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Publication Information
Affiliation
Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Section of Nephrology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Section of Nephrology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Section of Nephrology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.; Division of Nephrology, University of California, San Francisco, San Francisco, California, USA.; Kaiser Permanente Division of Research, Oakland, California, USA.; Division of Nephrology, University of California, San Francisco, San Francisco, California, USA.; Division of Nephrology, Vanderbilt University, Nashville, Tennessee, USA.; Division of Nephrology, Vanderbilt University, Nashville, Tennessee, USA.; Division of Nephrology, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA.; Division of Nephrology, New York University School of Medicine and VA New York Harbor Healthcare System, New York, New York, USA.; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH), Bethesda, Maryland, USA.; Division of Nephrology, University of Washington, Seattle, Washington, USA.; Section of Nephrology, Department of Medicine, Yale School of Medicine, New Haven, Connecticut, USA.; Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Authors
Wen Yumeng, Xu Leyuan, Melchinger Isabel, Thiessen-Philbrook Heather, Moledina Dennis G, Coca Steven G, Hsu Chi-Yuan, Go Alan S, Liu Kathleen D, Siew Edward D, Ikizler T Alp, Chinchilli Vernon M, Kaufman James S, Kimmel Paul L, Himmelfarb Jonathan, Cantley Lloyd G, Parikh Chirag R
Studies
Abstract
BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of biomarkers in murine models of repair and atrophy after ischemic reperfusion injury (IRI).RESULTSAfter 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney atrophy in mice after IRI.CONCLUSIONSustained tissue injury and inflammation, and slower restoration of tubular health, are associated with higher risk of kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.FUNDINGNIH and NIDDK (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, K01DK120783, and R01DK093771).