Abstract

Title

Serial Quantification of Urinary Protein Biomarkers to Predate Drug-Induced Acute Kidney Injury

Type
Oral Presentation
Theme
18th Asian Colloquium in Nephrology (18th ACN 2019)
Topic
Acute Kidney Injury

Authors

Main Author
YI DA1 2
Presenting Author
YI DA1 2
Co-Author
K AKALYA1 2
Tanusya Murali MURALI1 2
A VATHSALA1 2
Chuen-Seng TAN3
Sanmay LOW1 2
Horng-Ruey CHUA1 2

Authors' Institution

Department / Institution / Country
Division of Nephrology, University Medicine Cluster / National University Hospital / Singapore1
Department of Medicine, Yong Loo Lin School of Medicine, / National University of Singapore / Singapore2
Saw Swee Hock School of Public Health / National University of Singapore / Singapore3
Content
Abstract Content: Introduction, Method, Result, Conclusion

 

[Introduction] Drug-induced acute kidney injury (DI-AKI) develops in 10–15% of at-risk patients. We aim to determine urinary protein biomarkers that predate DI-AKI with lead-time for preventive strategies.

[Methods] Serial urine samples were collected in 21 patients while receiving aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors; including 7 patients who subsequently developed DI-AKI (KDIGO criterion), and 14 non-AKI controls matched for age, baseline kidney function, and culprit nephrotoxin. Their urine were batch-analysed for biomarkers including clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor-3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin, all normalized to urine creatinine; at time-intervals before AKI onset, and corresponding time-intervals before cessation of nephrotoxins in controls.

[Results] Mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2, for AKI versus non-AKI patients, respectively (all p=NS). Five biomarkers had median levels higher in AKI cases than controls that predated AKI by 1–3 days (all µg/mmol, p<0.05): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)]; their corresponding AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation.

[Conclusion] Rise in selected urinary protein biomarkers in patients receiving nephrotoxins predates DI-AKI by days.

Keywords: Acute kidney injury; Beta 2-microglobulin; Biomarkers; Clusterin; Drug-related side effects and adverse reactions.
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