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Kidney Week

Abstract: TH-PO1125

Magnetic Resonance Measurements of Intra-Renal Oxygenation and Fibrosis and Change in Kidney Function: COMBINE Trial

Session Information

Category: CKD (Non-Dialysis)

  • 1902 CKD (Non-Dialysis): Clinical, Outcomes, and Trials

Authors

  • Isakova, Tamara, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, United States
  • Kendrick, Cynthia A., Cleveland Clinic, Cleveland, Ohio, United States
  • Larive, Brett, Cleveland Clinic, Cleveland, Ohio, United States
  • Gassman, Jennifer J., Cleveland Clinic, Cleveland, Ohio, United States
  • Raphael, Kalani L., VA Salt Lake City Health Care System, Salt Lake City, Utah, United States
  • Raj, Dominic S., GWU Medical Faculty Associates, Washington, District of Columbia, United States
  • Fried, Linda F., VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania, United States
  • Abbott, Kevin C., The National Institutes of Health, NIDDK, Bethesda, Maryland, United States
  • Sprague, Stuart M., NorthShore University HealthSystem University of Chicago Pritzker School of Medicine, Chicago, Illinois, United States
  • Wolf, Myles, Duke University, Durham, North Carolina, United States
  • Block, Geoffrey A., Colorado Kidney Care, Denver, Colorado, United States
  • Cheung, Alfred K., University of Utah, Salt Lake City, Utah, United States
  • Ix, Joachim H., UCSD, San Diego, California, United States
  • Middleton, John Paul, Duke University, Durham, North Carolina, United States
  • Mendley, Susan R., NIDDK/NIH, Bethesda, Maryland, United States
  • Prasad, Pottumarthi V., NorthShore University HealthSystems, Evanston, Illinois, United States

Group or Team Name

  • CKD Optimal Management with Binders and NicotinamidE (COMBINE) Investigators
Background

Prior studies report differences between health and CKD in intrarenal oxygenation and fibrosis, as measured by MRI. Data on longitudinal relationships of MRI biomarkers with change in eGFR are limited.

Methods

We obtained baseline and follow up renal MRI in 87 of 205 participants of the COMBINE trial, which was a randomized, double-blinded, 12-month, 4-group parallel study of nicotinamide and lanthanum carbonate vs. placebo in individuals with CKD stages 3-4. Relaxation rate R2* was the BOLD MRI index; higher values of R2* may represent decreased oxygenation. Apparent diffusion coefficient (ADC) was the diffusion MRI index; lower values of ADC may be due to greater fibrosis. We evaluated longitudinal data from all 87 participants to test the hypotheses that higher R2* values and lower ADC values are associated with decline in eGFR.

Results

The mean baseline eGFR was 32.6±7.58 and the mean subject-specific eGFR slope was -2.1±4.15 ml/min/1.73 m2/year. We observed minimal changes in R2* and ADC values over 12 months. Baseline R2* and ADC did not correlate with eGFR slope (R2* cortex: r=0.03; p=0.76; ADC cortex: r=0.17, p=0.12). However, change in ADC from baseline to end of study correlated with eGFR slope (r=0.22; p=0.04). Participants with diabetes and rapid eGFR decline (>3 ml/min/1.73 m2/year) had the lowest baseline and follow up ADC values and individuals without diabetes and without rapid eGFR decline had the highest values (Table).

Conclusion

R2* and ADC remained stable during 12 months. While R2* did not correlate with change in eGFR, change in ADC correlated with faster decline in eGFR, and individuals with diabetes and rapid loss of eGFR had the lowest baseline and follow up ADC. Larger studies with longer duration are needed to further test BOLD and diffusion MRI measurements as possible imaging biomarkers of kidney function.

Funding

  • NIDDK Support