Dataset Information

Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria.

ABSTRACT:

Objectives

Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors.

Design

Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children.

Setting

Mulago National Referral Hospital in Kampala, Uganda.

Subjects

Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community children (n = 206) were followed for 24 months.

Interventions

None.

Measurements and main results

Children underwent neurocognitive evaluation at enrollment (community children) or a week following hospital discharge (severe malaria) and 6, 12, and 24 months follow-up. Endothelial activation was assessed at admission on plasma samples (von Willebrand factor, angiopoietin-1 and angiopoietin-2, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, soluble E-Selectin, and P-Selectin). False discovery rate was used to adjust for multiple comparisons. Severe malaria was associated with widespread endothelial activation compared with community children (p < 0.0001 for all markers). Acute kidney injury was independently associated with changes in von Willebrand factor, soluble intercellular adhesion molecule-1, soluble E-Selectin, P-Selectin, and angiopoietin-2 (p < 0.0001 for all). A log10 increase in angiopoietin-2 was associated with lower cognitive z scores across age groups (children < 5, ? -0.42, 95% CI, -0.69 to -0.15, p = 0.002; children ? 5, ? -0.39, 95% CI, -0.67 to -0.11, p = 0.007) independent of disease severity (coma, number of seizures, acute kidney injury) and sociodemographic factors. Angiopoietin-2 was associated with hemolysis (lactate dehydrogenase, total bilirubin) and inflammation (tumor necrosis factor-?, interleukin-10). In children with cerebral malaria who had a lumbar puncture performed, angiopoietin-2 was associated with blood-brain barrier dysfunction, and markers of neuroinflammation and injury in the cerebrospinal fluid (tumor necrosis factor-?, kynurenic acid, tau).

Conclusions

These data support angiopoietin-2 as a measure of disease severity and a risk factor for long-term cognitive injury in children with severe malaria.

SUBMITTER: Ouma BJ

PROVIDER: S-EPMC7780883 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria.

Ouma Benson J BJ Ssenkusu John M JM Shabani Estela E Datta Dibyadyuti D Opoka Robert O RO Idro Richard R Bangirana Paul P Park Gregory G Joloba Moses L ML Kain Kevin C KC John Chandy C CC Conroy Andrea L AL

Critical care medicine 20200901 9

<h4>Objectives</h4>Evaluate the relationship between endothelial activation, malaria complications, and long-term cognitive outcomes in severe malaria survivors.<h4>Design</h4>Prospectively cohort study of children with cerebral malaria, severe malarial anemia, or community children.<h4>Setting</h4>Mulago National Referral Hospital in Kampala, Uganda.<h4>Subjects</h4>Children 18 months to 12 years old with severe malaria (cerebral malaria, n = 253 or severe malarial anemia, n = 211) or community ...[more]

PMID: 32618701

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Project description:INTRODUCTION:Vancomycin associated acute kidney injury (vAKI) is a well known complication in pediatric patients. Identification and characterization of the incidence and risk factors for vAKI in the pediatric population would assist clinicians in potentially preventing or mitigating vAKI. METHODS AND MATERIALS:A 6 year retrospective cohort study was designed. Patients were included if they were < 19 years of age, received vancomycin as inpatients, and had a baseline SCr and one other SCr drawn during and up to 72 hours after the discontinuation of vancomycin. Data collection included patient demographics, vancomycin doses and length of therapy, vancomycin serum concentrations, and concomitant medications. The Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to characterize acute kidney injury. Descriptive statistical methods were used and ordinal logistic regression was employed to determine variables significantly associated with vAKI. RESULTS:A total of 7,095 patients met study criteria (55.4% male, median age 4.1 years (IQR 0.67-11.2 years)). Mechanical ventilation was used in 7.9% (n = 563) and mortality was 4.9% (n = 344). A total of 153 concomitant medications were identified. A median of 5 (IQR 3-7) SCr values were obtained and median SCr prior to vancomycin was 0.39 (IQR 0.28-0.57) mg/dL (CrCl 134±58 mL/min/1.73m2). Vancomycin was administered for a median of 2 (IQR 1-3) days (14.9±1.6 mg/kg/dose). vAKI was present in 12.2% (n = 862: KDIGO stage 1 (8.30%, n = 589), KDIGO stage 2 (1.94%, n = 138) KDIGO stage 3 (1.89%, n = 134)). Mean vancomycin serum concentration at 6-8 hours after a dose for patients with vAKI (10.7±8.9 mg/L) was significantly, but not clinically different for patients with no vAKI (7.5±6.3 mg/L). (p<0.05) Ordinal logistic regression identified total dose of vancomycin, vancomycin administration in the intensive care unit, and concomitant medication administration as significant for vAKI. In particular, concomitant administration of several different medications, including nafcillin, clindamycin, and acetazolamide, were noted for strong associations with vAKI. (p<0.05). CONCLUSIONS:Moderate to severe acute kidney injury due to vancomycin is infrequent in children and associated with concomitant medication use and total dose of vancomycin. Serum vancomycin concentrations are not useful predictors of vAKI in the pediatric population.

Dataset Information

Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria.

Objectives

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

Publications

Endothelial Activation, Acute Kidney Injury, and Cognitive Impairment in Pediatric Severe Malaria.

Similar Datasets

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