Abstract: FR-PO434
Association of Galectin-3 and MMP-2 with Risk of CKD Progression in the Chronic Renal Insufficiency Cohort (CRIC) Study
Session Information
- CKD: Risk Factors for Incidence and Progression - II
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 301 CKD: Risk Factors for Incidence and Progression
Authors
- Anderson, Amanda Hyre, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Orlandi, Paula Ferreira, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Roy, Jason, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Bansal, Nisha, The CRIC Study, Philadelphia, Pennsylvania, United States
- Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Kusek, John W., NIDDK, Bethesda, Maryland, United States
- Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
Group or Team Name
- CRIC Study
Background
Kidney fibrosis is a final common pathway of progressive chronic kidney disease (CKD). Markers of fibrosis may be independently associated with risk for CKD progression.
Methods
We measured galectin-3 and matrix metalloproteinase-2 (MMP-2) at baseline in a multi-center, prospective cohort study of men and women with CKD, the CRIC Study (N=3,828; mean estimated glomerular filtration rate (eGFR): 45 mL/min/1.73m2; age range: 21-75 years; 48% diabetes). CKD progression was defined as either the onset of end-stage renal disease or a 50% reduction in eGFR. Cox proportional hazards models were fit to estimate the relationships between galectin-3 and MMP-2 with CKD progression.
Results
Higher baseline galectin-3 levels were significantly associated with patient characteristics; in particular, strong associations existed for females, non-Hispanic blacks, lower eGFR, higher FGF23, and higher inflammatory markers. MMP-2 levels were elevated most significantly among those with higher systolic blood pressure, diabetes, higher urine protein excretion, and higher cardiac biomarker levels. Over a median follow-up of 6 years, the highest quartiles of galectin-3 and MMP-2 were associated with a 2-fold and 1.5-fold increased risk for CKD progression, respectively (Table), after adjusting for traditional risk factors with the exception of eGFR (Model 2), which may be an intermediate factor in this relationship. Although further adjustment for baseline eGFR attenuated this risk, it remained statistically significant.
Conclusion
Galectin-3 and MMP-2 were found to be independent risk factors for CKD progression. Future studies should investigate if these measures improve identification of high-risk subgroups within the population of individuals with CKD.
| Model 1 | Model 2 | Model 3 | |
| Galectin-3, ng/mL | |||
| Q1 (<10.2) | Ref | Ref | Ref |
| Q2 (10.2-14.3) | 1.48 (1.23-1.79) | 1.29 (1.06-1.57) | 1.06 (0.87-1.29) |
| Q3 (14.3-19.5) | 2.24 (1.87-2.67) | 1.82 (1.50-2.20) | 1.38 (1.14-1.67) |
| Q4 (19.5-83.9) | 2.97 (2.49-3.55) | 2.01 (1.67-2.44) | 1.25 (1.03-1.52) |
| MMP-2, ng/mL | |||
| Q1 (<243) | Ref | Ref | Ref |
| Q2 (244-311) | 1.20 (1.00-1.46) | 1.17 (0.96-1.43) | 1.16 (0.95-1.42) |
| Q3 (312-401) | 1.67 (1.40-2.02) | 1.32 (1.08-1.60) | 1.27 (1.04-1.54) |
| Q4 (402-1379) | 2.61 (2.20-3.11) | 1.53 (1.27-1.85) | 1.33 (1.10-1.61) |
| Model 1: unadjusted; Model 2: stratified by clinical site and adjusted for age, gender, race/ethnicity, urine protein, body mass index, systolic blood pressure, smoking, diabetes, and history of cardiovascular disease; Model 3: Model 2 + eGFR. | |||
Funding
- NIDDK Support