Periodontitis and high phosphate intake alone or in combination adversely affect the kidney

Abstract

Background: Periodontitis and high phosphate (HP) intake can negatively affect the kidney in the presence of renal disease. This study aimed to evaluate the effects of periodontitis or HP intake, either alone or concurrently, on the periodontal tissue and the kidney under normal renal conditions.

Methods: Rats were divided into normal diet (C), HP diet (HP), tooth ligation and normal diet (P), and tooth ligation and HP diet (P+HP) groups. The mandibular first molars were ligated, and a 0.9% HP diet was provided for 12 weeks from the day of ligation. An additional group (P+HP+IFX) was administered infliximab (IFX), a tumor necrosis factor-alpha (TNF-α) inhibitor, weekly to evaluate the TNF-α inhibitory effect.

Results: Alveolar bone loss and periodontal inflammation did not differ between the P and P+HP groups or between the C and HP groups. In the kidney, interstitial fibrosis and Col1a1 expression increased in the HP group, and ED1 expression increased in the P group, compared to the C group. Tubular basophilia, interstitial fibrosis, and the expression of Col1a1 and ED1 increased in the P+HP group compared to the other groups. The P+HP+IFX group showed a decrease in periodontal inflammation and these renal alterations compared to the P+HP group.

Conclusion: Regardless of periodontitis, 0.9% HP intake did not affect periodontal tissue. Renal fibrosis and macrophage infiltration induced by HP intake and periodontitis, respectively, worsened when combined, indicating a synergistic adverse effect. These changes were reversed by IFX, suggesting that TNF-α inhibition may alleviate renal injury caused by periodontitis and HP intake.

Plain language summary: Our study examined the impact of periodontitis and a 0.9% high phosphate (HP) diet, individually and together, on periodontal tissue and kidney. We divided rats into 4 groups: normal diet, HP diet, periodontitis with a normal diet, and periodontitis with an HP diet, and assessed various periodontal and renal parameters. Although we did not observe any effects of HP intake on periodontal tissue, we found that HP intake worsened kidney health by increasing fibrosis, while periodontitis did so by increasing macrophage infiltration. Combined, these conditions worsen kidney health more than when each condition exists alone, causing more tubular basophilia, fibrosis, and macrophage infiltration. However, these negative effects were reversed with TNF-α inhibition. These findings indicate that the combination of periodontitis and HP intake exacerbates renal damage, which can be ameliorated by TNF-α inhibition.

Keywords: fibrosis; high phosphate; inflammation; infliximab; periodontitis.