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. The kidney is a lobulated organ, but little is known regarding the clinical importance of the number and size of individual kidney lobes. 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. 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. 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.
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