Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with CKD

Abstract

Key Points:

1. Lower baseline apparent diffusion coefficient, indicative of greater cortical fibrosis, correlated with higher baseline concentrations of serum markers of inflammation.

2. No association between baseline cortical R2* and baseline serum markers of inflammation were found.

3. Baseline kidney functional magnetic resonance imaging biomarkers of fibrosis and oxygenation were not associated with changes in inflammatory markers over time, which may be due to small changes in kidney function in the study.

Background: Greater fibrosis and decreased oxygenation may amplify systemic inflammation, but data on the associations of kidney functional magnetic resonance imaging (fMRI) measurements of fibrosis (apparent diffusion coefficient [ADC]) and oxygenation (relaxation rate [R2*]) with systemic markers of inflammation are limited.

Methods: We evaluated associations of baseline kidney fMRI-derived ADC and R2* with baseline and follow-up serum IL-6 and C-reactive protein (CRP) in 127 participants from the CKD Optimal Management with Binders and NicotinamidE trial, a randomized, 12-month trial of nicotinamide and lanthanum carbonate versus placebo in individuals with CKD stages 3–4. Cross-sectional analyses of baseline kidney fMRI biomarkers and markers of inflammation used multivariable linear regression. Longitudinal analyses of baseline kidney fMRI biomarkers and change in markers of inflammation over time used linear mixed-effects models.

Results: Mean±SD eGFR, ADC, and R2* were 32.2±8.7 ml/min per 1.73 m², 1.46±0.17×10⁻³ mm²/s, and 20.3±3.1 s⁻¹, respectively. Median (interquartile range) IL-6 and CRP were 3.7 (2.4–4.9) pg/ml and 2.8 (1.2–6.3) mg/L, respectively. After multivariable adjustment, IL-6 and CRP were 13.1% and 27.3% higher per 1 SD decrease in baseline cortical ADC, respectively. Baseline cortical R2* did not have a significant association with IL-6 or CRP. Mean annual IL-6 and CRP slopes were 0.98 pg/ml per year and 0.91 mg/L per year, respectively. Baseline cortical ADC and R2* did not have significant associations with change in IL-6 or CRP over time.

Conclusions: Lower cortical ADC, suggestive of greater fibrosis, was associated with higher systemic inflammation. Baseline kidney fMRI biomarkers did not associate with changes in systemic markers of inflammation over time.

Trial registration: ClinicalTrials.gov NCT02258074.

Graphical abstract

Figure 1

Baseline cortical ADC correlates with baseline serum IL-6 and CRP concentrations. Scatterplots demonstrate a negative correlation between cortical ADC measurements, as assessed by diffusion-weighted MRI, and baseline IL-6 (r_s=−0.20; P = 0.023) and baseline CRP (r_s=−0.22, P = 0.015). ADC, apparent diffusion coefficient; CRP, C-reactive protein; MRI, magnetic resonance imaging.

Figure 2

Baseline cortical R2* does not correlate with baseline serum IL-6 and CRP concentrations. Scatterplots demonstrate no correlation between relaxation rate (R2*) measurements, as assessed by BOLD MRI, and baseline IL-6 (r_s=−0.087; P = 0.33) and baseline CRP (r_s=0.027, P = 0.76). BOLD, blood oxygen level–dependent.