PMID- 35812275 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230328 IS - 2468-0249 (Electronic) IS - 2468-0249 (Linking) VI - 7 IP - 7 DP - 2022 Jul TI - Considerations in Controlling for Urine Concentration for Biomarkers of Kidney Disease Progression After Acute Kidney Injury. PG - 1502-1513 LID - 10.1016/j.ekir.2022.03.026 [doi] AB - INTRODUCTION: Biomarkers of acute kidney injury (AKI) are often indexed to urine creatinine (UCr) or urine osmolarity (UOsm) to control for urine concentration. We evaluated how these approaches affect the biomarker-outcome association in patients with AKI. METHODS: The Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury Study was a cohort of hospitalized patients with and without AKI between 2009 and 2015. Using Cox proportional hazards regression, we assessed the associations and predictions (C-statistics) of urine biomarkers with a composite outcome of incident chronic kidney disease (CKD) and CKD progression. We used 4 approaches to account for urine concentration: indexing and adjusting for UCr and UOsm. RESULTS: Among 1538 participants, 769 (50%) had AKI and 300 (19.5%) developed composite CKD outcome at median follow-up of 4.7 years. UCr and UOsm during hospitalization were inversely associated with the composite CKD outcome. The associations and predictions with CKD were significantly strengthened after indexing or adjusting for UCr or UOsm for urine kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) in patients with AKI. There was no significant improvement with indexing or adjusting UCr or UOsm for albumin, neutrophil gelatinase-associated lipocalin (NGAL), and chitinase 3-like 1 (YKL-40). Uromodulin's (UMOD) inverse association with the outcome was significantly blunted after indexing but not adjusting for UCr or UOsm. CONCLUSION: UCr and UOsm during hospitalization are inversely associated with development and progression of CKD. Indexing or adjusting for UCr or UOsm strengthened associations and improved predictions for CKD for only some biomarkers. Incorporating urinary concentration should be individualized for each biomarker in research and clinical applications. CI - (c) 2022 International Society of Nephrology. Published by Elsevier Inc. FAU - Wen, Yumeng AU - Wen Y AD - Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Thiessen-Philbrook, Heather AU - Thiessen-Philbrook H AD - Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. FAU - Moledina, Dennis G AU - Moledina DG AD - Clinical and Translational Research Accelerator, Section of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut, USA. FAU - Kaufman, James S AU - Kaufman JS AD - Division of Nephrology, Department of Medicine, New York University School of Medicine, New York, New York, USA. AD - Department of Medicine, Veterans Affairs New York Harbor Health Care System, New York, New York, USA. FAU - Reeves, W Brian AU - Reeves WB AD - Department of Medicine, Joe R. and Teresa Lozano Long School of Medicine, University of Texas San Antonio, Texas, USA. FAU - Ghahramani, Nasrollah AU - Ghahramani N AD - Division of Nephrology, Department of Medicine, Pennsylvania State University College of Medicine, Hershey, Pennsylvania, USA. FAU - Ikizler, T Alp AU - Ikizler TA AD - Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA. FAU - Go, Alan S AU - Go AS AD - Kaiser Permanente Division of Research, Oakland, California, USA. FAU - Liu, Kathleen D AU - Liu KD AD - Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA. FAU - Siew, Eddie D AU - Siew ED AD - Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA. FAU - Himmelfarb, Jonathan AU - Himmelfarb J AD - Kidney Research Institute, Department of Medicine, University of Washington, Seattle, Washington, USA. FAU - Kimmel, Paul L AU - Kimmel PL AD - National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA. FAU - Hsu, Chi-Yuan AU - Hsu CY AD - Kaiser Permanente Division of Research, Oakland, California, USA. AD - Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California, USA. FAU - Parikh, Chirag R AU - Parikh CR AD - Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. LA - eng GR - R01 HL085757/HL/NHLBI NIH HHS/United States GR - R01 DK093770/DK/NIDDK NIH HHS/United States GR - R01 DK101507/DK/NIDDK NIH HHS/United States GR - U01 DK084012/DK/NIDDK NIH HHS/United States GR - R01 DK114014/DK/NIDDK NIH HHS/United States GR - U01 DK082185/DK/NIDDK NIH HHS/United States GR - K23 DK117065/DK/NIDDK NIH HHS/United States GR - UL1 TR001863/TR/NCATS NIH HHS/United States GR - U01 DK082183/DK/NIDDK NIH HHS/United States GR - R01 DK098233/DK/NIDDK NIH HHS/United States GR - R03 DK111881/DK/NIDDK NIH HHS/United States GR - U01 DK082192/DK/NIDDK NIH HHS/United States GR - UH3 DK114866/DK/NIDDK NIH HHS/United States GR - U01 DK082223/DK/NIDDK NIH HHS/United States GR - K23 DK100468/DK/NIDDK NIH HHS/United States PT - Journal Article DEP - 20220406 PL - United States TA - Kidney Int Rep JT - Kidney international reports JID - 101684752 PMC - PMC9263319 OTO - NOTNLM OT - acute kidney injury OT - biomarker OT - chronic kidney disease OT - urine concentration OT - urine creatinine OT - urine osmolarity EDAT- 2022/07/12 06:00 MHDA- 2022/07/12 06:01 PMCR- 2022/04/06 CRDT- 2022/07/11 03:44 PHST- 2021/10/12 00:00 [received] PHST- 2022/02/18 00:00 [revised] PHST- 2022/03/28 00:00 [accepted] PHST- 2022/07/11 03:44 [entrez] PHST- 2022/07/12 06:00 [pubmed] PHST- 2022/07/12 06:01 [medline] PHST- 2022/04/06 00:00 [pmc-release] AID - S2468-0249(22)01246-3 [pii] AID - 10.1016/j.ekir.2022.03.026 [doi] PST - epublish SO - Kidney Int Rep. 2022 Apr 6;7(7):1502-1513. doi: 10.1016/j.ekir.2022.03.026. eCollection 2022 Jul.