The Associations of Plasma Biomarkers of Inflammation With Histopathologic Lesions, Kidney Disease Progression, and Mortality-The Boston Kidney Biopsy Cohort Study

Anand Srivastava; Insa M Schmidt; Ragnar Palsson; Astrid Weins; Joseph V Bonventre; Venkata Sabbisetti; Isaac E Stillman; Helmut G Rennke; Sushrut S Waikar

doi:10.1016/j.ekir.2020.12.025

The Associations of Plasma Biomarkers of Inflammation With Histopathologic Lesions, Kidney Disease Progression, and Mortality-The Boston Kidney Biopsy Cohort Study

Kidney Int Rep. 2021 Jan 6;6(3):685-694. doi: 10.1016/j.ekir.2020.12.025. eCollection 2021 Mar.

Authors

Anand Srivastava¹, Insa M Schmidt^{2

3}, Ragnar Palsson^{3

4}, Astrid Weins⁵, Joseph V Bonventre³, Venkata Sabbisetti³, Isaac E Stillman⁶, Helmut G Rennke⁵, Sushrut S Waikar^{2

3}

Affiliations

¹ Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Division of Nephrology and Hypertension, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
² Section of Nephrology, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts, USA.
³ Renal Division, Brigham & Women's Hospital, Boston, Massachusetts, USA.
⁴ Division of Nephrology, Landspitali-The National University Hospital of Iceland, Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland.
⁵ Pathology Department, Brigham & Women's Hospital, Boston, Massachusetts, USA.
⁶ Department of Pathology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.

Abstract

Background: Soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, YKL-40, monocyte chemoattractant protein (MCP)-1, and soluble urokinase plasminogen activator receptor (suPAR) have emerged as promising biomarkers of inflammation but have not been evaluated across diverse types of kidney diseases.

Methods: We measured these plasma biomarkers in 523 individuals enrolled into a prospective, observational cohort study of patients undergoing clinically indicated native kidney biopsy at 3 tertiary care hospitals. Two kidney pathologists adjudicated biopsy specimens for semiquantitative scores of histopathology. Proportional hazard models tested associations between biomarkers and risks of kidney disease progression (composite of ≥40% estimated glomerular filtration rate [eGFR] decline or end-stage kidney disease [ESKD]) and death.

Results: Mean eGFR was 56.4±36 ml/min per 1.73 m² and the median proteinuria (interquartile range) was 1.6 (0.4, 3.9) g/g creatinine. The most common primary clinicopathologic diagnoses were proliferative glomerulonephritis (29.2%), nonproliferative glomerulopathy (18.1%), advanced glomerulosclerosis (11.3%), and diabetic kidney disease (11.1%). sTNFR-1, sTNFR-2, MCP-1, and suPAR were associated with tubulointerstitial and glomerular lesions. YKL-40 was not associated with any histopathologic lesions after multivariable adjustment. During a median follow-up of 65 months, 182 participants suffered kidney disease progression and 85 participants died. After multivariable adjustment, each doubling of sTNFR-1, sTNFR-2, YKL-40, and MCP-1 was associated with increased risks of kidney disease progression, with hazard ratios ranging from 1.21 to 1.47. Each doubling of sTNFR-2, YKL-40, and MCP-1 was associated with increased risks of death, with hazard ratios ranging from 1.33 to 1.45. suPAR was not significantly associated with kidney disease progression or death.

Conclusions: sTNFR-1, sTNFR-2, YKL-40, MCP-1, and suPAR are associated with underlying histopathologic lesions and adverse clinical outcomes across a diverse set of kidney diseases.

Keywords: biomarker; fibrosis; histopathology; inflammation; kidney biopsy; kidney disease.

Abstract

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