Urinary biomarkers as a predictor of outcome in pediatric sepsis

Abstract

Objectives: To determine the prognostic ability of urinary biomarkers in paediatric sepsis with or without AKI. Methodology: A single-center pilot prospective observational study was conducted in the 12-bedded multidisciplinary PICU of a tertiary referral and teaching hospital in South India over a period of 18 months. Children aged 1 month to 18 years admitted to PICU with diagnosis of sepsis were considered for inclusion. We excluded those with chronic kidney disease, anuria or brain death at admission and hospital stay < 24 hours. Demographic and clinical details, severity of illness, organ dysfunctions, details of PICU interventions and outcomes were recorded. Urine samples were collected within 24 hours of admission to test for 7 biomarkers (α1 microglobulin, FABP-1, MMP-8, NGAL, KIM-1, IGFBP-7, IL-18). All patients were followed up for 14 days and categorized into two groups: sepsis associated AKI (SA-AKI) and sepsis without AKI (Sepsis non-AKI, SN-AKI) using AKIN criteria. Results: Total of 45 children were enrolled, of which 25 had AKI (SA-AKI) and 20 did not (SN-AKI). Among SA-AKI patients, 9 had Stage 1 AKI, while rest had stage 3 AKI. Twenty patients with AKI required mechanical ventilation and 16 required renal replacement therapy. PRISM III, PELOD and SOFA score at admission were similar among SA-AKI and SN-AKI, however, PELOD and SOFA scores on day 3 were significantly higher among SA-AKI children (p<0.05). Median urinary concentrations of the 7 biomarkers tested were higher in SA-AKI group compared to SN-AKI group, but only KIM-1 and IGFBP-7 were statistically significant (p=0.0003 and p=0.0024 respectively). KIM-1 ≥18.18 pg/ml had area under receiver operating characteristics curve (AUC-ROC) of 0.85±0.07(CI0.70-0.95) with 83.3% sensitivity and 88.8% specificity, while IGFBP-7 ≥98pg/ml had AUC-ROC of 0.80±0.08(CI0.64-0.92) with 72.2% sensitivity and 83.3% specificity. None of the biomarkers showed significant correlation with AKI stage. In SA-AKI group, α1 microglobulin was significantly higher in those who died compared to those who survived (p=0.035). Overall mortality was more in SA-AKI group compared to SN-AKI group (44% vs 5.4%, p=0.003), there was no significant difference in length of PICU stay. Conclusion: SA-AKI is associated with high morbidity and mortality. Specific urinary biomarkers (KIM-1, IGFBP-7) were significantly elevated in the sepsis patients who developed AKI compared to those who did not. α1 microglobulin can predict survival in SA-AKI.