Abstract: TH-PO248

Shroom3 Contributes to a More Severe AKI after Ischemia Reperfusion

Session Information

Category: Acute Kidney Injury

  • 001 AKI: Basic

Authors

  • Bridgewater, Darren, McMaster University, Hamilton, Ontario, Canada
  • Drysdale, Thomas A, University of Western Ontario, London, Ontario, Canada
Background

Acute kidney injury (AKI) is a severe complication of ischemia reperfusion injury. Individuals who survive AKI have an increased risk of developing chronic kidney disease, end stage renal disease, and death. While several clinical risk factors are associated with AKI, the genetic contributions are limited. Genome-wide association studies (GWAS) identified 53 novel single nucleotide polymorphisms (SNPs) robustly associated with variations in kidney function. SHROOM3 is the second most significant gene identified in these studies. Shroom3 is an actin-associated protein that regulates tissue morphogenesis by regulating epithelial cell shape. In the kidney, Shroom3 is expressed in the parietal and visceral epithelial cells, in some tubular epithelial cells, and distal collecting ducts. While Shroom3 heterozygous mice develop chronic kidney disease at 1 year, the role of Shroom3 in AKI is not known.

Methods

Bilateral renal ischemia/reperfusion (I/R) procedure was performed in Shroom3 heterozygous mutant (Shroom3Gt/+) and wild type (WT) mice at 12 weeks to mimic the I/R renal injury experienced during transplant and cardiac surgery. Serum creatinine and urine protein at baseline, days 1, 2, 3, 5, 7, and 10 were measured. Kidneys were collected 48 hours and 10 days after I/R the procedure to compare the histopathological changes of the initial AKI insult and the kidneys ability to recover.

Results

Twelve-week old Shroom3Gt/+ and WT mice had similar serum creatinine and urinary protein levels at baseline. Twenty-four hours after I/R, Shroom3Gt/+ mice had a 1.5 fold (P=0.038) increase of serum creatinine from baseline (Fold Mean±SD, 3.89±1.35, N=10) compared to WT mice (Fold Mean±SD, 2.58±1.01, N=8). The Shroom3Gt/+ mice demonstrated worse histopathology as measured by tubular changes and cell death. Ten days after I/R, the serum creatinine in Shroom3Gt/+ and WT mice returned to baseline levels. However, the histopathological changes in Shroom3Gt/+ mice were markedly worse when compared to WT mice.

Conclusion

Our results demonstrate that genetic anomalies or aberrant expression of Shroom3 could lead to worse renal outcomes in patients after an I/R injury.

Funding

  • Government Support - Non-U.S.