Hydrodynamic isotonic fluid delivery ameliorates moderate-to-severe ischemia-reperfusion injury in rat kidneys

Jason A. Collett, Peter R. Corridon, Purvi Mehrotra, Alexander L. Kolb, George J. Rhodes, Caroline A. Miller, Bruce A. Molitoris, Janice G. Pennington, Ruben M. Sandoval, Simon J. Atkinson, Silvia B. Campos-Bilderback, David P. Basile, Robert L. Bacallao

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Highly aerobic organs like the kidney are innately susceptible to ischemia-reperfusion (I/R) injury, which can originate from sources includingmyocardial infarction, renal trauma, and transplant. Therapy ismainly supportive and dependson the cause(s) of damage. In the absenceof hypervolemia, intravenousfluiddelivery is frequently thefirst course of treatment but does not reverse established AKI. Evidence suggests that disrupting leukocyte adhesion may prevent the impairment of renal microvascular perfusion and the heightened inflammatory response that exacerbate ischemic renal injury.Weinvestigated the therapeutic potential of hydrodynamic isotonicfluid delivery (HIFD) to the left renal vein 24 hours after inducing moderate-to-severe unilateral IRI in rats. HIFD significantly increased hydrostatic pressure within the renal vein. When conducted after established AKI, 24 hours after I/R injury, HIFD produced substantial and statistically significant decreases in serum creatinine levels compared with levels in animals given an equivalent volume of saline via peripheral infusion (P,0.05). Intravital confocal microscopy performedimmediately after HIFDshowedimproved microvascularperfusion.Notably,HIFD alsoresulted in immediate enhancement of parenchymal labeling with the fluorescent dye Hoechst 33342. HIFD also associated with a significant reduction in the accumulation of renal leukocytes, including proinflammatory T cells.Additionally, HIFD significantly reduced peritubular capillary erythrocyte congestion and improved histologic scores of tubular injury 4days after IRI. Taken together, these results indicate that HIFDperformedafter establishment of AKI rapidly restores microvascular perfusion and small molecule accessibility, with improvement in overall renal function.

Original languageEnglish (US)
Pages (from-to)2081-2092
Number of pages12
JournalJournal of the American Society of Nephrology
Volume28
Issue number7
DOIs
StatePublished - Jul 2017

ASJC Scopus subject areas

  • Nephrology

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