Obesity and kidney and cardiac outcomes in people with glomerular disease
Prevalence of obesity is rising, and is a risk factor for the development and progression of both chronic kidney disease (CKD) and cardiovascular disease (CVD). People with glomerular kidney disease are also at higher risk of CKD and CVD than the general population. Investigators used data from participants in the Cure Glomerulonephropathy Network (CureGn) to examine the association between obesity severity and kidney and CVD outcomes in children and adults with glomerular disease.
CureGN is a prospective, multicentre, observational cohort study of adults and children with proven glomerular disease. The present study included data from all participants ≥5 years enrolled over an 8-year period. The adult cohort was categorised by BMI: 20–24 kg/m2 (healthy); 25–34 (overweight/class 1 obesity); and ≥35 (class 2/3 obesity). The paediatric cohort was categorised by BMI percentile for age: 5th–84th (healthy); 85th–94th (overweight); and >95th (obese).
The primary kidney outcome was a composite of end-stage kidney disease or a ≥40% decline in eGFR since enrolment, and the primary cardiovascular outcome was a composite of new coronary artery disease, heart failure hospitalisation, stroke or death. The times to primary outcomes by BMI category were estimated using Kaplan–Meier analysis. Adjusted associations between BMI and outcomes were estimated using Cox proportional hazards analysis.
The study included 2301 participants (1548 adults; 753 children), with a prevalence of overweight and obesity of 77% in adults and 51% in children. Median follow-up was 4.0 years, with a maximum follow-up of 7.1 years.
In both cohorts, the highest obesity class had a higher incidence of the primary kidney endpoint: 90.8 and 49.8 per 1000 person-years in the adult and paediatric cohorts, respectively, compared to 58.0 and 33.7 in those of healthy weight. In the univariable analysis, class 2/3 obesity was associated with the primary kidney outcome only in adults (HR, 1.6; 95% CI, 1.1–2.2; P=0.006) compared to the health weight groups. When controlling for baseline eGFR and proteinuria, class 2/3 obesity did not remain significant among adults.
The incidence of the cardiovascular composite outcome increased in adults with class 2/3 obesity: 19.7 events per 1000 person-years in the highest weight class, compared to 8.2 in the healthy weight group. In the adjusted analysis, class 2/3 obesity was associated with higher risk of the CVD outcome in adults (HR, 3.9; 95% CI, 1.4–10.7; P=0.009). In the smaller paediatric cohort, the number of events was too small to draw conclusions.
The finding that the association between obesity and kidney events in adults in CureGN was attenuated when controlling for baseline eGFR and proteinuria warrants further investigation, as the causal pathway by which obesity leads to kidney damage is complicated. The association of obesity with cardiovascular events in adults implies that obesity should be viewed as a modifiable risk factor for patients with glomerular disease.
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