dharnidharka, Leslie Walther, Vincent Faustino, Janet Taft, Joana Tala, Katja Gist, Danielle Soranno, Soo Ha Il, Gyung Kang Hee, Richard Hackbarth, Mary Avendt-Reeber, Chloe Butler, Doug DeGraaf, Dawn Eding, Nathalie Hautala, Akunne Ndika, Eka Laksmi Hidayati, Songming Huang, Sean Kennedy, Madeleine Didsbury, Hari Kushartono, Risky Prasetyo, Cherry Mammen, Matthew Paden, Cheryl Stone, Stefano Picca, Federica Connola, James Schneider, Todd Sweberg, Aaron Kessel, David Selewski, Susan Hieber, Brankica Spasojević-Dimitrijeva, Ivana Ivanisevic, Jovana Putnik, Snezana Ristic, Scott Sutherland, Amy Staples, Craig Wong, Senan Hadid, Catherine Joseph, Robert Woroniecki, Michael Zappitelli, Noha Elsaerafy, Joshua Zaritsky

Abstract

Background: Acute kidney injury (AKI) occurs in one in four children admitted to the intensive care unit (ICU) and AKI severity is independently associated with increased patient morbidity and mortality. Early prediction of AKI has the potential to improve outcomes. In smaller, single center populations, we have previously derived and validated the performance of the renal angina index (RAI), a context driven risk stratification system, to predict severe AKI.

Methods: A prospective, observational study (AWARE1, January-December 2014) was conducted in intensive care units from 32 centers in 9 countries. The primary outcome was the presence of severe AKI ("AKIS"; Stage 2-3 AKI KDIGO guidelines) on the third day after ICU admission (). We compared the performance of the RAI to changes in serum creatinine relative to baseline (SCr/Base) for prediction of the primary outcome and secondary outcomes of interest. A RAI ≥ 8 defined fulfillment of renal angina (RA+); RA+ was compared to SCr increased relative to baseline ("SCr>Base"; using maximum SCr in first 12 hours of ICU admission).

Findings: The 1590 patients studied were 55% male and had median age of 54.5 months. 286 patients (17.9%) were RA+. AKIS occurred in 121 (42.3%) RA+ vs. 247 (18.9%) RA-patients (relative risk (RR) 2.23; 95% confidence interval (CI): 1.87-2.66, p<0.001). 368 (23.1%) patients with AKIS had increased renal replacement therapy utilization (10.9% vs. 1.5%, p<0.001) and increased mortality (7.6% vs. 4.3%, p=0.01) compared to patients without AKIS. RA+ demonstrated better prediction for AKIS than SCr>Base (RR: 1.61; (1.33-1.93), p<0.001) which was maintained on multivariate regression (independent odds ratio (OR): RA+ 3.21; 95% CI (2.20-4.67) vs. SCr>Base 0.68; 95% CI (0.49-4.94)).

Interpretation: Earlier, better prediction of severe AKI has the potential to improve AKI associated patient outcomes. Compared to isolated, context-free changes in SCr, renal angina risk assessment improved accuracy for prediction of severe AKI in critically ill children and young adults.

Conflict of interest statement

Conflict of Interest: none

Figures

Figure 1. The Renal Angina Index
Figure 1. The Renal Angina Index
The index calculation for the fulfillment of renal angina is assessed 12 hours after a patient is admitted to the intensive care unit and used for prediction of severe AKI 72 hours (3 days) later. Risk factors are determined as described and assigned a point value (1, 3, and 5). Mechanical ventilation and vasoactive support should be used within the 12-hour time point but are not required to be simultaneously for a patient to be categorized as a “5”. Injury strata are described and assigned to a patient as appropriate. The index is a multiplication of the risk and injury scores assigned. SCr = serum creatinine/baseline = relationship to baseline serum creatinine, %FO = % fluid overload as described previously.
Figure 2. CONSORT Diagram
Figure 2. CONSORT Diagram
Inclusion in this analysis required full data on ICU Day 3 – inclusive of serum creatinine and urine output measurements. All patients included from the original AWARE study (1590/5237) had full data from the day of ICU admission, Day 3, and Day 28. Renal angina was fulfilled (RA+) on the day of admission in 17.9% of the studied patients. These patients were older and sicker and had worse outcome than patients without renal angina on admission (RA−). Although no different by multiple markers of severity of illness, patients with AKI on Day 3 (AKIS) were older and had worse outcome than patients without AKI. P values for comparison are listed in Supplement 2: Current patients (1590) vs. AWARE patients excluded for this study (3647), Table 1: Renal angina + vs. renal angina −, and Table 2: AKIS vs. No AKIS.

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