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Abstract: TH-PO1082

Urinary Chemokine (C-X-C Motif) Ligand 9 (CXCL9) and Neutrophil Gelatinase-Associated Lipocalin (NGAL) Identify Tubulointerstitial Disease and Histopathological Lesions in the Boston Kidney Biopsy Cohort Study

Session Information

Category: Pathology and Lab Medicine

  • 1700 Pathology and Lab Medicine

Authors

  • Kamboj, Kajal, Boston Medical Center, Boston, Massachusetts, United States
  • Schmidt, Insa Marie, Boston Medical Center, Boston, Massachusetts, United States
  • Huynh, Courtney, Boston Medical Center, Boston, Massachusetts, United States
  • Palsson, Ragnar, Harvard Medical School, Boston, Massachusetts, United States
  • Srivastava, Anand, University of Illinois Chicago, Chicago, Illinois, United States
  • Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States
Background

Current clinical markers often fail to capture active intra-renal pathology, including interstitial fibrosis, tubular atrophy (IFTA), and inflammation. Although kidney biopsy remains the gold standard, there is a need for non-invasive biomarkers to aid in clinical decision making. We evaluated two urinary biomarkers of tubulointerstitial injury, uCXCL9 and uNGAL, for the non-invasive detection of histopathologic lesions and diagnoses.

Methods

Urinary CXCL9 and NGAL, indexed to urine creatinine (cr), were measured in 300 adults undergoing clinically indicated native kidney biopsies at three tertiary centers. Two renal pathologists adjudicated histopathologic scores. Associations with eGFR and albuminuria were assessed using Spearman correlation, while multivariable linear regression tested associations with histopathologic lesions. Differences across clinicopathologic diagnoses were evaluated using Kruskal–Wallis tests. Biomarkers were quantified on the Meso Scale Discovery platform using urine collected on the day of biopsy.

Results

Mean age was 54 ± 17 years, mean eGFR was 55 ± 34 ml/min per 1.73 m2, and median albuminuria was 1.6 g/g [0.4–3.9 g/g]. uNGAL/cr and uCXCL9/cr both correlated inversely with eGFR (Rs = -0.51 and -0.47, respectively; P<0.001) and positively with proteinuria (Rs = 0.34 and 0.28, respectively; P<0.001). After multivariable adjustment for age, sex, race and eGFR, both markers were associated with acute tubular injury (ATI) and interstitial inflammation as follows: β per 1 SD increase uCXCL9/cr = 0.17 for ATI and 0.16 for interstitial inflammation; β per 1 SD increase uNGAL/cr = 0.19 for ATI and 0.13 for interstitial inflammation – all P<0.01). Both urinary markers were also elevated in patients with diagnoses of tubulointerstitial diseases compared to controls (Figure 1).

Conclusion

Both uNGAL and uCXCL9 were associated with tubulointerstitial lesions and diagnoses of tubulointerstitial diseases in patients undergoing native kidney biopsy.

Figure 1: Distribution of urinary NGAL/cr and CXCL9/cr by different diagnosis categories.

Funding

  • NIDDK Support