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Abstract: TH-OR47

Identification of Novel Biomarkers of Kidney Disease Histopathology and Prognosis: Results from the Boston Kidney Biopsy Cohort

Session Information

Category: Pathology and Lab Medicine

  • 1602 Pathology and Lab Medicine: Clinical

Authors

  • Schmidt, Insa Marie, Boston University Medical Center, Boston, Massachusetts, United States
  • Sarvode mothi, Suraj, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Palsson, Ragnar, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Srivastava, Anand, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Kibbelaar, Zoé A., Boston University Medical Center, Boston, Massachusetts, United States
  • Zhuo, Min, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Amodu, Afolarin Ayomide, Boston University Medical Center, Boston, Massachusetts, United States
  • Stillman, Isaac Ely, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States
  • Rennke, Helmut G., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Waikar, Sushrut S., Boston University Medical Center, Boston, Massachusetts, United States
Background

Biomarkers for non-invasive assessments of histopathology and prognosis are needed in patients with kidney disease.

Methods

Using a novel proteomics assay, we measured a multi-marker panel of 225 circulating plasma proteins in a prospective cohort study of 557 individuals with biopsy-confirmed kidney diseases and adjudicated semi-quantitative assessments of histopathologic lesions. We tested the associations of each biomarker with clinicopathologic diagnoses, histopathologic lesions, and the risks of kidney disease progression (≥40% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease) and death.

Results

After multivariable adjustment and correction for multiple testing, 39 proteins were independently associated with clinicopathologic diagnoses and 53 with different histopathologic lesions. Kidney-injury molecule-1 (KIM-1) associated with diabetic nephropathy and glomerular and tubulointerstitial diseases. The top performing markers for acute tubular injury and interstitial fibrosis and tubular atrophy were KIM-1 and tumor necrosis factor receptor superfamily member-9 (TNFRSF-9), respectively. Thirty proteins were significantly associated with kidney disease progression and 35 with death (Figure 1 A, B). The top performing markers for kidney disease progression were placental growth factor (PGF; HR 5.4 , 95% CI 3.4 to 8.7) and BMP and Activin Membrane Bound Inhibitor (BAMBI; HR 3.0, 95% CI 2.1 to 4.2); the top performing markers for death were TRAIL-receptor-2 (TRAIL-R2; HR 2.9, 95% CI 2.0 to 4.0) and CUB Domain Containing Protein-1 (CDCP1; HR 2.4, 95% CI 1.8, 3.3). Five proteins were significantly associated with decreased risks of death (Figure 1 B).

Conclusion

We identified several biomarkers of kidney disease histology, pathology, and prognosis – many of which have not been reported previously and may represent important avenues for future research.

Funding

  • NIDDK Support