Obesity, metabolic health, and the risk of end-stage renal disease

Abstract

Obesity is associated with chronic kidney disease progression. Whether metabolic risk factors modify this association is unclear. Here we examined associations of body mass index (BMI) and metabolic health with risk of end-stage renal disease (ESRD) in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Among 21,840 participants eligible for analysis, 247 developed ESRD (mean follow-up of 6.3 years). Metabolic health significantly modified the association of BMI with ESRD. In models stratified by the presence or absence of the metabolic syndrome and adjusted for demographic, lifestyle, and clinical factors, higher BMI was associated with lower risk of ESRD in those without (hazard ratio per 5 kg/m2 increase in BMI 0.70, 95% CI 0.52, 0.95) but not those with (hazard ratio, 1.06) the metabolic syndrome. In models stratified by weight and metabolic health, compared with normal weight (BMI 18.5-24.9 kg/m2) participants without the metabolic syndrome the overweight individuals (BMI 25-29.9) and obese individuals (BMI of 30 or more) with the metabolic syndrome had greater risk of ESRD (hazard ratios of 2.03 and 2.29, respectively), whereas obesity without the metabolic syndrome was associated with lower risk of ESRD (hazard ratio 0.47). Thus, higher BMI is associated with lower ESRD risk in those without but not those with the metabolic syndrome.

Figure 1

Hazard ratios for incident end-stage renal disease (ESRD) as a function of body mass index (BMI) in the fully study sample (1A) and stratified by absence (1B) or presence (1C) of metabolic syndrome. BMI was modeled as a continuous variable and fitted in a Cox proportional hazards model using restricted quadratic spline regression adjusted for age, race, sex, geographic region of residence, education, income, physical activity, current smoking, history of coronary heart disease, and history of stroke. Knots for the spline were placed at a BMI of 25 and 30 kg/m² and the reference point was a BMI of 22 kg/m². Dashed horizontal lines correspond to reference values. Shaded areas represent 95% confidence intervals for hazard ratios. Histograms present distributions of BMI in study participants.

Figure 2

Hazard ratios (95% confidence intervals) for incident ESRD among REGARDS participants by weight and metabolic subtype categories. Model was adjusted for age, race, sex, geographic region of residence, education, income, physical activity, current smoking, history of coronary heart disease, and history of stroke. P_trend for the association of weight categories (normal, overweight, obese) with ESRD risk in participants without the metabolic syndrome was 0.02; P_trend for the association of weight categories (normal, overweight, obese) with ESRD risk in participants with the metabolic syndrome was 0.16.