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

Acute Kidney Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06050525
• Other study ID #: K 2023-7065
• Status: Recruiting
• Start date: February 1, 2023
• Est. completion date: October 31, 2024

Study information

• Verified date: September 2023
• Source: Karolinska Institutet
• Contact: Urban Fläring, MD. Ph.D.
• Phone: +46078763900
• Email: urban.flaring[@]ki.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 118
• Est. completion date: October 31, 2024
• Est. primary completion date: June 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Minute to 2 Days

Eligibility

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.

Related Conditions & MeSH terms

• Acute Kidney Injury
• Congenital Diaphragmatic Hernia
• Hernia
• Hernia, Diaphragmatic
• Hernias, Diaphragmatic, Congenital
• Hypertension, Pulmonary
• Multiple Organ Failure
• Pulmonary Hypertension
• Wounds and Injuries

Locations

Country	Name	City	State
Sweden	Department of Pediatric Anesthesia and Intensive Care. Karolinska University Hospital	Stockholm

Sponsors (1)

Lead Sponsor	Collaborator
Karolinska Institutet

Country where clinical trial is conducted

Sweden, 

References & Publications (4)

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. — View Citation

Chatterjee D, Ing RJ, Gien J. Update on Congenital Diaphragmatic Hernia. Anesth Analg. 2020 Sep;131(3):808-821. doi: 10.1213/ANE.0000000000004324. — View Citation

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 kidn — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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)
Secondary	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.
Secondary	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
Secondary	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).