Abstract: PO2263
Inflammatory Biomarkers and Proteinuria Progression in CKD Patients: The CRIC Study
Session Information
- CKD: Associations and Electrolytes
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention
Authors
- Chen, Jing, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Hamm, L. Lee, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Batuman, Vecihi, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Geng, Siyi, Tulane University School of Medicine, New Orleans, Louisiana, United States
- Lash, James P., University of Illinois at Chicago, Chicago, Illinois, United States
- Hsu, Chi-yuan, University of California San Francisco, San Francisco, California, United States
- Rao, Panduranga S., Michigan Medicine and Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, Michigan, United States
- Anderson, Amanda Hyre, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
- Waikar, Sushrut S., Boston University, Boston, Massachusetts, United States
- Srivastava, Anand, Northwestern University, Evanston, Illinois, United States
- Horwitz, Edward J., MetroHealth Medical Center, Cleveland, Ohio, United States
- Rincon-Choles, Hernan, Cleveland Clinic, Cleveland, Ohio, United States
- Weir, Matthew R., University of Maryland Baltimore, Baltimore, Maryland, United States
- He, Hua, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
- Appel, Lawrence J., Johns Hopkins University School of Medicine, Baltimore, Maryland, United States
- He, Jiang, Tulane University School of Public Health and Tropical Medicine, New Orleans, Louisiana, United States
Background
Proteinuria progression is considered a surrogate endpoint for CKD progression. We studied prospective association of inflammatory biomarkers with proteinuria progression in the Chronic Renal Insufficiency Cohort (CRIC) Study participants.
Methods
The CRIC Study recruited 3939 CKD patients in the US. After excluding those without urine protein measures at baseline or follow-up and those with missing covariables at baseline, 3177 patients were included in this analysis. Proteinuria progression was defined as a ≥ 30% increase in urine protein-to-creatinine ratio (UPCR) from baseline and UPCR ≥150 mg/g at follow-up visits. Incident proteinuria was defined as UPCR ≥150 mg/g among patients without proteinuria at baseline. Cox proportional hazards models were used to examine multivariate association of inflammatory biomarkers with proteinuria progression and incidence, adjusting for age, sex, race, current smoking, body mass index, systolic blood pressure, total cholesterol, hemoglobin A1C, eGFR, baseline UPCR, and use of ACE-Is/ARBs, statins, and aspirin.
Results
Over a mean follow-up of 6.6 years, 1478 participants developed proteinuria progression and 625 participants developed proteinuria. Multivariable-adjusted hazard ratios (95% confidence intervals [CI]) of proteinuria progression for the highest quartile vs. lowest quartile of inflammatory biomarker levels were 1.20 (1.01-1.42; P=0.03) for fibrinogen, 1.21 (1.03-1.43; P=0.02) for interleukin-6 (IL-6), 1.54 (1.30-1.81; P<0.0001) for tumor necrosis factor-α (TNF-α), and 1.22 (1.04-1.42; P=0.01) for CXCL12. Among 1635 patients without baseline proteinuria, similar relationships of fibrinogen, IL-6, TNF-α and CXCL12 with incident proteinuria were identified. C-reactive protein, white blood cells, IL-1β, IL-1 receptor antagonist, fetuin-A, transforming growth factor-β, and fractalkine were not significantly associated with proteinuria progression or incidence.
Conclusion
Our findings suggest that higher levels of fibrinogen, IL-6, TNF-α, and CXCL12 are independently associated with proteinuria progression and incidence. Future studies may test whether targeting specific inflammatory pathways will improve proteinuria and reduce CKD progression.
Funding
- NIDDK Support