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Abstract: PO0248

Considerations in Controlling for Urine Concentration in Performance of Biomarkers of AKI

Session Information

Category: Acute Kidney Injury

  • 102 AKI: Clinical, Outcomes, and Trials

Authors

  • Wen, Yumeng, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Thiessen Philbrook, Heather, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
  • Moledina, Dennis G., Yale University School of Medicine, New Haven, Connecticut, United States
  • Kaufman, James S., New York University, New York, New York, United States
  • Reeves, William Brian, The University of Texas at San Antonio, San Antonio, Texas, United States
  • Ghahramani, Nasrollah, Penn State College of Medicine, Hershey, Pennsylvania, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Go, Alan S., Kaiser Permanente Northern California, Oakland, California, United States
  • Liu, Kathleen D., University of California San Francisco School of Medicine, San Francisco, California, United States
  • Himmelfarb, Jonathan, University of Washington, Seattle, Washington, United States
  • Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States
  • Hsu, Chi-yuan, University of California San Francisco School of Medicine, San Francisco, California, United States
  • Parikh, Chirag R., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States

Group or Team Name

  • ASSESS-AKI Investigators
Background

Urine biomarkers are often indexed to urine creatinine (UCr) to control for urine concentration. Whether the biomarker-outcome associations are altered using this or other approaches, such as indexing to urine osmolality (UOsm), in AKI patients has not been examined.

Methods

We studied 769 hospitalized patients with AKI enrolled in the multicenter prospective Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study. Using Cox proportional hazards regression, we assessed urine biomarkers’ associations with a composite outcome of incident chronic kidney disease (CKD) and CKD progression using four approaches to account for urine concentration: indexing to UCr or UOsm and adjusting for UCr or UOsm as covariates.

Results

207 (27%) participants developed composite CKD outcome at median follow-up of 4.7 years. UCr and UOsm during hospitalization were inversely associated with developing CKD (HR 0.84, 95% CI 0.73-0.96 for UCr; HR 0.81, 95% CI 0.71-0.93 for UOsm). Figure 1 shows the hazard ratio of urine biomarkers collected during hospitalization with the composite CKD outcome using the four approaches to account for urine concentration. The association between urine kidney injury molecule-1 (KIM-1), albumin and CKD strengthened after indexing to or adjusting for UCr or UOsm, but uromodulin’s (UMOD) inverse association with CKD was blunted after indexing to UCr or UOsm.

Conclusion

UCr and UOsm, potential markers for tubular health, are both associated with lower risk of developing CKD in hospitalized AKI patients. Indexing to UCr or UOsm strengthens the biomarker- CKD associations for urine KIM-1 and albumin, but attenuates UMOD’s inverse association with CKD.

Funding

  • NIDDK Support