한빛사논문
- 조회238
Kim, Taesoo1; Surapaneni, Aditya L.2; Schmidt, Insa M.3; Eadon, Michael T.4; Kalim, Sahir1; Srivastava, Anand5; Palsson, Ragnar1; Stillman, Isaac E.6; Hodgin, Jeffrey B.7; Menon, Rajasree8; Otto, Edgar A.9; Coresh, Josef10; Grams, Morgan E.2; Waikar, Sushrut S.3; Rhee, Eugene P.1,11,a; for the Kidney Precision Medicine Project
1Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA
2Department of Medicine, New York University Langone School of Medicine, New York, NY
3Section of Nephrology, Department of Medicine, Boston University Chobanian & Avedisian School of Medicine and Boston Medical Center, Boston, MA
4Department of Medicine, Indiana University School of Medicine, Indianapolis, IN
5Division of Nephrology, University of Illinois Chicago, Chicago, IL
6Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY
7Department of Pathology, University of Michigan, Ann Arbor, MI
8Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI
9Division of Nephrology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI
10Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
11Endocrine Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA
aCorresponding author: Eugene P. Rhee, M.D.
Abstract
Background: The severity of chronic histopathologic lesions on kidney biopsy is independently associated with higher risk of progressive chronic kidney disease (CKD). Because kidney biopsies are invasive, identification of blood markers that report on underlying kidney histopathology has the potential to enhance CKD care.
Methods: We examined the association between 6592 plasma protein levels measured by aptamers and the severity of interstitial fibrosis and tubular atrophy (IFTA), glomerulosclerosis, arteriolar sclerosis, and arterial sclerosis among 434 participants of the Boston Kidney Biopsy Cohort. For proteins significantly associated with at least one histologic lesion, we assessed renal arteriovenous protein gradients among 21 individuals who had undergone invasive catheterization and assessed the expression of the cognate gene among 47 individuals with single cell RNA sequencing data in the Kidney Precision Medicine Project.
Results: In models adjusted for estimated glomerular filtration rate (eGFR), proteinuria, and demographic factors, we identified 35 proteins associated with one or more chronic histologic lesions, including 20 specific for IFTA, 8 specific for glomerulosclerosis, and 1 specific for arteriolar sclerosis. In general, higher levels of these proteins were associated with more severe histologic score and lower eGFR. Exceptions included testican-2 and NELL1, which were associated with less glomerulosclerosis and IFTA, respectively, and higher eGFR; notably, both of these proteins demonstrated significantly higher levels from artery to renal vein, demonstrating net kidney release. In the Kidney Precision Medicine Project, 13 of the 35 protein hits had cognate gene expression enriched in one or more cell types in the kidney, including podocyte expression of select glomerulosclerosis markers (including testican-2) and tubular expression of several IFTA markers (including NELL1).
Conclusions: Proteomic analysis identified circulating proteins associated with chronic histopathologic lesions, some of which have concordant site-specific expression within the kidney.
논문정보
- Research article
- 2024년 04월 (BRIC 등록일 2024-04-26)
- 국외 연구진
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