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Kidney Week

Abstract: TH-PO759

Plasma Kidney Injury Molecule 1 Is Associated with Left Ventricular Hypertrophy in Children with CKD

Session Information

  • Pediatric CKD
    November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Greenberg, Jason Henry, Yale University, Woodbridge, Connecticut, United States
  • Abraham, Alison G., Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Xu, Yunwen, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States
  • Schelling, Jeffrey R., Case Western Reserve University, Cleveland, Ohio, United States
  • Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Sabbisetti, Venkata, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Cardenas-Gonzalez, Mariana, Harvard Medical School, Boston, Massachusetts, United States
  • Warady, Bradley A., Children's Mercy Kansas City, Kansas City, Missouri, United States
  • Kimmel, Paul L., National Institute of Diabetes and Digestive Kidney Diseases (NIDDK), Bethesda, Maryland, United States
  • Bonventre, Joseph V., Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Parikh, Chirag R., Johns Hopkins University, Baltimore, Maryland, United States
  • Mitsnefes, Mark, Cincinnati Children's Hospital, Cincinnati, Ohio, United States
  • Denburg, Michelle, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States
  • Furth, Susan L., The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, United States

Group or Team Name

  • CKD Biomarkers Consortium
Background

Left ventricular hypertrophy (LVH) is common in children with CKD and is associated with an increased risk of cardiovascular disease and mortality. Novel plasma biomarkers may help identify children at increased risk of developing LVH. We investigated whether the circulating plasma biomarkers of tubular injury (KIM-1) and inflammation (TNFR-1, TNFR-2, suPAR) are associated with LVH in children.

Methods

In the CKiD Cohort Study, children aged 6 months to 16 years old with an eGFR of 30-90 ml/min/1.73m2 were enrolled at 54 centers in the US and Canada. We measured plasma KIM-1, TNFR-1, TNFR-2, and suPAR in stored plasma collected 5 months after study enrollment. Echocardiograms were performed one year after study enrollment. We assessed the cross-sectional association between the log2 biomarker levels and LVH (left ventricular mass index ≥95th percentile) using a Poisson regression model, adjusted for demographics (i.e., age, sex, race), body mass index, hypertension, glomerular diagnosis, proteinuria, as well as estimated glomerular filtration rate at study entry.

Results

Of the 544 children included, median age was 11 years [IQR: 8, 15], 335 (62%) were male, 162 (30%) had a glomerular cause of CKD, 92 (17%) had hypertension, median baseline eGFR was 54 [IQR: 40, 68] ml/min/1.73m2, and median urine protein to creatinine ratio was 0.32 [IQR: 0.11, 0.94] mg/g. The overall LVH prevalence was 12% (N=65 events). All median biomarker levels were higher in children with LVH compared to those without LVH (p<0.05). In unadjusted models, two-fold greater plasma KIM-1, TNFR-1, TNFR-2, and suPAR concentrations were associated with LVH (KIM-1 relative risk [RR] per doubling: 1.39; TNFR-1 RR: 1.29; TNFR-2 RR: 1.54 and suPAR RR: 1.77) (Table). After adjusting for demographic and clinical characteristics, only higher plasma KIM-1 concentrations were associated with an increased risk of LVH (RR per doubling: 1.31, 95% CI: 1.04-1.64).

Conclusion

Elevated plasma KIM-1 is independently associated with LVH in children with CKD.

Funding

  • NIDDK Support