Scott L Weiss1,2,3, Fran Balamuth2,4,5, Cary W Thurm6, Kevin J Downes4,5, Julie C Fitzgerald7,2, Benjamin L Laskin4. 1. Departments of Anesthesiology and Critical Care and WeissS@Email.chop.edu. 2. Pediatric Sepsis Program at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 3. Center for Mitochondrial and Epigenomic Medicine at the Children's Hospital of Philadelphia, Philadelphia, Pennsylvania. 4. Pediatrics, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania. 5. Center for Pediatric Clinical Effectiveness, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; and. 6. Children's Hospital Association, Lenexa, Kansas. 7. Departments of Anesthesiology and Critical Care and.
Abstract
BACKGROUND AND OBJECTIVES: Major adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality. RESULTS: Of 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions. CONCLUSIONS: In children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.
BACKGROUND AND OBJECTIVES: Major adverse kidney events, a composite of death, new kidney replacement therapy, or persistent kidney dysfunction, is a potential patient-centered outcome for clinical trials in sepsis-associated kidney injury. We sought to determine the incidence of major adverse kidney events within 30 days and validate this end point in pediatric sepsis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a retrospective observational study using the Pediatric Health Information Systems Plus database of patients >6 months to <18 years old with a diagnosis of severe sepsis/septic shock; orders for bacterial blood culture, antibiotics, and at least one fluid bolus on hospital day 0/1; and known hospital disposition between January 2007 and December 2011. The primary outcome was incidence of major adverse kidney events within 30 days. Major adverse kidney events within 30 days were validated against all-cause mortality at hospital discharge, hospital length of stay, total hospital costs, hospital readmission within 30 days and 1 year, and lowest eGFR between 3 months and 1 year after discharge. We reported incidence of major adverse kidney events within 30 days with 95% confidence intervals using robust SEM and used multivariable logistic regression to test the association of major adverse kidney events within 30 days with hospital costs and mortality. RESULTS: Of 1685 admissions, incidence of major adverse kidney events within 30 days was 9.6% (95% confidence interval, 8.1% to 11.0%), including 4.5% (95% confidence interval, 3.5% to 5.4%) death, 1.7% (95% confidence interval, 1.1% to 2.3%) kidney replacement therapy, and 5.8% (95% confidence interval, 4.7% to 6.9%) persistent kidney dysfunction. Patients with versus without major adverse kidney events within 30 days had higher all-cause mortality at hospital discharge (28% versus 1%; P<0.001), higher total hospital costs ($61,188; interquartile range, $21,272-140,356 versus $28,107; interquartile range, $13,056-72,697; P<0.001), and higher proportion with eGFR<60 ml/min per 1.73 m2 between 3 months and 1 year after discharge (19% versus 4%; P=0.001). Major adverse kidney events within 30 days was not associated with length of stay or readmissions. CONCLUSIONS: In children with sepsis, major adverse kidney events within 30 days are common, feasible to measure, and a promising end point for future clinical trials.
Authors: Scott L Weiss; Luke Keele; Fran Balamuth; Neika Vendetti; Rachael Ross; Julie C Fitzgerald; Jeffrey S Gerber Journal: J Pediatr Date: 2017-01-04 Impact factor: 4.406
Authors: Scott L Weiss; Brandon Parker; Maria E Bullock; Sheila Swartz; Carolynn Price; Mark S Wainwright; Denise M Goodman Journal: Pediatr Crit Care Med Date: 2012-07 Impact factor: 3.624
Authors: Hester N Blufpand; Rik Westland; Joanna A E van Wijk; Elianne A Roelandse-Koop; Gertjan J L Kaspers; Arend Bökenkamp Journal: J Pediatr Date: 2013-10-02 Impact factor: 4.406
Authors: Ayse Akcan Arikan; Eric A Williams; Jeanine M Graf; Curtis E Kennedy; Binita Patel; Andrea T Cruz Journal: J Pediatr Date: 2015-09-26 Impact factor: 4.406
Authors: Amanda Ruth; Courtney E McCracken; James D Fortenberry; Matthew Hall; Harold K Simon; Kiran B Hebbar Journal: Pediatr Crit Care Med Date: 2014-11 Impact factor: 3.624
Authors: Marco Fiorentino; Fadi A Tohme; Shu Wang; Raghavan Murugan; Derek C Angus; John A Kellum Journal: PLoS One Date: 2018-06-05 Impact factor: 3.240
Authors: Fran Balamuth; Marlena Kittick; Peter McBride; Ashley L Woodford; Nicole Vestal; T Charles Casper; Melissa Metheney; Katherine Smith; Natalie J Atkin; Jill M Baren; J Michael Dean; Nathan Kuppermann; Scott L Weiss Journal: Acad Emerg Med Date: 2019-07-18 Impact factor: 3.451
Authors: Scott L Weiss; Fran Balamuth; Elliot Long; Graham C Thompson; Katie L Hayes; Hannah Katcoff; Marlena Cook; Elena Tsemberis; Christopher P Hickey; Amanda Williams; Sarah Williamson-Urquhart; Meredith L Borland; Stuart R Dalziel; Ben Gelbart; Stephen B Freedman; Franz E Babl; Jing Huang; Nathan Kuppermann Journal: Trials Date: 2021-11-06 Impact factor: 2.728