NIH Research Festival
FARE Award Winner
Introduction: Acute kidney injury (AKI) increases the mortality of sepsis. As kidney function worsens, glomerular filtration rate (GFR) falls and serum creatinine increases. The slow kinetics of creatinine prevent early clinical detection of renal injury. We measured GFR continuously using a novel transcutaneous fluorometer and a fluorescent GFR marker. Tubuloglomerular feedback (TgF) is hypothesized to reduce GFR to prevent renal salt wasting during sepsis (“acute renal success”). Because adenosine 1a receptor (A1aR) knockout mice lack TgF, we tested whether TgF contributes to sepsis-AKI. Methods: Sepsis was induced in A1aR knockout mice and littermate controls by cecal ligation and puncture. FITC-sinistrin was injected intravenously, and GFR measured via elimination kinetics using a miniaturized fluorimeter attached to the mouse back. Results: The baseline GFR was similar in A1aR WT and KO mice. During the first hour following sepsis induction the GFR was stable in WT mice. GFR slowly declined over hour two, and then fell rapidly by 5-fold, and remained low for 5 hours. Clinical symptoms of sepsis appear at 6 hours. In contrast, the GFR was lower in KO than in WT mice in the first hour following sepsis (p=0.0226), then fell gradually to 27% of normal, with a smaller decrease after 2 hours compared to WT (p=0.0286). Conclusions: Transcutaneous fluorescence reveals novel pathophysiology during early AKI. TgF modestly supports, not suppresses, GFR in the first hour following sepsis, and only later acts to suppress GFR.
Scientific Focus Area: Cell Biology
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