Periodontal Bacteria Aggravate Chronic Renal Failure Induced by Subtotal Nephrectomy in Mice
Norihiko Ashigaki, Jun-ichi Suzuki, Masahito Ogawa, Ryo Watanabe, Norio Aoyama, Naho Kobayashi, Yasunobu Hirata, Issei Komuro, Yuichi Izumi and Mitsuaki Isobe
Affiliation: Department of Advanced Clinical Science and Therapeutics, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-8655, Japan.
Periodontitis is associated with several systemic disorders, such as diabetes, cardiovascular disease and chronic
kidney disease (CKD). However, the pathophysiological relationship between periodontitis and CKD is yet to be elucidated.
We assessed the hypothesis that periodontal bacteria influence renal dysfunction. We used C57BL/6J mice and implanted
chambers subcutaneously in the back of each mouse. Two weeks after implantation, we injected Porphyromonas
gingivalis (P.g.), which is a major periodontal pathogen, or phosphate-buffered saline (PBS) into the chamber. The subcutaneous
injections were administered once a week for 6 weeks during the observation period. 5/6 nephrectomy (NTX) was
made by a two-step surgical procedure. The levels of anti-P.g. IgG in the serum were determined with an ELISA. After
the operation, we measured serum creatinine using an enzymatic method. On day 28, mice were sacrificed and pathological
evaluation was also performed. The repeated bacterial injections elevated the serum level of anti-P.g. IgG significantly.
NTX increased the serum creatinine level (0.35 ± 0.02mg/dl) compared to native mice (0.15 ± 0.01mg/dl). Neither
infection altered creatinine levels (P.g. 0.41 ± 0.04mg/dl) (n = 15) compared to the PBS injected group (n = 20). On days
1, 3 and 7, serum creatinine levels were significantly increased in the P.g. injected group compared to the PBS injected
group. Of note, P.g. infection deteriorated 28 days survival rate (46.9%, p<0.05) compared to the PBS injected group
(90.9%). It was suggested that periodontal pathogens deteriorated serum creatinine levels and the survival rate after NTX.
Keywords: 5/6 nephrectomy, calcium, chronic kidney disease, creatinine, MCP-1, MMP-2, Periodontitis, phosphate, Porphyromonas
gingivalis, survival rate.
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