Is mildly reduced kidney function linked to inflammation?
As kidney function declines, markers of inflammation and blood clotting rise steadily, and this is visible even in people without chronic kidney disease when kidney function is measured with cystatin C.
Source
Association of kidney function with inflammatory and procoagulant markers in a diverse cohort: a cross-sectional analysis from the Multi-Ethnic Study of Atherosclerosis (MESA)
Study at a glance
- Design
- Cross-sectional — Baseline (single time point) analysis of fasting blood and urine samples from a US multi-ethnic cohort; partial correlations and linear regression of biomarkers on cystatin C and on eGFR.
- N
- N=6814 · 6,814 MESA participants; CRP, IL-6, fibrinogen and factor VIII were measured in everyone, but ICAM-1 only in 2,614 people and TNF-αR1 only in a random subset of 995.
- Population
- Adults aged 45 to 84 from six US communities who identified as white, African-American, Hispanic or Chinese-American and had no clinical cardiovascular disease.
- Outcome
- Levels of CRP, IL-6, TNF-α receptor 1, ICAM-1, fibrinogen and factor VIII in relation to kidney function measured by cystatin C and by creatinine-based eGFR.
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What they did
The researchers used baseline blood tests from 6,814 middle-aged and older adults in the Multi-Ethnic Study of Atherosclerosis, none of whom had heart disease. They measured kidney function two ways: the blood protein cystatin C and the standard creatinine-based estimated glomerular filtration rate (eGFR). They then tested how each measure related to six inflammatory and procoagulant biomarkers, adjusting for age, sex, ethnicity and body mass index, separately in people with and without chronic kidney disease (eGFR below 60).
What they found
About 10% of participants had chronic kidney disease. Cystatin C was significantly correlated with all six biomarkers both in people with and without chronic kidney disease, and average biomarker levels climbed across each fifth of the cystatin C distribution. Creatinine-based eGFR tracked most biomarkers only in people with chronic kidney disease; above that threshold it was linked only to TNF-α receptor 1, which had the strongest correlation of all. The cystatin C links with CRP, IL-6, ICAM-1 and factor VIII differed by race/ethnicity, being stronger in white participants.
The limits
What it doesn't show
Because everything was measured at one time point, the study cannot say whether poorer kidney function causes inflammation or inflammation damages the kidneys. There was no gold-standard measured GFR, so the authors cannot fully rule out that cystatin C is tied to inflammation for reasons other than kidney filtration. TNF-α receptor 1 may simply rise because the kidney clears it, which is not the same as the body being more inflamed. The race/ethnicity differences may partly reflect assay or equation limitations rather than biology.
Key terms
- Cystatin C
- A small protein made by all nucleated cells and filtered by the kidneys; its blood level rises as kidney filtration falls and depends less on muscle mass than creatinine does.
- eGFR (estimated glomerular filtration rate)
- An estimate of how much blood the kidneys filter per minute, calculated here from serum creatinine plus age, sex and race using the MDRD equation.
- Chronic kidney disease (CKD)
- In this study, defined simply as an eGFR below 60 mL/min/1.73 m2.
- Procoagulant marker
- A blood protein, such as fibrinogen or factor VIII, whose higher levels favour clot formation.
- Partial correlation
- The correlation between two variables after statistically removing the influence of other variables such as age and sex.
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Common questions
Why use cystatin C instead of the usual creatinine test?
Creatinine-based eGFR is imprecise when kidney function is near normal because creatinine also depends on muscle mass and age. Cystatin C can pick up small differences in that range, which is why it revealed associations the creatinine test missed.
Does this mean inflammation causes kidney disease?
No. The data are cross-sectional, so the direction could run either way, or a third factor could drive both. A longitudinal study following people over time would be needed.
Why does this matter for heart disease?
Inflammatory and clotting markers such as CRP and fibrinogen are linked to cardiovascular disease, so a gradual rise with declining kidney function could help explain why even mild kidney impairment carries cardiovascular risk.
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