Analysis of the risk factors of acute tubulointerstitial nephritis caused by Yersinia pseudotuberculosis infection

Abstract

Five primary school children suffering from remittent fever and abdominal pain were admitted to our hospital; of these children, 2 girls also had acute kidney injury (AKI). Yersinia pseudotuberculosis (Ypt) was detected in the stool samples of 2 patients, serum levels of anti-Ypt 5a antibodies increased in another 2 patients, and the anti-Yersinia pseudotuberculosis derived mitogen (YPM) antibody titer was significantly increased in 1 patient. Thus, all 5 patients were diagnosed with Ypt infection.Ypt infection is an important cause of AKI in healthy children, and tubulointerstitial nephritis (TIN) is the most common histological diagnosis. Ypt infection is known to cause not only AKI but also various conditions such as Kawasaki disease and mesenteric lymphadenitis. YPM, a superantigen produced by Ypt, stimulates many T cells and causes these symptoms. We studied the serum proinflammatory cytokines and the soluble receptors of patients with and without TIN. Levels of serum soluble tumor necrosis factor receptor (sTNFR)-1, sTNFR-2, interleukin (IL)-6, IL-17, and sIL-2Rα were higher in patients with TIN than in patients without TIN. The high levels of sIL2-Rα and IL-17 suggested that the T lymphocytes were activated by YPM. The levels of sTNFR-1 and sTNFR-2 were markedly higher in TIN patients. The tumor necrosis factor alpha (TNF-α) levels in patients with TIN higher than the levels in patients without TIN, but the difference was slight. Although the exact physiological role of sTNFRs remains unknown, the circulatory forms of TNFRs may function as decoys for TNF-α or their concentrations may reflect long-term exposure to this proinflammatory cytokine. Cleavage of TNF-α and TNFRs from the cell surface by a disintegrin and metalloproteinase-17 results in the soluble forms. The regulatory mechanisms of sTNFRs have not been clarified thus far. Some studies have suggested that TNF-α is the main regulator, as it induces TNFR shedding. Thus high levels of sTNFRs in patients with TIN suggest that TNF-α is associated with AKI.