Acute kidney injury (AKI) is seen frequently in hospitalized patients and is associated with increased risk of mortality and adverse short- and long-term renal and systemic complications. Emerging ...data suggest that AKI is a heterogenous syndrome with a variety of underlying causes, predisposing illnesses, and range of clinical trajectories and outcomes. This mini-review aims to discuss emerging AKI subphenotype classifications as our understanding of the heterogeneity and underlying pathophysiology has improved.
Background
Continuous kidney replacement therapy (CKRT) has become an integral part of the care of critically ill children. However, uncertainty exists regarding the current state of how CKRT is ...prescribed and delivered in children. The main objective of this study was to identify the current practices for pediatric CKRT.
Methods
We conducted a systematic review of the literature from 2012 to 2022 to identify data regarding CKRT timing of initiation, dosing, anticoagulation, fluid removal, and quality monitoring. Using this data, we then performed a two-round modified Delphi process using a multinational internet-assisted survey of prescribers of CKRT.
Results
The survey was constructed using 172 articles that met inclusion criteria (12% of studies were pediatric focused). A total of 147 and 126 practitioners completed the survey in rounds 1 and 2, respectively. Participants represented Europe (9.5–11.6%) and North America including pediatric intensivists, nephrologists, and advance practice providers. Consensus (defined as a ≥ 75% participant response of “sometimes” or “always”) was achieved for 26 statements. There was consensus in the practices of CKRT initiation, dosing, method of anticoagulation, and fluid removal. In contrast, there appears to be greater variability in the methods used for monitoring anticoagulation and the quality of the delivered treatment.
Conclusions
Our study results suggest that the current state of pediatric CKRT practice is reflective of the literature over the last 10 years, which is largely based on the care of adult patients. This data provides a framework to study best practices to further improve outcomes for children receiving CKRT.
Graphical abstract
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Supplementary information
Acute kidney injury after cardiac surgery (CS-AKI) is common in neonatal and pediatric populations and is a risk factor for poor outcomes, such as mortality and increased hospital resource ...utilization. This review presents a summary of CS-AKI risk factors, integration of biomarkers, and the need to improve risk stratification for targeting future clinical trials. To date, studies examining CS-AKI risk factors cannot be generalized easily owing to variability in patient age, surgical complexity or population, AKI definition, and center-specific practices. However, certain risk associations, such as younger age at surgery, history of prematurity, cardiopulmonary bypass time, and surgical complexity, have been identified across multiple, but not all, studies. CS-AKI appears to have different severity and duration phenotypes, and serum creatinine is limited in its ability to identify CS-AKI early and predict CS-AKI course. Treatment strategies are largely supportive, and efforts are ongoing to use biomarkers and clinical features to risk-stratify patients, which in turn may facilitate differential CS-AKI phenotyping and management with supportive care bundles, clinical decision support techniques, and modulation of modifiable risk factors.
Acute kidney injury (AKI) is a common and serious medical condition associated with significant increases in morbidity, mortality, and cost of care. Because of the high incidence and poor outcomes ...associated with AKI, there has been significant interest in the development of new therapies for the prevention and treatment of the disease. A lack of efficacy in drug trials led to the concern that AKI was not being diagnosed early enough for an effective intervention and that a rise in serum creatinine itself is not a sensitive-enough marker. Researchers have been searching for novel biomarkers that can not only assess a decline in kidney function but also demonstrate structural damage to the kidney and at time points earlier than increases in serum creatinine measurements allow. Over the past 10 years, there have been 3300 new publications and hundreds of new biomarkers investigated, yet concern still remains regarding AKI biomarker performance. The AKI biomarkers are yet to be widely utilized in clinical practice, leading some to question whether AKI biomarkers will ever reach their initial promise. However, we believe that biomarkers are an important part of current and future AKI research and clinical management. In this review, we compare the historical contexts of acute myocardial ischemia and AKI biomarker development to illustrate the progress that has been made within AKI biomarker research in a relatively short period of time and also to point out key differences between the disease processes that have been barriers to widespread AKI biomarker adoption. Finally, we discuss potential paths by which biomarkers can lead to appropriate AKI treatment responses that lower morbidity and mortality.
Severe acute kidney injury (AKI) is associated with subsequent infection. Whether AKI followed by a return to baseline creatinine is associated with incident infection is unknown.
We hypothesized ...that risk of both short and long term infection would be higher among patients with AKI and return to baseline creatinine than in propensity score matched peers without AKI in the year following a non-infectious hospital admission.
Retrospective, propensity score matched cohort study.
We identified 494 patients who were hospitalized between January 1, 1999 and December 31, 2009 and had AKI followed by return to baseline creatinine. These were propensity score matched to controls without AKI.
The predictor variable was AKI defined by International Classification of Diseases, Ninth Revision (ICD-9) codes and by the Kidney Disease Improving Global Outcomes definition, with return to baseline creatinine defined as a decrease in serum creatinine level to within 10% of the baseline value within 7 days of hospital discharge. The outcome variable was incident infection defined by ICD-9 code within 1 year of hospital discharge.
AKI followed by return to baseline creatinine was associated with a 4.5-fold increased odds ratio for infection (odds ratio 4.53 95% CI, 2.43-8.45; p<0.0001) within 30 days following discharge. The association between AKI and subsequent infection remained significant at 31-60 days and 91 to 365 days but not during 61-90 days following discharge.
Among patients from an integrated health care delivery system, non-infectious AKI followed by return to baseline creatinine was associated with an increased odds ratio for infection in the year following discharge.
Cardiac surgery-associated acute kidney injury occurs commonly following congenital heart surgery and is associated with adverse outcomes. This study represents the first multicenter study of ...neonatal cardiac surgery-associated acute kidney injury. We aimed to describe the epidemiology, including perioperative predictors and associated outcomes of this important complication.
This Neonatal and Pediatric Heart and Renal Outcomes Network study is a multicenter, retrospective cohort study of consecutive neonates less than 30 days. Neonatal modification of The Kidney Disease Improving Global Outcomes criteria was used. Associations between cardiac surgery-associated acute kidney injury stage and outcomes (mortality, length of stay, and duration of mechanical ventilation) were assessed through multivariable regression.
Twenty-two hospitals participating in Pediatric Cardiac Critical Care Consortium.
Twenty-two-thousand forty neonates who underwent major cardiac surgery from September 2015 to January 2018.
None.
Cardiac surgery-associated acute kidney injury occurred in 1,207 patients (53.8%); 983 of 1,657 in cardiopulmonary bypass patients (59.3%) and 224 of 583 in noncardiopulmonary bypass patients (38.4%). Seven-hundred two (31.3%) had maximum stage 1, 302 (13.5%) stage 2, 203 (9.1%) stage 3; prevalence of cardiac surgery-associated acute kidney injury peaked on postoperative day 1. Cardiac surgery-associated acute kidney injury rates varied greatly (27-86%) across institutions. Preoperative enteral feeding (odds ratio = 0.68; 0.52-0.9) and open sternum (odds ratio = 0.76; 0.61-0.96) were associated with less cardiac surgery-associated acute kidney injury; cardiopulmonary bypass was associated with increased cardiac surgery-associated acute kidney injury (odds ratio = 1.53; 1.01-2.32). Duration of cardiopulmonary bypass was not associated with cardiac surgery-associated acute kidney injury in the cardiopulmonary bypass cohort. Stage 3 cardiac surgery-associated acute kidney injury was independently associated with hospital mortality (odds ratio = 2.44; 1.3-4.61). No cardiac surgery-associated acute kidney injury stage was associated with duration of mechanical ventilation or length of stay.
Cardiac surgery-associated acute kidney injury occurs frequently after neonatal cardiac surgery in both cardiopulmonary bypass and noncardiopulmonary bypass patients. Rates vary significantly across hospitals. Only stage 3 cardiac surgery-associated acute kidney injury is associated with mortality. Cardiac surgery-associated acute kidney injury was not associated with any other outcomes. Kidney Disease Improving Global Outcomes criteria may not precisely define a clinically meaningful renal injury phenotype in this population.
Neutrophil gelatinase associated lipocalin (NGAL, Lcn2) is the most widely studied biomarker of acute kidney injury (AKI). Previous studies have demonstrated that NGAL is produced by the kidney and ...released into the urine and plasma. Consequently, NGAL is currently considered a tubule specific injury marker of AKI. However, the utility of NGAL to predict AKI has been variable suggesting that other mechanisms of production are present. IL-6 is a proinflammatory cytokine increased in plasma by two hours of AKI and mediates distant organ effects. Herein, we investigated the role of IL-6 in renal and extra-renal NGAL production. Wild type mice with ischemic AKI had increased plasma IL-6, increased hepatic NGAL mRNA, increased plasma NGAL, and increased urine NGAL; all reduced in IL-6 knockout mice. Intravenous IL-6 in normal mice increased hepatic NGAL mRNA, plasma NGAL and urine NGAL. In mice with hepatocyte specific NGAL deletion (Lcn2hep-/-) and ischemic AKI, hepatic NGAL mRNA was absent, and plasma and urine NGAL were reduced. Since urine NGAL levels appear to be dependent on plasma levels, the renal handling of circulating NGAL was examined using recombinant human NGAL. After intravenous recombinant human NGAL administration to mice, human NGAL in mouse urine was detected by ELISA during proximal tubular dysfunction, but not in pre-renal azotemia. Thus, during AKI, IL-6 mediates hepatic NGAL production, hepatocytes are the primary source of plasma and urine NGAL, and plasma NGAL appears in the urine during proximal tubule dysfunction. Hence, our data change the paradigm by which NGAL should be interpreted as a biomarker of AKI.
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Background
Acute kidney injury (AKI) is common in neonatal encephalopathy (NE) and is associated with worse outcomes. Our objectives were to determine the incidence, risk factors, and outcomes of AKI ...in infants with NE.
Methods
We performed a retrospective analysis of infants ≥ 34 weeks’ gestational age with a diagnosis of NE from the Analysis of Worldwide Acute Kidney injury Epidemiology in Neonates (AWAKEN) database. AKI was defined using the modified Kidney Disease Improving Global Outcomes criteria. Perinatal and postnatal factors were evaluated. Multivariate logistic and linear regressions were performed.
Results
One hundred and thirteen patients with NE were included. 41.6% (47) developed AKI. Being born outside the admitting institution (OR 4.3; 95% CI 1.2–14.8;
p
= 0.02), intrauterine growth restriction (OR 10.3, 95% CI 1.1–100.5;
p
= 0.04), and meconium at delivery (OR 2.8, 95% CI 1.04–7.7;
p
= 0.04) conferred increased odds of AKI. After controlling for confounders, infants with AKI stayed in the hospital an average of 8.5 days longer than infants without AKI (95% CI 0.79–16.2 days;
p
= 0.03).
Conclusions
In this multi-national analysis, several important perinatal factors were associated with AKI and infants with both NE and AKI had longer length of stay than NE alone. Future research aimed at early AKI detection, renoprotective management strategies, and understanding the long-term renal consequences is warranted in this high-risk group of patients.
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