Multi-Parametric Evaluation of Chronic Kidney Disease by MRI: A Preliminary Cross-Sectional Study

Abstract

Background: The current clinical classification of chronic kidney disease (CKD) is not perfect and may be overestimating both the prevalence and the risk for progressive disease. Novel markers are being sought to identify those at risk of progression. This preliminary study evaluates the feasibility of magnetic resonance imaging based markers to identify early changes in CKD.

Methods: Fifty-nine subjects (22 healthy, 7 anemics with no renal disease, 30 subjects with CKD) participated. Data using 3D volume imaging, blood oxygenation level dependent (BOLD) and Diffusion MRI was acquired. BOLD MRI acquisition was repeated after 20 mg of iv furosemide.

Results: Compared to healthy subjects, those with CKD have lower renal parenchymal volumes (329.6±66.4 vs. 257.1±87.0 ml, p<0.005), higher cortical R2* values (19.7±3.2 vs. 23.2±6.3 s(-1), p = 0.013) (suggesting higher levels of hypoxia) and lower response to furosemide on medullary R2* (6.9±3.3 vs. 3.1±7.5 s(-1), p = 0.02). All three parameters showed significant correlation with estimated glomerular filtration rate (eGFR). When the groups were matched for age and sex, cortical R2* and kidney volume still showed significant differences between CKD and healthy controls. The most interesting observation is that a small number of subjects (8 of 29) contributed to the increase in mean value observed in CKD. The difference in cortical R2* between these subjects compared to the rest were highly significant and had a large effect size (Cohen's d = 3.5). While highly suggestive, future studies may be necessary to verify if such higher levels of hypoxia are indicative of progressive disease. Diffusion MRI showed no differences between CKD and healthy controls.

Conclusions: These data demonstrate that BOLD MRI can be used to identify enhanced hypoxia associated with CKD and the preliminary observations are consistent with the chronic hypoxia model for disease progression in CKD. Longitudinal studies are warranted to further verify these findings and assess their predictive value.

Fig 1. Box-and-whisker plots illustrating the distribution of R2* values in both CKD and control groups.

As shown in the annotations, the box-and-whisker plots represent five key values from the distribution (median (red line), 1^st quartile (q1), 3^rd quartile (q3), minimum and maximum values). For a normal distribution, the median value would be close to the center of the box. The plot for the CKD_All group clearly is skewed with the upper half showing much broader distribution. Also included are distributions separated by a threshold value of 27 s⁻¹ (> maximum value in the control group). The CKD_Low group appears to be similar to the control group, while CKD_High is distinctly different.

Fig 2. illustrates anatomic MRI and R2* maps from a representative subject from control, CKD_Low and CKD_High R2* groups.

The R2* maps of the kidneys are overlaid on the anatomic image and the color bar indicates high levels of hypoxia in red and progressively lower values with orange, yellow, green and blue. Note R2* values are low in the cortex of both the control and subject with CKD even though the eGFR values are significantly different, while the subject with CKD_High clearly shows higher R2* values, even though his/her eGFR values are high and comparable to the control subject. We have also included R2* values for muscle to rule out any systematic bias in R2* values in CKD_High.