Clinical value of serum MMP-3 in chronic kidney disease

Background: Chronic kidney disease (CKD) is defined as the progressive deterioration of renal parenchyma and decline in renal unit function. In the early stages of CKD(G1 + G2), symptoms are usually not obvious and cannot be effectively recognized on the basis of available clinical markers. Progression to the middle and late stages of CKD results in severe kidney damage with multiple complications causing adverse outcomes, including death. Therefore, the early diagnosis and monitoring of CKD is critical. Matrix metalloproteinase-3 (MMP-3), an extracellular matrix-degrading enzyme, plays an important role in kidney diseases. However, the clinical significance of serum MMP-3 levels in CKD has rarely been reported. Methods: We quantified the serum MMP-3 levels of 237 patients with CKD and 96 healthy individuals by using a highly sensitive time-resolved fluorescence immunoassay and analyzed differences in MMP-3 levels among the stages of CKD and the correlations of these changes with clinical indicators. Results: The serum MMP-3 concentrations of patients with CKD (171.76 +/- 165.22 ng/mL) were significantly higher than those of healthy controls (34.05 +/- 22.93 ng/mL; P < 0.0001). In CKD, serum MMP-3 levels were significantly correlated with estimated glomerular filtration rate (eGFR) (r = - 0.5804, P < 0.0001), serum creatinine (CREA) (r = 0.5823, P < 0.0001), blood urea nitrogen (BUN) (r = 0.6106, P < 0.0001), and protein-tocreatinine ratio (r = 0.4992, P < 0.0001). Randomized forest analysis finds CREA, BUN, and MMP-3 most significant influences on CKD disease severity. The critical value of MMP-3 concentration of 40.39 ng/mL combined with eGFR was effective in diagnosing positive patients in the early (G1 + G2) stage of CKD and showed a positivity rate of 73.45 %. Moreover, in the early stages of CKD, patients with CKD who had serum MMP-3 concentration > 100 ng/mL had more severe renal impairment and inflammation than those with CKD who have lower serum MMP-3 concentrations. Conclusion: Elevated serum MMP-3 levels are correlated with decreased kidney function in CKD progression, and patients with concomitant inflammation may express high levels of serum MMP-3. Serum MMP-3 may assist eGFR in improving the diagnosis of patients with early CKD.