Association of early hyponatremia and the development of acute kidney injury in critically ill children.

BACKGROUND: Hyponatremia is an independent prognostic factor for mortality; however, the reason for this remains unclear. An observed relationship between hyponatremia and the development of acute kidney injury (AKI) has been reported in certain disease states, but hyponatremia has not been evaluated as a predictor of AKI in critically ill patients or children. METHODS: This is a single-center retrospective cohort study of critically ill children admitted to a tertiary care center. We performed regression analysis to assess the association between hyponatremia at ICU admission and the development of new or worsening stage 2 or 3 (severe) AKI on days 2-3 following ICU admission. RESULTS: Among the 5057 children included in the study, early hyponatremia was present in 13.3% of children. Severe AKI occurred in 9.2% of children with hyponatremia compared to 4.5% of children with normonatremia. Following covariate adjustment, hyponatremia at ICU admission was associated with a 75% increase in the odds of developing severe AKI when compared to critically ill children with normonatremia (aOR 1.75, 95% CI 1.28-2.39). Evaluating sodium levels continuously, for every 1 mEq/L decrease in serum sodium level, there was a 0.05% increase in the odds of developing severe AKI (aOR 1.05, 95% CI 1.02-1.08). Hyponatremic children who developed severe AKI had a higher frequency of kidney replacement therapy, AKI or acute kidney disease at hospital discharge, and hospital mortality when compared to those without. CONCLUSIONS: Hyponatremia at ICU admission is associated with the development of new or worsening AKI in critically ill children. A higher resolution version of the Graphical abstract is available as Supplementary information.

Bladder Agenesis and Bilateral Ectopic Ureters in an Infant Male With Cystic Renal Dysplasia, Imperforate Anus, and Penoscrotal Transposition.

Bladder agenesis is a rare congenital anomaly infrequently reported in the literature, with an incidence of 1/600,000 patients.1 Commonly associated with other fatal malformations, the condition is often incompatible with life.2 Prior reports estimate that over 90% of living children born with this malformation are female, owing to renal preservation resulting from low pressure drainage of urine into the vagina, uterus, and vestibule.3,4 Herein we report a rare case of an infant male born with penoscrotal transposition and end stage renal disease secondary to bilateral cystic renal dysplasia found to have concurrent bladder agenesis and bilateral ureteral ectopia.

Association of Acute Kidney Injury With Subsequent Sepsis in Critically Ill Children.

OBJECTIVES: Acute kidney injury is a major cause of morbidity and mortality in critically ill children. A growing body of evidence has shown that acute kidney injury affects immune function, yet little is known about the association between acute kidney injury and subsequent infection in pediatric patients. Our objective was to examine the association of non-septic acute kidney injury with the development of subsequent sepsis in critically ill children. DESIGN: A single-center retrospective cohort study. SETTING: The pediatric and cardiac ICUs at a tertiary pediatric care center. PATIENTS: All patients 0-18 years old without a history of chronic kidney disease, who did not have sepsis prior to or within the initial 48 hours of ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed data for 5,538 children (median age, 5.3 yr; 58.2% male), and identified 255 (4.6%) with stage 2 or 3 acute kidney injury. Suspected sepsis occurred in 46 children (18%) with stage 2 or 3 acute kidney injury compared to 286 children (5.4%) with stage 1 or no acute kidney injury. On adjusted analysis, children with stage 2 or 3 acute kidney injury had 2.05 times greater odds of developing sepsis compared to those with stage 1 or no acute kidney injury (95% CI, 1.39-3.03; p < 0.001). Looking at acute kidney injury severity, children with stage 2 and 3 acute kidney injury had a 1.79-fold (95% CI, 1.15-2.79; p = 0.01) and 3.24-fold (95% CI, 1.55-6.80; p = 0.002) increased odds of developing suspected sepsis, respectively. CONCLUSIONS: Acute kidney injury is associated with an increased risk for subsequent infection in critically ill children. These results further support the concept of acute kidney injury as a clinically relevant immunocompromised state.

Outcomes of adults with congenital heart disease that experience acute kidney injury in the intensive care unit.

BACKGROUND: Young adults with congenital heart disease (CHD) are increasing in number with an increased risk for acute kidney injury. Little is known concerning the impact of non-recovery of kidney function for these patients. Therefore, we sought to explore the rates of acute kidney disease, persistent renal dysfunction, and their associations with adverse outcomes in young adults with CHD. METHODS: This is a single-centre retrospective study including all patients at the ages of 18-40 with CHD who were admitted to an intensive care unit between 2010 and 2014. Patients with a creatinine ≥ 1.5 times the baseline at the time of hospital discharge were deemed to have persistent renal dysfunction, while acute kidney disease was defined as a creatinine ≥ 1.5 times the baseline 7-28 days after a diagnosis of acute kidney injury. Outcomes of death at 5 years and length of hospital stay were examined using multivariable logistic regression and negative binomial regression, respectively. RESULTS: Of the (89/195) 45.6% of patients with acute kidney injury, 33.7% had persistent renal dysfunction and 23.6% met the criteria for acute kidney disease. Persistent renal dysfunction [odds ratio (OR), 3.27; 95% confidence interval (CI): 1.15-9.29] and acute kidney disease (OR: 11.79; 95% CI: 3.75-39.09) were independently associated with mortality at 5 years. Persistent renal dysfunction was associated with a longer duration of hospital stay (Incidence Rate Ratio: 1.96; 95% CI: 1.53-2.51). CONCLUSIONS: In young adults with CHD, acute kidney injury was common and persistent renal dysfunction, as well as acute kidney disease, were associated with increased mortality and length of hospitalisation.

Validation of an Electronic Pediatric Index of Mortality 2 Score in a Mixed Quaternary PICU.

OBJECTIVE: To assess the validity of an electronic version of the Pediatric Index of Mortality 2 score. DESIGN: Retrospective observational study. SETTING: Pediatric and cardiac ICUs at a quaternary medical center. PATIENTS: Patients more than 60 days old admitted to the PICU or cardiac ICU between January 1, 2010, and December 31, 2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: After adapting the Pediatric Index of Mortality 2 score into a version applicable to retrospective electronic health record data, it was validated in a mixed-ICU cohort. A manually ascertained Pediatric Index of Mortality 2 score was directly compared with the electronically derived electronic version of the Pediatric Index of Mortality 2 score in 100 randomly selected patients with good agreement between score components with nine out of 11 components having an intraclass correlation coefficient or Cohen κ greater than or equal to 0.6. In assessing the electronic version of the Pediatric Index of Mortality 2 score in the entire cohort of 12,582 patient encounters, it had good discrimination with area under the receiver operating curve of 0.89, appropriate calibration with no significant difference between observed and expected deaths, and excellent predictive ability with a Brier score of 0.0135. CONCLUSIONS: The Pediatric Index of Mortality 2 score can be adapted to utilize retrospective electronic health record data with acceptable discrimination, calibration and accuracy a large mixed-ICU cohort.

The use of urinary biomarkers to predict acute kidney injury in children after liver transplant.

BACKGROUND: AKI after pediatric liver transplantation is associated with increased morbidity and mortality. The role of urinary biomarkers for the prediction of AKI in pediatric patients after liver transplantation has not been previously reported. The primary objective of this prospective pilot study was to determine the predictive capabilities of urinary KIM-1, NGAL, TIMP-2, and IGFBP7 for diagnosing AKI. METHODS: Sixteen children undergoing liver transplantation were enrolled in the study over a 19-month time period. The Kidney Disease Improving Outcomes criteria for urine output and serum creatinine were used to define AKI. Predictive ability was evaluated using the area under the curve obtained by ROC analysis. RESULTS: AKI occurred in 6 (37.5%) of the patients between 2 and 4 days after transplant. There were no differences in any of the biomarkers prior to transplant. When obtained within 6 hours after transplant, the area under the ROC curve for predicting AKI was 0.758 (95% CI: 0.458-1.00) for KIM-1, 0.900 (95% CI: 0.724-1.00) for NGAL, and 0.933 (95% CI: 0.812-1.00) for the product of TIMP-2 and IGFBP7 ([TIMP-2]·[IGFBP7]). CONCLUSIONS: Our results show that both NGAL and [TIMP-2]·[IGFBP7] provide significant discrimination for AKI risk following liver transplant in children. Larger studies are needed to determine the optimal time point for measuring these biomarkers and to validate our findings.

Piperacillin/Tazobactam and Antibiotic-Associated Acute Kidney Injury in Critically Ill Children.

BACKGROUND: There continues to be uncertainty about whether piperacillin/tazobactam (TZP) increases the risk of AKI in critically ill pediatric patients. We sought to compare rates of AKI among critically ill children treated with TZP or cefepime, an alternative frequently used in intensive care units, with and without vancomycin. METHODS: We conducted a retrospective cohort study assessing the risk of AKI in pediatric intensive care unit patients after exposure to vancomycin, TZP, and cefepime, alone or in combination, within 48 hours of admission. The primary outcome was development of stage 2 or 3 AKI or an increase in AKI stage from 2 to 3 within the 6 days after the 48-hour exposure window. Secondary outcomes included lengths of stay, need for RRT, and mortality. RESULTS: Of 5686 patients included, 494 (8.7%) developed stage 2 or 3 AKI. The adjusted odds of developing AKI after medication exposure were 1.56 for TZP (95% confidence interval [95% CI], 1.23 to 1.99), 1.13 for cefepime (95% CI, 0.79 to 1.64), and 0.86 for vancomycin (95% CI, 0.69 to 1.07). The adjusted odds of developing AKI for vancomycin plus TZP versus vancomycin plus cefepime was 1.38 (95% CI, 0.85 to 2.24). CONCLUSIONS: Observational data in critically ill children show that TZP use is associated with increased odds of AKI. A weaker, nonsignificant association between vancomycin plus TZP and AKI compared with vancomycin plus cefepime, creates some uncertainty about the nature of the association between TZP and AKI. However, cefepime is an alternative not associated with AKI.

Evaluating Renal Stress Using Pharmacokinetic Urinary Biomarker Data in Critically Ill Patients Receiving Vancomycin and/or Piperacillin-Tazobactam: A Secondary Analysis of the Multicenter Sapphire Study.

INTRODUCTION: A drug combination that has gained recent attention for an additive risk of nephrotoxicity is vancomycin plus piperacillin-tazobactam. Clinicians need to better understand whether tubular cell stress occurs with piperacillin-tazobactam administration to establish whether renal injury associated with this combination is a valid clinical concern. OBJECTIVE: An evaluation of the pharmacokinetics of urinary tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding-protein 7 (IGFBP7) for patients receiving vancomycin alone, piperacillin-tazobactam alone, and vancomycin plus piperacillin-tazobactam in combination was conducted to understand the impact on acute kidney cell stress and compare the rates of dialysis or death at 9 months among these three drug exposure types. METHODS: A secondary analysis of the prospective, multicenter Sapphire study (ClinicalTrials.gov identifier NCT01209169) including 35 intensive care units (ICUs) in North America and Europe was performed. Critically ill adult patients at risk for acute kidney injury (AKI) were included. Urinary [TIMP-2]∙[IGFBP7] was measured serially. Patients who received vancomycin alone, piperacillin-tazobactam alone, or vancomycin plus piperacillin-tazobactam were grouped according to their maximum AKI stage within 3 days of the first drug dose. RESULTS: Of 723 critically ill adults admitted to the ICU, 46% received either piperacillin-tazobactam (n = 110), vancomycin (n = 156), or both (n = 67). The urinary [TIMP-2]∙[IGFBP7] was highest on day 1 for the combination group. AKI stage 2/3 occurred more frequently in patients receiving the drug combination than in those receiving piperacillin-tazobactam alone (p = 0.03) but not vancomycin alone (p = 0.29). Risk of death or dialysis at 9 months was greatest for vancomycin plus piperacillin-tazobactam (48%) and similar for patients receiving vancomycin alone (29%) or piperacillin-tazobactam alone (35%) (p = 0.03 for unadjusted and p = 0.048 after adjusting for covariates). CONCLUSION: After exposure to piperacillin-tazobactam and vancomycin in combination, there was a greater release of AKI biomarkers in patients who develop AKI than with piperacillin-tazobactam or vancomycin monotherapy and the combination is associated with possible increased long-term adverse outcomes.

eResearch in acute kidney injury: a primer for electronic health record research.

Acute kidney injury (AKI) has a significant impact on patient morbidity and mortality as well as overall health care costs. eResearch, which integrates information technology and information management to optimize research strategies, provides a perfect platform for necessary ongoing AKI research. With the recent adoption of a widely accepted definition of AKI and near-universal use of electronic health records, eResearch is becoming an important tool in AKI research. Conducting eResearch in AKI should ideally be based on a relatively uniform methodology. This article is the first of its kind to describe a methodology for pursuing eResearch specific to AKI and includes an illustrative database example for critically ill patients. We discuss strategies for using serum creatinine and urine output in large databases to identify and stage AKI and ways to interpolate missing values and validate data. Issues specific to the pediatric population include variation in serum creatinine with growth, varied severity of illness scoring systems and medication dosage based on weight. Many of these same strategies used to optimize AKI eResearch can be applicable to real-time AKI alerts with potential integration of additional clinical variables.

Drug-associated acute kidney injury: who's at risk?

The contribution of nephrotoxic medications to the development of acute kidney injury (AKI) is becoming better understood concomitant with the increased incidence of AKI in children. Treatment of AKI is not yet available, so prevention continues to be the most effective approach. There is an opportunity to mitigate severity and prevent the occurrence of AKI if children at increased risk are identified early and nephrotoxins are used judiciously. Early detection of AKI is limited by the dependence of nephrologists on serum creatinine as an indicator. Promising new biomarkers may offer early detection of AKI prior to the rise in serum creatinine. Early detection of evolving AKI is improving and offers opportunities for better management of nephrotoxins. However, the identification of patients at increased risk will remain an important first step, with a focus on the use of biomarker testing and interpretation of the results.