Ahmad Kaddourah

Epidemiology of Acute Kidney Injury in Critically Ill Children and Young Adults

BACKGROUND The epidemiologic characteristics of children and young adults with acute kidney injury have been described in single‐center and retrospective studies. We conducted a multinational, prospective study involving patients admitted to pediatric intensive care units to define the incremental risk of death and complications associated with severe acute kidney injury. METHODS We used the Kidney Disease: Improving Global Outcomes criteria to define acute kidney injury. Severe acute kidney injury was defined as stage 2 or 3 acute kidney injury (plasma creatinine level ≥2 times the baseline level or urine output <0.5 ml per kilogram of body weight per hour for ≥12 hours) and was assessed for the first 7 days of intensive care. All patients 3 months to 25 years of age who were admitted to 1 of 32 participating units were screened during 3 consecutive months. The primary outcome was 28‐day mortality. RESULTS A total of 4683 patients were evaluated; acute kidney injury developed in 1261 patients (26.9%; 95% confidence interval [CI], 25.6 to 28.2), and severe acute kidney injury developed in 543 patients (11.6%; 95% CI, 10.7 to 12.5). Severe acute kidney injury conferred an increased risk of death by day 28 after adjustment for 16 covariates (adjusted odds ratio, 1.77; 95% CI, 1.17 to 2.68); death occurred in 60 of the 543 patients (11.0%) with severe acute kidney injury versus 105 of the 4140 patients (2.5%) without severe acute kidney injury (P<0.001). Severe acute kidney injury was associated with increased use of mechanical ventilation and renal‐replacement therapy. A stepwise increase in 28‐day mortality was associated with worsening severity of acute kidney injury (P<0.001 by log‐rank test). Assessment of acute kidney injury according to the plasma creatinine level alone failed to identify acute kidney injury in 67.2% of the patients with low urine output. CONCLUSIONS Acute kidney injury is common and is associated with poor outcomes, including increased mortality, among critically ill children and young adults. (Funded by the Pediatric Nephrology Center of Excellence at Cincinnati Childrens Hospital Medical Center and others; AWARE ClinicalTrials.gov number, NCT01987921.)

Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology in Critically Ill Children (AWARE): study protocol for a prospective observational study

BackgroundAcute kidney injury (AKI) is associated with poor outcome in critically ill children. While data extracted from retrospective study of pediatric populations demonstrate a high incidence of AKI, the literature lacks focused and comprehensive multicenter studies describing AKI risk factors, epidemiology, and outcome. Additionally, very few pediatric studies have examined novel urinary biomarkers outside of the cardiopulmonary bypass population.Methods/DesignThis is a prospective observational study. We anticipate collecting data on over 5000 critically ill children admitted to 31 pediatric intensive care units (PICUs) across the world during the calendar year of 2014. Data will be collected for seven days on all children older than 90 days and younger than 25 years without baseline stage 5 chronic kidney disease, chronic renal replacement therapy, and outside of 90 days of a kidney transplant or from surgical correction of congenital heart disease. Data to be collected includes demographic information, admission diagnoses and co-morbidities, and details on fluid and vasoactive resuscitation used. The renal angina index will be calculated integrating risk factors and early changes in serum creatinine and fluid overload. On days 2–7, all hemodynamic and pertinent laboratory values will be captured focusing on AKI pertinent values. Daily calculated values will include % fluid overload, fluid corrected creatinine, and KDIGO AKI stage. Urine will be captured twice daily for biomarker analysis on Days 0–3 of admission. Biomarkers to be measured include neutrophil gelatinase lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (l-FABP), and interleukin-18 (IL-18). The primary outcome to be quantified is incidence rate of severe AKI on Day 3 (Day 3 – AKI). Prediction of Day 3 – AKI by the RAI and after incorporation of biomarkers with RAI will be analyzed.DiscussionThe Assessment of Worldwide Acute Kidney Injury, Renal Angina and Epidemiology (AWARE) study, creates the first prospective international pediatric all cause AKI data warehouse and biologic sample repository, providing a broad and invaluable resource for critical care nephrologists seeking to study risk factors, prediction, identification, and treatment options for a disease syndrome with high associated morbidity affecting a significant proportion of hospitalized children.Trial registrationClinicalTrials.gov: NCT01987921

Renal Replacement Therapy in Neonates

The incidence of acute kidney injury (AKI) has steadily increased in the last decade in neonates and infants. Despite the extensive proposed pharmacologic approaches to treat or prevent AKI, renal replacement therapy is the only available therapeutic approach to manage the consequences of significant AKI and maintain electrolyte homeostasis and fluid balance in infants with AKI. The objective of this article is to summarize the different approaches and modalities of renal replacement therapy in neonatal intensive care units.

Prevalence and predictors of aortic dilation as a novel cardiovascular complication in children with end-stage renal disease

Background: Cardiovascular disease is the leading cause of death in children with end-stage renal disease (ESRD). Isolated aortic dilation (AD) is rare in children. We aimed to determine the prevalence and the risk factors for AD in children with ESRD. Methods and study design: We reviewed records of all ESRD patients followed at our institution from January 2007 to October 2012. AD was defined as Z-score > 2 in the dimension of at least one of the following echocardiographic aortic parameters: annulus, root at the sinus, sino-tubular junction, ,or ascending aorta. Results: The records of 78 patients on dialysis and 19 kidney transplant recipients were available. 30 patients (30.9%) had AD. Multivariate analysis revealed independent associations of AD with body mass index (BMI) Z-score (OR = 0.52, 95% confidence interval (CI): 0.35 – 0.78) and ESRD secondary to glomerular disease (OR = 4.58, 95% CI: 1.45 – 14.46). We developed a classification and regression tree (CART) model to identify patients at low vs. high AD risk. Our model classified 62 patients of the cohort (64%) to be high- or low-risk, with a positive predictive value of 89% and a negative predictive value of 100%. Conclusion: Our data suggest that AD, as a possible marker of aortopathy and early aneurysm formation, is a novel and prevalent cardiovascular complication in ESRD children. Glomerular disease and low BMI Z-score appear to be potent predictors. CART modeling helps identify high-risk children, potentially guiding decisions regarding targeted echocardiographic evaluations.

Identifying evidence of cardio-renal syndrome in patients with Duchenne muscular dystrophy using cystatin C

Patients with Duchenne muscular dystrophy (DMD) develop dilated cardiomyopathy and are at risk for kidney injury. Creatinine based estimated glomerular filtration rate (eGFR) is limited by low muscle mass with low serum creatinine levels in DMD. We assessed the relationship between cardiac function, modified Schwartz eGFR and cystatin C eGFR in patients with DMD. Ninety-three patients with DMD were screened for renal dysfunction in an outpatient neuromuscular clinic. Patients with new nephrotoxic medications, recent hospitalization or decompensated heart failure were excluded from the analysis. Eleven (12%) patients had evidence of renal dysfunction identified by cystatin C eGFR, while no patients had renal dysfunction by Schwartz eGFR. There was no significant correlation between cystatin C eGFR and age (r = -0.2, p = 0.11), prednisone dose (r = 0.06, p = 0.89) or deflazacort dose (r = -0.01, p = 0.63). There was a significant correlation between left ventricular ejection fraction and cystatin C GFR among patients with chronic left ventricular dysfunction (r = 0.46, p < 0.01), but not normal function (r = -0.07, p = 0.77). There was no significant correlation between left ventricular ejection fraction and Schwartz eGFR among patients with (r = 0.07, p = 0.59) or without (r = -0.27, p = 0.07) chronic left ventricular dysfunction. Cystatin C eGFR correlates with cardiac dysfunction in patients with DMD, thus providing novel evidence of cardio-renal syndrome in this population. Routine monitoring of renal function is recommended in patients with DMD.

Thrombocytopenia-associated multi-organ failure caused by diabetic ketoacidosis

Thrombocytopenia‐associated multi‐organ failure (TAMOF) is an increasingly reported entity in the pediatric intensive care unit. The clinical presentation is similar to thrombotic thrombocytopenic purpura, but with no evidence of hemolysis and no schistocytes on peripheral smear. We report a case of TAMOF induced by diabetic ketoacidosis and treated with therapeutic plasma exchange (TPE). Early diagnosis and initiation of TPE significantly decrease the morbidity associated with TAMOF.

523: INCREASED MORTALITY RISK IN UNDERWEIGHT, NOT OBESE, CRITICALLY ILL CHILDREN

Critical Care Medicine • Volume 46 • Number 1 (Supplement) www.ccmjournal.org Learning Objectives: Endogastric tube (EGT) placement is a common pediatric intensive care unit patient procedure. Indications include feeding, gastric decompression, and medication administration. Drawbacks associated with EGT placement consist of pneumothorax, pneumonia, asphyxia, intracranial intubation and/or death. Between 2 – 4% (nearly 500,000) nasogastric. percutaneous endoscopic gastrostomy tubes and suction tubes are misplaced every year (Gilbert P J, Healthcare Risk Management; April 2015: 44–45). Confirmation of proper EGT placement in the stomach or gastrointestinal tract is essential to prevent these complications. The most reliable method of confirmation is a chest or abdominal x-ray which is standard hospital policy at many institutions. This X-ray is costly and exposes the patient to harmful radiation. Dislodgement of EGTs requires replacement with reconfirmation via X-ray; subjecting the child to additional radiation exposure. A self-illuminating stylet inserted into the EGT to identify proper placement with the naked eye could minimize improper placement, complications, radiation exposure, and cost. Methods: In previously anesthetized, expired neonatal lambs, a self-illuminating prototype stylet connected to a fiberoptic light source was used to insert a standard EGT into the gastric cavity via the mouth. Upon EGT placement, the light at the end of the stylet was followed as it passed through the lamb’s body. With identification of the translucent light below the ribcage, placement was believed to be in the correct position. The actual position of the tube was confirmed using direct dissection through the abdominal wall into the stomach cavity noting the tip of the EGT. Results: In seven neonatal lambs weighing 3.4–7.2 kg (mean 4.5) a standard orogastric tube was placed using the self-illuminating stylet. In all animals the translucent light was identified in the neck, disappeared in the thoracic cavity region, and reappeared just below the ribcage. The tube position was confirmed with direct dissection identifying the tip of the EGT in the stomach cavity in 100% of the lambs. Conclusions: EGTs may be successfully placed using a self-illuminating stylet and confirmed via location of the translucent light below the ribcage. No X-ray is necessary to check position. This can decrease cost, radiation exposure, and improper placement. Children in the intensive care unit can benefit from this technique.