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OBJECTIVE: To study creatine kinase (CK) activity in a large series of patients with systemic lupus erythematosus (SLE) and identify the clinical and immunological features related to reduced levels. METHODS: In a cross-sectional study, serum CK activity was measured in 300 consecutive patients with SLE (271 females and 29 males, with a mean age of 36 years). All patients fulfilled the 1982 revised criteria of the American College of Rheumatology. RESULTS: Low serum CK levels (< 33 IU/L) were detected in 118 (39%) of SLE patients. When compared to SLE patients with normal serum CK levels, those with SLE and low serum CK levels had a higher frequency of fever (53% vs. 34%, p = 0.017), renal involvement (43% vs. 27%, p = 0.004), and hemolytic anemia (13% vs. 6%, p = 0.037). In addition, SLE patients with low CK values also presented lower values of hemoglobin, total proteins, albumin, cholesterol and triglycerides, higher values of ESR and low C3 (44% vs. 27%, p = 0.004), C4 (57% vs. 37%, p = 0.001) and CH50 levels (60% vs. 41%, p = 0.02). We analysed in 69 patients the correlation between CK and 24-hour proteinuria values, and found that those with a 24-hour proteinuria > 1500 mg/day showed lower CK values than those with proteinuria < 1500 (31.95 vs 63.84 IU/L, p = 0.046). CONCLUSION: We observed that serum CK levels were reduced in 39% of SLE patients. Reduced serum CK activity was significantly related to some clinical (fever, nephropathy), hematological (high ESR, hemolytic anemia) and immunological (hypocomplementemia) features, which relate to disease activity. This suggest that reduced CK activity might be inversely correlated to inflammatory activity in SLE.