Overweight and obesity and progression of ADPKD

Abstract

Background and objectives On the basis of earlier observations, we evaluated the association between overweight and obesity and rapid progression of autosomal dominant polycystic kidney disease in participants in the Tolvaptan Efficacy and Safety inManagement ofAutosomalDominant Polycystic KidneyDisease and ItsOutcomes (TEMPO) 3:4 trial. More importantly, we also determined whether efficacy of tolvaptan was attenuated in individuals with baseline overweight or obesity. Design, setting, participants, & measurements A total of 1312 study participants with relatively early-stage autosomal dominant polycystic kidney disease (mean eGFR 78622 ml/min per 1.73 m2) whowere at high risk of rapidprogressionwere categorizedby bodymass index (BMI; calculatedusing nonkidneyweight) as normalweight (18.5-24.9 kg/m2; n5670), overweight (25.0-29.9 kg/m2; n5429), or obese ($30 kg/m2; n5213). Linear and multinomial logistic regression models were used to determine the association of baseline overweight and obesity with change in total kidney volume (TKV) over the 3-year study period. Results Infully adjustedmodels,higherBMIwas associatedwithgreater annualpercent changeinTKV(difference of 1.20 [95% confidence interval (95% CI), 0.85 to 1.55] per five-unit higher BMI). Overweight and obesity were associatedwith higher odds of annual percent change in TKVof$7%versus,5%(overweight: odds ratio, 2.04 [95% CI, 1.45 to 2.87]; obese: odds ratio, 4.31 [95% CI, 2.83 to 6.57] versus normal weight). eGFR decline did not differ according to BMI (fully adjusted difference in decline of 20.95 [95% CI, 22.32 to 0.40]ml/min per 1.73m2 per year per five-unit higher BMI). The three-way interaction (treatment3time3BMI group) was not statistically significant in linear mixed models with an outcome of TKV (log-transformed estimated coefficient comparing the treatment effect for overweight versus normal weight: 0.56%[95%CI,20.70% to 1.84%] per year; P50.38; obese versus normal weight: 0.07% [95% CI, 21.47% to 1.63%] per year; P50.93) or eGFR (estimated coefficient comparing overweight versus normal weight: 20.07 [95% CI, 20.95 to 0.82] ml/min per 1.73 m2 per year; P50.88; obese versus normal weight: 0.22 [95% CI, 20.93 to 1.36] ml/min per 1.73 m2 per year; P50.71). Conclusions Overweight and particularly obesity are strongly and independently associated with kidney growth, but not eGFR slope, in the TEMPO 3:4 trial, and tolvaptan efficacy is irrespective of BMI categorization.