Dataset Information

Predicting Acute Renal Injury in Cancer Patients Receiving Cisplatin Using Urinary Neutrophil Gelatinase-Associated Lipocalin and Cystatin C.

ABSTRACT: Acute kidney injury (AKI) limits cisplatin use. We tested whether urine cystatin C (uCyC) and neutrophil gelatinase-associated lipocalin (uNGAL) can preidentify patients at risk for AKI. Patients initiating cisplatin-based chemotherapy were prospectively enrolled. uNGAL/uCyC were measured pre/post-cisplatin administration and compared with serum creatinine (sCr). AKI was defined as sCr increase ?50% or ?0.3 mg/dL above baseline. In all, 102 patients were enrolled; 95 provided evaluable data. Twenty-five patients developed AKI. Median baseline and pre-cisplatin uNGAL levels were significantly higher in AKI patients. Although immediate changes in uNGAL/uCyC 2 h after cisplatin were not detectable, post-cisplatin peak values over the course of therapy were markedly and significantly elevated in AKI patients. In multivariate modeling with age, baseline glomerular filtration rate, and histology, maximum uCyC was a significant independent AKI predictor. These findings suggest pre-cisplatin uNGAL and peak uCyC levels can identify patients with increased AKI risk, potentially allowing for tailored modification of cisplatin-based treatment regimens.

SUBMITTER: Jelinek MJ

PROVIDER: S-EPMC6039203 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Predicting Acute Renal Injury in Cancer Patients Receiving Cisplatin Using Urinary Neutrophil Gelatinase-Associated Lipocalin and Cystatin C.

Jelinek Michael J MJ Lee Sang Mee SM Wyche Okpareke Alicia A Wing Claudia C Koyner Jay L JL Murray Patrick T PT Stadler Walter M WM O' Donnell Peter H PH

Clinical and translational science 20180424 4

Acute kidney injury (AKI) limits cisplatin use. We tested whether urine cystatin C (uCyC) and neutrophil gelatinase-associated lipocalin (uNGAL) can preidentify patients at risk for AKI. Patients initiating cisplatin-based chemotherapy were prospectively enrolled. uNGAL/uCyC were measured pre/post-cisplatin administration and compared with serum creatinine (sCr). AKI was defined as sCr increase ≥50% or ≥0.3 mg/dL above baseline. In all, 102 patients were enrolled; 95 provided evaluable data. Twe ...[more]

PMID: 29691991

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Project description:BackgroundAcute kidney injury (AKI) due to Diabetic Ketoacidosis (DKA) is rather common. Novel biomarkers to diagnose AKI are being increasingly used in different settings. The use of urinary Neutrophil Gelatinase-Associated Lipocalin (uNGAL) in predicting persistent AKI in pediatric DKA cases is still not thoroughly investigated.MethodsThis was a secondary analysis of Saline versus Plasma-Lyte in Ketoacidosis (SPinK) trial data; 66 children (> 1 month-12 years) with DKA, defined by the International Society for Pediatric and Adolescent Diabetes (ISPAD), were analyzed. Children with cerebral edema, chronic kidney disease and those who received pre-referral fluids and/or insulin were excluded. uNGAL and urine NGAL-creatinine ratio (uNCR) at 0 and 24 h were measured in all. Persistent AKI was defined as a composite outcome of continuance of AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) stage 2 or 3 beyond 48 h from AKI onset, progression of AKI from either KDIGO stage 0 or 1 to a worse stage, need of renal replacement therapy or death.Main outcomesThirty-five (53%) children had AKI at admission; 32 (91.4%) resolved within 48 h. uNGAL was significantly higher in the AKI group at admission [79.8 ± 27.2 vs 54.6 ± 22.0, p = 0.0002] and at 24 h [61.4 ± 28.3 vs 20.2 ± 14.5, p = 0.0003]. Similar trend was observed with uNCR at admission [6.7 ± 3.7 vs 4.1 ± 2.6, p = 0.002] and at 24 h [6.3 ± 2.5 vs 1.2 ± 1.0, p = 0.01]. Furthermore, uNGAL at admission showed a moderate positive linear correlation with serum creatinine. Additionally, elevated uNGAL at 0 and 24 h correlated with corresponding KDIGO stages. Admission uNGAL >88 ng/ml and uNCR of >11.3 ng/mg had a sensitivity of 66% and 67%, specificity of 76% and 95%, and Area under the receiver operating characteristic curve (AUC) of 0.78 and 0.89 respectively for predicting persistent AKI at 48 h.ConclusionsMajority of AKI resolved with fluid therapy. While uNGAL and uNCR both correlated with serum creatinine and AKI stages, serial uNCR was a better predictor of persistent AKI than uNGAL alone. However, feasibility of routine uNGAL measurement to predict persistent AKI in DKA needs further elucidation.Trial registrationThis was a secondary analysis of the data of SPinK trial [CTRI/2018/05/014042 ( ctri.nic.in )].

Project description:BackgroundFew studies have described associations between the AKI biomarkers urinary neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) with AKI in cisplatin-treated children. We aimed to describe excretion patterns of urine NGAL and KIM-1 and associations with AKI in children receiving cisplatin.MethodsParticipants (n=159) were enrolled between 2013 and 2017 in a prospective cohort study conducted in 12 Canadian pediatric hospitals. Participants were evaluated at early cisplatin infusions (at first or second cisplatin cycle) and late cisplatin infusions (last or second-to-last cycle). Urine NGAL and KIM-1 were measured (1) pre-cisplatin infusion, (2) post-infusion (morning after), and (3) at hospital discharge at early and late cisplatin infusions. Primary outcome: AKI defined by serum creatinine rise within 10 days post-cisplatin, on the basis of Kidney Disease Improving Global Outcomes guidelines criteria (stage 1 or higher).ResultsOf 159 children, 156 (median [interquartile range (IQR)] age: 5.8 [2.4-12.0] years; 78 [50%] female) had biomarker data available at early cisplatin infusions and 127 had data at late infusions. Forty six of the 156 (29%) and 22 of the 127 (17%) children developed AKI within 10 days of cisplatin administration after early and late infusions, respectively. Urine NGAL and KIM-1 concentrations were significantly higher in patients with versus without AKI (near hospital discharge of late cisplatin infusion, median [IQR] NGAL levels were 76.1 [10.0-232.7] versus 14.9 [5.4-29.7] ng/mg creatinine; KIM-1 levels were 4415 [2083-9077] versus 1049 [358-3326] pg/mg creatinine; P<0.01). These markers modestly discriminated for AKI (area under receiver operating characteristic curve [AUC-ROC] range: NGAL, 0.56-0.72; KIM-1, 0.48-0.75). Biomarker concentrations were higher and better discriminated for AKI at late cisplatin infusions (AUC-ROC range, 0.54-0.75) versus early infusions (AUC-ROC range, 0.48-0.65).ConclusionsUrine NGAL and KIM-1 were modest at discriminating for cisplatin-associated AKI. Further research is needed to determine clinical utility and applicability of these markers and associations with late kidney outcomes.

Dataset Information

Predicting Acute Renal Injury in Cancer Patients Receiving Cisplatin Using Urinary Neutrophil Gelatinase-Associated Lipocalin and Cystatin C.

Publications

Predicting Acute Renal Injury in Cancer Patients Receiving Cisplatin Using Urinary Neutrophil Gelatinase-Associated Lipocalin and Cystatin C.

Similar Datasets

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