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Kidney Week

Abstract: TH-PO1145

THY1/CD90: An Early Kidney Injury Biomarker in Cisplatin-Treated Patients with Cancer

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Wen, Xia, Rutgers The State University of New Jersey, New Brunswick, New Jersey, United States
  • Thompson, Lauren E., University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States
  • Yang, Julia, Rutgers The State University of New Jersey, New Brunswick, New Jersey, United States
  • Kim, Christine, Rutgers The State University of New Jersey, New Brunswick, New Jersey, United States
  • Zhuang, Yonghua L., University of Colorado Anschutz Medical Campus, Aurora, Colorado, United States
  • O'Bryant, Cindy L., University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States
  • Jaimes, Edgar A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Aleksunes, Lauren, Rutgers The State University of New Jersey, New Brunswick, New Jersey, United States
  • Joy, Melanie S., University of Colorado Anschutz Medical Campus Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, Colorado, United States
Background

Kidney injury secondary to cisplatin can occur after a single dose. We have previously characterized significant increases in the urinary secretion of several proteins distributed throughout the nephron (Kidney Injury Molecule 1 (KIM-1), β-2 Microglobulin (B2M), Calbindin (CALB) and Trefoil Factor 3 (TFF3); PMID 39726772, 28002630, 32382514. An untargeted proteomic screening of urine by our group revealed elevations of THY1 in cancer patients receiving cisplatin. THY1 is a glycophosphatidylinositol-anchored cell surface protein (CD90) on glomerular mesangial cells and proximal tubular cells. The purpose of the current study was to evaluate time-dependent changes in urinary THY1/CD90 in patients after treatment with cisplatin and benchmark against KIM-1, B2M, CALB and TFF3.

Methods

Urine collections occurred over 10-days (0, 4-24, 24-48, 48-72, 240 h) from cancer patients (N=41) receiving their first/second cycle of cisplatin (≥25 mg/m2) at U. of Colorado and Memorial Sloan Kettering Cancer Center. THY1, KIM-1, CALB, TFF3, and B2M were measured in urine supernatant (Novus Biologicals, R&D Systems) and normalized to urine creatinine (BioAssay Systems). Pearson correlations were calculated between THY1 and KIM-1, CALB, TFF3, and B2M and repeated measures ANOVA was used to account for within-patient correlation (p<0.05).(GraphPad Prism 10 Software Inc).

Results

Urinary THY1 increased following cisplatin treatment, with baseline concentrations of 205±218 pg/mg, peaked within the 4-24 h collection (304±281 pg/mg) and remained elevated at the 48-72 h collection (310±265 pg/mg) (p<0.05). There were moderate correlations between THY1 and 1) CALB at 4-24 h (3.8±3.0 ng/mg, r: 0.51) and 24-48 h (349±326 pg/mg and 4.4±3.9 ng/mg, r: 0.41, respectively), 2) TFF3 at 48-72 h (429±280 ng/mg, r: 0.45), and 3) B2M at 240 h (248±193 pg/mg and 251±274 ng/mg, r: 0.40, respectively). Moderate correlation with the targeted biomarkers reflects the specific injury locations detected (proximal tubule vs. tubulointerstitial vs. glomerular) and time course of changes after the cisplatin insult.

Conclusion

Our data align with previous reports suggesting THY1 may be a potential marker of tubulointerstitial fibrosis in cisplatin-treated rats. THY1 may serve as a potential early and sensitive biomarker for cisplatin-induced kidney injury, particularly in patients with higher exposures, pre-existing kidney damage, or early tubular injury.

Funding

  • Other NIH Support