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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/m 2 ; estimated glomerular filtration rate [eGFR, 2021 CKD-EPI creatinine], 103±18mL/min/1.73m 2 ; 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/1.73m 2 ; 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 11 C-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, χ 2 /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., (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Significance Statement: Segmentation of multiple structures in cross-sectional imaging is time-consuming and impractical to perform manually, especially if the end goal is clinical implementation. In this study, we developed, validated, and demonstrated the capability of a deep learning algorithm to segment individual medullary pyramids in a rapid, accurate, and reproducible manner. The results demonstrate that cortex volume, medullary volume, number of pyramids, and mean pyramid volume is associated with patient clinical characteristics and microstructural findings and provide insights into the mechanisms that may lead to CKD., Background: The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes., Methods: After applying a previously validated algorithm to segment the cortex and medulla, a deep-learning algorithm was developed and validated to segment and count individual medullary pyramids on contrast-enhanced computed tomography images of living kidney donors before donation. The association of cortex volume, medullary volume, number of pyramids, and mean pyramid volume with concurrent clinical characteristics (kidney function and CKD risk factors), kidney biopsy morphology (nephron number, glomerular volume, and nephrosclerosis), and short- and long-term GFR <60 or <45 ml/min per 1.73 m 2 was assessed., Results: Among 2876 living kidney donors, 1132 had short-term follow-up at a median of 3.8 months and 638 had long-term follow-up at a median of 10.0 years. Larger cortex volume was associated with younger age, male sex, larger body size, higher GFR, albuminuria, more nephrons, larger glomeruli, less nephrosclerosis, and lower risk of low GFR at follow-up. Larger pyramids were associated with older age, female sex, larger body size, higher GFR, more nephrons, larger glomerular volume, more nephrosclerosis, and higher risk of low GFR at follow-up. More pyramids were associated with younger age, male sex, greater height, no hypertension, higher GFR, lower uric acid, more nephrons, less nephrosclerosis, and a lower risk of low GFR at follow-up., Conclusions: Cortex volume and medullary pyramid volume and count reflect underlying variation in nephron number and nephron size as well as merging of pyramids because of age-related nephrosclerosis, with loss of detectable cortical columns separating pyramids., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

The objective of this study was to validate a fully automated total kidney volume measurement method for pre-clinical rodent trials that is fast, accurate, reproducible, and to provide these resources to the research community. Rodent studies that involve imaging are crucial for monitoring treatment efficacy in diseases such as polycystic kidney disease. Previous studies utilize manual or semi-automated segmentations, which are time consuming and potentially biased. To develop our automated system, a total of 150 axial magnetic resonance images (MRI) from a variety of mouse models were manually segmented and used to train/validate an automated algorithm. To test the longitudinal application of the model, four mutant and four wild-type mice were imaged sequentially over three to twelve weeks via MRI. Segmentations of the kidneys (excluding the renal pelvis) were generated by the automated method and two different readers, with one reader repeating the measurements. Similarity metrics and longitudinal analysis were calculated to assess the performance of the automated compared to the manual methods. The automated approach required no user input, besides a final visual quality control step. Similarity metrics of the automated method versus the manual segmentations were on par with inter- and intra-reader comparisons. Thus, our fully automated approach described here can be safely used in longitudinal, pre-clinical trials that involve the segmentation of rodent kidneys in T2-weighted MRIs., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)