Caffeine exposure and acute kidney injury in premature infants with necrotizing enterocolitis and spontaneous intestinal perforation

Aviles-Otero, Noelia; Kumar, Reeti; Khalsa, Dev Darshan; Green, Glen; Carmody, John

doi:10.1007/s00467-018-4140-y

Cited by 18 publications

(13 citation statements)

References 43 publications

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“…However, patients who received caffeine had lower peak serum creatinine (median 1.0 mg/dl vs. 1.5 mg/dl; p=0.008) and percentage change in baseline serum creatinine (62% vs. 105%; p=0.003) than those who did not. Similarly, patients receiving caffeine had a lower absolute change from baseline serum creatinine than those who did not receive caffeine [12].…”

Section: Discussionmentioning

confidence: 90%

Association between Caffeine Citrate and Incidence of Acute Kidney Injury in Preterms

Mansour

El-Sharkawy

Hazzaa

et al. 2021

JAMMR

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Background: As a result of prematurity, Acute kidney injury (AKI) occurs commonly in preterm neonates and is associated with increased morbidity and mortality. (AKI) is defined as a rapid, potentially reversible deterioration in renal functions sufficient to result in accumulation of nitrogenous wastes in the body. Aim of the Study: the aim of this study was to determine whether preterm neonates who took caffeine citrate from the first day after birth were less likely to AKI within the first 7 days. Patients and Methods: This case control study was conducted on 100 preterm neonates at Neonatal Intensive Care Units (NICUS), Pediatric Department, Tanta University with gestational age less than (30 weeks) were grouped into group A and B. Group A 50 preterm neonates who received caffeine citrate from the first day after birth with dose (20 mg/kg) loading dose, and (5 mg/kg/dose) every 24hrs of maintenance dose, given as slow intravenous infusion over twenty to thirty minutes for a week. Group B 50 preterm neonates who did not receive caffeine citrate. Inclusion Criteria: all preterms <30 weeks admitted within first 24 hours after birth presented by respiratory distress according to Downes score. Exclusion Criteria: newborns with congenital heart disease except non-significant PDA, neonatal mortality < 48 h of life, clinical signs suggest chromosomal anomalies, newborns with congenital renal anomalies. Hematological Investigations: serum albumin, serum creatinine, blood urea. Urinary Investigations: measuring urine output. Results: There was a statistically significant difference between the two studied groups as regard serum creatinine in day (5,7) (p<0.001), urea in day 7 (p value <0.001), serum albumin in day (5,7) (p value ≤ 0.05), urine output in day (4,5,6,7) (p value ≤0.05), AKI incidence (p value <0.001). Conclusion: Caffeine Citrate administration in preterm neonates from the first day of life for one week was associated with reduced occurrence and severity of AKI.

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Section: Discussionmentioning

confidence: 90%

Association between Caffeine Citrate and Incidence of Acute Kidney Injury in Preterms

Mansour

El-Sharkawy

Hazzaa

et al. 2021

JAMMR

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“…Caffeine and other methylxanthine adenosine receptor antagonists, such as aminophylline and theophylline, have been shown to be protective against AKI in other populations, particularly in preterm neonates and critically ill children without congenital heart disease. [22][23][24]56,57 While caffeine has not been studied in pediatric populations with congenital heart disease, other methylxanthine adenosine receptor antagonists have not shown an effect on rates of CS-AKI. 58 These studies were limited to postoperative methylxanthine administration due to concerns about safety related to a narrow therapeutic index and additional drug exposure in this fragile population.…”

Section: Discussionmentioning

confidence: 99%

“…20,21 Studies in preterm populations without congenital heart disease have shown an association between receipt of caffeine at labeled doses (loading dose of 20 mg/kg and 5-10 mg/kg/day) and reduced incidence and severity of AKI. [22][23][24] However, none of these studies quantitated plasma caffeine concentrations, and there are no studies of caffeine PK in neonates with congenital heart disease, where unique physiology may impact drug kinetics. As such, the caffeine plasma exposures that may be associated with protection against AKI and age-and congenital heart disease-related effects on caffeine PK are unknown.…”

mentioning

confidence: 99%

Population Pharmacokinetics of Caffeine in Neonates with Congenital Heart Disease and Associations with Acute Kidney Injury

Thompson,

Zimmerman,

Gonzalez

et al. 2023

The Journal of Clinical Pharma

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Cardiac surgery‐associated acute kidney injury (CS‐AKI) occurs in approximately 65% of neonates undergoing cardiac surgery on cardiopulmonary bypass and contributes to morbidity and mortality. Caffeine may reduce CS‐AKI by counteracting adenosine receptor upregulation after bypass, but pharmacokinetics (PK) in this population are unknown. The goal of our analysis is to address knowledge gaps in age‐, disease‐, and bypass‐related effects on caffeine disposition and explore preliminary associations between caffeine exposure and CS‐AKI using population PK modeling techniques and an opportunistic, electronic health record‐integrated trial design.We prospectively enrolled neonates receiving preoperative caffeine per standard of care and collected PK samples. We retrospectively identified neonates without caffeine exposure undergoing surgery on bypass as a control cohort. We followed US Food and Drug Administration guidance for population PK model development using NONMEM. Effects of clinical covariates on PK parameters were evaluated. We simulated perioperative exposures and used multivariable logistic regression to evaluate the association between caffeine exposure and CS‐AKI.Twenty‐seven neonates were included in model development. A 1‐compartment model with bypass time as a covariate on clearance and volume of distribution best fit the data. Twenty‐three neonates with caffeine exposure and 109 controls were included in the exposure‐response analysis. Over half of neonates developed CS‐AKI. On multivariable analysis, there were no significant differences between CS‐AKI with and without caffeine exposure. Neonates with single‐ventricle heart disease without CS‐AKI had consistently higher simulated caffeine exposures. Our results highlight areas for further study to better understand disease‐ and bypass‐specific effects on drug disposition and identify populations where caffeine may be beneficial.

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“…Aviles-Otero and colleagues [39] recently reported that among 146 patients with NEC/SIP, 119 (81.5%) received caffeine, and 91 (62.3%) developed AKI. AKI occurred less frequently in patients who received caffeine than in those who did not (55.5% vs. 92.6%; odds ratio (OR) 0.10; 95% confidence interval (CI) 0.02-0.44).…”

Section: Caffeine Exposure and Akimentioning

confidence: 99%

Necrotizing Enterocolitis-Associated Acute Kidney Injury—Transforming the Paradigm

Garg,

Shenberger,

South

et al. 2024

Am J Perinatol

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Necrotizing enterocolitis (NEC) is one of the most common conditions requiring emergency surgery in the neonatal intensive care unit and is associated with a septic shock-like state contributing to multi-organ dysfunction. NEC affects 6-10% of very-low birth-weight infants and remains a leading cause of death. The occurrence of severe AKI following surgical NEC is a harbinger of multiple morbidities. This review presents current evidence about the clinical impact of NEC associated AKI on the clinical outcomes. Studies evaluating nephro-protective strategies to prevent AKI and its consequences are greatly needed to improve the post-operative recovery and clinical outcomes in neonates with NEC. Future observational studies and clinical trials in preterm-born infants with NEC prioritize measuring short-term (AKI) and longer term (chronic kidney disease) kidney outcomes. Impact: 1. Severe AKI (stage 2 and 3) occurs in 32.6% of neonates after NEC diagnosis and in 58.7% following surgical NEC diagnosis. 2. NEC associated AKI is associated with severe postoperative course, moderate to severe bronchopulmonary dysplasia, surgical complications, brain injury and longer hospital stay in preterm infants. 3. Severity of NEC associated AKI can be utilized by bedside providers for the prognostication of clinical outcomes in preterm infants.

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Caffeine exposure and acute kidney injury in premature infants with necrotizing enterocolitis and spontaneous intestinal perforation

Cited by 18 publications

References 43 publications

Association between Caffeine Citrate and Incidence of Acute Kidney Injury in Preterms

Association between Caffeine Citrate and Incidence of Acute Kidney Injury in Preterms

Population Pharmacokinetics of Caffeine in Neonates with Congenital Heart Disease and Associations with Acute Kidney Injury

Necrotizing Enterocolitis-Associated Acute Kidney Injury—Transforming the Paradigm

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