Obesity, Metabolic Health, and the Risk of End-stage Renal Disease

Bhupesh Panwar; Lynae J Hanks; Rikki M Tanner; Paul Muntner; Holly Kramer; William M McClellan; David G Warnock; Suzanne E Judd; Orlando M Gutiérrez


Kidney Int. 2015;87(6):1216-1222. 

In This Article

Abstract and Introduction


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.


In the general population, obesity (defined as a body mass index (BMI)≥30 kg/m2) has been associated with adverse cardiovascular outcomes and increased mortality.[1,2] Obesity has also been implicated in the development and progression of chronic kidney disease (CKD).[3–9] However, there is accumulating evidence that obesity may confer protective benefits in individuals with chronic disease conditions, including coronary artery disease and CKD.[10–18] The reasons for why obesity is associated with a protective effect in certain subgroups are unclear but may be related to the presence or absence of concurrent metabolic risk factors, such as insulin resistance, lipid disorders, and visceral adiposity. Studies have shown that individuals who are obese on the basis of BMI criteria but have a metabolically healthy profile have better outcomes compared with those who have a metabolically unhealthy profile.[18,19] For example, in a population of black and white adults with CKD, we recently showed that overweight and obese individuals who were metabolically healthy had a lower risk for mortality as compared with normal weight individuals who were metabolically healthy.[19] In contrast, we observed no differences in mortality when comparing metabolically unhealthy overweight and obese individuals to metabolically healthy normal weight individuals.[19] Whether metabolic health similarly modifies the association of BMI with the incidence of end-stage renal disease (ESRD) is unclear. The primary focus of this analysis was to examine the independent and joint associations of BMI and metabolic health with risk of ESRD within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a large prospective cohort of 30,239 black and white adults from across the United States.