TY - JOUR
T1 - Kidney functional magnetic resonance imaging and change in eGFR in individuals with CKD
AU - Srivastava, Anand
AU - Cai, Xuan
AU - Lee, Jungwha
AU - Li, Wei
AU - Larive, Brett
AU - Kendrick, Cynthia
AU - Gassman, Jennifer J.
AU - Middleton, John P.
AU - Carr, James
AU - Raphael, Kalani L.
AU - Cheung, Alfred K.
AU - Raj, Dominic S.
AU - Chonchol, Michel B.
AU - Fried, Linda F.
AU - Block, Geoffrey A.
AU - Sprague, Stuart M.
AU - Wolf, Myles
AU - Ix, Joachim H.
AU - Prasad, Pottumarthi V.
AU - Isakova, Tamara
N1 - Funding Information:
Dr. Block reports grants from National Institutes of Health (NIH) during conduct of the study, other funding from Reata Pharmaceuticals, grants, personal fees, and nonfinancial support from Akebia, Inc., and Ardelyx, Inc., personal fees and nonfiancial support from Keryx, Inc., Kyowa Hakko Kirin, and OPKO, outside the submitted work. Dr. Carr reports other financial support from Circle and GE Healthcare, and grants from Bayer, Guerbet, and Siemens, outside the submitted work. Dr. Cheung reports grants from NIH, during the conduct of the study. Dr. Chonchol reports grants from Otsuka, Sanofi, and Kadmon, outside the submitted work, and grants from NIH/NIDDK during conduct of the study. Dr. Isakova reports nonfinancial support from Shire during the conduct of the study, and personal fees from Kirin and Guidepoint Global, outside the submitted work. Dr. Ix reports grants from NIDDK during the conduct of the study and grants from Baxter International, outside the submitted work. Dr. Middleton reports grants and personal fees from Relypsa, personal fees from AstraZeneca, Tricida, and NIDDK, outside the submitted work. Dr. Raphael reports grants from NIH and U.S. Department of Veterans Affairs, during the conduct of the study. Dr. Sprague reports grants from NIH, during the conduct of the study. Dr. Srivastava reports personal fees from Horizon Pharma, PLC, and CVS Caremark, outside the submitted work. Dr. Wolf reports personal fees from Akebia, Amag, Amgen, Ardelyx, Diasorin, Keryx, Lutipold, and Sanofi, and grants from Shire, outside the submitted work. All remaining authors have nothing to disclose.
Funding Information:
The COMBINE trial is supported by NIH grants U01DK099877, U01DK097093, U01DK099930, U01DK099933, U01DK099924, and R01DK102438 (to Dr. Isakova). Work also supported in part by NIH grant R01DK093793 (to Dr. Prasad). Dr. Isakova is also supported by NIH grants R01DK110087, U01DK099930, and K24HL150235. Dr. Srivastava is supported by NIH grant K23DK120811, the Dixon Translational Research Grants Initiative at Northwestern Medicine and the Northwestern University Clinical and Translational Sciences Institute (UL1TR001422), and a Pilot & Feasibility Grant from the Center for Kidney Research and Therapeutics at Northwestern UniversityFeinbergSchoolofMedicine.Dr.IsakovaandDr.Srivastava are supported by core resources from the George M. O’Brien Kidney Research Center at Northwestern University (NU-GoKIDNEY; NIH grant P30DK114857).
Publisher Copyright:
© 2020 by the American Society of Nephrology.
PY - 2020/6/8
Y1 - 2020/6/8
N2 - 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 1.73m2. 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 therewas 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 1.73m2 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 1.73m2 per year, ADC×time interaction P50.04). 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.
AB - 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 1.73m2. 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 therewas 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 1.73m2 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 1.73m2 per year, ADC×time interaction P50.04). 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.
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U2 - 10.2215/CJN.13201019
DO - 10.2215/CJN.13201019
M3 - Article
C2 - 32345747
AN - SCOPUS:85086935429
VL - 15
SP - 776
EP - 783
JO - Clinical journal of the American Society of Nephrology : CJASN
JF - Clinical journal of the American Society of Nephrology : CJASN
SN - 1555-9041
IS - 6
ER -