Abstract: PO0445
Urinary Fibrosis Markers and Risk for ESKD: The Chronic Renal Insufficiency Cohort (CRIC) Study
Session Information
- CKD Epidemiology, Biomarkers, Predictors
October 22, 2020 | Location: On-Demand
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Anderson, Amanda Hyre, Tulane University, New Orleans, Louisiana, United States
- Baudier, Robin Leigh, Tulane University, New Orleans, Louisiana, United States
- Yang, Wei, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Susztak, Katalin, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Dobre, Mirela A., Case Western Reserve University, Cleveland, Ohio, United States
- He, Hua, Tulane University, New Orleans, Louisiana, United States
- Rahman, Mahboob, Case Western Reserve University, Cleveland, Ohio, United States
- Rosas, Sylvia E., Joslin Diabetes and Endocrinology Research Center, Boston, Massachusetts, United States
- Srivastava, Anand, Northwestern University, Evanston, Illinois, United States
- Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
- Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
Group or Team Name
- The CRIC Study
Background
Connective tissue growth factor (CCN2) and amino-terminal peptide of procollagen type III (PIIINP) are both correlated with kidney fibrosis. However, it is unclear if these markers are independently associated with the risk for ESKD.
Methods
We measured CCN2 and PIIINP in baseline urine and standardized to urine creatinine (Cr) in a multi-center cohort study of men and women with chronic kidney disease (CKD), the CRIC Study (N=3727). ESKD was defined as initiation of kidney replacement therapy (N=1118 events). Cox proportional hazards models were adjusted hierarchically as indicated (Table).
Results
The mean age of the study population was 58 years; mean eGFR: 45 mL/min/1.73m2; and 48% had diabetes. After multivariable adjustment and median follow-up of 10 years, the highest quartiles of CCN2/Cr and PIIINP/Cr were associated with a 1.8-fold and 1.7-fold higher risk for ESKD compared to the lowest quartiles, respectively (Table). The association was no longer statistically significant after adjustment for proteinuria.
Conclusion
Urinary CCN2 and PIIINP are strongly associated with risk for ESKD, an association that may be mediated through proteinuria. Future studies should investigate if these markers add to the identification of those at highest risk for progression to ESKD.
| Model 1 | Model 2 | Model 3 | Model 4 | |
| CCN2/Cr, ng/g | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) |
| Q1: <1403 | reference | reference | reference | reference |
| Q2: 1404-3291 | 1.5 (1.2-1.8) | 1.4 (1.1-1.8) | 1.4 (1.1-1.8) | 1.0 (0.8-1.3) |
| Q3: 3292-8125 | 2.8 (2.2-3.4) | 2.5 (2.0-3.1) | 1.6 (1.2-2.0) | 1.0 (0.8-1.3) |
| Q4: >8126 | 7.0 (5.7-8.6) | 5.4 (4.4-6.7) | 1.8 (1.4-2.3) | 0.9 (0.7-1.2) |
| PIIINP/Cr, ng/g | ||||
| Q1: <733 | reference | reference | reference | reference |
| Q2: 733-1886 | 1.3 (1.0-1.6) | 1.2 (0.9-1.5) | 1.3 (1.0-1.6) | 0.9 (0.7-1.1) |
| Q3: 1889-3974 | 2.2 (1.8-2.7) | 1.8 (1.5-2.2) | 1.3 (1.1-1.7) | 0.8 (0.6-1.0) |
| Q4: >3975 | 5.5 (4.5-6.6) | 3.7 (3.0-4.5) | 1.7 (1.3-2.1) | 0.7 (0.5-0.9) |
Abbreviations: CI: confidence interval; HR: hazard ratio. Model 1: unadjusted; Model 2: stratified by clinical site and adjusted for age, gender, race/ethnicity, education, BMI, SBP, Hgb, smoking, diabetes, and history of CVD; Model 3: Model 2 + urine Na, urine K, serum phosphate, FGF-23, serum bicarbonate, hsCRP, IL-1β, IL-6, TGF-β, TNF-α, hs-Troponin T, NTproBNP, urine NGAL, eGFR; Model 4: Model 3 + proteinuria.
Funding
- NIDDK Support