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Kidney Week

Abstract: PO0422

Impaired Renal Hemodynamic Reserve Following Ischemic AKI Is Associated with Inflammation and Capillary Rarefaction and Reversed by Retrograde Hydrodynamic Isotonic Fluid Delivery

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Ullah, Md Mahbub, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Collett, Jason Andrieu, Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Bacallao, Robert L., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Basile, David P., Indiana University School of Medicine, Indianapolis, Indiana, United States

We have 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 (IRI). This improvement was associated with decreased inflammation and vascular congestion and improved microvascular perfusion. However, it is unknown whether HIFD results in sustained effects on renal hemodynamic reserve and CKD progression


Male Sprague Dawley rats underwent left unilateral IRI-35 min with right unilateral nephrectomy to induce AKI. 24 hours later, serum creatinine (SCre) was measured and rats received either HIFD via the renal vein or 0.5ml of isotonic saline into the vena cava (VC) as control. After 5 weeks, renal hemodynamic responses were assessed in response to i.v. L-arginine infusion (450 mg/kg/hr) in anesthetized rats. Kidneys were evaluated for further analysis


At 5 weeks of recovery from surgery, baseline renal blood flow (RBF) and renal vascular resistance (RVR) were similar in the experimental groups (sham-, HIFD-, and VC-treated rats). Following 40 minutes of arginine infusion RBF
increased similarly in both the sham group and the I/R HIFD group (22.6% and 19.8% compared to their corresponding baseline value (P<0.001). However, I/R-VC treated rats showed an impaired response to arginine infusion relative to the sham group (P<0.001). As expected, RVR to blood flow was decreased significantly by 14% and 17% in sham operated and HIFD treated rats compared to their corresponding baseline respectively. In the kidney, HIFD treatment attenuated recruitment of inflammatory CD4+IL17+ cells (777659 vs. 417609, p<0.05), as assessed by flow cytometry compared to the VC-treated rats. Peritubular capillary density in medulla, measured by cablin immunofluorescence, was significantly reduced by (41%) in VC-treated rats compared to sham group. HIFD treatment significantly improved capillary density after 35 days of IRI


HIFD treatment shown improved impaired renal blood flow response to arginine infusion following 35 days IRI. This is associated with improved capillary density and attenuated infiltration of CD4+IL17+ cells. This data shows that HIFD treatment has long-term protective effects following I/R injury


  • NIDDK Support