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Determinants of circulating matrix metalloproteinase-2 and pregnancy-associated plasma protein-A in patients with chronic kidney disease

O. Zakiyanov, M. Kalousová, M. Kratochvilová, V. Kríha, T. Zima, V. Tesar

. 2012 ; 58 (5-6) : 471-480.

Language English Country Germany

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc12034432

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.

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$a Determinants of circulating matrix metalloproteinase-2 and pregnancy-associated plasma protein-A in patients with chronic kidney disease / $c O. Zakiyanov, M. Kalousová, M. Kratochvilová, V. Kríha, T. Zima, V. Tesar
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$a 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.
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$a Kalousová, Marta, $d 1974- $7 mzk2005318016 $u Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. marta.kalousova@seznam.cz
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$a Kratochvilová, Markéta $7 xx0268890 $u Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic. mkazderova@centrum.cz
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$a Kríha, Vítezslav $u Department of Physics, Faculty of Electrical Engineering, Czech Technical University in Prague, Prague, Czech Republic
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$a Zima, Tomáš, $d 1966- $7 jn20000620440 $u Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
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$a Tesař, Vladimír, $d 1957- $7 jn20000402349 $u Department of Nephrology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic
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