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

Abstract

Key Points:

1. Higher body mass index increased risk of progression to ESKD in patients with early-stage autosomal dominant polycystic kidney disease.

2. 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 m²) and late-stage ADPKD (study B; N=483; eGFR: 48±12 ml/min per 1.73 m²) 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/m²; ref; n=357), overweight (25.0–29.9 kg/m²; n=384), or obese (≥30 kg/m²; 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.

Trial registration: ClinicalTrials.gov NCT04907799.

Keywords: ADPKD; ESKD; clinical epidemiology; cystic kidney disease; obesity.