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Adalimumab induced chronic interstitial nephritis: a controlled blinded trial in mice

Sultan M. Al Mogairen

Background: Adalimumab is a known drug modifying agent for rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) treatment. However little is known about the risk of nephrotoxicity. To determine whether the inhibition of tumor necrosis factor (TNF) binding to cell-surface TNF receptor sites by adalimumab result in acute nephritis in BALB/c mice.

Method: Twenty Balb/c mice were studied. Ten mice received subcutaneous (SC) injection of adalimumab (0.0175 mg per 25 kg body weight per 0.03 ml normal saline) biweekly (0, 2, 4, 6 and 8 weeks). For the control group, 10 mice received a SC injection of normal saline (NS) (0.03ml). At the 10th week post injection, the mice were sacrificed, and histopathological studies were conducted.

Results: Of the adalimumab-treated group, 4/10 mice died. Kidney histology for the adalimumab-treated group showed that 6/6 displayed histopathological changes manifested as patchy chronic interstitial inflammation with focal tubular epithelial cells vaculation. In contrast, only minimal inflammation was observed in 4/10 mice in the control group (p=0.01). Conclusion: Adalimumab may play a role in inducing chronic interstitial nephritis.