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Abstract: FR-PO064

Hydrodynamic Isotonic Fluid Delivery Following Renal I/R Reduces Inflammation Associated with the AKI-to-CKD Transition

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Mehrotra, Purvi, Indiana School of Medicine, Indianapolis, Indiana, United States
  • Collett, Jason Andrieu, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • O'Shaughnessy, Riley P., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States
Background

AKI represents a significant risk factor for CKD. T cells, most notably, Th17 cells, play an important role in the transition from AKI to CKD. We’ve previously shown that retrograde hydrodynamic delivery of isotonic fluid (HIFD) improved renal function in established AKI between 24-48 hours following ischemia and reperfusion injury. This improvement was associated with decreased inflammation and vascular congestion. However, it is unknown whether HIFD manifests sustained effects on renal function, inflammation and secondary development of CKD.

Methods

S.D. rats underwent left unilateral I/R: 35 min with right Unx to induce AKI. 24 hours later, renal function was evaluated (serum creatinine; SCre) and rats received either HIFD into the renal vein or 0.5ml of saline into the vena cava (VC) as control. The animals were then allowed to recover for 20 weeks while regularly monitoring renal function. Inflammatory cells were evaluated in kidney 20 weeks post-surgery.

Results

Rats were stratified into either moderate (SCre <3.0 mg/dl) and severe (SCre >3.0 mg/dl) injury groups based upon serum creatinine at 24 hours post I/R. In the severe injury group, sCre tended to be reduced between 24 to 48hrs by HIFD treatment relative to VC-treated rats (HIFD: -0.34 vs. VC: +0.03 mg/dl); HIFD had no effect on SCre between 24-48 hours in the mild injury group. At 20 weeks post I/R, the number of renal mononuclear cells were significantly reduced by HIFD treatment in both moderate (41%) and severe (54%) injury as compared to VC-treated rats. In addition, there was a significant reduction in Th17 cells (CD4+IL17+) following HIFD in both the moderate (HIFD: 889.7 vs. VC: 2480 cells/gram kidney; p<0.05) and severe groups (HIFD: 1351 vs. VC: 3838 cells/gram kidney; p<0.05). HIFD-treated rats also demonstrated significant reductions in CD4+IFNy+ T cells (HIFD: 477.4 vs. VC: 1529 cell/gram kidney; p<0.05) compared with VC-treated rats in the severe group.

Conclusion

Renal vein HIFD treatment following established AKI reduces inflammation associated CKD progression. HIFD treatment improved chronic renal inflammation despite the lack of improvement in renal function in moderately injured animals. Therefore, HIFD represent a novel therapeutic strategy for prevention of CKD following AKI.

Funding

  • NIDDK Support