BACKGROUND: Matrix metalloproteinase-2 (MMP-2) and pregnancy-associated plasma protein-A (PAPP-A) have been implicated in chronic kidney disease (CKD) and cardiovascular disease (CVD). However, the serum determinants of MMP-2 and PAPP-A in CKD are unknown. The aim of the present study is to evaluate the clinical significance of MMP-2 and PAPP-A and their determinants in patients with CKD. METHODS: The studied group consisted of 203 subjects: 159 patients with chronic kidney disease stages 1 - 5 (CKD 1 - 5), and 44 healthy control subjects. MMP-2 levels were assessed immunochemically using ELISA (enzyme linked immunosorbent assay), PAPP-A levels were determined immunochemically with TRACE (time-resolved amplified cryptate emission), and routine biochemical parameters were measured using standard methods. RESULTS: Compared with healthy controls, CKD patients (3 - 5) had no significant changes in MMP-2 levels. MMP-2 levels (195 +/- 76 vs. 255 +/- 77 ng/mL, p < 0.0001) were significantly lower in CKD patients (1 - 2) and PAPP-A levels (12.1 +/- 8.5 vs. 9.3 +/- 2.2 mIU/L, p = 0.001) were significantly higher in CKD 4 compared to control subjects. Multivariate analysis revealed that PAPP-A (p < 0.0001), proteinuria (p = 0.002), alpha-2-macroglobulin (p = 0.01), and negatively albumin (p = 0.02) and haemoglobin (p = 0.0002), were independent correlates of MMP-2 after adjustment for age and glomerular filtration rate. Proteinuria (p = 0.02), creatinine (p < 0.0001), and negatively albumin (p = 0.01), were independent correlates of PAPP-A adjusted for age and glomerular filtration rate. CONCLUSIONS: The present study demonstrated that serum MMP-2 and PAPP-A were independent correlates of proteinuria, albumin, and other examined parameters. Our results suggest the possibility that circulating MMP-2 and PAPP-A be used as indicators for renal damage in CKD patients on conservative treatment.

Department of Nephrology 1st Faculty of Medicine Charles University General University Hospital Prague Czech Republic