Acute kidney injury in the pediatric intensive care unit: outpatient follow-up.

BACKGROUND: Few studies have characterized follow-up after pediatric acute kidney injury (AKI). Our aim was to describe outpatient AKI follow-up after pediatric intensive care unit (PICU) admission. METHODS: Two-center retrospective cohort study (0-18 years; PICU survivors (2003-2005); noncardiac surgery; and no baseline kidney disease). Provincial administrative databases were used to determine outcomes. EXPOSURE: AKI (KDIGO (Kidney Disease: Improving Global Outcomes) definitions). OUTCOMES: post-discharge nephrology, family physician, pediatrician, and non-nephrology specialist visits. Regression was used to evaluate factors associated with the presence of nephrology follow-up (Cox) and the number of nephrology and family physician or pediatrician visits (Poisson), among AKI survivors. RESULTS: Of n = 2041, 355 (17%) had any AKI; 64/355 (18%) had nephrology; 198 (56%) had family physician or pediatrician; and 338 (95%) had family physician, pediatrician, or non-nephrology specialist follow-up by 1 year post discharge. Only 44/142 (31%) stage 2-3 AKI patients had nephrology follow-up by 1 year. Inpatient nephrology consult (adjusted hazard ratio (aHR) 7.76 [95% confidence interval (CI) 4.89-12.30]), kidney admission diagnosis (aHR 4.26 [2.21-8.18]), and AKI non-recovery by discharge (aHR 2.65 [1.55-4.55]) were associated with 1-year nephrology follow-up among any AKI survivors. CONCLUSIONS: Nephrology follow-up after AKI was uncommon, but nearly all AKI survivors had follow-up with non-nephrologist physicians. This suggests that AKI follow-up knowledge translation strategies for non-nephrology providers should be a priority. IMPACT: Pediatric AKI survivors have high long-term rates of chronic kidney disease (CKD) and hypertension, justifying regular kidney health surveillance after AKI. However, there is limited pediatric data on follow-up after AKI, including the factors associated with nephrology referral and extent of non-nephrology follow-up. We found that only one-fifth of all AKI survivors and one-third of severe AKI (stage 2-3) survivors have nephrology follow-up within 1 year post discharge. However, 95% are seen by a family physician, pediatrician, or non-nephrology specialist within 1 year post discharge. This suggests that knowledge translation strategies for AKI follow-up should be targeted at non-nephrology healthcare providers.

24-Hour ambulatory blood pressure monitoring 7 years after intensive care unit admission.

BACKGROUND: Children who develop acute kidney injury (AKI) in the pediatric intensive care unit (PICU) may be at higher risk of long-term chronic kidney disease and hypertension. The objectives of this study were to determine the prevalence of post-discharge hypertension and albuminuria using reference-standard measurements in children admitted to the PICU, and evaluate their association with AKI. METHODS: Single-center longitudinal cohort study of children admitted to the PICU from 2005 to 2010 with 7-8 years of follow-up (n = 207). Patients were excluded if they had pre-existing chronic kidney disease, were deceased, lived > 3.5-h drive away, were unwilling/unable to provide consent/assent, or had a clotting disorder. AKI was defined by the Kidney Disease: Improving Global Outcomes creatinine definition. Office blood pressure was evaluated using age, sex, and height-based percentiles. Hypertension was defined using 24-h ambulatory blood pressure monitoring (ABPM). Albuminuria was defined as first morning urine albumin:creatinine ratio ≥ 30 mg/g. Prevalence of blood pressure outcomes was calculated. The association between AKI and outcomes was evaluated using multivariable regression. RESULTS: Sixty of 207 (29%) children developed AKI during PICU admission. Overall, 6% had albuminuria and 21% had elevated office blood pressure or worse. One-hundred-and-seventy-seven (86%) patients had successful ABPM data. Of these, 10 (6%) had white coat, 18 (10%) had masked, and 5 (3%) had ambulatory hypertension. There was no statistically significant difference in outcomes across AKI stages. CONCLUSIONS: Blood pressure abnormalities are common in children 7 years after PICU admission. Future studies with longer follow-up are needed to further evaluate the association between AKI and hypertension. A higher-resolution version of the graphical abstract is available as Supplementary information.

Association of pediatric cardiac surgery-associated acute kidney injury with post-discharge healthcare utilization, mortality and kidney outcomes.

BACKGROUND: Acute kidney Injury (AKI) in children undergoing cardiac surgery (CS) is strongly associated with hospital morbidity. Post-discharge CS AKI outcomes are less clear. We evaluated associations between AKI and post-discharge (a) healthcare utilization, (b) chronic kidney disease (CKD) or hypertension and (c) mortality. METHODS: This is a retrospective two-centre cohort study of children surviving to hospital discharge after CS. Primary exposures were post-operative ≥Stage 1 AKI and ≥Stage 2 AKI defined by Kidney Disease Impoving Global Outcomes. Association of AKI with time to outcomes was determined using multivariable Cox-Proportional Hazards analysis. RESULTS: Of 350 participants included (age 3.1 (4.5) years), 180 [51.4%] developed AKI and 60 [17.1%] developed ≥Stage 2 AKI. Twenty-eight (9%) participants developed CKD or hypertension (composite outcome), and 17 (5%) died within 5 years of discharge. Post-operative ≥Stage 1 and ≥Stage 2 AKI were not associated with post-discharge hospitalizations, emergency room (ER) visits, physician visits or CKD or hypertension in adjusted analyses. A trend was observed between ≥Stage 2 AKI and mortality but was not statistically significant. In unadjusted stratified analyses, AKI was associated with post-discharge hospitalizations in children with RACHS-1 score ≥3, complex chronic disease classification and children living in urban areas. CONCLUSIONS: Post-CS AKI is not associated with post-discharge healthcare utilization, death and CKD or hypertension, though it may be associated with healthcare utilization in more complex paediatric CS children. Studies should aim to better understand post-CS healthcare utilization patterns and non-AKI risk factors for CKD, hypertension and mortality, to reduce adverse long-term outcomes after CS.

24-hour ambulatory blood pressure monitoring 9 years after pediatric cardiac surgery: a pilot and feasibility study.

BACKGROUND: Children undergoing cardiac surgery are at risk of high blood pressure (BP), a risk factor for cardiovascular and kidney disease. Twenty-four-hour ambulatory BP monitoring (ABPM) is a reference standard hypertension (HTN) test. Little data exist on ABPM abnormalities in children several years post cardiac surgery. This study aimed to (a) determine ABPM feasibility; (b) describe and compare ABPM measures and abnormalities (percent load, masked HTN [MH]; non-dipping, mean systolic/diastolic BP > 95th percentile; pre-HTN (ABPM); white-coat HTN [WCH]) to casual BP; and (c) compare BP in patients with and without acute kidney injury (AKI). METHODS: Prospective, follow-up pilot study of children (0-18 years) who underwent cardiac surgery from 2007 to 2009 at Montreal Children's Hospital. We recorded if participants had post-operative AKI and assessed the following outcomes at 9-year follow-up: casual BP classified by three single-visit measures (normal; elevated BP [eBPSingleVisit]; HTNSingleVisit); ABPM. Bivariable analyses were used to compare characteristics between groups. RESULTS: Twenty-three patients (median [interquartile range], 8.6 [8.0, 9.0] years post cardiac surgery) were included; 16 (70%) male. Six participants (26%) had eBPSingleVisit or higher. On ABPM, 11 (48%) had ≥ 1 abnormality: 9 (39%) had non-dipping; 3 (13%) had pre-HTN; 3 (13%) had WCH; none had HTN or MH. There were no differences in ABPM according to AKI status. CONCLUSION: Our pilot study determined that ABPM was feasible in children years after cardiac surgery and frequently identified ABPM abnormalities. Future research in larger populations is needed to define specific risk factors for HTN in children after cardiac surgery.

Kidney and blood pressure abnormalities 6 years after acute kidney injury in critically ill children: a prospective cohort study.

BACKGROUND: Acute kidney injury (AKI) in pediatric intensive care unit (PICU) children may be associated with long-term chronic kidney disease or hypertension. OBJECTIVES: To estimate (1) prevalence of kidney abnormalities (low estimated glomerular filtration rate (eGFR) or albuminuria) and blood pressure (BP) consistent with pre-hypertension or hypertension, 6 years after PICU admission; (2) if AKI is associated with these outcomes. METHODS: Longitudinal study of children admitted to two Canadian PICUs (January 2005-December 2011). Exposures (retrospective): AKI or stage 2/3 AKI (KDIGO creatinine-based definition) during PICU. Primary outcome (single visit 6 years after admission): presence of (a) low eGFR (<90 ml/min/1.73 m2) or albuminuria (albumin to creatinine ratio >30 mg/g) (termed "CKD signs") or (b) BP consistent with ≥pre-hypertension (≥90th percentile) or hypertension (≥95th percentile). RESULTS: Of 277 children, 25% had AKI. AKI and stage 2/3 AKI were associated with 2.2- and 6.6-fold higher adjusted odds, respectively, for the 6-year outcomes. Applying new hypertension guidelines attenuated associations; stage 2/3 AKI was associated with 4.5-fold higher adjusted odds for 6-year CKD signs or ≥elevated BP. CONCLUSIONS: Kidney and BP abnormalities are common 6 years after PICU admission and associated with AKI. Other risk factors must be elucidated to develop follow-up recommendations and reduce cardiovascular risk.

Acute kidney injury in critically ill children and 5-year hypertension.

BACKGROUND: To develop a pediatric-specific hypertension algorithm using administrative data and use it to evaluate the association between acute kidney injury (AKI) in the intensive care unit (ICU) and hypertension diagnosis 5 years post-discharge. METHODS: Two-center retrospective cohort study of children (≤ 18 years old) admitted to the pediatric ICU in Montreal, Canada, between 2003 and 2005 and followed until 2010. Patients with a valid healthcare number and without end-stage renal disease were included. Patients who could not be merged with the provincial database, did not survive admission, underwent cardiac surgery, had pre-existing renal disease associated with hypertension or a prior diagnosis of hypertension were excluded. AKI defined using the Kidney Disease: Improving Global Outcomes (KDIGO) definition. Using diagnostic codes and medications from administrative data, novel pediatric-specific hypertension definitions were designed. Both the evaluation of the prevalence of hypertension diagnosis and the association between AKI and hypertension occurred. RESULTS: Nineteen hundred and seventy eight patients were included (median age at admission [interquartile range] 4.3 years [1.1-11.8], 44% female, 325 (16.4%) developed AKI). Of these patients, 130 (7%) had a hypertension diagnosis 5 years after discharge. Patients with AKI had a higher prevalence of hypertension diagnosis [non-AKI: 84/1653 (5.1%) vs. AKI: 46/325 (14.2%), p < .001]. Children with AKI had a higher adjusted risk of hypertension diagnosis (hazard ratio [95% confidence interval] 2.19 [1.47-3.26]). CONCLUSIONS: Children admitted to the ICU have a high prevalence of hypertension post-discharge and children with AKI have over two times higher risk of hypertension compared to those with no AKI.

Follow-up after neonatal heart disease repair: watch out for chronic kidney disease and hypertension!

BACKGROUND: With advances in care, neonates undergoing cardiac repairs are surviving more frequently. Our objectives were to 1) estimate the prevalence of chronic kidney disease (CKD) and hypertension 6 years after neonatal congenital heart surgery and 2) determine if cardiac surgery-associated acute kidney injury (CS-AKI) is associated with these outcomes. METHODS: Two-center prospective, longitudinal single-visit cohort study including children with congenital heart disease surgery as neonates between January 2005 and December 2012. CKD (estimated glomerular filtration rate < 90 mL/min/1.73m2 or albumin/creatinine ≥3 mg/mmol) and hypertension (systolic or diastolic blood pressure ≥ 95th percentile for age, sex, and height) prevalence 6 years after surgery was estimated. The association of CS-AKI (Kidney Disease: Improving Global Outcomes definition) with CKD and hypertension was determined using multiple regression. RESULTS: Fifty-eight children with median follow-up of 6 years were evaluated. CS-AKI occurred in 58%. CKD and hypertension prevalence were 17% and 30%, respectively; an additional 15% were classified as having elevated blood pressure. CS-AKI was not associated with CKD or hypertension. Classification as cyanotic postoperatively was the only independent predictor of CKD. Postoperative days in hospital predicted hypertension at follow-up. CONCLUSIONS: The prevalence of CKD and hypertension is high in children having neonatal congenital heart surgery. This is important; early identification of CKD and hypertension can improve outcomes. These children should be systematically followed for the evolution of these negative outcomes. CS-AKI defined by current standards may not be a useful clinical tool to decide who needs follow-up and who does not.

Paucity of renal follow-up by school age after neonatal cardiac surgery.

INTRODUCTION: There are little data about renal follow-up of neonates after cardiovascular surgery and no guidelines for long-term renal follow-up. Our objectives were to assess renal function follow-up practice after neonatal cardiac surgery, evaluate factors that predict follow-up serum creatinine measurements including acute kidney injury following surgery, and evaluate the estimated glomerular filtration rate during follow-up using routinely collected laboratory values. METHODS: Two-centre retrospective cohort study of children 5-7 years of age with a history of neonatal cardiac surgery. Univariable and multivariable analyses were performed to determine factors associated with post-discharge creatinine measurements. Glomerular filtration rate was estimated for each creatinine using a height-independent equation. RESULTS: Seventeen of 55 children (30%) did not have any creatinine measured following discharge after surgery until the end of study follow-up, which occurred at a median time of 6 years after discharge. Of the 38 children who had the kidney function checked, 15 (40%) had all of their creatinine drawn only in the context of a hospitalisation or emergency department visit. Acute kidney injury following surgery did not predict the presence of follow-up creatinine measurements. CONCLUSIONS: A large proportion of neonates undergoing congenital heart repair did not have a follow-up creatinine measured in the first years following surgery. In those that did have a creatinine measured, there did not appear to be any identified pattern of follow-up. A follow-up system for children who are discharged from cardiac surgery is needed to identify children with or at risk of chronic kidney disease.

Long-term renal follow-up of children treated with cisplatin, carboplatin, or ifosfamide: a pilot study.

BACKGROUND: Childhood cancer survivors treated with cisplatin, ifosfamide, or carboplatin are at risk for late kidney and blood pressure (BP) abnormalities. Few studies have comprehensively evaluated kidney outcomes and 24-h ambulatory BP monitoring (ABPM) in this population. We aimed to describe chemotherapy-associated acute kidney injury (AKI) and late kidney outcomes using standardized definitions. METHODS: This was a single-center longitudinal pilot study of 23 children who participated in a previous study during cisplatin, carboplatin, or ifosfamide treatment. Medical charts were reviewed retrospectively. Available patients were approached for a study visit for blood and urine collection, BP measurement, and ABPM. AKI is defined by serum creatinine (SCr) rise (Kidney Disease: Improving Global Outcomes definition [SCr-AKI]). Electrolyte-AKI is defined by hypokalemia, hypophosphatemia, or hypomagnesemia. Chronic kidney disease (CKD) is defined by estimated glomerular filtration rate < 90 mL/min/1.73 m2, albuminuria, or proteinuria. Electrolyte-CKD is defined by low serum electrolyte concentration or electrolyte supplementation. RESULTS: Median age at chemotherapy start was 8.3 years; 9/23 (39%) were boys. Fourteen out of 23 (61%) patients had SCr-AKI during therapy; all developed electrolyte-AKI. Median 5.7 years post-chemotherapy, 7/22 (32%) had CKD, 11/23 (48%) had electrolyte-CKD, and 2/20 (10%) had hypertension. Fifteen out of 23 patients (65%) had either CKD, electrolyte-CKD, or hypertension. In ten patients available for a study visit (median 4.9 years post-chemotherapy), 1/10 (10%) had hypertension by ABPM; none had masked or white coat hypertension. All ten had at least one kidney abnormality (CKD, electrolyte-CKD, office pre-hypertension, or abnormal ABPM). CONCLUSIONS: Using standardized outcome definitions, children treated with cisplatin, carboplatin, or ifosfamide have a high prevalence of late kidney abnormalities. Research must elucidate best practice for post-cancer treatment follow-up and kidney complication treatment.

Evaluation of height-dependent and height-independent methods of estimating baseline serum creatinine in critically ill children.

BACKGROUND: Baseline serum creatinine (bSCr) is required for diagnosing acute kidney injury (AKI). In children, bSCr is commonly defined as the lowest measurement within 3 months of admission. Measured values are often missing and estimating bSCr using height-based glomerular filtration rate (GFR) equations is problematic when height is unavailable. METHODS: This is a retrospective cohort study including 538 children admitted to the intensive care unit (ICU) between 2003 and 2005 at two centers in Canada, with measured bSCr, height, and ICU-SCr values. We evaluated the bias, accuracy, and precision of back-calculating bSCr from height-dependent and height-independent GFR equations. Agreement of AKI defined using measured and estimated bSCr was calculated. Multivariate analyses were performed to assess the impact of bSCr estimation methods on the association between AKI and ICU mortality, length of stay, and duration of mechanical ventilation. RESULTS: Both methods underestimated bSCr by 1-3%, showed good accuracy (∼30% of patients with estimated bSCr within 10% of measured bSCr), but poor precision (wide 95% limits of agreement). The agreement between AKI defined by estimated versus measured bSCr was >80% (κ >0.5). The height-independent method performed best in children >13 years old; however, overall, both methods performed similarly across age subgroups. AKI was associated with longer stay, prolonged mechanical ventilation, and ICU mortality using measured and estimated bSCr. CONCLUSIONS: Height-dependent and height-independent bSCr estimation methods were comparable. This may have significant implications for performing pediatric AKI research using large databases, and in clinical care to define AKI when height is unknown.

Renal Function Follow-Up and Renal Recovery After Acute Kidney Injury in Critically Ill Children.

OBJECTIVES: To evaluate factors associated with renal recovery from acute kidney injury in critically ill children and the extent to which serum creatinine is measured before discharge. DESIGN: Retrospective cohort study. SETTING: Two PICUs at tertiary centers in Montreal, QC, Canada. PATIENTS: Children (< 18 yr old) admitted to the PICU between 2003 and 2005. Patients with end-stage renal disease, no healthcare number, died during admission, or admitted postcardiac surgery were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Acute kidney injury was defined using internationally accepted criteria (Kidney Disease: Improving Global Outcomes). Two renal recovery outcomes commonly used in the literature were evaluated: hospital discharge serum creatinine less than 1.5 and less than 1.15 times baseline. Proportions of patients with 1) serum creatinine measurements between PICU and hospital discharge and 2) renal recovery were calculated. Univariate and multivariate analyses were performed to determine factors associated with serum creatinine monitoring and nonrecovery after acute kidney injury. Of 2,033 patients included, 829 (40.8%) had serum creatinine measurements between PICU and hospital discharge. The odds of having a discharge serum creatinine measurement increased with acute kidney injury severity (stages 1, 2, 3 adjusted odds ratio [95% CI]: 1.49 [1.03-2.15], 2.52 [1.40-4.54], 7.87 [3.16-19.60], respectively). Acute kidney injury recovery was 92.5% when defined as serum creatinine less than 1.5 times baseline versus 75.9% when defined as less than 1.15 times baseline (p < 0.001). Stage 3 acute kidney injury was associated with having a discharge serum creatinine greater than or equal to 1.5 times baseline (adjusted odds ratio = 3.51 [1.33-9.19]). CONCLUSIONS: Less than half the PICU population had serum creatinine measured before hospital discharge. More severe acute kidney injury was associated with higher likelihood of serum creatinine monitoring and lower probability of acute kidney injury recovery. Future research should address knowledge translation on post-PICU acute kidney injury follow-up before hospital discharge.

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

Acute kidney injury is common in critically ill children, but the long-term outcomes are not well defined. OBJECTIVES: Evaluated whether nonrecovery of kidney function, following acute kidney injury, was associated with postdischarge mortality, healthcare utilization, and chronic kidney disease. DESIGN: Retrospective, two-center, observational study. SETTING: Two ICUs at tertiary children's hospitals in Montreal, QC. PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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. MAIN RESULTS: 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). CONCLUSIONS AND RELEVANCE: 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.

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.

Frailty inclusive care in acute and community-based settings: a systematic review protocol.

BACKGROUND: Frailty is a known risk factor for an array of adverse outcomes including more frequent and prolonged health services use and high health care costs. Aging of the population has implications for care provision across the care continuum, particularly for people living with frailty. Despite known risks associated with frailty, there has been limited research on care pathways that address the needs of persons living with frailty. Our study aims to review and examine, in a rigorous way, the quality of evidence for multi-component interventions and care pathways focused on frailty. METHODS: A comprehensive electronic search strategy will be used to identify studies that evaluate multi-component interventions or care pathways for persons living with frailty. The search strategy will include terms for frailty, multi-component interventions, effectiveness, and cost effectiveness applied to the following databases: MEDLINE (OVID), EMBASE (OVID), CINAHL (EBSCO), Cochrane Central Register of Controlled Trials (CENTRAL), and Cochrane Database of Systematic Reviews. An adapted search for Google Scholar and gray literature databases will also be used. References of included studies will be hand-searched for additional citations of frailty-inclusive care. Known experts and corresponding authors of identified articles will be contacted by email to identify further eligible studies. Risk of bias will be assessed using the Effective Public Health Practice Project Quality Assessment tool. Data will be extracted from eligible studies and it is anticipated that narrative analysis will be used. If studies with sufficient homogeneity are found, then pooled effects will be reported using meta-analysis. DISCUSSION: This review will appraise the evidence currently available on multi-component frailty interventions. Results will inform on clinical pathway development for people living with frailty across the care continuum and will guide future research to address gaps in the literature and areas in need of further development. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020166733.

Acute Kidney Injury in Critically Ill Children Is Not all Acute: Lessons Over the Last 5 Years.

Acute kidney injury (AKI) in the pediatric intensive care unit (PICU) is an important risk factor for increased morbidity and mortality during hospitalization. Over the past decade, accumulated data on children and young people indicates that acute episodes of kidney dysfunction can have lasting consequences on multiple organ systems and health outcomes. To date, there are no guidelines for follow-up of surviving children that may be at risk of long-term sequelae following AKI in the PICU. This narrative review aims to describe literature from the last 5 years on the risk of medium and long-term kidney and non-kidney outcomes after AKI in the PICU. More specifically, we will focus on outcomes in children and young people following AKI in the general PICU population and children undergoing cardiac surgery. These outcomes include mortality, hypertension, proteinuria, chronic kidney disease, and healthcare utilization. We also aim to highlight current gaps in knowledge in medium and long-term outcomes in this pediatric population. We suggest a framework for future research to develop evidence-based guidelines for follow-up of children surviving an episode of critical illness and AKI.

Epidemiology, clinical characteristics and treatment of critically ill patients with COVID-19): a protocol for a living systematic review.

INTRODUCTION: In December 2019, the first cases of COVID-19 associated with SARS-CoV-2 viral infection were described in Wuhan, Hubei Province, China. Since then, it has spread rapidly affecting 188 countries and was declared a pandemic by the WHO on 11 March 2020. Preliminary reports suggest up to 30% of patients require intensive care unit (ICU) admission and case fatality rate estimate is 2.3%-7.2%. The primary reason for ICU admission is hypoxaemic respiratory failure, while factors associated with ICU admission include increased age, presence of comorbidities and cytokine storm. Case series and retrospective trials initially assessed proposed treatments with randomised controlled trials now reporting early outcomes. We conduct a systematic review and meta-analysis to identify epidemiological factors, treatments and complications that predict mortality among critically ill patients with COVID-19. METHODS AND ANALYSIS: Our comprehensive search strategy was developed in consultation with a research librarian. We will search electronic databases: Ovid Medline, Ovid Embase, Ovid Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Wiley Cochrane Library. The search strategy combines concepts from COVID-19, validated COVID-19 search filters and geographical locations of large outbreaks. Citation screening, selection, quality assessment and data abstraction will be performed in duplicate. Clinically homogenous epidemiological characteristics, interventions and complications will be pooled in statistical meta-analysis. Within the framework of a living systematic review, the search and data analysis will be updated every 6 months. ETHICS AND DISSEMINATION: Our systematic review will synthesise literature on risk factors and interventions associated with mortality in critically ill patients with COVID-19. Results will be presented at national and international conferences and submitted for peer-reviewed publication. The pooled analysis can provide guidance to inform clinical guidelines for care of critically ill patients with COVID-19. Iterative updates will be made public through open access. Research ethics approval is not required. PROSPERO REGISTRATION NUMBER: CRD42020176672.

Sex-specific prevalence and outcomes of frailty in critically ill patients.

BACKGROUND: The prevalence of frailty, an important risk factor for short- and long-term outcomes in hospitalized adults, differs by sex. Studies in critically ill adults have also found differences in mortality and organ support rates in males and females. The objective of this study was to determine if these observed differences in mortality and organ support rates can be explained by sex and frailty alone, or if the interaction between sex and frailty is an important risk factor. METHODS: This is a retrospective multi-centre population-based cohort study of all adult patients (≥ 18 years) admitted to the seventeen intensive care units (ICUs) across Alberta, Canada, between 2016 and 2017. On admission, physicians assigned a Clinical Frailty Scale (CFS) score (1 = very fit, 9 = terminally ill) to all patients. Patients with missing CFS scores or who died within 24 h of ICU admission were excluded. Frailty was defined as CFS ≥ 5. Outcomes included all-cause hospital mortality, ICU mortality, and organ support rates. A propensity score for female sex was generated and 1:1 matching on sex was performed. Multivariable Cox regression or logistic regression, as appropriate, was performed to evaluate the association between sex, frailty, and the sex-frailty interaction term with outcomes. RESULTS: Of 15,238 patients included in the cohort, after propensity score matching 11,816 patients remained (mean [standard deviation] age 57.3 [16.9]). In the matched cohort, females had a higher prevalence of frailty than males (32% vs. 27%, respectively) and higher odds of frailty (odds ratio [95% confidence interval (CI)] 1.29 [1.20-1.40]). Though females were less likely to receive invasive mechanical ventilation (hazard ratio [95% CI] 0.78 [0.71-0.86]), the interaction between sex and frailty (i.e., males and females with and without frailty) was not associated with differences in organ support rates. Receipt of dialysis and vasoactive support, as well as hospital mortality and ICU mortality were associated with frailty but were not associated with female sex or the interaction between sex and frailty. CONCLUSIONS: Although frailty and sex were individually associated with mortality and differences in organ support in the ICU, there does not appear to be a significant interaction between sex and frailty with regards to these outcomes.

Acute Kidney Injury in Critically Ill Children and Subsequent Chronic Kidney Disease.

BACKGROUND: The progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children. OBJECTIVES: We aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge. DESIGN: Retrospective cohort study using chart collection and administrative data. SETTING: Two-center study in Montreal, Canada. PATIENTS: Children (≤18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease. MEASUREMENTS: Acute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ≥1 CKD diagnostic code or ≥1 CKD-specific medication prescription. METHODS: Chart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association. RESULTS: A total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively (P < .001). LIMITATIONS: Results may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further. CONCLUSIONS: Acute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.

CONTEXTE: Chez l'enfant, la progression de l'insuffisance rénale aigüe (IRA) vers l'insuffisance rénale chronique (IRC) est encore mal connue. OBJECTIFS: Nous souhaitions élaborer une définition de l'IRC pédiatrique à partir des données administratives, et l'employer pour évaluer l'association entre l'IRA chez les enfants gravement malades et un diagnostic d'IRC cinq ans après leur sortie de l'hôpital. TYPE D'ÉTUDE: Étude de cohorte rétrospective réalisée à partir des dossiers médicaux et des données administratives. CADRE: Deux centres hospitaliers de Montréal (Canada). SUJETS: L'étude porte sur des enfants (≤18 ans) admis à deux unités de soins intensifs (USI) pédiatriques entre 2003 et 2005. Les patients atteints d'insuffisance rénale terminale ou sans numéro d'assurance-maladie ont été exclus d'emblée. Seule la première admission survenue au cours de l'étude a été retenue. Les patients n'ayant pu être reliés aux données administratives, n'ayant pas survécu à l'hospitalisation ou souffrant d'une néphropathie préexistante ont été exclus. MESURES: L'IRA a été définie selon les critères KDIGO (Kidney Disease: Improving Global Outcomes) et l'IRC cinq ans après la sortie de l'hôpital par la présence d'au moins un code diagnostique pour l'IRC ou la prise d'au moins un médicament spécifique au traitement de l'IRC. MÉTHODOLOGIE: Les données des dossiers médicaux, utilisées pour définir l'exposition (IRA), ont été couplées aux données administratives provinciales, utilisées pour définir le résultat (IRC). Un modèle de régression de Cox a servi à établir l'association entre IRA et IRC. RÉSULTATS: Ont été inclus 2 235 patients (56 % de garçons), dont l'âge médian à l'admission était de 3,7 ans. De ce nombre, 464 (21 %) ont développé une IRA en cours d'hospitalisation à l'USI pédiatrique. Cinq ans après leur sortie de l'hôpital, 43 patients (2 %) avaient reçu un diagnostic d'IRC. Les patients atteints d'une IRA de stade 1 et de stade 2-3 ont présenté un plus grand risque de progresser vers l'IRC (rapport de risque ajusté [IC à 95 %] 2,2 [1,1 ­ 4,5] et 2,5 [1,1 ­ 5,7] respectivement, P < 0,001). LIMITES: Les résultats pourraient ne pas s'appliquer aux patients non admis aux USI pédiatriques. Nous n'avons pu ajuster les résultats avec les variables après la sortie de l'hôpital. Des études futures devraient examiner plus attentivement ces potentiels facteurs de risque supplémentaires. CONCLUSION: L'IRA chez l'enfant a été associée à une progression vers l'IRC cinq ans après la sortie de l'hôpital, telle que définie par les données administratives de santé.

A Validation Study of Administrative Health Care Data to Detect Acute Kidney Injury in the Pediatric Intensive Care Unit.

BACKGROUND: Large studies evaluating pediatric acute kidney injury (AKI) epidemiology and outcomes are lacking, partially due to underuse of large administrative health care data. OBJECTIVE: To assess the diagnostic accuracy of administrative health care data-defined AKI in children admitted to the pediatric intensive care unit (PICU). DESIGN: Retrospective cohort study utilizing chart and administrative data. SETTING: Children admitted to the PICU at 2 centers in Montreal, QC. PATIENTS: Patients between 0 and 18 years old with a provincial health insurance number, without end-stage renal disease and admitted to the PICU between January 1, 2003, and March 31, 2005, were included. MEASUREMENTS: The AKI was defined from chart data using the Kidney Disease: Improving Global Outcomes (KDIGO) definition (Chart-AKI). The AKI defined using administrative health data (Admin-AKI) was based on International Classification of Disease, Ninth Revision (ICD-9) AKI codes. METHODS: Data available from retrospective chart review, including baseline and PICU patient characteristics, and serum creatinine (SCr) and urine output (UO) values during PICU admission, were merged with provincial administrative health care data containing diagnostic and procedure codes used for ascertaining Admin-AKI. Sensitivity, specificity, positive, and negative predictive value of Admin-AKI compared with Chart-AKI (reference standard) were calculated. Univariable associations between Admin-AKI and hospital mortality were evaluated. RESULTS: A total of 2051 patients (55% male, mean age at admission 6.1 ± 5.8 years, 355 cardiac surgery, 1696 noncardiac surgery) were included. The AKI defined by SCr or UO criteria occurred in 52% of cardiac surgery patients and 24% of noncardiac surgery patients. Overall, Admin-AKI detected Chart-AKI with low sensitivity, but high specificity in cardiac and noncardiac surgery patients. Sensitivity increased by 1.5 to 2 fold with each increase in AKI severity stage. Admin-AKI was associated with hospital mortality (13% in Admin-AKI vs 2% in non-AKI, P < .001). LIMITATIONS: These data were generated in a PICU population; future research should study non-PICU populations. CONCLUSIONS: Use of administrative health care data to define AKI in children leads to AKI incidence underestimation. However, for detecting more severe AKI, sensitivity is higher, while maintaining high specificity.

CONTEXTE: On dispose de peu d'études à grande échelle évaluant l'épidémiologie et l'évolution de l'insuffisance rénale aigüe (IRA) chez les enfants, notamment en raison d'une sous-utilisation des données administratives du système de santé. OBJECTIF: Évaluer la précision diagnostique de l'IRA définie à partir des données administratives en santé chez des enfants admis aux unités de soins intensifs pédiatriques (USIP). TYPE D'ÉTUDE: Une étude de cohorte rétrospective utilisant des données administratives et les données provenant des dossiers médicaux. CADRE: Les USIP de deux centres hospitaliers de Montréal, au Canada. SUJETS: Ont été inclus les patients âgés de 0 à 18 ans possédant un numéro d'assurance-maladie provincial qui ont été admis aux USIP entre le 1er janvier 2003 et le 31 mars 2005 avec une insuffisance rénale non terminale. MESURES: L'IRA-Dos a été définie à partir des dossiers médicaux en utilisant les critères du KDIGO (Kidney Disease: Improving Global Outcomes). L'IRA-Admin a été définie à partir des données administratives en santé avec les codes d'IRA de la neuvième révision de la Classification internationale des maladies (CIM-9). MÉTHODOLOGIE: Les données tirées de l'examen rétrospectif des dossiers médicaux, soit les valeurs de créatinine sérique (SCr) et de diurèse pendant le séjour aux USIP et les caractéristiques des patients, initiales et à l'admission, ont été fusionnées aux données administratives provinciales en santé contenant les codes de diagnostic et de procédure utilisés pour établir l'IRA-Admin. La sensibilité, la spécificité et les valeurs prédictives négative et positive de l'IRA-Admin, en comparaison à l'IRA-Dos (standard de référence), ont été calculées. L'association univariée entre l'IRA-Admin et la mortalité à l'hôpital a également été évaluée. RÉSULTATS: Un total de 2 051 patients ont été inclus (355 ayant subi une cardiochirurgie et 1 696 non opérés). L'âge moyen des sujets à l'admission était de 6,1 ± 5,8 ans et 55 % étaient des garçons. L'IRA définie par les critères de SCr et de diurèse a été diagnostiquée chez 52 % des patients opérés et chez 24 % des patients non opérés. Pour l'ensemble de la cohorte (patients opérés ou non), l'IRA-Admin a détecté l'IRA-Dos avec une faible sensibilité, mais avec une spécificité élevée. La sensibilité s'est accrue de 1,5 à 2 fois pour chaque passage à un stade supérieur de gravité de l'IRA. Enfin, l'IRA-Admin a été associée à un taux plus élevé de mortalité à l'hôpital (13 % des patients IRA-Admin contre 2 % des patients sans IRA, p<0,001). LIMITATIONS: Ces résultats concernent une population de patients hospitalisés aux USIP. Des études futures devraient inclure des populations non admises aux USIP. CONCLUSIONS: L'utilisation des données administratives en santé pour définir l'IRA chez les enfants a mené à une sous-estimation de son incidence. Cependant, la méthode montre une plus grande sensibilité dans la détection des cas plus graves d'IRA, tout en conservant une spécificité élevée.

Long-term Mortality After Acute Kidney Injury in the Pediatric ICU.

OBJECTIVES: (1) To evaluate the association between acute kidney injury (AKI) in the PICU and long-term mortality and (2) to determine the extent to which adding the urine output (UO)-defined AKI alters the association. METHODS: A 2-center retrospective cohort study of children (≤18 years old) admitted to the PICU between 2003 and 2005 for noncardiac surgery, with follow-up until 2010. Patients with end stage renal disease, no provincial health insurance number, who died during hospitalization, or could not be linked to administrative data were excluded. One hospitalization per patient was included. AKI was defined by using serum creatinine criteria and/or UO criteria. Mortality was ascertained by using administrative data. Cox regression analysis was performed to evaluate the association between AKI and long-term mortality. RESULTS: The study population included 2041 patients (55.7% male, mean admission age 6.5 ± 5.8 years). Of 2041 hospital survivors, 9 (0.4%) died within 30 days, 51 (2.5%) died within 1 year, and 118 (5.8%) died within 5 to 7 years postdischarge. AKI was independently associated with 5- to 7-year mortality (adjusted hazard ratio [95% confidence interval]: 3.10 [1.46-6.57] and 3.38 [1.63-7.02], respectively). Including UO did not strengthen the association. CONCLUSIONS: AKI is associated with 5- to 7-year mortality. Because this is an observational study we cannot determine if AKI is causative of mortality or of the pathophysiology. However, patients with AKI represent a high-risk group. It is reasonable that these patients be considered for targeted follow-up until future researchers better elucidate these relationships.