ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO393

Experimental CKD Reduces Tubuloglomerular Feedback Synchronization and Impairs Autoregulation

Session Information

  • CKD: Mechanisms - II
    November 08, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
    Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Zehra, Tayyaba, University of Alberta, Edmonton, Alberta, Canada
  • More, Heather L., Simon Fraser University, Burnaby, British Columbia, Canada
  • Hamza, Shereen M., University of Alberta, Edmonton, Alberta, Canada
  • Cupples, William A., Simon Fraser University, Burnaby, British Columbia, Canada
  • Braam, Branko, University of Alberta, Edmonton, Alberta, Canada
Background

Tubuloglomerular feedback (TGF) is an important component of autoregulation of renal blood flow and can prevent transmission of high blood pressure to glomeruli. We have previously shown that the TGF mechanism operates in a network fashion, leading to TGF synchronization. Eventually, this ensures that each nephron receives appropriate perfusion to match the energy-intensive reabsorption of Na+. We have shown that loss of synchronization impairs autoregulation which is implicated in chronic kidney disease (CKD). We hypothesized that structural damage to the nephron-network would impair TGF-synchronization.

Methods

Male Lewis rats underwent uni-nephrectomy followed by partial nephrectomy to induce CKD (n=6) or underwent sham-operations (n=6). Six weeks later, the rats were anesthetized and mean arterial pressure (MAP), renal blood flow (RBF), and glomerular filtration rate (GFR) were assessed. Renal cortical perfusion was recorded with laser speckle contrast imaging (LSCI; Moor Instruments). After filtering to isolate TGF frequencies, we quantified phase coherence (PC) and used graph analysis to provide information about TGF synchronization between nephrons.

Results

Within the CKD group, RBF (8.0±0.6 to 6.7±1.0 mL/min) and GFR (0.89±0.33 to 0.37±0.7 mL/min) were decreased compared to controls (7.4±1.3 to 7.0±1.4 mL/min), (0.63±0.38 to 0.55±0.14 mL/min) respectively, although this did not reach significance. MAP showed no differences between CKD (102±7 to 89±5 mmHg) and controls (104±6 to 91±4 mmHg). Strength of TGF-synchronization between nephrons is indicated by higher values for phase coherence (PC). PC values were decreased for CKD rats (0.3±0.02) versus controls (0.5±0.03) which indicates weaker synchronization (p<0.005). Each pixel in the image is treated as a node and connected to other nodes via edges with significant PC; the CKD group had a lower number of connecting edges (780±532) compared to controls (36932±22589) (p<0.005). The number of synchronized regions (clusters) decreased for CKD rats (1±0.08) compared to controls (2±0.3) (p<0.005).

Conclusion

In this model of CKD, we demonstrate an impaired ability of nephrons to synchronize TGF in the renal cortex as assessed by LSCI. Since this network synchronization could prevent hypertensive injury further investigations are on improving network function.

Funding

  • Government Support - Non-U.S.