Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 1;4(3):308-315.
doi: 10.34067/KID.0005082022.

Risk and Timing of De Novo Sepsis in Critically Ill Children after Acute Kidney Injury

Cassandra L Formeck  1   2 , Robert Feldman  3 , Andrew D Althouse  3 , John A Kellum  2   4
Affiliations

Risk and Timing of De Novo Sepsis in Critically Ill Children after Acute Kidney Injury

Cassandra L Formeck et al. Kidney360. .

Abstract

Key Points:

  1. Critically ill children who developed AKI have a 42% increase in the probability of developing subsequent hospital-acquired sepsis when compared with children without AKI.

  2. When evaluating risk of sepsis over time, children with stage 3 AKI remain at increased risk for sepsis for at least 2 weeks after AKI onset.

  3. Medical providers should monitor for signs of sepsis after AKI and limit exposures that may increase the risk for infection.

Background: AKI is common among critically ill children and is associated with an increased risk for de novo infection; however, little is known about the epidemiology and temporal relationship between AKI and AKI-associated infection in this cohort.

Methods: We conducted a single-center retrospective cohort study of children admitted to the pediatric and cardiac intensive care units (ICUs) at a tertiary pediatric care center. The relationship between nonseptic AKI and the development of hospital-acquired sepsis was assessed using Cox proportional hazards models using AKI as a time-varying covariate.

Results: Among the 5695 children included in this study, AKI occurred in 20.2% from ICU admission through 30 days. Hospital-acquired sepsis occurred twice as often among children with AKI compared with those without AKI (10.1% versus 4.6%) with an adjusted hazard ratio of 1.42 (95% confidence interval, 1.12 to 1.81). Among the 117 children who developed sepsis after AKI, 80.3% developed sepsis within 7 days and 96.6% within 14 days of AKI onset, with a median time from AKI onset to sepsis of 2.6 days (interquartile range, 1.5–4.7). When assessing change in risk over time, the hazard rate for sepsis remained elevated for children with stage 3 AKI compared with children without AKI at 13.5 days after AKI onset, after which the estimation of hazard rates was limited by the number of children remaining in the hospital.

Conclusions: AKI is an independent risk factor for de novo sepsis. Critically ill children with stage 3 AKI remain at increased risk for sepsis at 13.5 days after AKI onset.

PubMed Disclaimer

Conflict of interest statement

J.A. Kellum reports the following: Employer: Spectral Medical; University of Pittsburgh School of Medicine; University of Pittsburgh Medical Center (on leave); Consultancy: AM Pharma, Astellas, Astute Medical, Baxter, bioMerieux, Cytosorbents, Grifols, Klotho, Mallinckrodt, NxStage, PhotoPhage, Potrero, RenalSense; Ownership Interest: J3RM, Klotho, Photophage, Spectral Medical; Research Funding: Astute Medical, Astellas, Baxter, bioMerieux, Grifols, Cytosorbents, Atox Bio, Astellas, Bioporto, RenalSense; Patents or Royalties: Astute Medical, Cytosorbents, J3RM, Klotho, Photophage; and Advisory or Leadership Role: Editor: Critical Care Clinics of North America; Editorial Boards: Nephrology Dialysis Transplantation; Critical Care; Critical Care Medicine; Blood Purification. All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Flow diagram of study cohort with exclusions. CKD, chronic kidney disease; ICU, intensive care unit.
Figure 2
Figure 2
Freedom from hospital-acquired sepsis. Cox proportional hazards models showing the probability of remaining sepsis free for children with AKI versus no AKI after ICU admission. In these models, AKI was treated as a time-varying covariate with the value “0” assigned if the patient had not yet reached AKI onset; if the patient had met criteria for AKI, the value assigned was the highest KDIGO stage reached as of that time since ICU admission. (A) Probability according to AKI stage. (B) Probability according to any AKI stage. ICU, intensive care unit; KDIGO, Kidney Disease: Improving Global Outcomes.
Figure 3
Figure 3
Hazard rate of hospital-acquired sepsis in critically ill children by AKI stage. This hazard plot shows the time-varying hazard rate for developing hospital-acquired sepsis among critically ill children with and without AKI. Time zero is time at ICU admission. ICU, intensive care unit.
See this image and copyright information in PMC

Comment in

  • Sepsis and AKI: A Two-Way Street.
    Basalely A, Menon S. Basalely A, et al. Kidney360. 2023 Mar 1;4(3):289-290. doi: 10.34067/KID.0000000000000106. Kidney360. 2023. PMID: 36996291 Free PMC article. No abstract available.

References

    1. Kaddourah A, Basu RK, Bagshaw SM, et al. Epidemiology of acute kidney injury in critically ill children and young adults. N Engl J Med. 2017;376(1):11–20. doi:10.1056/NEJMoa1611391 - DOI - PMC - PubMed
    1. Singbartl K, Joannidis M. Short-term effects of acute kidney injury. Crit Care Clin. 2015;31(4):751–762. doi:10.1016/j.ccc.2015.06.010 - DOI - PubMed
    1. Faubel S, Edelstein CL. Mechanisms and mediators of lung injury after acute kidney injury. Nat Rev Nephrol. 2016;12(1):48–60. doi:10.1038/nrneph.2015.158. - DOI - PubMed
    1. Liu M, Liang Y, Chigurupati S, et al. Acute kidney injury leads to inflammation and functional changes in the brain. J Am Soc Nephrol. 2008;19(7):1360–1370. doi:10.1681/ASN.2007080901 - DOI - PMC - PubMed
    1. Park SW, Chen SW, Kim M, et al. Cytokines induce small intestine and liver injury after renal ischemia or nephrectomy. Lab Invest. 2011;91(1):63–84. doi:10.1038/labinvest.2010.151 - DOI - PMC - PubMed

Publication types