Increased water intake dilutes protective uromodulin levels in urine and results in increased rates of pyelonephritis in a murine model

Aim

Urinary tract infections (UTIs) rank among the most prevalent infections in humans, carrying substantial implications for public health. Women experiencing recurrent UTIs are often advised to boost their fluid intake to help eliminate bacteria. In this study, we explored the impact of elevated fluid consumption during UTIs using a mouse model of pyelonephritis.

Methods

UTI was induced in 8–10 w female BALB/cJ-mice by surgically injecting Escherichia coli (O6:K13:H1) into the bladder whereafter mice were randomized to gel food (GF) or regular chow. Immune response and infection severity were determined 24-h post-infection. In vitro bacterial growth (OD₆₀₀) was determined in urine from mice or from human volunteers.

Results

Gel feeding increased urine output (1.40 ± 0.77 μL min⁻¹, p < 0.01) and diluted the urine (668.7 ± 177 mOsmol kg⁻¹, p < 0.0001) compared to controls on regular chow (urine output: 0.34 ± 0.27 μL min⁻¹, osmolality: 1439 ± 473.5 mOsmol kg⁻¹). Mice on GF had a higher risk of pyelonephritis (87.5%) and more severe infections (26.22 ± 9.88 CFU mg⁻¹ tissue) compared to controls (43.75%; 3.87 ± 3.56 CFU mg⁻¹, p < 0.01). Correspondingly, the growth of E. coli was markedly reduced at osmolalities above 1200 mOsmol kg⁻¹ compared to 600 mOsmol kg⁻¹ and GF mice had lower urine levels of uromodulin (13.70 ± 1.89 μg mL⁻¹, p < 0.01) compared to controls (24.65 ± 2.70 μg mL⁻¹).

Conclusion

Increased water intake and urine flow in mice will markedly increase the risk of pyelonephritis. The increased risk may reflect reduced urine uromodulin combined with optimized growth conditions for E. coli. The study does not immediately support the notion that established UTIs can be eliminated by increased water intake.