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Published on: June 16, 2014
Matrix Metalloproteinases and Subclinical Atherosclerosis in Chronic Kidney Disease: A Systematic Review
Andreas Kousios1, Panayiotis Kouis2, Andrie G Panayiotou2
1Department of Nephrology, Nicosia General Hospital, 2230 Nicosia, Cyprus.
Insights
Matrix Metalloproteinases (MMPs) show potential as biomarkers for subclinical atherosclerosis in Chronic Kidney Disease (CKD). However, more research is needed to confirm their role due to limited data and inconsistent methodologies.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Research
Background:
- Cardiovascular disease (CVD) is a major complication in Chronic Kidney Disease (CKD).
- Noninvasive methods for detecting subclinical atherosclerosis could enhance CVD risk prediction in CKD patients.
- Current noninvasive methods are often inaccessible in clinical settings.
Purpose of the Study:
- To systematically review the association between circulating levels of Matrix Metalloproteinases (MMPs) and tissue inhibitors (TIMPs) and subclinical atherosclerosis in CKD patients.
- To evaluate the potential of MMPs and TIMPs as biomarkers for subclinical atherosclerosis in CKD.
- To identify potential pharmacologic targets for managing atherosclerosis in CKD.
Main Methods:
- Systematic literature search of major electronic databases from inception to May 2015.
- Inclusion of studies involving CKD patients with data on circulating MMPs/TIMPs and atherosclerosis.
- Quality assessment of included studies and synthesis of findings (qualitative and quantitative).
Main Results:
- 16 studies were included for qualitative synthesis, and 9 for quantitative synthesis.
- MMP-2 and TIMP-1 were the most frequently studied MMPs/TIMPs.
- MMP-2 showed a consistent positive association with carotid Intima-Media Thickness (cIMT), a measure of subclinical atherosclerosis.
- Significant variability in cIMT measurement and plaque assessment methods was noted across studies.
Conclusions:
- MMPs show promise as biomarkers for subclinical atherosclerosis in CKD.
- Current data is insufficient for a definitive meta-analysis due to under-study and methodological heterogeneity.
- Larger, standardized studies are required to validate MMPs' role in assessing atherosclerotic burden in CKD.
Abstract:
Background. Cardiovascular disease (CVD) remains a significant problem in Chronic Kidney Disease (CKD). Subclinical atherosclerosis identified by noninvasive methods could improve CVD risk prediction in CKD but these methods are often unavailable. We therefore systematically reviewed whether circulating levels of Matrix Metalloproteinases (MMPs) and tissue inhibitors (TIMPs) are associated with subclinical atherosclerosis in CKD, as this would support their use as biomarkers or pharmacologic targets. Methods. All major electronic databases were systematically searched from inception until May 2015 using appropriate terms. Studies involving CKD patients with data on circulating MMPs levels and atherosclerosis were considered and subjected to quality assessment. Results. Overall, 16 studies were identified for qualitative synthesis and 9 studies were included in quantitative synthesis. MMP-2 and TIMP-1 were most frequently studied while most studies assessed carotid Intima-Media Thickness (cIMT) as a measure of subclinical atherosclerosis. Only MMP-2 demonstrated a consistent positive association with cIMT. Considerable variability in cIMT measurement methodology and poor plaque assessment was found. Conclusions. Although MMPs demonstrate great potential as biomarkers of subclinical atherosclerosis, they are understudied in CKD and not enough data existed for meta-analysis. Larger studies involving several MMPs, with more homogenized approaches in determining the atherosclerotic burden in CKD, are needed.
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