Insa M Schmidt1,2, Suraj Sarvode Mothi3, Parker C Wilson4, Ragnar Palsson5, Anand Srivastava6, Ingrid F Onul1,2, Zoe A Kibbelaar1,2, Min Zhuo2,7, Afolarin Amodu1,2, Isaac E Stillman8, Helmut G Rennke9, Benjamin D Humphreys10, Sushrut S Waikar11,2. 1. Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts. 2. Renal Division, Brigham & Women's Hospital, Boston, Massachusetts. 3. Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee. 4. Department of Pathology and Immunology, Washington University, St. Louis, Missouri. 5. Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts. 6. Division of Nephrology and Hypertension, Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois. 7. Division of Nephrology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 8. Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts. 9. Department of Pathology, Brigham & Women's Hospital, Boston, Massachusetts. 10. Division of Nephrology, Department of Medicine, Washington University, St. Louis, Missouri. 11. Section of Nephrology, Department of Medicine, Boston University School of Medicine, Boston Medical Center, Boston, Massachusetts swaikar@bu.edu.
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.
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.
Authors: Bert-Jan H van den Born; Niels V van der Hoeven; Evelyn Groot; Peter J Lenting; Joost C M Meijers; Marcel Levi; Gert A van Montfrans Journal: Hypertension Date: 2008-03-10 Impact factor: 10.190
Authors: Francesco S Loffredo; Matthew L Steinhauser; Steven M Jay; Joseph Gannon; James R Pancoast; Pratyusha Yalamanchi; Manisha Sinha; Claudia Dall'Osso; Danika Khong; Jennifer L Shadrach; Christine M Miller; Britta S Singer; Alex Stewart; Nikolaos Psychogios; Robert E Gerszten; Adam J Hartigan; Mi-Jeong Kim; Thomas Serwold; Amy J Wagers; Richard T Lee Journal: Cell Date: 2013-05-09 Impact factor: 41.582
Authors: Anand Srivastava; Ragnar Palsson; Arnaud D Kaze; Margaret E Chen; Polly Palacios; Venkata Sabbisetti; Rebecca A Betensky; Theodore I Steinman; Ravi I Thadhani; Gearoid M McMahon; Isaac E Stillman; Helmut G Rennke; Sushrut S Waikar Journal: J Am Soc Nephrol Date: 2018-06-04 Impact factor: 10.121
Authors: Andrew S Levey; Lesley A Stevens; Christopher H Schmid; Yaping Lucy Zhang; Alejandro F Castro; Harold I Feldman; John W Kusek; Paul Eggers; Frederick Van Lente; Tom Greene; Josef Coresh Journal: Ann Intern Med Date: 2009-05-05 Impact factor: 25.391
Authors: Insa M Schmidt; Mia R Colona; Anand Srivastava; Guanghao Yu; Venkata Sabbisetti; Joseph V Bonventre; Sushrut S Waikar Journal: Kidney Med Date: 2022-06-02