Urine Neutrophil Gelatinase-associated Lipocalin (NGAL) for Prediction of Persistent AKI and Major Adverse Kidney Events

Abstract

We aimed to determine whether urinary neutrophil gelatinase-associated lipocalin (uNGAL) can accurately predict persistent AKI, major adverse kidney events at 30 days (MAKE30) and 365 days (MAKE365) in hospitalized AKI patients. This is a retrospective study of adult patients who were admitted at King Chulalongkorn Memorial Hospital. We performed multivariable logistic regression for persistent AKI, MAKE30, and MAKE365. We developed equations for predicting MAKE30 and MAKE365 and divided the dataset into derivation and validation cohorts. uNGAL performance and predictive models were assessed using the area under the receiver operating characteristic curve (AROC). Among 1,322 patients with AKI, 76.9%, 45.1%, and 61.7% had persistent AKI, MAKE30, and MAKE365. The AROC were 0.75 (95% confidence interval[CI] 0.70-0.80), 0.66 (95%CI 0.61-0.71), and 0.64 (95%CI 0.59-0.70) for prediction of persistent AKI, MAKE30, and MAKE365 by uNGAL. The AROC in the validation dataset combining uNGAL with clinical covariates were 0.74 (95%CI 0.69-0.79) and 0.72 (95%CI 0.67-0.77) for MAKE30 and MAKE365. We demonstrated an association between uNGAL and persistent AKI, MAKE30, and MAKE365. Prediction models combining uNGAL can modestly predict MAKE30 and MAKE365. Therefore, uNGAL is a useful tool for improving AKI risk stratification. Acute kidney injury (AKI) is reported in 52.9-57.3% of critically ill patients and strongly associated with increased morbidity and mortality 1-3. In addition, AKI survivors have increased risk of developing chronic kidney disease (CKD), CKD progression, and end-stage kidney disease (ESRD). Factors associated with an increased risk of long-term complications include diabetes, older age, number of AKI episodes, AKI severity and serum albumin 4-6. Recently, AKI duration was ascertained as another prognostic factor for short-term and long-term mortality 7-10. Novel biomarkers measured at the time of intensive care unit (ICU) admission have been reported to predict short-term and long-term outcomes. Examples include urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary interleukin-18 (IL-18), urinary kidney injury molecule-1 (KIM-1), urinary insulin-like growth factor-binding protein-7 and tissue inhibitor of metalloproteinases-2 (TIMP-2xIGFBP-7) 11-13. uNGAL is a 25-kDa protein belonging to the lipocalin family. uNGAL is produced in renal epithelia and leukocytes in response to tubular injury and systemic inflammation. High uNGAL can be used to predict AKI 14-17 , discriminate intrinsic AKI from pre-renal AKI 18,19 , predict renal non-recovery, in-hospital mortality 20-22 , long-term

Correlation and Diagnostic Value of Serum Cys-C, RBP4, and NGAL with the Condition of Patients with Traumatic Acute Kidney Injury

“…Under normal physiological conditions, NGAL has stable low expression in a variety of organs, including the bone marrow, stomach, and colon. A study by Lumlertgul et al [ 20 ] found that, in patients with renal impairment, NGAL values were well outside the normal range values while serum creatinine was still in the normal range, which suggests that NGAL has a high application value for early diagnosis of AKI.…”

Development and External Verification of a Nomogram for Patients with Persistent Acute Kidney Injury in the Intensive Care Unit

“… 29 Using the data of 1322 AKI patients’ registry at King Chulalongkorn Memorial Hospital, Nuttha et al also demonstrated that uNGAL was associated with pAKI as well as prognosis of AKI patients. 30 In addition, several factors have been shown to be associated with pAKI in previous studies. Firstly, comorbidities, especially for patients with pre-existing renal dysfunction, were associated with longer AKI duration.…”

Kinetic changes in serum procalcitonin predict persistent acute kidney injury in critical patients

“…6,7,20 Renal function that does not return to normal within 48 h was defined as persistent AKI by the ADQI in 2017. Subsequent studies showed that the morbidity of persistent AKI in critically ill patients is up to 45%-76.9%, 4,5,8,15,21,22 and the ICU mortality rate is 33.1-34%. 5,8 Our study found that the morbidity of persistent AKI was 60.43%, which is similar to the findings of previous studies.…”