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Abstract: SA-PO133

Urinary EGF and ICAM-1 Predict Glomerular Number Using Cationic Ferritin Enhanced-MRI in a Murine Model Folic Acid Nephropathy

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Charlton, Jennifer R., University of Virginia, Charlottesville, Virginia, United States
  • Deronde, Kimberly, University of Virginia, Charlottesville, Virginia, United States
  • Xu, Yanzhe, Arizona State University, Tempe, Arizona, United States
  • Wu, Teresa, Arizona State University, Tempe, Arizona, United States
  • Bennett, Kevin M., Washington University in St. Louis, St. Louis, Missouri, United States
Background

Chronic kidney disease (CKD) is difficult to detect in the earliest stages. Cationic ferritin enhanced-MRI (CFE-MRI) has been used to measure glomerular number (Nglom) in the entire kidney in 3D in animals and human kidneys. Although urinary biomarkers are used as early and sensitive predictors of acute kidney injury (AKI), there is little data correlating urinary biomarkers to nephron number following AKI. We hypothesize that urinary biomarkers can predict microstructural changes detected by CFE-MRI in the transition from AKI to CKD.

Methods

To induce CKD, male mice were injected with intraperitoneal folic acid (125 mg/kg, n=5); controls received NaHCO3 (n=5). Urine was collected on day 4 after folic acid and at 12 wks following AKI. The mice received horse spleen cationic ferritin 12 wks after injury. Kidneys were imaged ex vivo using a 7T Bruker ClinScan MRI (3D T2*-weighted, TE:20, TR:80, 60 µm, 640x640). MRI-derived biomarkers included Nglom and cluster size (volume where glomeruli were detectable but lacked tubules). Forty urinary biomarkers (inflammation and growth factors) were analyzed using Mouse Cytokine Array Q1000 (RayBiotech).

Results

By CFE-MRI, the CKD group had 28% fewer glomeruli (8008 ± 2880) as compared to the controls (11105 ± 818, p=0.04). In the CKD cohort, nearly 9% of the kidney had labeled glomeruli with a lack of surrounding tubules designated as “clusters” (CKD: 8.8±2.4% vs. controls: 2.3±0.59%, p=0.03). Urinary EGF was higher 4 days after injury (AKI:11538 vs controls: 5087 pg/ml, 0.0004) and ICAM-1 was lower at 12 weeks (CKD: 2621 vs controls: 6629 pg/ml, p=0.007). Four days after injury urinary EGF correlated to Nglom at 12 weeks after injury (r=-0.71, 0.02) and cluster size (r=0.78, p=0.008). At 12 weeks after injury, urinary ICAM-1 correlated to Nglom (r=0.76, p=0.01) and cluster size (r=-0.80, p=0.005).

Conclusion

In this murine model of AKI transitioning to CKD, urinary EGF at the time of AKI correlate with both a lower Nglom and larger cluster size. At CKD, 12 weeks after injury, ICAM-1 strongly correlated with glomerular number and cluster size. Further work to define the pathophysiology of these biomarkers in AKI and CKD is needed, however this work highlights the utility of urinary biomarkers and CFE-MRI to noninvasively detect early nephron injury and track progression of CKD.

Funding

  • NIDDK Support