Incidence of Acute Kidney Injury and Risk Factors in Newborns With Congenital Diaphragmatic Hernia

The main aim of this project is to elucidate the incidence of acute kidney injury (AKI) in newborns with congenital diaphragmatic hernia during stay in the Pediatric intensive care unit. (PICU). This patient group often presents with severe circulatory and respiratory dysfunction requiring intensive care treatment. Characterization of risk factors to AKI will also be performed.

Study Overview

• Status: Recruiting
• Conditions: Acute Kidney Injury; Pulmonary Hypertension; Congenital Diaphragmatic Hernia; Multiple Organ Failure; Hyperchloremia

Detailed Description

There is an overwhelming number of studies showing that complication with acute kidney injury (AKI) in critically ill patients, including children and newborns results in increased morbidity and mortality. The more severe AKI, the higher risk of bad outcome. In the neonatal intensive care unit (NICU), the incidence of AKI is approximately 30 %, even higher in full-term babies (36 %).

Newborns with congenital diaphragmatic hernia (CDH) often present with severe cardio-respiratory dysfunction, often complicated by pulmonary hypertension (PPHN) requiring mechanical ventilation and vasoactive/inotropic drugs, especially during the first week in the intensive care. Some of these patients deteriorates and cannot maintain vital parameters despite conventional treatment and will therefore require extra corporeal membrane oxygenation). During the ICU-stay, the patients are subjected to several risk factors for developing AKI. Among physiological risk factors, PPHN, low oxygenation and blood pressure may result in renal dysfunction. Iatrogenic factors include the need for nephrotoxic drugs, not least antibiotics (Vancomycin, Gentamycin) and antimycotics. In addition, hyperchloremia may contribute to the development of AKI, since impaired renal blood flow is associated with hyperchloremia. The AKI incidence and its risk factors in CDH patients is not well studied.

The objectives of this well characterized retrospective cohort study is to establish AKI incidence in critically ill CDH-patients and investigate possible associations between risk factors and AKI (exposure to nephrotoxic drugs, degree of multiple organ failure, PPHN, vasoactive/inotropic requirement, oxygenation index, fluid overload and hyperchloremia) during PICU stay. The association of the risk factors to different stages of AKI will also be investigated.

• Study Type: Observational
• Enrollment (Estimated): 118

Contacts and Locations

• Study Contact: Name: Urban Fläring, MD. Ph.D.; Phone Number: +46812370394 +46078763900; Email: urban.flaring@ki.se
• Study Contact Backup: Name: Andreas Andersson, MD. Ph.D.; Phone Number: +46704997886; Email: andreas.andersson@regionstockholm.se

Study Locations

• Sweden
  • Stockholm, Sweden, 17176
    • Recruiting
    • Department of Pediatric Anesthesia and Intensive Care. Karolinska University Hospital
    • Contact: Urban Fläring, MD. Ph:D.; Phone Number: +46708763900; Email: urban.flaring@ki.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Newborns with congenital diaphragmatic hernia, intubated and started invasive ventilation within 2 days, referred to Karolinska University Hospital, Stockholm, Sweden.

Description

Inclusion Criteria: Newborns with congenital diaphragmatic hernia intubated and started invasive ventilation within 2 days.

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Exclusion Criteria:

• Invasive ventilation initiated after 2 days.
• Severe comorbidity not compatible with life and/or not possible to correct surgically.
• Death occurring within 2 days.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of acute kidney injury in newborn patients with congenital diaphragmatic hernia (CDH) (n=108)	Patients having or not having acute kidney injury will be determined by the score: neonatal Kidney Diseases: Improving Global Outcomes (n-KDIGO), based upon creatinine concentration (mikromoles/L). A 1.5-fold increase in creatinine concentration increase from first sampling will be classified as acute kidney injury.	Acute kidney injury evolving during PICU-stay (from birth up to 10 weeks, which is the longest PICU-stay among the patients).)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary hypertension	A patient is classified as having PPHN on the first echocardiogram if the right ventricular systolic blood pressure is 67% or more of the systemic blood pressure. Acute kidney injury will be determined using n-KDIGO described in Primary Outcome Measure. In the statistic analysis, the variables will be dichotomous. Possible association will be analysed using logistic regression analysis in this cohort of newborn patients with CDH (n=108)	Developing during PICU-stay (from birth up to 10 weeks)
Use of nephrotoxic drugs	If given 3 days or more during PICU-stay, Nephrotoxic drugs (Vancomycin, Meropenem, Gentamycin, Amphotericin B, Tazobactam and Fluconazole) will be investigated using logistic regression analysis to elucidate if there is an association with the development of acute kidney injury (defined by n-KDIGO) in this cohort of newborn patients with CDH (n=108)	Given during PICU-stay (from birth up to 10 weeks)
Duration (days during first week in the PICU) of hyperchloremia	Plasma chloride concentration has been obtained from blood gas analysis on a daily basis during the first week in the PICU. It will be investigated if days with a chloride concentration >110mmol/L is associated with the development of acute kidney injury (defined by n-KDIGO) using logistic regressionin this cohort of newborn patients with CDH (n=108)	From birth up to one week in the. PICU.
Development of multiple organ failure.	Maximum development of multiple organ failure during the first week in the PICU will be determined defined by the PEdiatric Logistic Organ Dysfunction Score (PELOD-2-score). Higher values means a worse. outcome. A possible association between PELOD-2 score and the development of acute kidney injury will be investigated using logistic regression in this cohort of newborn patients with CDH (n=108)	From birth up to one week in the PICU
Mortality during PICU-stay (max 10 weeks).	Association between the development of acute kidney injury defined by n-KDIGO and mortality occurring during PICU stay will be investigated using logistic regression in this cohort of newborn patients with CDH (n=108)	PICU-stay. (up to 10 weeks).

Collaborators and Investigators

• Sponsor: Karolinska Institutet
• Investigators: Principal Investigator: Urban Fläring, MD. Ph.D., Department of Pediatric Anesthesia and Intensive Care. Karolinska University Hospital. Stockholm. Sweden.

Publications and helpful links

General Publications

• Jetton JG, Boohaker LJ, Sethi SK, Wazir S, Rohatgi S, Soranno DE, Chishti AS, Woroniecki R, Mammen C, Swanson JR, Sridhar S, Wong CS, Kupferman JC, Griffin RL, Askenazi DJ; Neonatal Kidney Collaborative (NKC). Incidence and outcomes of neonatal acute kidney injury (AWAKEN): a multicentre, multinational, observational cohort study. Lancet Child Adolesc Health. 2017 Nov;1(3):184-194. doi: 10.1016/S2352-4642(17)30069-X.
• Barhight MF, Lusk J, Brinton J, Stidham T, Soranno DE, Faubel S, Goebel J, Mourani PM, Gist KM. Hyperchloremia is independently associated with mortality in critically ill children who ultimately require continuous renal replacement therapy. Pediatr Nephrol. 2018 Jun;33(6):1079-1085. doi: 10.1007/s00467-018-3898-2. Epub 2018 Feb 5.
• Chatterjee D, Ing RJ, Gien J. Update on Congenital Diaphragmatic Hernia. Anesth Analg. 2020 Sep;131(3):808-821. doi: 10.1213/ANE.0000000000004324.
• Liberio BM, Brinton JT, Gist KM, Soranno DE, Kirkley MJ, Gien J. Risk factors for acute kidney injury in neonates with congenital diaphragmatic hernia. J Perinatol. 2021 Aug;41(8):1901-1909. doi: 10.1038/s41372-021-01119-1. Epub 2021 Jun 12.

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2023
• Primary Completion (Estimated): June 15, 2024
• Study Completion (Estimated): October 31, 2024

Study Registration Dates

• First Submitted: September 6, 2023
• First Submitted That Met QC Criteria: September 21, 2023
• First Posted (Actual): September 22, 2023

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Acute Kidney Injury; Congenital Diaphragmatic Hernia
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Renal Insufficiency; Shock; Pathological Conditions, Anatomical; Internal Hernia; Hypertension; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Hernia; Wounds and Injuries; Acute Kidney Injury; Hypertension, Pulmonary; Hernias, Diaphragmatic, Congenital; Hernia, Diaphragmatic; Multiple Organ Failure
• Other Study ID Numbers: K 2023-7065

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No