Abstract 13529: Non-Invasive Assessment of the Effects of Proximal Tubule and Loop Duiretics on Tubuloglomerular Feedback
Introduction: Tubuloglomerular feedback (TGF) is a mechanism by which the kidney uses to regulate its glomerular filtration rate (GFR). When the macula densa (MD) detects elevated luminal sodium level via NKCC2 in the early distal convoluted tubule (DCT), it releases signaling molecules to decrease renal blood flow and GFR. The purpose of the study was to evaluate the feasibility of assessing changes in TGF activity with an imaging based approach.
Hypothesis: Intact TGF activity attenuates any change in luminal sodium concentration in DCT. Since the DCT segment of the nephron is located in cortical region of the kidney, an increase in its luminal sodium concentration will result in an apparent increase in overall cortical sodium content. It is expected that furosemide, a NKCC2 blocker, will attenuate the TGF activity and allow cortical sodium content to rise to a higher level than acetazolamide, which is not a NKCC2 blocker.
Methods: We quantified the effect of two different diuretics (furosemide, acetazolamide) on the cortical renal sodium contents in SD rats. 23Na-MRI was used to monitor cortical sodium contents in rat kidneys following administration of diuretics for > 2 hours on a Bruker 9.4T MRI scanner.
Results: Normally, the renal medullary and cortical sodium contents were kept at different constant levels, establishing a large corticomedullary sodium concentration gradient. Sodium content in the renal cortical region was found to rise reproducibly in response to both diuretic injections. The induced increases in sodium content were eventually clamped to different asymptotic plateaus, which were determined to be 1.40±0.02 and 1.23±0.02 times of their respective baselines for furosemide and acetazolamide (p<0.0004, N=6/group).
Conclusions: A set of in vivo pharmacological data were obtained from intact animals regarding renal cortical sodium contents following injections of two different diuretics. The significantly larger increase in cortical sodium content induced by furosemide than acetazolamide is consistent with the fact that the negative feedback activity of TGF is attenuated by furosemide, not by acetazolamide. Monitoring renal cortical sodium content with 23Na-MRI offers a means of direct assessment of TGF activity in vivo.
- © 2011 by American Heart Association, Inc.