SAT-292 MR IMAGING BIOMARKERS OF DIABETIC KIDNEY DISEASE

Abstract

New drug development tools are needed for monitoring response to therapy in chronic kidney disease (CKD) with increased precision and repeatability. Magnetic resonance imaging (MRI) has great potential to non-invasively assess functional and morphologic changes in the kidney to improve patient selection and response monitoring in clinical trials for CKD. In this study, we have assessed multiple MRI variables in a diabetic nephropathy (DN) population. The study examined T2DM patients with an established diagnosis of DN and an eGFR between 15-60 ml/min/1.73 m2 as well as age- and gender-matched healthy controls. The analysis evaluated 20 CKD4 and 16 CKD3 patients and 20 healthy controls. Measured glomerular filtration rate (mGFR) was assessed using iohexol clearance. A wide range of non-contrast MRI techniques were assessed. MRI techniques included:R2* for assessment of renal hypoxiaApparent Diffusion Coefficient (ADC) as a potential measurement of renal fibrosisR1 for interstitial water balanceArterial Spin Labelling (ASL) for cortical perfusionRenal artery blood flow (peak systolic and end diastolic velocity, mean arterial flow, renal artery resistive index (RARI))Global perfusion (mean arterial flow/kidney volume)Kidney volume corrected for body surface area Tabled 1Healthy controlsCKD3CKD4correlation with mGFR (r2)p-value of correlationR2* cortex (s-1)17.3 (1.4)17.2 (1.6)17.0 (1.2)0.0060.59R2* medulla (s-1)26.0 (2.3)24.5 (3.7)22.8 (3.6)0.1240.008ADC cortex (mm2s-1 x 10-3)2.14 (0.24)1.96 (0.17)1.87 (0.32)0.1940.0007ADC medulla (mm2s-1 x 10-3)2.04 (0.27)1.86 (0.17)1.85 (0.23)0.1260.007R1 cortex (s-1)1.17 (0.10)1.02 (0.07)0.95 (0.12)0.493<0.0001R1 medulla (s-1)0.77 (0.05)0.78 (0.04)0.76 (0.07)0.0070.53ASL perfusion cortex (ml/100g/min)250 (61)144 (60)94 (51)0.519<0.0001Peak velocity max (cm/s)54.3 (8.3)59.8 (14.2)43.1 (11.1)0.1020.015Peak velocity min (cm/s)17.0 (3.9)11.3 (3.2)6.72 (2.45)0.618<0.0001RARI0.68 (0.06)0.81 (0.06)0.84 (0.06)0.576<0.0001Mean arterial flow (ml/s)9.43 (1.76)6.39 (1.46)4.30 (1.28)0.725<0.0001PC Perfusion (ml/100g/min)458 (54)339 (54)266 (86)0.616<0.0001Kidney volume/BSA (ml)63.0 (7.4)56.7 (14.8)49.9 (11.0)0.1790.0009 Open table in a new tab Several of the measured MRI variables correlate strongly with mGFR, indicating that these biomarkers are biologically relevant while providing additional information on pathophysiology. Given the known relationship between MRI biomarkers and mGFR plus the intra-subject CoV, the number of subjects needed to detect, for example, a 2 ml/min/1.73m2change in mGFR can be calculated.