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Kidney Week

Abstract: TH-PO457

Proximal Tubular Secretory Clearance Is Associated with the Progression of CKD: The CRIC Study

Session Information

Category: CKD (Non-Dialysis)

  • 2102 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Chen, Yan, University of Washington, Seattle, Washington, United States
  • Zelnick, Leila R., Kidney Research Institute, Seattle, Washington, United States
  • Wang, Ke, University of Washington, Seattle, Washington, United States
  • Hsu, Chi-yuan, University of California San Francisco, San Francisco, California, United States
  • Go, Alan S., Kaiser Permanente Northern California, Oakland, California, United States
  • Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
  • Mehta, Rupal, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
  • Lash, James P., University of Illinois at Chicago, Chicago, Illinois, United States
  • Waikar, Sushrut S., Harvard Medical School, Boston, Massachusetts, United States
  • Hamm, L. Lee, Tulane University School of Medicine, New Orleans, Louisiana, United States
  • Shafi, Tariq, University of Mississippi Medical Center, Jackson, Mississippi, United States
  • Seliger, Stephen L., University of Maryland School of Medicine, Baltimore, Maryland, United States
  • Shlipak, Michael, San Francisco VA Medical Center, San Francisco, California, United States
  • Rahman, Mahboob, Case Western Reserve University, Cleveland, Ohio, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States
Background

The secretion of organic solutes by the proximal tubules is an essential intrinsic kidney function. The clinical significance of tubular secretory clearance is uncertain.

Methods

We evaluated 3,416 participants from the Chronic Renal Insufficiency Cohort (CRIC) Study. We estimated the kidney clearances of 11 endogenous secretory solutes based on their measured concentrations in paired 24-hour urine and plasma samples at baseline using targeted mass spectrometry. CKD progression was defined by a 50% decline in the estimated glomerular filtration rate (eGFR), initiation of maintenance dialysis, or kidney transplantation. We used Cox proportional hazards regression to test associations of secretory solute clearances with CKD progression and all-cause mortality, adjusting for eGFR, albuminuria, and other potential confounders.

Results

There were 1,206 CKD progression events and 1,004 mortality events over a median follow-up of 6.0 and 9.6 years, respectively. After adjustment for eGFR, albuminuria, and other risk factors, lower kidney clearances of six secretory solutes (cinnamoylglycine, indoxyl sulfate, isovalerylglycine, kynurenic acid, pyridoxic acid, and xanthosine) were associated with greater risks of CKD progression (11%-21% greater risk per 50% lower secretory clearance; Table). Lower clearances of four solutes (hippurate, isovalerylglycine, tiglylglycine, and trimethyluric acid) were associated with all-cause mortality after adjustment.

Conclusion

Lower proximal tubular secretory solute clearance is associated with greater risks of CKD progression and all-cause mortality independent of eGFR and albuminuria. These findings suggest that estimates of tubular secretory clearances may provide complementary information to existing measures of glomerular filtration and integrity.

Funding

  • NIDDK Support