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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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.

Original languageEnglish
Pages (from-to)27-37
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Issue number1
StatePublished - Jan 2022


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