СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Schmidt Insa M, Surapaneni Aditya L, Zhao Runqi, Upadhyay Dhairya, Yeo Wan-Jin, Schlosser Pascal, Huynh Courtney, Srivastava Anand, Palsson Ragnar, Kim Taesoo, Stillman Isaac E, Barwinska Daria, Barasch Jonathan, Eadon Michael T, El-Achkar Tarek M, Henderson Joel, Moledina Dennis G, Rosas Sylvia E, Claudel Sophie E, Verma Ashish, Wen Yumeng, Lindenmayer Maja, Huber Tobias B, Parikh Samir V, Shapiro John P, Rovin Brad H, Stanaway Ian B, Sathe Neha A, Bhatraju Pavan K, Coresh Josef, Kidney Precision Medicine Project, Rhee Eugene P, Grams Morgan E, Waikar Sushrut S
Аннотация
The kidney tubules constitute two-thirds of the cells of the kidney and account for the majority of the organ's metabolic energy expenditure. Acute tubular injury (ATI) is observed across various types of kidney diseases and may significantly contribute to progression to kidney failure. Non-invasive biomarkers of ATI may allow for early detection and drug development. Using the SomaScan proteomics platform on 434 patients with biopsy-confirmed kidney disease, we here identify plasma biomarkers associated with ATI severity. We employ regional transcriptomics and proteomics, single-cell RNA sequencing, and pathway analysis to explore biomarker protein and gene expression and enriched biological pathways. Additionally, we examine ATI biomarker associations with acute kidney injury (AKI) in the Kidney Precision Medicine Project (KPMP) (n = 44), the Atherosclerosis Risk in Communities (ARIC) study (n = 4610), and the COVID-19 Host Response and Clinical Outcomes (CHROME) study (n = 268). Our findings indicate 156 plasma proteins significantly linked to ATI with osteopontin, macrophage mannose receptor 1, and tenascin C showing the strongest associations. Pathway analysis highlight immune regulation and organelle stress responses in ATI pathogenesis.