Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD

Abstract

Background and objectives: Kidney functional magnetic resonance imaging (MRI) requires further investigation to enhance the noninvasive identification of patients at high risk of CKD progression.

Design, setting, participants, & measurements: In this exploratory study, we obtained baseline diffusion-weighted and blood oxygen level-dependent MRI in 122 participants of the CKD Optimal Management with Binders and Nicotinamide trial, which was a multicenter, randomized, double-blinded, 12-month, four-group parallel trial of nicotinamide and lanthanum carbonate versus placebo conducted in individuals with eGFR 20-45 ml/min per 1.73 m2. Lower values of apparent diffusion coefficient (ADC) on diffusion-weighted MRI may indicate increased fibrosis, and higher values of relaxation rate (R2*) on blood oxygen level-dependent MRI may represent decreased oxygenation. Because there was no effect of active treatment on eGFR over 12 months, we tested whether baseline kidney functional MRI biomarkers were associated with eGFR decline in all 122 participants. In a subset of 87 participants with 12-month follow-up MRI data, we evaluated whether kidney functional MRI biomarkers change over time.

Results: Mean baseline eGFR was 32±9 ml/min per 1.73 m2, and mean annual eGFR slope was -2.3 (95% confidence interval [95% CI], -3.4 to -1.1) ml/min per 1.73 m2 per year. After adjustment for baseline covariates, baseline ADC was associated with change in eGFR over time (difference in annual eGFR slope per 1 SD increase in ADC: 1.3 [95% CI, 0.1 to 2.5] ml/min per 1.73 m2 per year, ADC×time interaction P=0.04). This association was no longer significant after further adjustment for albuminuria (difference in annual eGFR slope per 1 SD increase in ADC: 1.0 (95% CI, -0.1 to 2.2) ml/min per 1.73 m2 per year, ADC×time interaction P=0.08). There was no significant association between baseline R2* and change in eGFR over time. In 87 participants with follow-up functional MRI, ADC and R2* values remained stable over 12 months (intraclass correlation: 0.71 and 0.68, respectively).

Conclusions: Baseline cortical ADC was associated with change in eGFR over time, but this association was not independent of albuminuria. Kidney functional MRI biomarkers remained stable over 1 year.

Clinical trial registry name and registration number: CKD Optimal Management with Binders and Nicotinamide (COMBINE), NCT02258074.

Keywords: Biomarkers; Chronic; Diffusion Magnetic Resonance Imaging; ESRD; Follow-Up Studies; Lanthanum; MRI; Magnetic Resonance Imaging; Niacinamide; Oxygen; Renal Insufficiency; albuminuria; chronic kidney disease; fibrosis; glomerular filtration rate; hypoxia; lanthanum carbonate.

Copyright © 2020 by the American Society of Nephrology.

Figures

Graphical abstract

Figure 1.

Cortical ADC, as assessed by diffusion-weighted MRI, correlates with annual patient-specific eGFR slope. Scatterplots demonstrate a positive correlation between cortical apparent diffusion coefficient (ADC) measurements and annual patient-specific eGFR (r=0.20; P=0.03) and no association between cortical relaxation rate (R2*) measurements and annual patient-specific eGFR slope (r=0.07; P=0.44).