@article{816590fb0ce547e1a21d72ecbfd80be6,
title = "Urinary EGF and MCP-1 and risk of CKD after cardiac surgery",
abstract = "BACKGROUND. Assessment of chronic kidney disease (CKD) risk after acute kidney injury (AKI) is based on limited markers primarily reflecting glomerular function. We evaluated markers of cell integrity (EGF) and inflammation (monocyte chemoattractant protein-1, MCP-1) for predicting longterm kidney outcomes after cardiac surgery. METHODS. We measured EGF and MCP-1 in postoperative urine samples from 865 adults who underwent cardiac surgery at 2 sites in Canada and the United States and assessed EGF and MCP-1's associations with the composite outcome of CKD incidence or progression. We used single-cell RNA-Seq (scRNA-Seq) of AKI patient biopsies to perform transcriptomic analysis of programs corregulated with the associated genes. RESULTS. Over a median (IQR) follow-up of 5.8 (4.2-7.1) years, 266 (30.8%) patients developed the composite CKD outcome. Postoperatively, higher levels of urinary EGF were protective and higher levels of MCP-1 were associated with the composite CKD outcome (adjusted HR 0.83, 95% CI 0.73-0.95 and 1.10, 95% CI 1.00-1.21, respectively). Intrarenal scRNA-Seq transcriptomes in patients with AKI-defined cell populations revealed concordant changes in EGF and MCP-1 levels and underlying molecular processes associated with loss of EGF expression and gain of CCL2 (encoding MCP-1) expression. CONCLUSION. Urinary EGF and MCP-1 were each independently associated with CKD after cardiac surgery. These markers may serve as noninvasive indicators of tubular damage, supported by tissue transcriptomes, and provide an opportunity for novel interventions in cardiac surgery.",
author = "Steven Menez and Wenjun Ju and Rajasree Menon and Moledina, {Dennis G.} and Philbrook, {Heather Thiessen} and Eric McArthur and Yaqi Jia and Wassim Obeid and Mansour, {Sherry G.} and Koyner, {Jay L.} and Shlipak, {Michael G.} and Coca, {Steven G.} and Garg, {Amit X.} and Bomback, {Andrew S.} and Kellum, {John A.} and Matthias Kretzler and Parikh, {Chirag R.}",
note = "Funding Information: receiving consultancy fees from the University of Washington; Johns Hopkins University, the University of North Carolina; Cricket Health, Inc; and Intercept Pharmaceuticals and has equity in TAI Diagnostics. SGC and CRP reported serving as members of the advisory board of and owning equity in RenalytixAI. SGC reported receiving consulting fees from Goldfinch Bio, CHF Solutions, Quark Biopharma, Janssen Pharmaceuticals, Takeda Pharmaceuticals, and Relypsa in the past 3 years. JLK reported receiving research fees from Bioporto and Astute Medical and consulting fees from Baxter, Astute Medical, and Sphingotec. JAK reported receiving grant support from BioMerieux/Astute Medical, Baxter, and RenalSense and consulting fees from BioMerieux/ Astute Medical, Baxter, Fresenius/ NxStage, and Potrero. MK is receiving via the University of Michigan funding support from AstraZeneca, Novo Nordisk, Eli Lilly, Gilead, Goldfinch Bio, Janssen Pharmaceuticals, Boehringer-Ingelheim, Moderna, Certa, Chinook, Angion Pharmaceuticals, RenalytixAI, Travere Therapeutics, Regeneron, and IONIS and is coinventor of “Biomarkers and methods for progression prediction for chronic kidney disease” patent WO2015063248A2. Funding Information: The study was further supported by P30 DK081943 University of Michigan O{\textquoteright}Brien Kidney Translational Core Center to MK, via KPMP (funded by the following grants from the National Institute of Diabetes and Digestive and Kidney Diseases, NIH: U2C DK114886, UH3DK114861, UH3DK114866, UH3DK114870, UH3DK114908, UH3DK114915, UH3DK114926, UH3DK114907, UH3DK114920, UH3DK114923, UH3DK114933, and UH3DK114937), and by NIH U2C DK114886 and UH3 DK114907 to MK and CP, via the Chan Zuckerberg Initiative Human Cell Atlas Kidney Seed Network to MK. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Funding Information: SM has received support from an NIH T32 grant (HL007024). DGM is supported by an NIH K23 grant (K23DK117065) and by the Yale O{\textquoteright}Brien Kidney Center (P30DK079310). SGM is supported by American Heart Association (18CDA34110151), the Yale O{\textquoteright}Brien Kidney Center, and the Patterson Trust Fund. NIH (R01HL085757 to CRP) funded the TRIBE-AKI Consortium. CRP is supported by NIH grant K24DK090203 and the P30DK079310 Yale O{\textquoteright}Brien Kidney Center grant. SGC has salary support from NIH grants R01DK115562, UO1DK106962, R01HL085757, R01DK112258, and U01OH011326. JLK is supported by NIH grant R21DK113420. SGC, AXG, and CRP are members of the NIH-sponsored ASSESS-AKI Consortium (U01DK082185). AXG is supported by the Dr. Adam Linton Chair in Kidney Health Analytics, and a Clinician Investigator Award from the Canadian Institutes of Health Research. This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). Some analyses were conducted at the ICES Western facility by members of the ICES Kidney, Dialysis and Transplantation Program. Core funding for ICES Western is provided by the Academic Medical Organization of Southwestern Ontario, the Schulich School of Medicine & Dentistry, Western University, and the Lawson Health Research Institute. The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. Publisher Copyright: {\textcopyright} 2021 American Society for Clinical Investigation. All rights reserved.",
year = "2021",
month = jun,
day = "8",
doi = "10.1172/jci.insight.147464",
language = "English (US)",
volume = "6",
journal = "JCI Insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "11",
}