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Abstract: FR-PO113

Renal Proteome Changes Reveal a Substantial Renal Acute Phase Response in Sepsis-Induced AKI in Mice

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Hamar, Peter, Semmelweis University, Budapest, Hungary
  • Róka, Beáta, Semmelweis University, Budapest, Hungary
  • Tod, Pál, Semmelweis University, Budapest, Hungary
  • Kaucsár, Tamás, Semmelweis University, Budapest, Hungary
  • Fonovic, Marko, Jozef Stefan Institute, Ljubljana, Slovenia
  • Turk, Boris, Jozef Stefan Institute, Ljubljana, Slovenia
  • Vizovisek, Matej, Jozef Stefan Institute, Ljubljana, Slovenia
  • Vidmar, Robert, Jozef Stefan Institute, Ljubljana, Slovenia
  • Szénási, Gábor, Semmelweis University, Budapest, Hungary
Background

Sepsis-induced acute kidney injury (AKI) is the most common form of AKI with poor outcomes. Both differential diagnosis and management of septic AKI are unresolved issues. Our aim was to study the temporal profile of the renal proteome changes in bacterial lipopolysaccharide (LPS)-induced AKI.

Methods

Male NMRI mice were injected with LPS or saline (control). AKI was studied at early (EP, 1.5 and 6 h after LPS at 40 mg/kg i.p.) and late phases (LP, 24 and 48 h after LPS at 10 mg/kg i.p.) by HPLC-MS/MS screening. Renal mRNA expression of 13 acute phase proteins (APP) was measured by qPCR.

Results

AKI was indicated by increased renal TNFα, IL-6 and neutrophil gelatinase-associated lipocalin (Lcn-2) mRNA expression from 1.5 h after endotoxin administration. At 24 and at 48 h 53% of the top 30 significantly upregulated proteins were APPs, with complement C3, fibrinogen, haptoglobin and hemopexin demonstrating the greatest increases. LPS upregulated renal ceruloplasmin and haptoglobin mRNA expression from 1.5 h, and fibrinogen-α, -β, -γ, serum amyloid A, hemopexin, ferritin heavy chain and inter alpha-trypsin inhibitor 4 mRNA from 6 h. Complement C3 and transferrin mRNA were upregulated only in LP. Expression of most APP mRNAs peaked at 24 h and some mRNA started to recover by 48 h. Albumin mRNA was downregulated in LP.

Conclusion

Our proteomic analysis demonstrated a marked upregulation of local renal APR that commenced a few hours after treatment and peaked at 24 h in LPS-induced AKI in mice. Many more APPs were involved in the renal APR than previously identified.

Funding

  • Government Support - Non-U.S.