TY - JOUR
T1 - Associations of Kidney Functional Magnetic Resonance Imaging Biomarkers with Markers of Inflammation in Individuals with CKD
AU - Trujillo, Jacquelyn
AU - Alotaibi, Manal
AU - Seif, Nay
AU - Cai, Xuan
AU - Larive, Brett
AU - Gassman, Jennifer
AU - Raphael, Kalani L.
AU - Cheung, Alfred K.
AU - Raj, Dominic S.
AU - Fried, Linda F.
AU - Sprague, Stuart M.
AU - Block, Geoffrey
AU - Chonchol, Michel
AU - Middleton, John Paul
AU - Wolf, Myles S
AU - Ix, Joachim H.
AU - Prasad, Pottumarthi
AU - Isakova, Tamara
AU - Srivastava, Anand
N1 - Publisher Copyright:
© 2024 Lippincott Williams and Wilkins. All rights reserved.
PY - 2024/5/1
Y1 - 2024/5/1
N2 - Key PointsLower baseline apparent diffusion coefficient, indicative of greater cortical fibrosis, correlated with higher baseline concentrations of serum markers of inflammation.No association between baseline cortical R2* and baseline serum markers of inflammation were found.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.BackgroundGreater 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.MethodsWe 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.ResultsMean±SD eGFR, ADC, and R2* were 32.2±8.7 ml/min per 1.73 m2, 1.46±0.17×10-3mm2/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.ConclusionsLower 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.
AB - Key PointsLower baseline apparent diffusion coefficient, indicative of greater cortical fibrosis, correlated with higher baseline concentrations of serum markers of inflammation.No association between baseline cortical R2* and baseline serum markers of inflammation were found.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.BackgroundGreater 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.MethodsWe 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.ResultsMean±SD eGFR, ADC, and R2* were 32.2±8.7 ml/min per 1.73 m2, 1.46±0.17×10-3mm2/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.ConclusionsLower 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.
KW - CKD
KW - chronic inflammation
KW - fibrosis
KW - hypoxia
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U2 - 10.34067/KID.0000000000000437
DO - 10.34067/KID.0000000000000437
M3 - Article
C2 - 38570905
AN - SCOPUS:85194972625
SN - 2641-7650
VL - 5
SP - 681
EP - 689
JO - Kidney360
JF - Kidney360
IS - 5
ER -