Determinants of circulating matrix metalloproteinase-2 and pregnancy-associated plasma protein-A in patients with chronic kidney disease.
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, First Faculty of Medicine, Charles University, General University Hospital, Prague, Czech Republic.
Oskar
O
Zakiyanov
Marta
M
Kalousová
Markéta
M
Kratochvilová
Vítezslav
V
Kríha
Tomás
T
Zima
Vladimír
V
Tesar
D000328:Adult; D015415:Biomarkers / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000201:enzymology*; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D008875:Middle Aged; D011266:Pregnancy-Associated Plasma Protein-A / Q000378:metabolism*; D011507:Proteinuria / Q000175:diagnosis; D012709:Serum Albumin / Q000032:analysis
D015415:Biomarkers; D012709:Serum Albumin; D011266:Pregnancy-Associated Plasma Protein-A; D020778:Matrix Metalloproteinase 2