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Kidney Week

Abstract: PO0174

Fractional Excretion of NGAL Is Useful to Distinguish Prerenal Azotemia (PRA) from Acute Tubular Injury (ATI) in Mice

Session Information

  • AKI Mechanisms - 1
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Skrypnyk, Nataliya, University of Colorado, Denver, Colorado, United States
  • Altmann, Chris, University of Colorado, Denver, Colorado, United States
  • Faubel, Sarah, University of Colorado, Denver, Colorado, United States
Background

NGAL (Lcn2) is one of the most widely studied biomarkers of acute kidney injury (AKI). Our previous studies demonstrated that the primary source of plasma and urine NGAL after AKI is the liver and it is IL-6 dependent. Since the primary source of urine NGAL is from the plasma, our next step was to examine the renal handling of plasma NGAL.

Methods

Mice: C57Bl/6J. Interventions: bilateral kidney ischemia reperfusion (IR) - 27 minutes; maleic acid (MA) (400mg/kg pH7.4 in saline, IP); furosemide (4mg, IP); uninjured vehicle animals served as a control. Recombinant human (rh) NGAL (5µg, IV) was injected to determine the fate of circulating NGAL. Measurements: transcutaneous glomerular filtration rate (tGFR), rhNGAL and mouse (m) NGAL in the plasma and urine, megalin in the urine. To link proximal tubular (PT) function with plasma and urine NGAL levels, we calculated the fractional excretion of rhNGAL (FE-rhNGAL): FE-rhNGAL = ([urine {rhNGAL} x plasma creatinine]/ [plasma {rhNGAL} x urine creatinine]) x 100.

Results

Uninjured vehicle: mice had 100% tGFR and low levels of plasma and urine (rh)NGAL. IR (ATI model) and MA (PT injury model): 1% and 29% tGFR respectively, increased plasma and urine rhNGAL in both models. Furosemide (PRA model): tGFR – 30%, plasma rhNGAL was slightly elevated, urine rhNGAL was similar to control. FE-rhNGAL was less than 1% in normal and PRA mice, and it was greater than 20% in IR and MA treated mice. mNGAL plasma and urine levels, and FE-mNGAL were similar to rhNGAL levels and FE-rhNGAL respectively. Urine concentration of megalin correlated with FE-rhNGAL in every intervention (see Figure). Megalin is expressed on the brush border of PT and is responsible for the resorption of most filtered proteins, including NGAL.

Conclusion

Our data suggest that normal PT function is required for the clearance of plasma NGAL. Consideration of plasma NGAL with FE-NGAL is important to interpret urine NGAL levels and PT function and effectively distinguishes PRA from ATI.

Funding

  • Veterans Affairs Support