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Published on: November 10, 2021
Inflammation and Progression of CKD: The CRIC Study
Richard L Amdur1, Harold I Feldman, Jayanta Gupta
1Due to the number of contributing authors, the affiliations are provided in the Supplemental Material .
Insights
High levels of fibrinogen and TNF-alpha, along with low serum albumin, predict faster kidney function decline in chronic kidney disease (CKD) patients. These biomarkers are crucial for understanding CKD progression.
Area of Science:
- Nephrology
- Biomarkers
- Chronic Kidney Disease (CKD) Research
Background:
- Chronic kidney disease (CKD) represents a significant global health challenge, contributing to substantial mortality and morbidity.
- Understanding the factors that drive CKD progression is critical for developing effective interventions.
Purpose of the Study:
- To investigate the association between plasma levels of various inflammatory markers and proteins with the progression of CKD.
- To identify key biomarkers that predict a decline in kidney function or end-stage renal disease (ESRD).
Main Methods:
- The study analyzed data from 3430 participants in the Chronic Renal Insufficiency Cohort (CRIC) study.
- Plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin were measured.
- Multivariable regression models were used to assess the association with CKD progression over a median follow-up of 6.3 years.
Main Results:
- Elevated plasma fibrinogen, IL-6, and TNF-α, along with lower serum albumin, were associated with a faster decline in estimated glomerular filtration rate (eGFR).
- After multivariable adjustment, higher quartiles of fibrinogen, IL-6, and TNF-α, and the lowest quartile of serum albumin, were significantly associated with CKD progression.
- Associations for fibrinogen, serum albumin, and TNF-α remained significant after further adjustment for albuminuria, though attenuated.
Conclusions:
- Elevated plasma fibrinogen and TNF-α, and decreased serum albumin, are independently associated with a more rapid loss of kidney function in patients with CKD.
- These biomarkers may serve as important indicators for predicting CKD progression.
- Further research can explore therapeutic strategies targeting these markers to slow CKD advancement.
Background And Objectives:
CKD is a global public health problem with significant mortality and morbidity.
Design, Setting, Participants, & Measurements:
We examined the multivariable association of plasma levels of IL-1, IL-1 receptor antagonist, IL-6, TNF-α, TGF-β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin with progression of CKD in 3430 Chronic Renal Insufficiency Cohort study participants.
Results:
Over a median follow-up time of 6.3 years, 899 participants reached the composite end point of ≥50% decline in eGFR from baseline or onset of ESRD. Elevated plasma levels of fibrinogen, IL-6, and TNF-α and lower serum albumin were associated with a greater decline in eGFR over time. After adjusting for demographics, BP, laboratory variables, medication use, and baseline eGFR, hazard ratios for the composite outcome were greater for the patients in the highest quartile of fibrinogen (hazard ratio, 2.05; 95% confidence interval, 1.64 to 2.55; P<0.001), IL-6 (hazard ratio, 1.44; 95% confidence interval, 1.17 to 1.77; P<0.01), and TNF-α (hazard ratio, 1.94; 95% confidence interval, 1.52 to 2.47; P<0.001) compared with those in the respective lowest quartiles. The hazard ratio was 3.48 (95% confidence interval, 2.88 to 4.21; P<0.001) for patients in the lowest serum albumin quartile relative to those in the highest quartile. When also adjusted for albuminuria, the associations of fibrinogen (hazard ratio, 1.49; 95% confidence interval, 1.20 to 1.86; P<0.001), serum albumin (hazard ratio, 1.52; 95% confidence interval, 1.24 to 1.87; P<0.001), and TNF-α (hazard ratio, 1.42; 95% confidence interval, 1.11 to 1.81; P<0.001) with outcome were attenuated but remained significant.
Conclusions:
Elevated plasma levels of fibrinogen and TNF-α and decreased serum albumin are associated with rapid loss of kidney function in patients with CKD.
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