Kidney Week

Abstract: FR-OR061

A Single Gastric K+ Load Induces Acute Diuresis in Mice

Session Information

• Fluids and Electrolytes: New Insights on Balance
  October 26, 2018 | Location: 8, San Diego Convention Center
  Abstract Time: 05:06 PM - 05:18 PM

Category: Fluid and Electrolytes

• 901 Fluid and Electrolytes: Basic

Authors

• Svendsen, Samuel L.C., Aarhus University, Aarhus, Denmark

Samuel L.C. Svendsen, MD

• Kornvig, Simon, Aarhus University, Aarhus, Denmark

Simon Kornvig,

• Larsen, Casper Kornbech, LEO Pharma, Copenhagen SV, Denmark

Casper Kornbech Larsen,

• Jensen, Iben Skov, Aarhus University, Aarhus, Denmark

Iben Skov Jensen,

• Leipziger, Jens G., Aarhus University, Aarhus, Denmark

Jens G. Leipziger,

• Sorensen, Mads Vaarby, Aarhus University, Aarhus, Denmark

Mads Vaarby Sorensen,

Background

K⁺ balance relies on regulated renal K⁺ excretion to match variable dietary K⁺ intake. Upon a K⁺ rich meal, rapid and effective urinary K⁺ excretion is obligatory. The renal adaptation to an acute K⁺ load involves an increase of the driving force for K⁺ secretion by shifting the distal tubular Na⁺ reabsorption from being electroneutral (NCC) to electrogenic (ENaC). In addition, K⁺ secretion in the CD is stimulated by increased luminal flow. Here we asked, if a high K⁺ intake acutely increases urinary flow.

Methods

Mice were K⁺ challenged through gavage, diets or a combination of these. After K⁺ loading urinary volume, [K⁺]_u and [Na⁺]_u ,plasma osmolality, [K⁺]_p and [Na⁺]_p were measured.

Results

1) Mice switched from a 1% to a 2% K⁺ diet increased their diuresis markedly within 12h. 2) Mice switched from a 1% to a 0.01% K⁺ diet had a biphasic diuretic response. During the first 12h their diuresis decreased, whereas it increased from 12 to 36h. 3) A single K⁺ load, by gastric gavage, corresponding to 25-50% of daily K⁺ intake induced diuresis within 30 min. This occurred despite augmented plasma osmolality. [K⁺]_u remained unchanged and therefore the increased urinary K⁺ excretion depended on the volume effect 4) K⁺ gavage did not changes urinary creatinine excretion suggesting a constant GFR. 5) Subsequently, a possible direct and acute effect of a plasma [K⁺] ([K⁺]_bl) increase was tested in isolated perfused mTALs and CDs. An acute [K⁺]_bl increase (from 3.6 to 6.5 mM) did not affect TAL NaCl absorption (measured 5 and 25 minutes post K⁺ jump). In contrast, the same manoeuver reduced the CDs sensitivity to stimulated AVP-mediated water absorption (measured 10 minutes post K⁺ jump).

Conclusion

Dietary K⁺ load induces a rapidly on setting diuresis. This increase in urinary volume appears crucial for a powerful K⁺ elimination since it appears prior to alteration in [K⁺]_u. Based on preliminary data we suggest that the physiological mechanism of K⁺-induced diuresis involves AVP desensitization of the CD.

Funding

• Government Support - Non-U.S.