Overweight and Obesity Are Associated with Lower Kidney Blood Flow in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Background: We have previously reported that overweight and obesity are independently associated with more rapid progression in adults with early-stage ADPKD. Renal blood flow (RBF) precedes the decline in eGFR and is associated with faster kidney growth. We now evaluated whether overweight and obesity are also associated with changes in renal blood flow. Methods: 150 non-diabetic adults (25-60 years of age) with ADPKD and an eGFR ≥60 ml/min/1.73m2 who participated in a randomized controlled trial of pravastatin therapy were categorized based on baseline body mass index (BMI) as normal weight (n=68 [45%], overweight (n=53 [35%], or obese (n=26 [17%]. RBF was measured by phase contrast MRI, analyzed using Segment for Research (Medviso), and adjusted for body surface area (BSA) prior to analysis. The association of baseline BMI with baseline RBF was assessed using multivariable linear regression. Results: Participants were 40±10 years (mean+s.d), 65% female, with a baseline RBF of 635±214 ml/min/1.73m2, and a baseline eGFR of 90±21 ml/min/1.73m2. BSA-adjusted RBF was lower in a stepwise manner with increasing BMI category (Figure). After adjustment for demographics, systolic blood pressure, blood glucose, HDL, eGFR, and height-adjusted total kidney volume, both overweight (β-estimate: -116.8; 95% CI: -168.8 -64.8) and obesity (β-estimate: -289.2; 95% CI: -361.5, -216.9) remained significantly associated with lower RBF as compared to normal weight participants. For every one unit increase in BMI, RBF was 20.6 ml/min/1.73m2 lower (95% CI: -25.2, -16.1) in the fully adjusted model. Conclusion: Overweight and obesity are associated with lower RBF in patients with early-stage ADPKD. Prior research in adults without ADPKD have been discordant, reporting both higher and lower RBF with overweight or obesity. Further research is needed to evaluate whether reduced RBF may be a mechanism by which obesity is associated with faster progression in patients with ADPKD. Funding: NIDDK Support, Other U.S. Government Support, Private Foundation Support, Clinical Revenue Support