Overweight and Obesity are Associated with Lower Renal Blood Flow in Autosomal Dominant Polycystic Kidney Disease

INTRODUCTION: We have previously reported that overweight and obesity are independently associated with more rapid disease progression in adults with autosomal dominant polycystic kidney disease (ADPKD). In this study, we perform a cross-sectional analysis to evaluate whether overweight and obesity are also associated with renal blood flow in this patient population. METHODS: 134 non-diabetic adults with ADPKD and estimated glomerular filtration rate (eGFR) ≥60 mL/min/1. 73m² who participated in a randomized controlled trial of pravastatin therapy were categorized as normal weight, overweight, or obese, based on baseline adjusted body mass index (BMI), calculated after subtracting MRI-derived kidney and liver mass from body weight. Renal blood flow (RBF) was measured by phase contrast magnetic resonance imaging (MRI) and adjusted for body surface area (BSA) prior to analysis. The association of baseline BMI with baseline RBF was assessed using multivariable linear regression models. RESULTS: Participants were 40±10 years (mean+s. d. ), 67% female, with a baseline RBF of 635±214 mL/min/1. 73m², and a baseline Chronic Kidney Disease Epidemiology (CKD-EPID) eGFR of 90±21 mL/min/1. 73m². Body surface area-adjusted RBF was lower in a stepwise manner with increasing BMI category. After adjustment for demographics, systolic blood pressure, blood glucose, high density lipoprotein, blood pressure medication usage, eGFR, and height-adjusted total kidney volume (htTKV), both overweight (β-estimate: -78. 4; 95% CI: -155. 3, -1. 6) and obesity (β-estimate: -190. 6; 95% CI: -307. 4, -73. 7) remained significantly associated with lower RBF as compared to normal weight participants. For every one unit increase in BMI, RBF was 10. 4 mL/min/1. 73m2 lower (95% CI: -16. 9, -3. 9) in the fully adjusted model CONCLUSION: Overweight and obesity are cross-sectionally associated with lower RBF in patients with early-stage ADPKD; however, these findings reflect associations only, and do not provide insight into causality. Further research and longitudinal studies are needed to establish the temporal and causal nature of these relationships, and to evaluate whether reduced RBF may be a mechanism by which obesity is associated with faster progression in patients with ADPKD.