Abstract: FR-PO428
High Repeatability and Sensitivity of MR Imaging Biomarkers of CKD
Session Information
- Diabetic Kidney Disease: Clinical - I
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 602 Diabetic Kidney Disease: Clinical
Authors
- Hockings, Paul, Antaros Medical, Molndal, Sweden
- Makvandi, Kianoush, Sahlgrenska University Hospital, Gothenburg, Sweden
- Unnerstall, Tim, Sahlgrenska University Hospital, Gothenburg, Sweden
- Leonhardt, Henrik, Sahlgrenska University Hospital, Gothenburg, Sweden
- Frödén löwenmark, Anna, Antaros Medical, Molndal, Sweden
- Jarl, Lisa, Antaros Medical, Molndal, Sweden
- Englund, Camilla, Antaros Medical, Molndal, Sweden
- Francis, Susan, Sir Peter Mansfield Magnetic Resonance Center,, Nottingham, United Kingdom
- Jensen, Gert, Sahlgrenska University Hospital, Gothenburg, Sweden
- Erlandsson, Fredrik, AstraZeneca, Gaithersburg, Maryland, United States
- Sundgren andersson, Anna K., AstraZeneca, Gaithersburg, Maryland, United States
- Hulthe, Johannes, Antaros Medical, Molndal, Sweden
- Baid-Agrawal, Seema, Sahlgrenska University Hospital, Gothenburg, Sweden
Background
New drug development tools are needed for monitoring response to therapy in chronic kidney disease (CKD) with increased precision and repeatability. We evaluated 18 CKD4 and 10 CKD3 subjects with type 2 diabetic nephropathy, and 20 age- and sex-matched healthy volunteers with a wide range of non-contrast magnetic resonance Imaging (MRI) techniques. Measured GFR (mGFR) was assessed using iohexol clearance. Half of the subjects were re-scanned after 2-4 weeks to assess repeatability.
Methods
MRI techniques included R2* for assessment of renal hypoxia, apparent diffusion coefficient (ADC) for fibrosis, R1for interstitial water balance, arterial spin labelling (ASL) for cortical perfusion, renal artery blood flow (peak systolic velocity, end diastolic velocity, mean arterial flow, and renal artery resistive index (RARI)), global perfusion (mean arterial flow/kidney volume), and kidney volume corrected for body surface area.
Results
see Table
Conclusion
Several MR parameters 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, e.g. a 2 ml/min/1.73m2 change in mGFR can be calculated. To conclude, a 30 min non-contrast MRI protocol characterising important aspects of CKD with a high repeatability and sensitivity was identified. Repeatability data allows future CKD intervention studies to be correctly powered.
| Healthy Controls | CKD Stage 3 | CKD Stage 4 | Correlation with mGFR (r) | p-value of correlation | Coefficient of variation | |
| R2* cortex (s-1) | 18.0 (1.4) | 17.6 (1.9) | 17.4 (1.4) | 0.15 | 0.33 | 0.04 |
| R2* medulla (s-1) | 28.3 (3.1) | 24.5 (3.6) | 24.3 (3.9) | 0.44 | 0.002 | 0.05 |
| ADC cortex (mm2s-1 x 10-3) | 2.48 (0.17) | 2.47 (0.17) | 2.21 (0.24) | 0.44 | 0.002 | 0.06 |
| ADC medulla (mm2s-1 x 10-3) | 2.36 (0.17) | 2.29 (0.21) | 2.22 (0.22) | 0.29 | 0.051 | 0.07 |
| R1 cortex (s-1) | 1.10 (0.17) | 0.97 (0.23) | 0.97 (0.18) | 0.36 | 0.011 | 0.08 |
| R1 medulla (s-1) | 0.69 (0.03) | 0.73 (0.04) | 0.74 (0.09) | 0.38 | 0.008 | 0.06 |
| ASL perfusion cortex (ml/100g/min) | 206 (65) | 99 (63) | 76 (59) | 0.65 | <.0001 | 0.28 |
| Peak systolic velocity (cm/s) | 54.3 (8.3) | 60.7 (18.2) | 42.1 (11.2) | 0.35 | 0.015 | 0.09 |
| End diastolic velocity (cm/s) | 17.0 (3.9) | 10.9 (2.4) | 6.39 (2.26) | 0.81 | <.0001 | 0.11 |
| RARI | 0.68 (0.06) | 0.81 (0.05) | 0.84 (0.06) | 0.79 | <.0001 | 0.03 |
| Mean arterial flow (ml/s) | 0.43 (1.76) | 6.31 (1.50) | 4.15 (1.24) | 0.86 | <.0001 | 0.07 |
| Global Perfusion (ml/100g/min) | 436 (59) | 346 (53) | 248 (85) | 0.76 | <.0001 | 0.08 |
| Kidney volume (ml) | 66.5 (9.6) | 56.6 (18.4) | 52.5 (11.5) | 0.448 | 0.001 | 0.06 |
mean (SD)
Funding
- Commercial Support – Antaros Medical; AstraZeneca