Hydroxyproline increases inflammation and Uropathogenic E. coli (UPEC) infection in female rats

Calcium oxalate (CaOx) kidney stones may be associated with urinary tract infections (UTIs). However, the mechanisms for this association are not well-established. The objective of this study was to investigate the effect of oxalate on immunity and UTI development in vivo. Female Sprague-Dawley rats were fed a control diet for 3 days before continuing this diet or starting a 5% Hydroxy-L-proline diet (HLP; oxalate precursor) for 7 days. Rats were subsequently infected transurethrally with Uropathogenic E. coli (UPEC, a bacterium that causes UTI) and sacrificed 3 days later. Urine, blood, kidney, and bladder samples were collected. Urinary oxalate levels, renal CaOx crystal deposition, inflammatory markers, and the bacterial load were assessed using ion chromatography-mass spectrometry, immunohistochemistry, qRT-PCR, western blotting, enzyme-linked immunosorbent assays, or colony forming unit assays. Animals fed HLP and infected with UPEC had a significant increase in urinary oxalate levels, renal CaOx deposition, pro-inflammatory macrophages, pro-inflammatory cytokines, and bacterial loads compared to animals fed the control diet with UPEC infection. In addition, HLP-fed animals had significantly reduced anti-inflammatory renal macrophages and anti-inflammatory cytokine levels in their plasma, urine, and kidneys. These findings suggest that oxalate may play a novel role in the propagation of UTI development.