ImportanceIncreasing evidence indicates that acute kidney injury (AKI) occurs frequently in children and young adults and is associated with poor short-term and long-term outcomes. Guidance is required to focus efforts related to expansion of pediatric AKI knowledge.ObjectiveTo develop expert-driven pediatric specific recommendations on needed AKI research, education, practice, and advocacy.Evidence ReviewAt the 26th Acute Disease Quality Initiative meeting conducted in November 2021 by 47 multiprofessional international experts in general pediatrics, nephrology, and critical care, the panel focused on 6 areas: (1) epidemiology; (2) diagnostics; (3) fluid overload; (4) kidney support therapies; (5) biology, pharmacology, and nutrition; and (6) education and advocacy. An objective scientific review and distillation of literature through September 2021 was performed of (1) epidemiology, (2) risk assessment and diagnosis, (3) fluid assessment, (4) kidney support and extracorporeal therapies, (5) pathobiology, nutrition, and pharmacology, and (6) education and advocacy. Using an established modified Delphi process based on existing data, workgroups derived consensus statements with recommendations.FindingsThe meeting developed 12 consensus statements and 29 research recommendations. Principal suggestions were to address gaps of knowledge by including data from varying socioeconomic groups, broadening definition of AKI phenotypes, adjudicating fluid balance by disease severity, integrating biopathology of child growth and development, and partnering with families and communities in AKI advocacy.Conclusions and RelevanceExisting evidence across observational study supports further efforts to increase knowledge related to AKI in childhood. Significant gaps of knowledge may be addressed by focused efforts.

Morphine dependence is characterized by somatic and motivational signs of withdrawal that likely contribute to the maintenance of addictive behavior. The nucleus accumbens (NAc) receives extensive dopaminergic input and is an important substrate for mediating these aversive states. In the NAc, the function of the transcription factor cAMP response element binding protein (CREB) and AMPA glutamate receptor subunit, type 1 (GluR1) can be regulated by dopamine (DA) D 1 receptor-mediated phosphorylation (P-CREB, P-GluR1). However, the roles of D 1 receptors, CREB, and GluR1 in morphine dependence are not well understood. Here, we show that somatic signs of naloxone-precipitated withdrawal were associated with increased P-CREB, but not P-GluR1, in the NAc of morphinedependent rats. The D 1 receptor agonist chloro-APB hydrobromide (SKF 82958) was rewarding in morphine-dependent rats and blocked naloxone-induced place aversions and somatic signs of withdrawal. Surprisingly, SKF 82958 increased P-GluR1, but not P-CREB, in the NAc, and naloxone reduced SKF 82958-mediated P-GluR1 induction specifically in morphine-dependent rats. Together, these results confirm that aversive treatments can increase CREB function in the NAc. Furthermore, they suggest a dependence-associated shift in the molecular mechanisms that regulate the consequences of D 1 receptor stimulation, favoring activation of GluR1 rather than CREB. These data raise the possibility that the rewarding effects of SKF 82958 in morphine-dependent rats involve increased P-GluR1 in the NAc, although the involvement of other brain regions cannot be ruled out. Regardless, these findings suggest for the first time that D 1 agonists might be useful for the treatment of withdrawal symptoms that contribute to the maintenance of opiate addiction in humans.Key words: nucleus accumbens; CREB; GluR1; AMPA; place conditioning; SKF 82958 IntroductionOpiate withdrawal causes somatic abstinence signs as well as a motivational syndrome characterized by dysphoria and depression (Koob and Le Moal, 1997;De Vries and Shippenberg, 2002) in humans. These negative affective states are thought to contribute to addictive behaviors (Koob and Le Moal, 1997;Markou et al., 1998). The nucleus accumbens (NAc), which receives extensive dopaminergic input, plays a key role in opiate reward (Wise, 1989) as well as the motivational and somatic signs of opiate withdrawal (Koob et al., 1992;Harris and Aston-Jones, 1994). The opioid receptor antagonist naloxone precipitates physical withdrawal signs in morphine-dependent rats and produces behaviors, such as conditioned place aversions, that reflect aversive states mediated within the NAc (Stinus et al., 1990).Acute morphine decreases formation of cAMP (Childers, 1991), whereas chronic morphine causes super-sensitivity of cAMP pathways in areas including the NAc (Nestler and Aghajanian, 1997). Precipitated opiate withdrawal unmasks upregulated cAMP pathways, which likely contribute to aversive states. Hypothetically, activation of dopamine (DA) D 1 rece...

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