Visceral Adiposity and Progression of ADPKD: A Cohort Study of Patients From the TEMPO 3:4 Trial.

Autor:	Nowak KL; Anschutz Medical Campus, University of Colorado, Aurora, Colorado. Electronic address: Kristen.Nowak@cuanschutz.edu., Moretti F; Orobix Life, Bergamo, Italy., Bussola N; Orobix Life, Bergamo, Italy., Steele CN; Anschutz Medical Campus, University of Colorado, Aurora, Colorado., Gregory AV; Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota., Kline TL; Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota., Ramanathan S; Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota., Trapletti G; Orobix Life, Bergamo, Italy., Furlanello C; Orobix Life, Bergamo, Italy., McCormick L; Otsuka Pharmaceutical Development and Commercialization, Princeton, New Jersey., Chonchol M; Anschutz Medical Campus, University of Colorado, Aurora, Colorado.
Jazyk:	angličtina
Zdroj:	American journal of kidney diseases : the official journal of the National Kidney Foundation [Am J Kidney Dis] 2024 Sep; Vol. 84 (3), pp. 275-285.e1. Date of Electronic Publication: 2024 Apr 10.
DOI:	10.1053/j.ajkd.2024.02.014
Abstrakt:	Rationale & Objective: Body mass index (BMI) is an independent predictor of kidney disease progression in individuals with autosomal dominant polycystic kidney disease (ADPKD). Adipocytes do not simply act as a fat reservoir but are active endocrine organs. We hypothesized that greater visceral abdominal adiposity would associate with more rapid kidney growth in ADPKD and influence the efficacy of tolvaptan. Study Design: A retrospective cohort study. Setting & Participants: 1,053 patients enrolled in the TEMPO 3:4 tolvaptan trial with ADPKD and at high risk of rapid disease progression. Predictor: Estimates of visceral adiposity extracted from coronal plane magnetic resonance imaging (MRI) scans using deep learning. Outcome: Annual change in total kidney volume (TKV) and effect of tolvaptan on kidney growth. Analytical Approach: Multinomial logistic regression and linear mixed models. Results: In fully adjusted models, the highest tertile of visceral adiposity was associated with greater odds of annual change in TKV of≥7% versus<5% (odds ratio [OR], 4.78 [95% CI, 3.03-7.47]). The association was stronger in women than men (interaction P<0.01). In linear mixed models with an outcome of percent change in TKV per year, tolvaptan efficacy (% change in TKV) was reduced with higher visceral adiposity (3-way interaction of treatment ∗ time ∗ visceral adiposity, P=0.002). Visceral adiposity significantly improved classification performance of predicting rapid annual percent change in TKV for individuals with a normal BMI (DeLong's test z score: -2.03; P=0.04). Greater visceral adiposity was not associated with estimated glomerular filtration rate (eGFR) slope in the overall cohort; however, visceral adiposity was associated with more rapid decline in eGFR slope (below the median) in women (fully adjusted OR, 1.06 [95% CI, 1.01-1.11] per 10 unit increase in visceral adiposity) but not men (OR, 0.98 [95% CI, 0.95-1.02]). Limitations: Retrospective; rapid progressors; computational demand of deep learning. Conclusions: Visceral adiposity that can be quantified by MRI in the coronal plane using a deep learning segmentation model independently associates with more rapid kidney growth and improves classification of rapid progression in individuals with a normal BMI. Tolvaptan efficacy decreases with increasing visceral adiposity. Plain-Language Summary: We analyzed images from a previous study with the drug tolvaptan conducted in patients with autosomal dominant polycystic kidney disease (ADPKD) to measure the amount of fat tissue surrounding the kidneys (visceral fat). We had previously shown body mass index can predict kidney growth in this population; now we determined whether visceral fat was an important factor associated with kidney growth. Using a machine learning tool to automate measurement of fat in images, we observed that visceral fat was independently associated with kidney growth, that it was a better predictor of faster kidney growth in lean patients than body mass index, and that having more visceral fat made treatment of ADPKD with tolvaptan less effective. (Copyright © 2024 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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