@article{43d5eb4f6d824cc3bbbe61f91c015089,
title = "Biomarkers of inflammation and repair in kidney disease progression",
abstract = "Introduction. Acute kidney injury and chronic kidney disease (CKD) are common in hospitalized patients. To inform clinical decision making, more accurate information regarding risk of long-term progression to kidney failure is required. Methods. We enrolled 1538 hospitalized patients in a multicenter, prospective cohort study. Monocyte chemoattractant protein 1 (MCP-1/CCL2), uromodulin (UMOD), and YKL-40 (CHI3L1) were measured in urine samples collected during outpatient follow-up at 3 months. We followed patients for a median of 4.3 years and assessed the relationship between biomarker levels and changes in estimated glomerular filtration rate (eGFR) over time and the development of a composite kidney outcome (CKD incidence, CKD progression, or end-stage renal disease). We paired these clinical studies with investigations in mouse models of renal atrophy and renal repair to further understand the molecular basis of these markers in kidney disease progression. Results. Higher MCP-1 and YKL-40 levels were associated with greater eGFR decline and increased incidence of the composite renal outcome, whereas higher UMOD levels were associated with smaller eGFR declines and decreased incidence of the composite kidney outcome. A multimarker score increased prognostic accuracy and reclassification compared with traditional clinical variables alone. The mouse model of renal atrophy showed greater Ccl2 and Chi3l1 mRNA expression in infiltrating macrophages and neutrophils, respectively, and evidence of progressive renal fibrosis compared with the repair model. The repair model showed greater Umod expression in the loop of Henle and correspondingly less fibrosis. Conclusions. Biomarker levels at 3 months after hospitalization identify patients at risk for kidney disease progression.",
author = "Jeremy Puthumana and Heather Thiessen-Philbrook and Leyuan Xu and Coca, {Steven G.} and Garg, {Amit X.} and Jonathan Himmelfarb and Bhatraju, {Pavan K.} and Ikizler, {T. Alp} and Siew, {Edward D.} and Ware, {Lorraine B.} and Liu, {Kathleen D.} and Go, {Alan S.} and Kaufman, {James S.} and Kimmel, {Paul L.} and Chinchilli, {Vernon M.} and Cantley, {Lloyd G.} and Parikh, {Chirag R.}",
note = "Funding Information: Conflict of interest: SGC reports personal income and equity and stock options from RenaltyixAI and pulseData; he also reports personal income from 3ive, Bayer, Boehringer-Ingelheim, CHF Solutions, inRegen, Quark, Relypsa, and Takeda. JH reports personal income from Akebia Therapeutics, Chinook Therapeutics, Maze Therapeutics, Pfizer, RenalytixAI, and Seattle Genetics. EDS reports personal income from Akebia Therapeutics, Da Vita, and UpToDate; he also serves as an associate editor for the Clinical Journal of the American Society of Nephrology. LBW reports personal incoime from Bayer, Boehringer Ingelheim, Citius, CSL Behring, Foresee, Merck, and Quark; she also received research funding from CSL Behring and Genentech. KDL reports personal income from Astra Zeneca, Baxter, Biomerieux, Durect, Potrero Med, Quark, Theravance, and UpToDate; she also holds stock in Amgen and is an associate editor at the American Thoracic Society. PLK reports being an editor of the textbook Chronic Renal Disease. LGC reports personal income from MPM Capital and Vivace Therapeutics. CRP reports personal income and equity and stock options from RenaltyixAI; he also reports personal income from Genfit Biopharmaceutical Company and Akebia Therapeutics. Role of funding source: The study was supported by cooperative agreements from the NIDDK. Representatives from the NIDDK participated in all phases of the study and approved the final manuscript for submission. Copyright: {\textcopyright} 2021, American Society for Clinical Investigation. Submitted: May 5, 2020; Accepted: December 1, 2020; Published: February 1, 2021. Reference information: J Clin Invest. 2021;131(3):e139927. https://doi.org/10.1172/JCI139927. Funding Information: The authors would like to thank all of the ASSESS-AKI study participants, research coordinators, and support staff for making this study possible. The ASSESS-AKI was supported by cooperative agreements from the NIDDK (U01DK082223, U01DK082185, U01DK082192, and U01DK082183). We also acknowledge funding support from NIH grants R01HL085757, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, R01DK093771, K01DK120783, P30DK079310, and P30DK114809. Publisher Copyright: Copyright {\textcopyright} 2021, American Society for Clinical Investigation. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = feb,
day = "1",
doi = "10.1172/JCI139927",
language = "English (US)",
volume = "131",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "3",
}