Pediatric Acute Kidney Injury Research Articles

Long-term Health Care Utilization and Associated Costs After Dialysis-Treated Acute Kidney Injury in Children

Acute kidney injury (AKI) is common among hospitalized children and is associated with increased hospital length of stay and costs. However, there are limited data on postdischarge health care utilization after AKI hospitalization. Our objectives were to evaluate health care utilization and physician follow-up patterns after dialysis-treated AKI in a pediatric population. Retrospective cohort study, using provincial health administrative databases. All children (0-18 years) hospitalized between 1996 and 2017 in Ontario, Canada. Excluded individuals comprised non-Ontario residents; those with metabolic disorders or poisoning; and those who received dialysis or kidney transplant before admission, a kidney transplant by 104 days after discharge, or were receiving dialysis 76-104 days from dialysis start date. Episodes of dialysis-treated AKI, identified using validated health administrative codes. AKI survivors were matched to 4 hospitalized controls without dialysis-treated AKI by age, sex, and admission year. Our primary outcome was postdischarge hospitalizations, emergency department visits, and outpatient physician visits. Secondary outcomes included outpatient visits by physician type and composite health care costs. Proportions with≥1 event and rates (per 1,000 person-years). Total and median composite health care costs. Adjusted rate ratios using negative binomial regression models. We included 1,688 pediatric dialysis-treated AKI survivors and 6,752 matched controls. Dialysis-treated AKI survivors had higher rehospitalization and emergency department visit rates during the analyzed follow-up periods (0-1, 0-5, and 0-10 years postdischarge, and throughout follow-up), and higher outpatient visit rates in the 0-1-year follow-up period. The overall adjusted rate ratio for rehospitalization was 1.46 (95% CI, 1.25-1.69; P<0.0001) and for outpatient visits was 1.16 (95% CI, 1.09-1.23; P=0.01). Dialysis-treated AKI survivors also had higher health care costs. Nephrologist follow-up was infrequent among dialysis-treated AKI survivors (18.6% by 1 year postdischarge). Potential miscoding of study exposures or outcomes. Residual uncontrolled confounding. Data for health care costs and emergency department visits was unavailable before 2006 and 2001, respectively. Dialysis-treated AKI survivors had greater postdischarge health care utilization and costs versus hospitalized controls. Strategies are needed to improve follow-up care for children after dialysis-treated AKI to prevent long-term complications.

Comparison of diagnostic criteria for acute kidney injury in critically ill children: a multicenter cohort study

BackgroundSubstantial interstudy heterogeneity exists in defining acute kidney injury (AKI) and baseline serum creatinine (SCr). This study assessed AKI incidence and its association with pediatric intensive care unit (PICU) mortality under different AKI and baseline SCr definitions to determine the preferable approach for diagnosing pediatric AKI.MethodsIn this multicenter prospective observational cohort study, AKI was defined and staged according to the Kidney Disease: Improving Global Outcome (KDIGO), modified KDIGO, and pediatric reference change value optimized for AKI (pROCK) definitions. The baseline SCr was calculated based on the Schwartz formula or estimated as the upper normative value (NormsMax), admission SCr (AdmSCr) and modified AdmSCr. The impacts of different AKI definitions and baseline SCr estimation methods on AKI incidence, severity distribution and AKI outcome were evaluated.ResultsDifferent AKI definitions and baseline SCr estimates led to differences in AKI incidence, from 6.8 to 25.7%; patients with AKI across all definitions had higher PICU mortality ranged from 19.0 to 35.4%. A higher AKI incidence (25.7%) but lower mortality (19.0%) was observed based on the Schwartz according to the KDIGO definition, which however was overcome by modified KDIGO (AKI incidence: 16.3%, PICU mortality: 26.1%). Furthermore, for the modified KDIGO, the consistencies of AKI stages between different baseline SCr estimation methods were all strong with the concordance rates > 90.0% and weighted kappa values > 0.8, and PICU mortality increased pursuant to staging based on the Schwartz. When the NormsMax was used, the KDIGO and modified KDIGO led to an identical AKI incidence (13.6%), but PICU mortality did not differ among AKI stages. For the pROCK, PICU mortality did not increase pursuant to staging and AKI stage 3 was not associated with mortality after adjustment for confounders.ConclusionsThe AKI incidence and staging vary depending on the definition and baseline SCr estimation method used. The modified KDIGO definition based on the Schwartz method leads AKI to be highly relevant to PICU mortality, suggesting that it may be the preferable approach for diagnosing AKI in critically ill children and provides promise for improving clinicians’ ability to diagnose pediatric AKI.

The Neglected Price of Pediatric Acute Kidney Injury: Non-renal Implications.

Preclinical models and emerging translational data suggest that acute kidney injury (AKI) has far reaching effects on all other major organ systems in the body. Common in critically ill children and adults, AKI is independently associated with worse short and long term morbidity, as well as mortality, in these vulnerable populations. Evidence exists in adult populations regarding the impact AKI has on life course. Recently, non-renal organ effects of AKI have been highlighted in pediatric AKI survivors. Given the unique pediatric considerations related to somatic growth and neurodevelopmental consequences, pediatric AKI has the potential to fundamentally alter life course outcomes. In this article, we highlight the challenging and complex interplay between AKI and the brain, heart, lungs, immune system, growth, functional status, and longitudinal outcomes. Specifically, we discuss the biologic basis for how AKI may contribute to neurologic injury and neurodevelopment, cardiac dysfunction, acute lung injury, immunoparalysis and increased risk of infections, diminished somatic growth, worsened functional status and health related quality of life, and finally the impact on young adult health and life course outcomes.

Trajectory of kidney recovery in pediatric patients requiring continuous kidney replacement therapy for acute kidney injury.

Acute kidney injury (AKI) is commonly seen in the PICU and is associated with poor short-term and long-term outcomes, especially in patients who required continuous kidney replacement therapy (CKRT). However, as the trajectory of kidney recovery in these patients remain uncertain, determination of the timing to convert to permanent kidney replacement therapy (KRT) remains a major challenge. We aimed to examine the frequency and timing of kidney recovery in pediatric AKI survivors that required CKRT. We performed a retrospective study of patients under 18years old who received CKRT for AKI in a tertiary-care PICU over 6years. Primary outcomes were the rate of KRT withdrawal due to kidney recovery and KRT-dependent days for those who survived to hospital discharge. Secondary outcomes were all-cause mortality, dialysis dependence, and occurrences of estimated glomerular filtration rate (eGFR) < 90mL/min/1.73m2 and eGFR < 60mL/min/1.73m2 one year after initiation of the index CKRT in survivors. Thirty-nine patients were included. Of the 28 children who survived to hospital discharge, 26 (93%) withdrew from dialysis due to kidney recovery, all within 30days. Twenty-three patients were followed up. One had died, five had an eGFR of 60mL/min/1.73m2 or more but less than 90mL/min/1.73m2, and two had an eGFR < 60mL/min/1.73m2, of which one required peritoneal dialysis. Over 90% of the survivors withdrew CKRT within 30days. However, the frequency of abnormal eGFR one year after initiation of CKRT in survivors exceeded 30% and supports the recommendation of post-AKI follow-up.

Outcome prediction for acute kidney injury among hospitalized children via eXtreme Gradient Boosting algorithm

Acute kidney injury (AKI) is common among hospitalized children and is associated with a poor prognosis. The study sought to develop machine learning-based models for predicting adverse outcomes among hospitalized AKI children. We performed a retrospective study of hospitalized AKI patients aged 1 month to 18 years in the Second Xiangya Hospital of Central South University in China from 2015 to 2020. The primary outcomes included major adverse kidney events within 30 days (MAKE30) (death, new renal replacement therapy, and persistent renal dysfunction) and 90-day adverse outcomes (chronic dialysis and death). The state-of-the-art machine learning algorithm, eXtreme Gradient Boosting (XGBoost), and the traditional logistic regression were used to establish prediction models for MAKE30 and 90-day adverse outcomes. The models’ performance was evaluated by split-set test. A total of 1394 pediatric AKI patients were included in the study. The incidence of MAKE30 and 90-day adverse outcomes was 24.1% and 8.1%, respectively. In the test set, the area under the receiver operating characteristic curve (AUC) of the XGBoost model was 0.810 (95% CI 0.763–0.857) for MAKE30 and 0.851 (95% CI 0.785–0.916) for 90-day adverse outcomes, The AUC of the logistic regression model was 0.786 (95% CI 0.731–0.841) for MAKE30 and 0.759 (95% CI 0.654–0.864) for 90-day adverse outcomes. A web-based risk calculator can facilitate the application of the XGBoost models in daily clinical practice. In conclusion, XGBoost showed good performance in predicting MAKE30 and 90-day adverse outcomes, which provided clinicians with useful tools for prognostic assessment in hospitalized AKI children.

Derivation and evaluation of baseline creatinine equations for hospitalized children and adolescents: the AKI baseline creatinine equation.

Acute kidney injury (AKI) definitions incorporate baseline creatinine (Crb) values, but Crb are frequently unknown in pediatrics. Our primary aim was to derive and validate a novel AKI Baseline Creatinine (ABC) estimation equation and compare it to existing methods of estimating Crb values. We conducted a single-center retrospective analysis of pediatric patients (0-25years) admitted from 2012 to 2019. Included patients required at least one outpatient Crb prior to hospitalization (gold standard). Novel equations were developed with demographic and initial creatinine data. Existing methods included back-calculating Crb based on Schwartz, Full Age Spectrum (FAS), and CKiD-under-25 (U25) equations. To determine an optimal equation, we compared novel and existing equations to the gold standard. The optimal simplified equation (ABC) included only age and had R2 = 59.9% and 73.2% of values within 30% of true Crb. The precision increased significantly when the equation included age and minimum creatinine within initial 72h (ABC-cr): R2 = 75.4% and 86.5% of values within 30% of true Crb. The best performing existing equation was the age-based FAS, which had R2 = 61.0% and 78.0% of values within 30% of true Crb. All other existing equations performed worse, some methods as low as 52.6% within 30% of true Crb. The newly derived ABC equation is simple, and the ABC-cr equation can more accurately estimate Crb by ≥ 25% compared to previous methods. The potential applicability of these equations is vast, including faster recognition of AKI on initial patient contact and improved standardization of pediatric AKI definitions, enhancing health services research. A higher resolution version of the Graphical abstract is available as Supplementary information.

MO1024: Exposures and Susceptibilities in Paediatric Acute Kidney Injury—Impact on Awareness and Survival

Abstract BACKGROUND AND AIMS Acute kidney injury (AKI) is a growing global healthcare problem in the adult and paediatric population. In comparison with the adult population where the coexisting chronic conditions (e.g. diabetes, hypertension) increase the mortality risk during AKI, in children without chronic conditions one can assess the direct impact of AKI on mortality. Current paediatric studies state the need for increased awareness of AKI, for identifying susceptibilities and for the need to correct modifiable exposures in order to improve outcomes. METHOD We conducted a retrospective observational study in the ‘Louis Turcanu’ Emergency County Hospital for Children in Timisoara, Romania. Data were extracted from the hospital electronic database, between 1 January 2014 and 31 December 2020. The study cohort included 127 457 patients (aged 1 day–18 years) who had at least two serum creatinine levels determined during the same hospital admission. AKI was defined and staged according to Kidney Disease Improving Global Outcome (KDIGO) guidelines (and 2021 Consensus Conference) using Acute Kidney Injury Network (AKIN) criteria. Baseline serum creatinine was considered the nadir serum creatinine in 7 days from admission. AKI awareness in different medical clinics was considered the recognition of AKI diagnosis during admission as noted in the medical records according to ICD-10 Clinical Modification codes (N17.0, N17.1, N17.2, N17.8, N19, N99.0 and P96.0). AKI non-awareness was considered in patients presenting AKI according to AKIN without diagnoses recognition in the medical reports. RESULTS Over the 7-year study, 1867 patients developed AKI (out of 127 457 hospital admissions). The overall AKI incidence was 1.46%. The diagnosis of AKI was lacking (non-awareness) in 72.5% of AKI cases. We evaluated the exposures and susceptibilities of AKI patients and their impact on awareness and mortality. Taking into account the fact that the study addressed paediatric patients, exposures and susceptibilities have been changed accordingly. The considered exposures were: sepsis, critical illness, circulatory shock, burns, trauma, major non-cardiac surgery, nephrotoxic drugs, contact with poisonous plants and mechanical ventilation. Our regression equation proved to be a good fit for the model, explaining only 3.8% of AKI awareness (R2 = 0.038) and 22.9% of death events (R2 = 0.229). AKI awareness increases with the presence of dehydration (by 2.29-fold, P &amp;lt; .05) and heart failure (by 2.54-fold, P &amp;lt; .001). The risk of death increases with the presence of prematurity (by 2.33-fold, P &amp;lt; .0001), cancer (by 2.45-fold, P &amp;lt; .0001), anaemia (by 4.06-fold, P &amp;lt; .0001) and chronic illness (by 2.65-fold, P &amp;lt; .0001). The susceptibilities were: female gender, chronic kidney disease, chronic diseases (heart, lung, liver), diabetes mellitus, cancer, anaemia, very low birth weight, heart failure, arterial hypertension and stem cell transplant. Our regression equation proved to be a good fit for the model, explaining only 9.4% of AKI awareness (R2 = 0.094) and 43.6% of deaths (R2 = 0.436). The awareness increases with the presence of sepsis (by 1.73-fold, P &amp;lt; .0001), of critical illness (by 2.41-fold, P &amp;lt; .0001) and mechanical ventilation (by 1.54-fold, P &amp;lt; .0001). The risk of death increases in the presence of sepsis (by 3.26-fold, P &amp;lt; .0001), of critical illness (by 7.42-fold, P &amp;lt; .0001), of mechanical ventilation (by 10.58-fold, P &amp;lt; .0001) and hypovolemic shock (by 10.58-fold, P &amp;lt; .0001). CONCLUSION The presence of more severe exposures and susceptibilities increased the awareness of AKI but also increased the risk of death. The diagnosis of AKI in our medical records is late, therefore late diagnosis has no benefits concerning the evolution and mortality of paediatric patients with AKI.

Long-Term Healthcare Cost Savings of a Pediatric Nephrotoxic Medication-Associated Acute Kidney Injury Reduction Program in a Simulated Sample

Background: Nephrotoxic medication exposure is a common cause of acute kidney injury (AKI) in hospitalized children and is associated with chronic kidney disease (CKD). The pharmacist-reliant NINJA program reduced nephrotoxic medication exposure and associated AKI. Objectives: We assess potential healthcare cost savings from reduced CKD by preventing AKI with the NINJA program for a pediatric population through age 21. Methods: We simulated a cohort of 1000 hospitalized non-critically ill children. From the published literature, 310 develop AKI, 267 survive to 6 months, and 10-70% develop CKD, and NINJA implementation reduced AKI by 23.8%. Allowing for varying CKD rates, we estimated a range of NINJA’s savings. We assumed an annual GFR decline of 1.2 (noHTN) ml/min/1.73 m2 for half the sample and 1.7 (HTN) ml/min/1.73 m2 for the other half to account for CKD progression without and with hypertension (HTN). We model attributable costs including CKD stage-related medications and outpatient visits/tests in 2018 dollars discounted at 3%. We subtract the cost of NINJA screening (daily serum creatinine and pharmacist time) from net savings. We exclude end-stage renal disease (ESRD) and hospitalization costs. Results: No intervention estimated CKD related costs are $761,852 to $5,735,027. Post-NINJA cost decreases to $616,086 to $4,312,183 (net savings: $145,766 to $1,422 183). Total savings, accounting for NINJA screening ($256,680) are -$110,914 to $1,1 165 503. The breakeven AKI to CKD conversion rate is 13-14% with growth hormone cost included, and 64-65% without. Conclusion: The NINJA program is likely cost beneficial, with greater savings into adulthood by avoiding/delaying ESRD and its costs.

Perioperative acute kidney injury: impact and recent update.

Acute kidney injury (AKI) is common in hospitalized patients and is a major risk factor for increased length of stay, morbidity, and mortality in postoperative patients. There are multiple barriers to reducing perioperative AKI - the etiology is multi-factorial and the diagnosis is fraught with issues. We review the recent literature on perioperative AKI and some considerations for anesthesiologists that examine the far-reaching effects of AKI on multiple organ systems. This review will discuss recent literature that addresses the epidemiology, use of novel biomarkers in risk stratification, and therapeutic modalities for AKI in burn, pediatrics, sepsis, trauma, cardiac, and liver disease, contrast-induced AKI, as well as the evidence assessing goal-directed fluid therapy. Recent studies address the use of risk stratification models and biomarkers, more sensitive than creatinine, in the preoperative identification of patients at risk for AKI. Although exciting, these scores and models need validation. There is a need for research assessing whether early AKI detection improves outcomes. Enhanced recovery after surgery utilizing goal-directed fluid therapy has not been shown to make an appreciable difference in the incidence of AKI. Reducing perioperative AKI requires a multi-pronged and possibly disease-specific approach.

Association of Nonrecovery of Kidney Function After Pediatric Acute Kidney Injury With 5-Year Kidney and Nonkidney Outcomes.

Evaluated whether nonrecovery of kidney function, following acute kidney injury, was associated with postdischarge mortality, healthcare utilization, and chronic kidney disease. Retrospective, two-center, observational study. Two ICUs at tertiary children's hospitals in Montreal, QC. Pediatric patients (age ≤ 18 yr) with index admission to intensive care between January 1, 2003, and March 31, 2005. Children were excluded if they 1) died during admission, 2) did not have serum creatinine or urine output measured, 3) did not develop acute kidney injury, 4) could not be linked to administrative health data, and 5) (for chronic kidney disease outcome) had pre-existing renal disease by chart review, baseline estimated glomerular filtration rate measurement, or administrative health data codes. Three-hundred seventy-eight patients' data were included for long-term mortality and healthcare utilization outcomes; 316 patients for long-term chronic kidney disease outcome. Outcomes were defined using provincial administrative healthcare data diagnosis, procedure, and billing codes. Nonrecovery of kidney function, defined as serum creatinine greater than or equal to 1.5× baseline at ICU discharge, occurred in 51 patients (13%). Nonrecovery of kidney function was not associated with long-term mortality (at 5-7 yr following hospital discharge), increased hospitalizations or emergency department visits (at 30-days, 1-year, and 5-yr follow-up), or increased physician visits (at 1- and 5-yr follow-up). Nonrecovery was associated with increased 30-day physician visits (adjusted relative risk, 1.40; 95% CI, 1.13-1.73) and chronic kidney disease diagnosis within 5 years of discharge (adjusted hazard ratio, 4.92, 95% CI, 1.77-13.70). Nonrecovery of kidney function following an episode of acute kidney injury in critically ill children is associated with nearly five-fold increased risk for long-term chronic kidney disease. Acute kidney injury nonrecovery may be a useful marker to identify patients that are particularly important to follow-up post discharge for chronic kidney disease detection.

Major adverse kidney events after acute kidney injury in the pediatric intensive care unit: a propensity score-matched cohort study.

Acute kidney injury (AKI) in patients admitted to the pediatric intensive care unit (PICU) is associated with poor short-term and long-term outcomes. Greater awareness of long-term AKI-associated outcomes is needed to optimally plan follow-up and management after ICU discharge. We used propensity score methods to study associations between pediatric AKI and major adverse kidney outcomes, including mortality. We included all children 6 months-18 years admitted to PICU at Seattle Children's Hospital from 7/1/2009 to 12/31/2018. Our primary outcome measure was Major Adverse Kidney Events at 30 days (MAKE30): creatinine > 200% of baseline, eGFR < 60 mL/min/1.73 m2, dialysis dependence, or mortality. Propensity scores for AKI development in PICU were generated using demographic, medical history, admission, and PICU hospitalization variables. Patients with AKI were matched to control patients without AKI. Logistic regression was used to test association between AKI status and MAKE30. In the unmatched cohort (n = 878), patients with AKI had lower platelet count (160 vs. 222) and higher PRISM III score (11 vs. 3.5). After propensity score matching, those with AKI vs. no AKI had similar PRISM III scores (9 vs. 10) and platelet count (163 vs. 159). AKI was significantly associated with MAKE30 after propensity score matching (OR: 2.97; 95% CI 1.82-4.84). Propensity score matching significantly reduced imbalance in baseline characteristics between those with and without AKI. After matching, AKI remained significantly associated with MAKE30. Patients who developed AKI were more likely to have abnormal kidney function at 30 and 90 days after ICU admission and may be at high risk for developing CKD in the future. A higher resolution version of the Graphical abstract is available as Supplementary information.

Urinary metabolomics to develop predictors for pediatric acute kidney injury.

Acute kidney injury (AKI) is characterized by an abrupt decline in glomerular filtration rate (GFR). We sought to identify separate early urinary metabolomic signatures at AKI onset (with-AKI) and prior to onset of functional impairment (pre-AKI). Pre-AKI (n=15), AKI (n=22), and respective controls (n=30) from two prospective PICU cohort studies provided urine samples which were analyzed by GC-MS and DI-MS mass spectrometry (193 metabolites). The cohort (n=58) was 8.7±6.4 years old and 66% male. AKI patients had longer PICU stays, higher PRISM scores, vasopressors requirement, and respiratory diagnosis and less commonly had trauma or post-operative diagnosis. Urine was collected within 2-3 days after admission and daily until day 5 or 14. The metabolite classifiers for pre-AKI samples (1.5±1.1 days prior to AKI onset) had a cross-validated area under receiver operator curve (AUC)=0.93 (95%CI 0.85-1.0); with-AKI samples had an AUC=0.94 (95%CI 0.87-1.0). A parsimonious pre-AKI classifier with 13 metabolites was similarly robust (AUC=0.96, 95%CI 0.89-1.0). Both classifiers were similar and showed modest correlation of high-ranking metabolites (tau=0.47, p<0.001). This exploratory study demonstrates the potential of a urine metabolite classifier to detect AKI-risk in pediatric populations earlier than the current standard of diagnosis with the need for external validation. A higher resolution version of the Graphical abstract is available as Supplementary information with inner reference to ESM for GA.

Clinical Outcomes of Renal Replacement Therapy in Pediatric Acute Kidney Injury: A 10-Year Retrospective Observational Study

Children with severe acute kidney injury (AKI) have had a high mortality rate despite the use of advanced renal replacement therapy (RRT). This study aims to determine the clinical outcomes and the predictors of survival in pediatric AKI requiring RRT in Thailand. All patients aged 1 month to 18 years with AKI requiring RRT in the Department of Pediatrics, Ramathibodi Hospital from January 1st, 2010 to December 31st, 2019 were enrolled. Clinical and laboratory data were obtained through a medical record review. There were 92 patients with a 45% survival rate. Five factors associated with mortality included multi-organ dysfunction syndrome, presence of sepsis, high pediatric risk of mortality III, use of nephrotoxic drugs, and use of vasopressors. By multivariate analysis, the presence of sepsis and the use of nephrotoxic drugs were independently associated with mortality. Patients with fluid overload ≥10% was associated with poor survival.

Urine Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 to Detect Pediatric Cisplatin-Associated Acute Kidney Injury.

Few studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin. Participants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher). Of 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65). Urine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Acute kidney injury in pediatrics: an overview focusing on pathophysiology.

Acute kidney injury (AKI) is defined as an abrupt decline in glomerular filtration rate, with increased serum creatinine and nitrogenous waste products due to several possible etiologies. Incidence in the pediatric population is estimated to be 3.9 per 1,000 hospitalizations, and prevalence among children admitted to intensive care units is 26.9%. Despite being a condition with important incidence and morbimortality, further evidence on pathophysiology and management among the pediatric population is still lacking. This narrative review aimed to summarize and discuss current data on AKI pathophysiology in the pediatric population, considering all the physiological particularities of this age range and common etiologies. Additionally, we reported current diagnostic tools, novel biomarkers, and newly proposed medications that have been studied with the aim of early diagnosis and appropriate treatment of AKI in the future.

Outpatient Nephrotoxic Medication Prescription after Pediatric Intensive Care Acute Kidney Injury.

Background: Nephrotoxic medication (NTM) avoidance may prevent further kidney damage in children with acute kidney injury (AKI). We compared outpatient NTM prescriptions in children with or without AKI during pediatric intensive care (PICU) hospitalization. We hypothesize that children with AKI are prescribed NTMs at the same rate as those without it. Methods: This was a retrospective administrative data study of children <18 years, admitted to two PICUs in Montreal, Canada, from 2003 to 2005, with ≥30 days of provincial drug coverage. We evaluated the presence of ≥3 outpatient NTM prescriptions during the first year and 5 years after PICU discharge. Results: Of 970 children, 23% had PICU AKI. In the 1st–5th years after discharge, 18% AKI vs. 10% non-AKI and 13% AKI vs. 4% non-AKI patients received ≥3 NTM prescriptions, respectively. There was no association between PICU AKI and prescription of ≥3 NTMs during the first year (adjusted RR 1.02 [95% CI 0.95–1.10]) nor in the first 5 years post-discharge (adjusted RR 1.04 [95%CI 0.96–1.12]). Conclusions: By offering a better understanding of the current state of outpatient NTM prescription to children with AKI, our study is a step toward considering strategies such as knowledge translation interventions for decreasing NTM exposure and improving outcomes in children with AKI.

Early and late acute kidney injury: temporal profile in the critically ill pediatric patient.

ABSTRACTBackgroundIncreasing AKI diagnosis precision to refine the understanding of associated epidemiology and outcomes is a focus of recent critical care nephrology research. Timing of onset of acute kidney injury (AKI) during pediatric critical illness and impact on outcomes has not been fully explored.MethodsThis was a secondary analysis of the Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) database. AKI was defined as per Kidney Disease: Improving Global Outcomes criteria. Early AKI was defined as diagnosed at ≤48 h after intensive care unit (ICU) admission, with any diagnosis >48 h denoted as late AKI. Transient AKI was defined as return to baseline serum creatinine ≤48 h of onset, and those without recovery fell into the persistent category. A second incidence of AKI ≥48 h after recovery was denoted as recurrent. Patients were subsequently sorted into distinct phenotypes as early-transient, late-transient, early-persistent, late-persistent and recurrent. Primary outcome was major adverse kidney events (MAKE) at 28 days (MAKE28) or at study exit, with secondary outcomes including AKI-free days, ICU length of stay and inpatient renal replacement therapy.ResultsA total of 1262 patients had AKI and were included. Overall mortality rate was 6.4% (n = 81), with 34.2% (n = 432) fulfilling at least one MAKE28 criteria. The majority of patients fell in the early-transient cohort (n = 704, 55.8%). The early-persistent phenotype had the highest odds of MAKE28 (odds ratio 7.84, 95% confidence interval 5.45–11.3), and the highest mortality rate (18.8%). Oncologic and nephrologic/urologic comorbidities at AKI diagnosis were associated with MAKE28.ConclusionTemporal nature and trajectory of AKI during a critical care course are significantly associated with patient outcomes, with several subtypes at higher risk for poorer outcomes. Stratification of pediatric critical care-associated AKI into distinct phenotypes is possible and may become an important prognostic tool.

Controversies in paediatric acute kidney injury and continuous renal replacement therapy: can paediatric care lead the way to precision acute kidney injury medicine?

Paediatric patients represent a unique challenge for providers managing acute kidney injury (AKI). Critical care for these children requires a precise approach to assessment, diagnostics and management. Primarily based on observational data, large epidemiologic datasets have demonstrated a strong association between AKI prevalence (one in four critically ill children) and poor patient outcome. Drivers of AKI itself are multifactorial and the causal links between AKI and host injury remain incompletely defined, creating a management paradigm primarily supportive in nature. The previous decades of research have focused primarily on elucidating the population-level epidemiologic signal of AKI and use of renal replacement therapy (RRT), but in order to reverse the course of the AKI 'epidemic', future decades will require more attention to the individual patient. A patient-level approach to AKI in children will require sophisticated approaches to risk stratification, diagnostics and targeted utilization of therapies (both supportive and targeted towards drivers of injury). In this review, we will summarize the past, present and future of AKI care in children, discussing the ongoing work and future goals of a personalized approach to AKI medicine.

Machine learning model for early prediction of acute kidney injury (AKI) in pediatric critical care

BackgroundAcute kidney injury (AKI) in pediatric critical care patients is diagnosed using elevated serum creatinine, which occurs only after kidney impairment. There are no treatments other than supportive care for AKI once it has developed, so it is important to identify patients at risk to prevent injury. This study develops a machine learning model to learn pre-disease patterns of physiological measurements and predict pediatric AKI up to 48 h earlier than the currently established diagnostic guidelines.MethodsEHR data from 16,863 pediatric critical care patients between 1 month to 21 years of age from three independent institutions were used to develop a single machine learning model for early prediction of creatinine-based AKI using intelligently engineered predictors, such as creatinine rate of change, to automatically assess real-time AKI risk. The primary outcome is prediction of moderate to severe AKI (Stage 2/3), and secondary outcomes are prediction of any AKI (Stage 1/2/3) and requirement of renal replacement therapy (RRT). Predictions generate alerts allowing fast assessment and reduction of AKI risk, such as: “patient has 90% risk of developing AKI in the next 48 h” along with contextual information and suggested response such as “patient on aminoglycosides, suggest check level and review dose and indication”.ResultsThe model was successful in predicting Stage 2/3 AKI prior to detection by conventional criteria with a median lead-time of 30 h at AUROC of 0.89. The model predicted 70% of subsequent RRT episodes, 58% of Stage 2/3 episodes, and 41% of any AKI episodes. The ratio of false to true alerts of any AKI episodes was approximately one-to-one (PPV 47%). Among patients predicted, 79% received potentially nephrotoxic medication after being identified by the model but before development of AKI.ConclusionsAs the first multi-center validated AKI prediction model for all pediatric critical care patients, the machine learning model described in this study accurately predicts moderate to severe AKI up to 48 h in advance of AKI onset. The model may improve outcome of pediatric AKI by providing early alerting and actionable feedback, potentially preventing or reducing AKI by implementing early measures such as medication adjustment.

Acute kidney injury in critically Ill children and young adults with suspected SARS-CoV2 infection.

BackgroundWe aimed to study the association of suspected versus confirmed infection with the novel SARS-CoV2 virus with the prevalence of acute kidney injury (AKI) in critically ill children.MethodsSequential point-prevalence study of children and young adults aged 7 days to 25 years admitted to intensive care units under investigation for SARS-CoV2 infection. AKI was staged in the first 14 days of enrollment using KDIGO creatinine-based staging. SARS-CoV2 positive (CONFIRMED) were compared to SUSPECTED (negative or unknown). Outcome data was censored at 28-days.ResultsIn 331 patients of both sexes, 179 (54.1%) were CONFIRMED, 4.2% (14) died. AKI occurred in 124 (37.5%) and severe AKI occurred in 63 (19.0%). Incidence of AKI in CONFIRMED was 74/179 (41.3%) versus 50/152 (32.9%) for SUSPECTED; severe AKI occurred in 35 (19.6%) of CONFIRMED and 28 (18.4%) of SUSPECTED. Mortality was 6.2% (n = 11) in CONFIRMED, but 9.5% (n = 7) in those CONFIRMED with AKI. On multivariable analysis, only Hispanic ethnicity (relative risk 0.5, 95% CI 0.3–0.9) was associated with less AKI development among those CONFIRMED.ConclusionsAKI and severe AKI occur commonly in critically ill children with SARS-CoV2 infection, more than double the historical standard. Further investigation is needed during this continuing pandemic to describe and refine the understanding of pediatric AKI epidemiology and outcomes.Trial registrationNCT01987921.Impact What is the key message of the article? AKI occurs in children exposed to the novel SARS-CoV2 virus at high prevalence (~40% with some form of AKI and 20% with severe AKI). What does it add to the existing literature? Acute kidney injury (AKI) occurs commonly in adult patients with SARS-CoV2 (COVID), very little data describes the epidemiology of AKI in children exposed to the virus. What is the impact? A pediatric vaccine is not available; thus, the pandemic is not over for children. Pediatricians will need to manage significant end-organ ramifications of the novel SARS-CoV2 virus including AKI.