The outcome of acute kidney injury substages based on urinary cystatin C in critically ill children.

BACKGROUND: The concept of acute kidney injury (AKI) substages has been recommended to better phenotype AKI and identify high-risk patient groups and therefore improve the diagnostic accuracy of AKI. However, there remains a gap between the recommendation and the clinical application. The study aimed to explore the incidence of AKI substages based on a sensitive AKI biomarker of urinary cystatin C (uCysC), and to determine whether AKI substages were relevant with respect to outcome in critically ill children. RESULTS: The multicenter cohort study enrolled 793 children in pediatric intensive care unit (PICU) of four tertiary hospitals in China. Children were classified as non-AKI, sub-AKI and AKI substages A and B according to uCysC level at PICU admission. Sub-AKI was defined by admission uCysC level ≥ 1.26 mg/g uCr in children not meeting the KDIGO criteria of AKI. In children who fulfilled KDIGO criteria, those with uCysC < 1.26 was defined as AKI substage A, and with ≥ 1.26 defined as AKI substage B. The associations of AKI substages with 30-day PICU mortality were assessed. 15.6% (124/793) of patients met the definition of sub-AKI. Of 180 (22.7%) patients with AKI, 90 (50%) had uCysC-positive AKI substage B and were more likely to have classical AKI stage 3, compared to substage A. Compared to non-AKI, sub-AKI and AKI substages A and B were risk factors significantly associated with mortality, and the association of sub-AKI (adjusted hazard ratio HR = 2.42) and AKI substage B (adjusted HR = 2.83) with mortality remained significant after adjustment for confounders. Moreover, AKI substage B had increased risks of death as compared with sub-AKI (HR = 3.10) and AKI substage A (HR = 3.19). CONCLUSIONS: Sub-AKI defined/based on uCysC occurred in 20.2% of patients without AKI and was associated with a risk of death close to patients with AKI substage A. Urinary CysC-positive AKI substage B occurred in 50% of AKI patients and was more likely to have classical AKI stage 3 and was associated with the highest risk of mortality.

Prediction of urinary dickkopf-3 for AKI, sepsis-associated AKI, and PICU mortality in children.

BACKGROUND: Preoperative urinary dickkopf-3 (DKK3) is proposed as an early biomarker for the prediction of acute kidney injury (AKI) in patients undergoing cardiac surgery. We explored the clinical utility of urinary DKK3 for the early predictive value for AKI, sepsis-associated AKI (SA-AKI), and pediatric intensive care unit (PICU) mortality in critically ill children. METHODS: Urine samples were collected during the first 24 h after admission for measurement of DKK3. AKI diagnosis was based on serum creatinine and urine output using the KDIGO criteria. SA-AKI was defined as AKI that occurred in children who met the sepsis criteria in accordance with the surviving sepsis campaign international guidelines for children. RESULTS: Of the 420 children, 73 developed AKI, including 24 with SA-AKI, and 30 died during the PICU stay. The urinary DKK3 level was significantly associated with AKI, SA-AKI, and PICU mortality, even after adjustment for confounders. The area under the receiver operating characteristic curve of urinary DKK3 for the discrimination of AKI, SA-AKI, and PICU mortality was 0.70, 0.80, and 0.78, respectively. CONCLUSION: Urinary DKK3 was independently associated with an increased risk for AKI, SA-AKI, and PICU mortality and may be predictive of the aforementioned issues in critically ill children. IMPACT: Urinary dickkopf-3 (DKK3) has been identified as a preoperative biomarker for the prediction of acute kidney injury (AKI) following cardiac surgery or coronary angiography in adult patients. However, little is known about the clinical utility of urinary DKK3 in pediatric cohorts. This study demonstrated that urinary DKK3 is capable of early predicting AKI and pediatric intensive care unit (PICU) mortality and discriminating sepsis-associated AKI (SA-AKI) from other types of AKI. Urinary DKK3 may be an early biomarker for predicting AKI, SA-AKI, and PICU mortality in critically ill children.

Comparison of diagnostic criteria for acute kidney injury in critically ill children: a multicenter cohort study.

BACKGROUND: Substantial interstudy heterogeneity exists in defining acute kidney injury (AKI) and baseline serum creatinine (SCr). This study assessed AKI incidence and its association with pediatric intensive care unit (PICU) mortality under different AKI and baseline SCr definitions to determine the preferable approach for diagnosing pediatric AKI. METHODS: In this multicenter prospective observational cohort study, AKI was defined and staged according to the Kidney Disease: Improving Global Outcome (KDIGO), modified KDIGO, and pediatric reference change value optimized for AKI (pROCK) definitions. The baseline SCr was calculated based on the Schwartz formula or estimated as the upper normative value (NormsMax), admission SCr (AdmSCr) and modified AdmSCr. The impacts of different AKI definitions and baseline SCr estimation methods on AKI incidence, severity distribution and AKI outcome were evaluated. RESULTS: Different AKI definitions and baseline SCr estimates led to differences in AKI incidence, from 6.8 to 25.7%; patients with AKI across all definitions had higher PICU mortality ranged from 19.0 to 35.4%. A higher AKI incidence (25.7%) but lower mortality (19.0%) was observed based on the Schwartz according to the KDIGO definition, which however was overcome by modified KDIGO (AKI incidence: 16.3%, PICU mortality: 26.1%). Furthermore, for the modified KDIGO, the consistencies of AKI stages between different baseline SCr estimation methods were all strong with the concordance rates > 90.0% and weighted kappa values > 0.8, and PICU mortality increased pursuant to staging based on the Schwartz. When the NormsMax was used, the KDIGO and modified KDIGO led to an identical AKI incidence (13.6%), but PICU mortality did not differ among AKI stages. For the pROCK, PICU mortality did not increase pursuant to staging and AKI stage 3 was not associated with mortality after adjustment for confounders. CONCLUSIONS: The AKI incidence and staging vary depending on the definition and baseline SCr estimation method used. The modified KDIGO definition based on the Schwartz method leads AKI to be highly relevant to PICU mortality, suggesting that it may be the preferable approach for diagnosing AKI in critically ill children and provides promise for improving clinicians' ability to diagnose pediatric AKI.

In PICU acute kidney injury stage 3 or mortality is associated with early excretion of urinary renin.

BACKGROUND: Urinary renin is proposed to be a novel prognostic biomarker of acute kidney injury (AKI) in adults. The intention of our study was to evaluate the early predictive value of urinary renin for AKI and pediatric intensive care unit (PICU) mortality in critically ill children. METHODS: The first available urine sample during the first 24 h after admission was collected upon PICU admission for the measurement of renin using ELISA. Urinary renin concentrations were corrected for urinary creatinine (urinary renin-to-creatinine ratio, uRenCR). AKI was defined based on KDIGO criteria. RESULTS: Of the 207 children, 22 developed AKI, including 6 with stage 1, 6 with stage 2, and 10 with stage 3, and 14 died during PICU stay. There was a significant difference in uRenCR between non-AKI children and those with AKI stage 3 (P = 0.001), but not with AKI stage 1 or 2. The uRenCR remained associated with AKI stage 3 and PICU mortality after adjustment for potential confounders. The area under the receiver operating characteristic curve of uRenCR for discrimination of AKI stage 3 was 0.805, and PICU mortality was 0.801. CONCLUSIONS: Urinary renin was associated with the increased risk for AKI stage 3 and PICU mortality in critically ill children. IMPACT: Urinary renin is proposed to be a novel prognostic biomarker of AKI in adult patients. There are some differences between children and adults in physiological and pathophysiological characteristics. This study demonstrated that urinary renin was associated with the increased risk for AKI stage 3 and PICU mortality in critically ill children. Accurate identification of patients with severe renal injury or at high risk for mortality early in the disease course could augment the efficacy of available interventions and improve patient outcomes.