Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with Chronic Kidney Disease.

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 interleukin-6 (IL-6) and C-reactive protein (CRP) in 127 participants from the COMBINE trial, a randomized, 12-month trial of nicotinamide and lanthanum carbonate vs. 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/1.73m2, 1.46±0.17 x10-3 mm2/s, and 20.3±3.1 s-1, respectively. Median [IQR] IL-6 and CRP were 3.7 [2.4-4.9] pg/mL and 2.8 [1.2-6.3] mg/L. After multivariable adjustment, IL-6 and CRP were 13.1% and 27.3% higher per 1 SD decrease in baseline cortical ADC. 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.