Kidney Week

Abstract: TH-PO057

Urinary TIMP2 and IGFBP7 as Early Biomarkers of Nephrotoxicity

Session Information

• AKI: Epidemiology, Risk Factors, Prevention - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 101 AKI: Epidemiology, Risk Factors, and Prevention

Authors

• K, Akalya, National University Hospital, Singapore, Singapore, Singapore

Akalya K,

• Chua, Horng-Ruey, National University Health System, Singapore, Singapore

Horng-Ruey Chua,

• Murali, Tanusya M., Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Tanusya M. Murali,

• Teo, Boon Wee, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

Boon Wee Teo,

• Low, Sanmay, National University Hospital System, Singapore, Singapore

Sanmay Low,

Background

Elevated levels of urinary tissue inhibitor of metalloproteinases-2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) predate severe AKI by >12 hours in critical illness; these biomarkers may help predate and predict drug-induced acute kidney injury (DI-AKI).

Methods

Prospective study involving serial urine collection in hospitalized patients, during course of therapy with nephrotoxic drugs. Absolute and normalized (against urine creatinine) levels of TIMP2 and IGFBP7 were examined in days leading up to study endpoint: onset of AKI by KDIGO criteria, or final day of nephrotoxic drug therapy in non-AKI patients.

Results

Twenty-two of 135 patients developed DI-AKI (16%), including 8 patients with KDIGO stage 2/3 AKI. Urinary biomarker analyses were performed for 21 AKI patients with available pre-AKI samples, and 28 non-AKI matched-controls. They were aged 57(±14) and 52(±15) years with baseline eGFR of 102(92-116) and 103(89-118) mL/min/1.73m², respectively, with corresponding drug therapy duration of 15(14-25) versus 14(10-21) days (all p=NS). Comparing biomarker trends at 4–6 days, 2–3 days, and 1–2 days before study endpoint; significantly higher TIMP2 and IGFBP7 levels (p<0.05) were observed in the absolute(ng/mL), normalized (µg/mmol) and composite ((ng/mL)²/1000) of these markers as early as 2-3 days prior to AKI onset. The respective absolute and normalized TIMP2 levels (2-3 days prior) in AKI versus non-AKI patients were 4.9 versus 2.2 (p=0.02) and 1.2 versus 0.6 (p=0.005); corresponding levels for absolute and normalized IGFBP7 were 12.9 versus 1.2 (p=0.005) and 1.9 versus 0.3 (p=0.01); absolute [TIMP2]*[IGFBP7] level was 0.07 versus 0.005(p=0.007). Highest absolute and normalized TIMP2 levels at 2–3 days pre-AKI predicts AKI with an average AUROC of 0.75 and 0.81 respectively; correspondingly the average AUROC for both IGFBP7 values was 0.73. [TIMP2] *[IGFBP7] was able to predict AKI with 74% accuracy and the optimal biomarker cut-off level was determined to be 0.01(ng/mL) ²/1000.

Conclusion

Elevated urinary TIMP2 or IGFBP7 predate and predict DI-AKI by 2–3 days during course of nephrotoxic drug therapy in hospitalized patients.

Funding

• Private Foundation Support