Kidney Week

Abstract: FR-PO929

Developmental Loss of Intercalated Cells increases but Pharmacological Carbonic Anhydrase Suppression Decreases Pyelonephritis Susceptibility

Session Information

• Development, Stem Cells, Regenerative Medicine - II
  October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Development, Stem Cells, and Regenerative Medicine

• 501 Development, Stem Cells, and Regenerative Medicine: Basic

Authors

• Schwaderer, Andrew L., Indiana University, Zionsville, Indiana, United States

Andrew L. Schwaderer,

• Saxena, Vijay, Indiana University, Zionsville, Indiana, United States

Vijay Saxena,

• Ketz, John, Nationwide Children''s Hospital, Columbus, Ohio, United States

John Ketz,

• Schwartz, George J., University of Rochester, Rochester, New York, United States

George J. Schwartz,

• Hains, David S., Indiana University, Zionsville, Indiana, United States

David S. Hains,

• Fairchild, Robert L., Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, United States

Robert L. Fairchild,

Background

We had previously shown that carbonic anhydrase (CA) 2 knockout mice (Car2^-/-) have an intercalated cell deficiency and are susceptible to pyelonephritis. However it was not known whether this pyelonephritis risk is due to systemic absense CA, renal absence of CA, decreased CA activity or developmental depletement of intercalated cells. We hypothesized that the pyelonephritis susceptibility in Car2^-/- mice is secondary to intercalated cell deficiency

Methods

We compared pyelonephritis susceptiblity following transplantation of Car2^-/- kidneys into wild type mice (isolated renal Car2 absence), transplantation of wild type (WT) kidneys into Car2^-/-mice (nonrenal Car2 absence) and transpantation of control WT kidneys into WT mice. To determine whether pharmacological suppression of CA results in a similar pyelonephritis risk to developmental intercalated cell absence, we identified the dose of acetazolamide that suppressed renal carbonic anhydrase activity then compared pyelonephritis risk in treated versus untreated C57Bl/6J WT mice. Experimental pyelonephritis was induced by transurethral inoculation of uropathogenic E.coli (UPEC).

Results

Results are presented in Figure 1: Compared WT donor/WT recipient, the Car2^-/-donor/WT recipient, but not the WT donor/Car2^-/-recipient group had higher kidney (A) but not bladder (B) bacterial burdens at 24-hours post UPEC inoculation. Both 50 mg and 100 mg of acetazolamide given intraperitoneally suppressed CA (C) and increased urine pH (D). There was no difference between kidney (E-F) or bladder (G) bacterial burdens at 24 hours between acetazolamide treated and control mice. Mice treated with acetazolamide had lower kidney (H-I), but not bladder (K) bacterial burdens at 6-hours.

Conclusion

Developmental absence of intercalated cells is responsible for the pyelonephritis risk in Car2^-/-mice. Surprisingly acetazolamide appears to be protective against pyelonephritis, at least at an early time point.

Funding

• NIDDK Support