Mechanism Underlying Linezolid‑induced Thrombocytopenia in a Chronic Kidney Failure Mouse Model

Objective: To investigate the relationship between renal function and linezolid (LZD)‑induced thrombocytopenia and elucidate the underlying mechanism using a chronic renal disease (CRD) mouse model. Materials and Methods: CRD was induced in 5‑week‑old male Institute of Cancer Research (ICR) mice by 5/6 nephrectomy. After this procedure, LZD (25 and 100 mg/kg) was administered intraperitoneally once every day for 28 days. Platelet counts, white blood cell (WBC) counts, and hematocrit (HCT) levels were measured every 7 days. 2‑14C‑thymidine (0.185 MBq) was administrated intravenously to LZD‑administered mice to evaluate the thymidine uptake ability of bone marrow. Results: Platelet counts were significantly lower in the LZD‑administered CRD group than in the LZD‑nonadministered groups at 14, 21, and 28 days (P < 0.05); however, these changes were not observed in LZD‑administered mice with normal renal function, regardless of the duration of LZD administration. No significant changes were observed in WBC counts or HCT levels in any LZD‑administered CRD mouse. Moreover, radioactive levels in bone marrow were not significantly different in each group. Conclusions: These results indicate that LZD‑induced decreases in platelet counts were enhanced by renal impairment in vivo, suggesting that LZD‑induced thrombocytopenia is not caused by nonimmune‑mediated bone marrow suppression.