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We compared pyelonephritis susceptibility following reciprocal renal transplantations between Car2<jats:sup>\u2212\/\u2212<\/jats:sup>and wild-type mice. We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine model of urinary tract infection. Car2<jats:sup>\u2212\/\u2212<\/jats:sup>versus wild-type mice were compared for differences in renal innate immunity. In our transplant scheme, mice lacking CA-II in the kidney had increased pyelonephritis risk. Mice treated with acetazolamide had lower kidney bacterial burdens at 6 h postinfection, which appeared to be due to tubular flow from diuresis because comparable results were obtained when furosemide was substituted for acetazolamide. Isolated Car2<jats:sup>\u2212\/\u2212<\/jats:sup>kidney cells enriched for intercalated cells demonstrated altered intercalated cell innate immune gene expression, notably increased calgizzarin and insulin receptor expression. 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