Overweight Status, Obesity, and Progression to ESKD in Patients with Autosomal Dominant Polycystic Kidney Disease

Key Points Higher body mass index increased risk of progression to ESKD in patients with early-stage autosomal dominant polycystic kidney disease. Higher body mass index did not increase the risk of progression to ESKD in patients with late-stage autosomal dominant polycystic kidney disease. Background 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 patients with early- and late-stage ADPKD with progression to ESKD. Methods Participants with early-stage ADPKD (study A; N =556; eGFR: 91±17 ml/min per 1.73 m 2 ) and late-stage ADPKD (study B; N =483; eGFR: 48±12 ml/min per 1.73 m 2 ) who participated in the Halt Progression of Polycystic Kidney Disease (HALT) polycystic kidney disease 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 United States Renal Data System) over a median (interquartile range) 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 versus normal weight ( n =12) but not in 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% confidence interval)], 1.09 [1.03 to 1.15] per unit higher BMI) but not in study B (HR, 0.98 [0.96 to 1.00]). Obesity was associated with increased risk of ESKD (HR, 2.71 [1.22 to 6.02] versus 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 patients with early-stage ADPKD but not in those with late-stage ADPKD.