Risk of nonsteroidal anti-inflammatory drug-associated renal dysfunction among neonates diagnosed with patent ductus arteriosus and treated with gentamicin

Constance, Jonathan E.; Reith, David; Ward, Robert M.; Balch, Alfred H.; Korgenski, E. Kent; Thorell, Emily A.; Sherwin, Catherine M.T.

doi:10.1038/jp.2017.80

Cited by 15 publications

(12 citation statements)

References 62 publications

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“…PDA may impair the kidney perfusion and thus lead to a decreased clearance of aminoglycosides 24,25 ; aminoglycosides themselves are supposed to be nephrotoxic, 26 and nonsteroidal anti-inflammatory drugs may further increase the nephrotoxic risk by decreasing renal perfusion. 16,27 In our cohort, we did not find a higher mortality in infants treated with ampicillin and cefotaxime, which Clark et al 10 found in a cohort of 128 914 neonates admitted to a NICU. On the contrary, we found a lower mortality in those NICUs, which used other than aminoglycosides as first-line antibiotics.…”

Section: Discussioncontrasting

confidence: 45%

“…Acute kidney injury was associated with gentamicin use and birthweight. PDA may impair the kidney perfusion and thus lead to a decreased clearance of aminoglycosides 24,25 ; aminoglycosides themselves are supposed to be nephrotoxic, 26 and nonsteroidal anti‐inflammatory drugs may further increase the nephrotoxic risk by decreasing renal perfusion 16,27 …”

Section: Discussionmentioning

confidence: 99%

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Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants

Marißen¹,

Böckenholt³

et al. 2020

Acta Paediatrica

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Aim In animal studies, aminoglycosides induced ductus arteriosus relaxation in a dose‐dependent fashion. We tested the hypothesis that antibiotic treatment of preterm infants with aminoglycosides is associated with higher rates of surgical patent ductus arteriosus (PDA) closure. Methods Preterm infants (birthweight <1000 grams or gestational age <29 weeks) enrolled in 62 German neonatal intensive care units (NICUs) were analysed. NICUs were stratified according to the use of aminoglycosides as first‐line antibiotics. Results Baseline data were not different when NICUs using aminoglycosides (n = 9965 infants) were compared to NICUs using other antibiotics (n = 1948 infants). Rates of surgical PDA closure were 5.9% for NICUs using aminoglycosides; 6.2% for units using gentamicin; and 5.0% for NICUs using tobramycin compared to 4.1% in NICUs using other antibiotics (P < .001, P < .001 and P = .140, respectively, Fisher's exact test). Indomethacin and ibuprofen use was more common in NICUs using aminoglycosides (41% vs 33%, P < .001, Fisher's exact test). Gentamicin trough levels were higher in NICUs with surgical closure rates above the mean (median 2.0 µg/mL, inter‐quartile range 0.8‐4.0 µg/mL vs 1.2 µg/mL, IQR 0.8‐1.7, P < .001, Mann‐Whitney U test). Conclusion First‐line antibiotic treatment of preterm infants with aminoglycosides was associated with higher rates of surgical PDA closure.

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Section: Discussioncontrasting

confidence: 45%

Section: Discussionmentioning

confidence: 99%

Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants

Marißen¹,

Böckenholt³

et al. 2020

Acta Paediatrica

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“…[24][25][26] Hence these eight studies were excluded from this meta-analysis as well. The remaining seven studies (four case-control studies and three retrospective cohort studies) [27][28][29][30][31][32][33] examining NSAID-associated AKI risk in 54 852 hospitalized pediatric patients met our inclusion criteria (Figure 1). The detailed characteristics and Newcastle-Ottawa quality assessment scale of all included studies were described in Table 1.…”

Section: Resultsmentioning

confidence: 99%

“…Two studies 30,33 reported integrated NSAIDs use OR while the other five studies [27][28][29]31,32 only reported individual NSAID-related risks (three studies reported two individual medications and two studies focused on ibuprofen singly). We analyzed the ORs of these five studies with the same method: We considered the OR of each individual medication as the OR of an independent separate study.…”

Section: Resultsmentioning

confidence: 99%

Nonsteroidal anti‐inflammatory drugs associated acute kidney injury in hospitalized children: A systematic review and meta‐analysis

Gong

et al. 2021

Pharmacoepidemiology and Drug

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Introduction: Nonsteroidal anti-inflammatory drugs (NSAIDs) are regarded as nephrotoxins. Children commonly use NSAIDs and are susceptible to nephropathy, but the relationship between acute kidney injury (AKI) and use of NSAIDs is not well examined yet.Objective: To evaluate the relationship between AKI and use of NSAIDs in hospitalized pediatric patients who are susceptible to nephropathy. Methods:We conducted this systematic review and meta-analysis of observational studies by searching PubMed, Embase, and Cochrane Database for articles published up to June 1, 2020. Reports included involved children (age < 18 years) who used NSAIDs for various reasons and were admitted in the hospital. The main outcome measure was whether AKI occurred, and pooled odds ratio (OR) and 95% confidence intervals (CI) were calculated using generic inverse variance methods.Results: Seven studies reporting risk of AKI in the hospitalized pediatric patients receiving NSAIDs were included applying a random-effects model. In the hospitalized pediatric population, the pooled OR of AKI for present NSAID exposure was 1.55 (95%CI 1.26-1.92).Conclusions: NSAID exposure was associated with an approximate 1.6-fold rise in the odds of developing AKI in hospitalized pediatric patients. Avoidance, cautious use of NSAIDs and further evidence are needed. This study was registered with PROSPERO (identifier: CRD42021219779).

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“…The newborn kidney is particularly vulnerable to maldevelopment and dysfunction in an ex utero environment due to various stresses, mostly caused by decreased renal perfusion [23]. In a few studies, nephrotoxic injury is usually associated with the use of NSAID to close a PDA, especially with concomitant use of aminoglycosides [8,34,35]. However, the attributable risk of AKI associated with these 2 nephrotoxic agents is not clear.…”

Section: Discussionmentioning

confidence: 99%

Acute kidney injury among preterm infants receiving non-steroidal anti-inflammatory drugs for patent ductus arteriosus

Ting¹,

McDougal²,

Mello³

et al. 2020

Preprint

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Background: Nonsteroidal anti-inflammatory drugs (NSAID) are a frequently prescribed class of medication in the neonatal intensive care unit (NICU). Hospitalized patients receiving NSAID therapy are at an increased risk of acute kidney injury (AKI). Our primary objective was to reveal AKI epidemiology in NSAID-exposed premature infants admitted to the NICU using a standardized definition.Methods: This retrospective study included infants born at ≤34 weeks gestational age who received NSAID for intraventricular haemorrhage prophylaxis [“prophylaxis group”] or symptomatic treatment for patent ductus arteriosus (PDA) [“treatment group”] between January and December 2014 at British Columbia Women’s Hospital NICU. All available serum creatinine (SCr) and 12-hour urine output (UO) were recorded from admission till day 7 post NSAID exposure. AKI incidence was determined using the modified Kidney Disease: Improving Global Outcomes (KDIGO) classification with an increase in SCr (ΔSCr) (50% rise from prior SCr within 7 days or 26.5 mmol/L rise within 48 hours) and/or UO < 1 mL/kg/hour, excluding the first 24 h of life.Results: We identified 70 eligible subjects, 32 of whom received prophylactic NSAID (prophylaxis group), and 38 received indomethacin or ibuprofen for treatment of symptomatic PDA (treatment group), with an overall AKI incidence of 23% (16/70). The treatment group had a higher proportion of infants with SCr monitoring during the NSAID than the prophylaxis group (87% vs. 13%, p<0.001). Based upon the above defined criteria (fulfilling at least one—either the UO or SCr monitoring criteria), the prophylaxis group had a significantly lower AKI rate compared with the treatment group (9% vs. 34%; p=0.014). Conclusions: AKI incidence is higher in infants treated with NSAID for symptomatic PDA than in those treated prophylactically during the first day of life, based on the criteria applied. However, the burden of AKI may be underestimated in the prophylaxis group due to fewer available SCr values after exposure, and inability to utilize UO criteria in the 1st 24 hours of life. Standardized protocols for monitoring daily SCr and UO after exposure should be implemented for all neonates with NSAID exposure and should be considered to improve AKI recognition.

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Risk of nonsteroidal anti-inflammatory drug-associated renal dysfunction among neonates diagnosed with patent ductus arteriosus and treated with gentamicin

Abstract: Among neonates with PDA and receiving gentamicin, NSAID therapy increases the risk of AKI by about 6%.

Cited by 15 publications

References 62 publications

Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants

Aminoglycosides were associated with higher rates of surgical patent ductus arteriosus closure in preterm infants

Nonsteroidal anti‐inflammatory drugs associated acute kidney injury in hospitalized children: A systematic review and meta‐analysis

Acute kidney injury among preterm infants receiving non-steroidal anti-inflammatory drugs for patent ductus arteriosus

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