Kidney Functional Magnetic Resonance Imaging and Change in eGFR in Individuals with CKD.

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 1.73 m2. 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 there was 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 1.73 m2 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 1.73 m2 per year, ADC×time interaction P=0.04). 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. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER CKD Optimal Management with Binders and Nicotinamide (COMBINE), NCT02258074.

[1]  Long Jiang Zhang,et al.  Combination of Functional Magnetic Resonance Imaging and Histopathologic Analysis to Evaluate Interstitial Fibrosis in Kidney Allografts. , 2019, Clinical journal of the American Society of Nephrology : CJASN.

[2]  S. Francis,et al.  Quantitative assessment of renal structural and functional changes in chronic kidney disease using multi-parametric magnetic resonance imaging , 2019, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[3]  A. Cheung,et al.  Effects of Nicotinamide and Lanthanum Carbonate on Serum Phosphate and Fibroblast Growth Factor-23 in CKD: The COMBINE Trial. , 2019, Journal of the American Society of Nephrology : JASN.

[4]  M. Burnier,et al.  Acute hyperglycemia increases renal tissue oxygenation as measured by BOLD-MRI in healthy overweight volunteers. , 2019, Diabetes research and clinical practice.

[5]  B. Hack,et al.  Cortical Perfusion and Tubular Function as Evaluated by Magnetic Resonance Imaging Correlates with Annual Loss in Renal Function in Moderate Chronic Kidney Disease , 2019, American Journal of Nephrology.

[6]  Tsutomu Inoue,et al.  Reduced oxygenation but not fibrosis defined by functional magnetic resonance imaging predicts the long-term progression of chronic kidney disease. , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[7]  Xavier Golay,et al.  Magnetic resonance imaging biomarkers for chronic kidney disease: a position paper from the European Cooperation in Science and Technology Action PARENCHIMA , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[8]  Anna Caroli,et al.  Functional magnetic resonance imaging of the kidneys: where do we stand? The perspective of the European COST Action PARENCHIMA , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  Iosif A Mendichovszky,et al.  Renal blood oxygenation level-dependent magnetic resonance imaging to measure renal tissue oxygenation: a statement paper and systematic review , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[10]  Nicolas Grenier,et al.  Diffusion-weighted magnetic resonance imaging to assess diffuse renal pathology: a systematic review and statement paper , 2018, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  A. Cheung,et al.  Multicenter Study Evaluating Intrarenal Oxygenation and Fibrosis Using Magnetic Resonance Imaging in Individuals With Advanced CKD , 2018, Kidney international reports.

[12]  M. Stuber,et al.  Reduced cortical oxygenation predicts a progressive decline of renal function in patients with chronic kidney disease. , 2018, Kidney international.

[13]  Xiaoqiang Ding,et al.  Intravoxel incoherent motion diffusion-weighted imaging for the assessment of renal fibrosis of chronic kidney disease: A preliminary study. , 2018, Magnetic resonance imaging.

[14]  Wei Li,et al.  Renal Blood Oxygenation Level-Dependent Magnetic Resonance Imaging: A Sensitive and Objective Analysis , 2015, Investigative radiology.

[15]  Wei Li,et al.  Multi-Parametric Evaluation of Chronic Kidney Disease by MRI: A Preliminary Cross-Sectional Study , 2015, PloS one.

[16]  A. Cheung,et al.  Rationale and Approaches to Phosphate and Fibroblast Growth Factor 23 Reduction in CKD. , 2015, Journal of the American Society of Nephrology : JASN.

[17]  Y. Li,et al.  Assessment of renal fibrosis in chronic kidney disease using diffusion-weighted MRI. , 2014, Clinical radiology.

[18]  Minming Zhang,et al.  Diffusion-weighted imaging in assessing renal pathology of chronic kidney disease: A preliminary clinical study. , 2014, European journal of radiology.

[19]  Chapter 2: Definition, identification, and prediction of CKD progression , 2012, Kidney international supplements.

[20]  J. Neugarten Renal BOLD-MRI and assessment for renal hypoxia. , 2012, Kidney international.

[21]  Tsutomu Inoue,et al.  Noninvasive evaluation of kidney hypoxia and fibrosis using magnetic resonance imaging. , 2011, Journal of the American Society of Nephrology : JASN.

[22]  J. Stockman,et al.  A New Equation to Estimate Glomerular Filtration Rate , 2011 .

[23]  O. Togao,et al.  Assessment of renal fibrosis with diffusion-weighted MR imaging: study with murine model of unilateral ureteral obstruction. , 2010, Radiology.

[24]  M. Burnier,et al.  Effect of Sodium Loading/Depletion on Renal Oxygenation in Young Normotensive and Hypertensive Men , 2010, Hypertension.

[25]  B. Kestenbaum,et al.  Rapid decline of kidney function increases cardiovascular risk in the elderly. , 2009, Journal of the American Society of Nephrology : JASN.

[26]  C. Schmid,et al.  A new equation to estimate glomerular filtration rate. , 2009, Annals of internal medicine.

[27]  J. Norman,et al.  Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. , 2008, Kidney international.

[28]  S. Shankland,et al.  Proteinuria in diabetic kidney disease: a mechanistic viewpoint. , 2008, Kidney international.

[29]  Pottumarthi V. Prasad,et al.  Evaluation of Intra-Renal Oxygenation by BOLD MRI , 2006, Nephron Clinical Practice.

[30]  C. Orphanides,et al.  Progressive renal disease: the chronic hypoxia hypothesis. , 1998, Kidney international. Supplement.

[31]  R R Edelman,et al.  Noninvasive evaluation of intrarenal oxygenation with BOLD MRI. , 1996, Circulation.

[32]  D. Le Bihan,et al.  Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging. , 1988, Radiology.