Subclinical Kidney Injury in Children Receiving Nonsteroidal Anti-Inflammatory Drugs After Cardiac Surgery

Nehus, Edward; Kaddourah, Ahmad; Bennett, Michael; Pyles, Olivia; Devarajan, Prasad

doi:10.1016/j.jpeds.2017.06.045

Cited by 16 publications

(15 citation statements)

References 35 publications

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“…We then further classified AKI by integrating the functional biomarkers creatinine and cystatin C with the damage biomarker NGAL, in accordance with the paradigm set forth by the Tenth Consensus Conference of the Acute Dialysis Quality Initiative and applied in other populations (Fig. 2) [21,22,[31][32][33]. We used the definitions of Composite AKI Types shown in Fig.…”

Section: Aki Definitionsmentioning

confidence: 99%

A novel strategy for identifying early acute kidney injury in pediatric hematopoietic stem cell transplantation

Benoit

Dixon

Goldstein

et al. 2019

Bone Marrow Transplant

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Acute kidney injury (AKI) is a common complication in pediatric hematopoietic stem cell transplantation (HSCT). Serum creatinine is an imprecise biomarker of AKI. We hypothesized that combining creatinine with serum cystatin C (cysC) and urinary neutrophil gelatinase-associated lipocalin (NGAL) more effectively characterizes AKI during the first 28 days of HSCT and better identifies patients at risk of adverse outcomes than creatinine alone. We prospectively assessed the type and severity of AKI in 80 consecutive allogeneic HSCT patients using weekly creatinine, cysC, and NGAL. We combined the biomarkers to define 7 Composite Types of AKI, including All Positive AKI (simultaneously detected creatinine, cysC, and NGAL AKI). Outcomes included renal replacement therapy and transplant-related mortality. In all, 75% of patients had AKI by at least one measure; 33% developed >1 type of AKI. Mild AKI often preceded Severe AKI. Patients with creatinine or NGAL AKI that were Severe or Repeated tended to have worse outcomes. The five patients with All Positive AKI had the highest rates of morbidity and mortality. AKI evaluation with creatinine, cysC, and NGAL provides a comprehensive profile of early AKI and narrowly identifies patients at highest risk of adverse outcomes, providing opportunities for early, impactful intervention.

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Section: Aki Definitionsmentioning

confidence: 99%

A novel strategy for identifying early acute kidney injury in pediatric hematopoietic stem cell transplantation

Benoit

Dixon

Goldstein

et al. 2019

Bone Marrow Transplant

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“…In a retrospective study of cardiac surgical patients using the NINJA collaboration definition (17), Uber et al found that 85% of cardiac ICU patients received at least 1 nephrotoxin and 21% received ≥3 nephrotoxins, demonstrating suboptimal adherence this recommendation as well (18). The most common nephrotoxin that was administered was non-steroidal anti-inflammatory agents (ketorolac and/or ibuprofen), which are used widely in post-operative pediatric cardiac patients and have been associated with subclinical kidney injury even in patients without AKI (19).…”

Section: Therapeutic Targetsmentioning

confidence: 99%

Cardiopulmonary Bypass and AKI: AKI Is Bad, So Let's Get Beyond the Diagnosis

Krawczeski

2019

Front. Pediatr.

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It is now well-established that AKI is a serious and common complication following cardiopulmonary bypass (CPB) in both children and adults, adverse outcomes may occur in the short term as well as long term, with higher incidence of chronic kidney disease, increased healthcare utilization and higher frequency of cardiovascular events in patients who develop post-CPB AKI. Despite the advances in our understanding of the pathogenesis of the disease and the improvement in diagnostic tools, our therapeutic options have remained suboptimal. There are multiple challenges in designing a clinical therapeutic AKI trial, including a multi-factorial etiology, difficulties with accurate diagnosis of AKI, achievement of adequate study power, and determination of appropriate outcomes. We are often left with “supportive” care. Studies have shown some benefit to AKI bundles, but adherence to bundle guidelines may be suboptimal. Current best practices should include maintenance of adequate renal perfusion pressure and avoidance of fluid overload, with consideration of early renal replacement therapy. Finally, multi-center trials of AKI therapies are crucial to finding treatment for this devastating complication of CPB.

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“…Several kidney tubule biomarkers are used by the U.S. Food and Drug Administration for drug safety evaluation in early phase studies, and many of these markers have been leveraged to characterize nephrotoxicity associated with tenofovir and antihypertensive therapy 29,30,44,45 . Studies of children and adults undergoing NSAID therapy showed that even with brief high‐intensity NSAID use, tubule injury biomarkers rise before and independently of serum creatinine 31,46 . However, we observed no evidence of kidney tubule injury or dysfunction among NSAID users in the Health ABC cohort despite the use of an array of biomarkers capturing multiple dimensions of kidney health in a large sample of at‐risk individuals.…”

Section: Discussionmentioning

confidence: 56%

“…Measures include biomarkers of tubule injury (kidney injury molecule‐1 (KIM‐1), interleukin‐18 (IL‐18), and neutrophil gelatinase‐associated lipocalin (NGAL)); tubulointerstitial fibrosis (propeptide type III procollagen (PIIINP)); proximal tubule resorptive function (alpha‐1 microglobulin (α1m)); and tubule synthetic function (uromodulin (UMOD)). These investigational biomarkers are sensitive indicators of early kidney tubule damage in the setting of medication toxicity, including NSAID nephrotoxicity, and are also associated with long‐term outcomes 22‐31 . Importantly, they have been applied across the age spectrum and are associated with cardiovascular disease, heart failure, and mortality in older adults 32‐34 …”

Section: Introductionmentioning

confidence: 99%

Association of Non‐Steroidal Anti‐Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

Amatruda

Katz

Peralta

et al. 2020

J American Geriatrics Society

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Background/Objectives Non‐steroidal anti‐inflammatory drugs (NSAIDs) can cause kidney injury, especially in older adults. However, previously reported associations between NSAID use and kidney health outcomes are inconsistent and limited by reliance on serum creatinine‐based GFR estimates. This analysis investigated the association of NSAID use with kidney damage in older adults using multiple kidney health measures. Design Cross‐sectional and longitudinal analyses. Setting Multicenter, community‐based cohort. Participants Two thousand nine hundred and ninty nine older adults in the Health ABC Study. A subcohort (n = 500) was randomly selected for additional biomarker measurements. Exposure Prescription and over‐the‐counter NSAID use ascertained by self‐report. Measurements Baseline estimated glomerular filtration rate (eGFR) by cystatin C (cysC), urine albumin‐to‐creatinine ratio (ACR), kidney injury molecule‐1 (KIM‐1), and interleukin‐18 (IL‐18) were measured in 2,999 participants; alpha‐1 microglobulin (α1m), neutrophil gelatinase‐associated lipocalin (NGAL), propeptide type III procollagen (PIIINP), and uromodulin (UMOD) were measured in 500 participants. GFR was estimated three times over 10 years and expressed as percent change per year. Results Participants had a mean age of 74 years, 51% were female, and 41% African‐American. No eGFR differences were detected between NSAID users (n = 655) and non‐users (n = 2,344) at baseline (72 ml/min/1.73 m2 in both groups). Compared to non‐users, NSAID users had lower adjusted odds of having ACR greater than 30 mg/g (0.67; 95% confidence interval (CI) = 0.51–0.89) and lower mean urine IL‐18 concentration at baseline (−11%; 95% CI = −4% to −18%), but similar mean KIM‐1 (5%; 95% CI = −5% to 14%). No significant differences in baseline concentrations of the remaining urine biomarkers were detected. NSAID users and non‐users did not differ significantly in the rate of eGFR decline (−2.2% vs ‐2.3% per year). Conclusion Self‐reported NSAID use was not associated with kidney dysfunction or injury based on multiple measures, raising the possibility of NSAID use without kidney harm in ambulatory older adults. More research is needed to define safe patterns of NSAID consumption.

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Subclinical Kidney Injury in Children Receiving Nonsteroidal Anti-Inflammatory Drugs After Cardiac Surgery

Cited by 16 publications

References 35 publications

A novel strategy for identifying early acute kidney injury in pediatric hematopoietic stem cell transplantation

A novel strategy for identifying early acute kidney injury in pediatric hematopoietic stem cell transplantation

Cardiopulmonary Bypass and AKI: AKI Is Bad, So Let's Get Beyond the Diagnosis

Association of Non‐Steroidal Anti‐Inflammatory Drugs with Kidney Health in Ambulatory Older Adults

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