Kidney Energetics and Cyst Burden in Autosomal Dominant Polycystic Kidney Disease: A Pilot Study.

RATIONALE & OBJECTIVE: In this pilot study, we hypothesized that autosomal dominant polycystic kidney disease (ADPKD) is characterized by impaired kidney oxidative metabolism that associates with kidney size and cyst burden. STUDY DESIGN: Cross-sectional study. SETTING & PARTICIPANTS: Twenty adults with ADPKD (age, 31±6 years; 65% women; body mass index [BMI], 26.8 [22.7-30.4] kg/m2; estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103±18mL/min/1.73m2; height-adjusted total kidney volume [HTKV], 731±370mL/m; Mayo classifications 1B [5%], 1C [42%], 1D [21%], and 1E [32%]) and 11 controls in normal weight category (NWC) (age, 25±3 years; 45% women; BMI, 22.5 [21.7-24.2] kg/m2; eGFR, 113±15mL/min/1.73m2; HTKV, 159±31mL/m) at the University of Colorado Anschutz Medical Campus. PREDICTORS: ADPKD status (yes/no) and severity (Mayo classifications). OUTCOME: HTKV and cyst burden by magnetic resonance imaging, kidney oxidative metabolism, and perfusion by 11C-acetate positron emission tomography/computed tomography, insulin sensitivity by hyperinsulinemic-euglycemic clamps (presented as ratio of M-value of steady state insulin concentration [M/I]). ANALYTICAL APPROACH: For categorical variables, χ2/Fisher's exact tests, and for continuous variables t tests/Mann-Whitney U tests. Pearson correlation was used to estimate the relationships between variables. RESULTS: Compared with NWC individuals, the participants with ADPKD exhibited lower mean±SD M/I ratio (0.586±0.205 vs 0.424±0.171 [mg/kg lean/min]/(µIU/mL), P=0.04), lower median cortical perfusion (1.93 [IQR, 1.80-2.09] vs 0.68 [IQR, 0.47-1.04] mL/min/g, P<0.001) and lower median total kidney oxidative metabolism (0.17 [IQR, 0.16-0.19] vs. 0.14 [IQR, 0.12-0.15] min-1, P=0.001) in voxel-wise models excluding cysts. HTKV correlated inversely with cortical perfusion (r: -0.83, P < 0.001), total kidney oxidative metabolism (r: -0.61, P<0.001) and M/I (r: -0.41, P = 0.03). LIMITATIONS: Small sample size and cross-sectional design. CONCLUSIONS: Adults with ADPKD and preserved kidney function exhibited impaired renal perfusion and kidney oxidative metabolism across a wide range of cysts and kidney enlargements. FUNDING: Grants from government (National Institutes of Health, Centers for Disease Control and Prevention) and not-for-profit (JDRF) entities. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study numbers NCT04407481 and NCT04074668. PLAIN-LANGUAGE SUMMARY: In our study, we explored how a common genetic kidney condition, autosomal dominant polycystic kidney disease (ADPKD), relates to kidney metabolism. ADPKD leads to the growth of numerous cysts in the kidneys, which can impact their ability to work properly. We wanted to understand the kidneys' ability to process oxygen and blood flow in ADPKD. Our approach involved using advanced imaging techniques to observe kidney metabolism and blood flow in people with ADPKD compared with healthy individuals. We discovered that those with ADPKD had significant changes in kidney oxygen metabolism even when their kidney function was still normal. These findings are crucial as they provide deeper insights into ADPKD, potentially guiding future treatments to target these changes.

Prospective motion correction in kidney MRI using FID navigators.

PURPOSE: Abdominal MRI scans may require breath-holding to prevent image quality degradation, which can be challenging for patients, especially children. In this study, we evaluate whether FID navigators can be used to measure and correct for motion prospectively, in real-time. METHODS: FID navigators were inserted into a 3D radial sequence with stack-of-stars sampling. MRI experiments were conducted on 6 healthy volunteers. A calibration scan was first acquired to create a linear motion model that estimates the kidney displacement due to respiration from the FID navigator signal. This model was then applied to predict and prospectively correct for motion in real time during deep and continuous deep breathing scans. Resultant images acquired with the proposed technique were compared with those acquired without motion correction. Dice scores were calculated between inhale/exhale motion states. Furthermore, images acquired using the proposed technique were compared with images from extra-dimensional golden-angle radial sparse parallel, a retrospective motion state binning technique. RESULTS: Images reconstructed for each motion state show that the kidneys' position could be accurately tracked and corrected with the proposed method. The mean of Dice scores computed between the motion states were improved from 0.93 to 0.96 using the proposed technique. Depiction of the kidneys was improved in the combined images of all motion states. Comparing results of the proposed technique and extra-dimensional golden-angle radial sparse parallel, high-quality images can be reconstructed from a fraction of spokes using the proposed method. CONCLUSION: The proposed technique reduces blurriness and motion artifacts in kidney imaging by prospectively correcting their position both in-plane and through-slice.

Hyperpolarized pyruvate to measure the influence of PKM2 activation on glucose metabolism in the healthy kidney.

The purpose of the current study was to investigate if hyperpolarized [1-13 C]pyruvate can inform us on the metabolic consequences for the kidney glucose metabolism upon treatment with the pyruvate kinase M2 (PKM2) activator TEPP-46, which has shown promise as a novel therapeutic target for diabetic nephropathy. A healthy male Wistar rat model was employed to study the conversion of [1-13 C]pyruvate to [1-13 C]lactate in the kidney 2 and 4 h after treatment with TEPP-46. All rats were scanned with hyperpolarized [1-13 C]pyruvate kidney MR and vital parameters and blood samples were taken after scanning. The PKM2 activator TEPP-46 increases the glycolytic activity in the kidneys, leading to an increased lactate production, as seen by hyperpolarized pyruvate-to-lactate conversion. The results are supported by an increase in blood lactate, a decreased blood glucose level and an increased pyruvate kinase (PK) activity. The metabolic changes observed in both kidneys following treatment with TEPP-46 are largely independent of renal function and could as such represent a new and extremely sensitive metabolic readout for future drugs targeting PKM2. These results warrant further studies in disease models to evaluate if [1-13 C]pyruvate-to-[1-13 C]lactate conversion can predict treatment outcome.

Dissolved hyperpolarized xenon-129 MRI in human kidneys.

PURPOSE: To assess the feasibility of using dissolved hyperpolarized xenon-129 (129 Xe) MRI to study renal physiology in humans at 3 T. METHODS: Using a flexible transceiver RF coil, dynamic and spatially resolved 129 Xe spectroscopy was performed in the abdomen after inhalation of hyperpolarized 129 Xe gas with 3 healthy male volunteers. A transmit-only receive-only RF coil array was purpose-built to focus RF excitation and enhance sensitivity for dynamic imaging of 129 Xe uptake in the kidneys using spoiled gradient echo and balanced steady-state sequences. RESULTS: Using spatially resolved spectroscopy, different magnitudes of signal from 129 Xe dissolved in red blood cells and tissue/plasma could be identified in the kidneys and the aorta. The spectra from both kidneys showed peaks with similar amplitudes and chemical shift values. Imaging with the purpose-built coil array was shown to provide more than a 3-fold higher SNR in the kidneys when compared with surrounding tissues, while further physiological information from the dissolved 129 Xe in the lungs and in transit to the kidneys was provided with the transceiver coil. The signal of dissolved hyperpolarized 129 Xe could be imaged with both tested sequences for about 40 seconds after inhalation. CONCLUSION: The uptake of 129 Xe dissolved in the human kidneys was measured with spectroscopic and imaging experiments, demonstrating the potential of hyperpolarized 129 Xe MR as a novel, noninvasive technique to image human kidney tissue perfusion.

Intravoxel incoherent motion analysis of renal allograft diffusion with clinical and histopathological correlation in pediatric kidney transplant patients: A preliminary cross-sectional observational study.

The purpose of this study was to compare IVIM values in pediatric renal transplants with histopathology and clinical management change. Fifteen pediatric renal transplant recipients (mean 15.7±2.9 years) were prospectively scanned on a 3T MR scanner with multi-b DTI, prior to same-day transplant biopsy. IVIM maps from 14 subjects were analyzed (one excluded due to motion). Mean values were computed from cortical ROIs and medullary ROIs corresponding to the biopsy site. Subjects were also grouped according to whether or not the biopsy resulted in a change in clinical management. Cortico-medullary IVIM estimates and histopathologic Banff scores were correlated with KT. Cortico-medullary IVIM differences between the "change" and "no change" groups was compared with Mann-Whitney U test. Cortical Dp showed significant moderate negative correlation with Banff t and ci scores (KT=-0.497, P=.035 and KT=-0.46, P=.046) and moderate positive correlation with Banff i score (KT=0.527, P=.028). Cortical Pf showed significant moderate correlation with ci and ct scores (KT=0.489, P=.035 and KT=0.457, P=.043). Tissue diffusivity, Dt , estimated with IVIM was significantly different between the "change" and "no change" groups in medullary ROIs (U=6, P=.021). IVIM analysis has potential as a noninvasive biomarker in assessment of pediatric renal allograft pathology.

A Comparability of Renal Length and Volume Measurements in MRI and Ultrasound in Children.

Introduction: Despite the significant increase in use of magnetic resonance imaging (MRI) in children, there is still a lack of normal reference values of renal size in this method and reference values are being interpolated from the ultrasound (US) studies. The study provides comparative analysis of agreement in renal length and volume measurements between MRI and ultrasound. Materials and Methods: Ninety-three children with a mean age of 8.0 ± 6.0 years, who had undergone both renal US and MRI exams, were included in the study. Participants were divided into three subgroups; each kidney was considered separately. Group 1 included 106 kidneys without any anomalies. Group 2 comprised 48 kidneys with a dilated collecting system. Group 3 included 32 kidneys with a duplicated collecting system. Measurements were taken in three dimensions, and renal volume was calculated from the ellipsoid formula. Results: We found no significant difference between US and MRI measurements in Group 1 and Group 2. In Group 3, the difference between measurements in both imaging methods was significant. The mean difference varied from 0.05% in Group 1, 2.95% in Group 2, to 4.99% in Group 3. Conclusion: The US and MRI are comparable methods in renal size measurements. The interpolation of sonographic renal length and volume reference values to the MRI in the pediatric population is justified, as there is a strong agreement between both methods. Both methods can be used interchangeably for following up of the renal size changes in the pediatric population.