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Kidney Week

Abstract: FR-OR09

Assessment of Kidney Proximal Tubular Secretion in Critical Illness

Session Information

Category: Acute Kidney Injury

  • 101 AKI: Epidemiology, Risk Factors, and Prevention


  • Bhatraju, Pavan K., University of Washington, Seattle, Washington, United States
  • Siew, Edward D., Division of Nephrology and Hypertension Vanderbilt University, Nashville, Tennessee, United States
  • Himmelfarb, Jonathan, University of Washington, Seattle, Washington, United States
  • Hoofnagle, Andrew N., University of Washington, Seattle, Washington, United States
  • Wurfel, Mark M., University of Washington, Seattle, Washington, United States
  • Kestenbaum, Bryan R., University of Washington, Seattle, Washington, United States

Serum creatinine concentrations (SCr) are used to determine the presence and severity of acute kidney injury. SCr is primarily eliminated by glomerular filtration; however, most mechanisms of kidney injury in critical illness involve kidney proximal tubules, where tubular secretion occurs. Proximal tubular secretory clearance is not currently measured in the ICU. To estimate the kidney clearance of secretory solutes in critically ill adults.


We collected matched blood and spot urine samples from 170 ICU patients and from a comparison group of 70 adults with normal kidney function. We measured seven endogenously produced secretory solutes using liquid chromatography-tandem mass spectrometry. We computed a composite secretion score incorporating all seven solutes, and evaluated associations with 28-day major adverse kidney events (MAKE28), defined as doubling of SCr, dialysis dependence, or death.


The urine/plasma ratio of six of seven secretory solutes were lower in critically ill patients compared with normal individuals after adjustment for SCr. The composite secretion score was moderately correlated with SCr and cystatin C (r = -0.51 and r = -0.53, respectively). Each standard deviation higher composite secretion score was associated with a 52% lower risk of MAKE28 (95% CI 25% - 70% lower) independent of ICU severity of illness and SCr. Higher urine to plasma ratios of individual secretory solutes isovalerylglycine and tiglylglycine were associated with MAKE28 after accounting for multiple testing (p<0.001).


Among critically ill adults, tubular secretory clearance is associated with adverse outcomes, independent of SCr and SOFA score, and measurement could improve assessment of kidney function.


  • NIDDK Support