TY - JOUR
T1 - Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease
AU - Schmidt, Insa M.
AU - Mothi, Suraj Sarvode
AU - Wilson, Parker C.
AU - Palsson, Ragnar
AU - Srivastava, Anand
AU - Onul, Ingrid F.
AU - Kibbelaar, Zoe A.
AU - Zhuo, Min
AU - Amodu, Afolarin
AU - Stillman, Isaac E.
AU - Rennke, Helmut G.
AU - Humphreys, Benjamin D.
AU - Waikar, Sushrut S.
N1 - Publisher Copyright:
© 2022 by the American Society of Nephrology.
PY - 2022/1
Y1 - 2022/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85123377744&partnerID=8YFLogxK
U2 - 10.2215/CJN.09380721
DO - 10.2215/CJN.09380721
M3 - Article
C2 - 34759008
AN - SCOPUS:85123377744
SN - 1555-9041
VL - 17
SP - 27
EP - 37
JO - Clinical Journal of the American Society of Nephrology
JF - Clinical Journal of the American Society of Nephrology
IS - 1
ER -