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Original ArticleChronic Kidney Disease
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Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease

Insa M. Schmidt, Suraj Sarvode Mothi, Parker C. Wilson, Ragnar Palsson, Anand Srivastava, Ingrid F. Onul, Zoe A. Kibbelaar, Min Zhuo, Afolarin Amodu, Isaac E. Stillman, Helmut G. Rennke, Benjamin D. Humphreys and Sushrut S. Waikar
CJASN January 2022, 17 (1) 27-37; DOI: https://doi.org/10.2215/CJN.09380721
Insa M. Schmidt
1Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
2Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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Suraj Sarvode Mothi
3Department of Biostatistics, St. Jude Children’s Research Hospital, Memphis, Tennessee
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Parker C. Wilson
4Department of Pathology and Immunology, Washington University, St. Louis, Missouri
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Ragnar Palsson
5Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
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Anand Srivastava
6Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
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Ingrid F. Onul
1Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
2Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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Zoe A. Kibbelaar
1Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
2Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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Min Zhuo
2Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
7Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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Afolarin Amodu
1Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
2Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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Isaac E. Stillman
8Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts
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Helmut G. Rennke
9Department of Pathology, Brigham & Women’s Hospital, Boston, Massachusetts
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Benjamin D. Humphreys
10Division of Nephrology, Department of Medicine, Washington University, St. Louis, Missouri
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Sushrut S. Waikar
1Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts
2Renal Division, Brigham & Women’s Hospital, Boston, Massachusetts
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Abstract

Background and objectives Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease.

Design, setting, participants, & measurements Using a proteomics assay, we measured a multimarker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semiquantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of KRT) and death.

Results After multivariable adjustment and correction for multiple testing, 46 different proteins were associated with histopathologic lesions. The top-performing markers positively associated with acute tubular injury and interstitial fibrosis/tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and Ig domain-containing protein 2 (VSIG2), respectively. Thirty proteins were significantly associated with kidney disease progression, and 35 were significantly associated with death. The top-performing markers for kidney disease progression were placental growth factor (hazard ratio per doubling, 5.4; 95% confidence interval, 3.4 to 8.7) and BMP and activin membrane-bound inhibitor (hazard ratio, 3.0; 95% confidence interval, 2.1 to 4.2); the top-performing markers for death were TNF-related apoptosis-inducing ligand receptor-2 (hazard ratio, 2.9; 95% confidence interval, 2.0 to 4.0) and CUB domain-containing protein-1 (hazard ratio, 2.4; 95% confidence interval, 1.8 to 3.3).

Conclusion We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases.

Podcast This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_28_CJN09380721.mp3

  • kidney disease
  • proteomics
  • kidney biopsy
  • histopathology
  • Boston
  • cohort studies
  • biomarkers
  • nephrectomy
  • causality
  • plasma
  • Received July 9, 2021.
  • Accepted November 2, 2021.
  • Copyright © 2022 by the American Society of Nephrology
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Clinical Journal of the American Society of Nephrology: 17 (1)
Clinical Journal of the American Society of Nephrology
Vol. 17, Issue 1
January 2022
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Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease
Insa M. Schmidt, Suraj Sarvode Mothi, Parker C. Wilson, Ragnar Palsson, Anand Srivastava, Ingrid F. Onul, Zoe A. Kibbelaar, Min Zhuo, Afolarin Amodu, Isaac E. Stillman, Helmut G. Rennke, Benjamin D. Humphreys, Sushrut S. Waikar
CJASN Jan 2022, 17 (1) 27-37; DOI: 10.2215/CJN.09380721

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Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease
Insa M. Schmidt, Suraj Sarvode Mothi, Parker C. Wilson, Ragnar Palsson, Anand Srivastava, Ingrid F. Onul, Zoe A. Kibbelaar, Min Zhuo, Afolarin Amodu, Isaac E. Stillman, Helmut G. Rennke, Benjamin D. Humphreys, Sushrut S. Waikar
CJASN Jan 2022, 17 (1) 27-37; DOI: 10.2215/CJN.09380721
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Original Article

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  • Boston
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  • plasma

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