Developmental loss, but not pharmacological suppression, of renal carbonic anhydrase 2 results in pyelonephritis

John Ketz1, Vijay Saxena2, Samuel Arregui2

  • 1Center for Clinical and Translational Medicine, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.

Insights

Mice lacking carbonic anhydrase II (CA-II) showed increased urinary tract infection risk due to fewer renal intercalated cells. CA-II impacts kidney immune cell function and infection susceptibility.

Area of Science:

  • Nephrology
  • Immunology
  • Microbiology

Background:

  • Renal intercalated cells are crucial innate immune effectors.
  • Carbonic anhydrase II (CA-II) deficiency impacts renal intercalated cell populations.
  • Understanding CA-II's role in kidney infection is vital.

Purpose of the Study:

  • To investigate the role of CA-II in pyelonephritis susceptibility.
  • To compare renal innate immunity in CA-II knockout and wild-type mice.
  • To assess the effect of carbonic anhydrase inhibition on urinary tract infection.

Main Methods:

  • Reciprocal renal transplantation between CA-II knockout and wild-type mice.
  • Pharmacological carbonic anhydrase suppression using acetazolamide.
  • Murine model of urinary tract infection with bacterial burden assessment.

Main Results:

  • Mice lacking CA-II in the kidney exhibited increased pyelonephritis risk.
  • Acetazolamide treatment led to reduced kidney bacterial load, attributed to diuresis-induced tubular flow.
  • Isolated CA-II knockout kidney cells showed altered innate immune gene expression in intercalated cells.

Conclusions:

  • Intercalated cell number and function are key determinants of pyelonephritis risk.
  • CA-II plays a significant role in renal innate immunity and defense against urinary tract infections.
  • Targeting tubular flow may offer a therapeutic strategy for managing kidney infections.

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