Overweight and Obesity and Progression to End-Stage Kidney Disease in Patients with Autosomal Dominant Polycystic Kidney Disease

Background and Objectives: Prior research has linked higher body-mass index (BMI) and greater visceral adiposity with more rapid progression of early-stage autosomal dominant polycystic kidney disease (ADPKD). We now evaluate the association between overweight and obesity in early- and late-stage patients with ADPKD with progression to end-stage kidney disease (ESKD). Design, Setting, Participants, and Measurements: Participants with early-stage ADPKD (Study A; N=556; eGFR: 91±17 mL/min/1.73m 2 ) and late-stage (Study B; N=483; eGFR: 48±12 mL/min/1.73m 2 ) ADPKD who participated in the HALT PKD trials were categorized by BMI as normal weight (18.5-24.9 kg/m 2 ; ref; N=357), overweight (25.0-29.9 kg/m 2 ; N=384), or obese (≥30 kg/m 2 ; N=298). Kaplan Meier survival analysis and multivariate Cox proportional hazard models were used to determine the association of baseline BMI as a continuous and categorical variable with risk of ESKD (according to the US Renal Data System) over median (IQR) follow-up period of 12.2 (7.5, 13.3) [Study A] and 7.3 (5.1, 11.7) [Study B] years (primary outcome). All-cause mortality (National Death Index) was also considered as a competing risk (Fine and Gray method). Results: The number of ESKD events was greater with overweight (N=24) and obesity (N=23) in HALT Study A vs. normal weight (12) but not HALT Study B (normal weight: N=89, overweight: N=102, obese: N=92). In fully adjusted models, higher BMI was associated with risk of progression to ESKD in Study A (Hazard Ratio [HR (95% CI)] 1.09 [1.03, 1.15] per unit higher BMI) but not Study B (HR: 0.98 [0.96, 1.00]). Obesity was associated with increased risk of ESKD (HR: 2.71 [1.22, 6.02] vs. normal weight) in Study A only. Results were similar when considering death as a competing risk. Conclusions: Higher BMI, particularly obesity, increased the risk of progression to ESKD in early- but not late-stage patients with ADPKD.