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Kidney Week

Abstract: SA-PO986

Effects of the Loop Diuretic Furosemide on Renal Hemodynamics and Synchronization Among Nearby Nephrons

Session Information

  • CKD: Pathobiology - II
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2203 CKD (Non-Dialysis): Mechanisms

Authors

  • Poursharif, Shayan, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
  • Hamza, Shereen M., University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
  • Braam, Branko, University of Alberta Faculty of Medicine & Dentistry, Edmonton, Alberta, Canada
Background

Autoregulation of renal blood flow (RBF) among nearby nephrons is presumably synchronized via tubuloglomerular feedback (TGF). TGF controls macula densa solute delivery by adjusting afferent arteriolar diameter and thereby single nephron GFR. As high doses of the diuretic furosemide impair TGF via inhibition of NKCC2 transporters and thus macula densa sodium sensing, we hypothesized that deactivating TGF with furosemide would impair nephron synchronization.

Methods

Mean arterial pressure, RBF, urine flow and GFR were measured in anesthetized rats (300-400 g). Left kidney cortical perfusion was recorded using laser speckle imaging, to assess surface perfusion and TGF-mediated nephron synchronization. After baseline, furosemide was infused (10, 20 or 30 mg/kg; n=8) to inhibit TGF. Mean phase coherence (PC), which assesses the degree of phase-locking (synchronization) among multiple oscillators (TGF-driven rhythmic changes of multiple afferent arterioles resistance), the magnitude of decay of TGF PC and length constant associated with initial decay of TGF PC were used to assess strength of synchronization among nephrons.

Results

Furosemide did not change MAP (101+10 to 105+39 mmHg, NS) or RBF (7.1+2.3 to 6.9+2.5 ml/min, NS). Right kidney GFR increased after furosemide (1.10+0.22 to 1.27+0.27 ml/min, p<0.05), while left kidney GFR was slightly reduced (1.06+0.22 to 0.92+0.16 ml/min, p<0.05). Furosemide strongly increased right (8+5 to 134+18 uL/min, p<0.001) and left (10+3 to 124+16 uL/min, p<0.001) urine flow. Furosemide decreased the magnitude of the decay of TGF PC (0.46+0.06 to 0.42+0.06, P<0.05) and length constant associated with initial decay of TGF PC (-0.28+0.11 to -0.53+0.06, P<0.001). Furosemide did not affect average PC. Correlation analysis of urine flow, RVR and GFR with parameters of synchronization did not reveal any further support for a decrease in synchronization after furosemide.

Conclusion

High dose furosemide decreased the magnitude of decay of TGF PC and length constant associated with initial decay of TGF PC. This indicates weaker synchronization among nephrons within lobules. However, the absence of a change in mean PC makes it likely that mechanisms other than the TGF sensing step in the macula densa differentially affect synchronization amongst nephrons.

Funding

  • Government Support – Non-U.S.