Abstract
Obesity is associated with higher mortality in the general population, but this association is reversed in patients on dialysis. The nature of the relationship of obesity with adverse clinical outcomes in nondialysis-dependent CKD and the putative interaction of the severity of disease with this association are unclear. We analyzed data from a nationally representative cohort of 453,946 United States veterans with eGFR<60 ml/min per 1.73 m(2). The associations of body mass index categories (<20, 20 to <25, 25 to <30, 30 to <35, 35 to <40, 40 to <45, 45 to <50, and ≥50 kg/m(2)) with all-cause mortality and disease progression (using multiple definitions, including incidence of ESRD, doubling of serum creatinine, and the slopes of eGFR) were examined in Cox proportional hazards models and logistic regression models. Multivariable adjustments were made for age, race, comorbidities and medications, and baseline eGFR. Body mass index showed a relatively consistent U-shaped association with clinical outcomes, with the best outcomes observed in overweight and mildly obese patients. Body mass index levels <25 kg/m(2) were associated with worse outcomes in all patients, independent of severity of CKD. Body mass index levels ≥35 kg/m(2) were associated with worse outcomes in patients with earlier stages of CKD, but this association was attenuated in those patients with eGFR<30 ml/min per 1.73 m(2). Thus, until clinical trials establish the ideal body mass index, a cautious approach to weight management is warranted in this patient population.
Highlights
Obesity defined by elevated body mass index (BMI) has been regarded as a cardiovascular risk factor in the general population.[1,2,3,4] Obesity is associated with increased risk of incident CKD5–9 and ESRD.[10,11,12,13] Negative effects of obesity include those effects mediated by conditions caused or worsened by it, such as diabetes mellitus (DM) or hypertension, and direct adverse metabolic effects, such as inflammation, increased synthesis of apolipoprotein B and very LDLs, increased production of insulin, and insulin resistance.[14]
Similar U-shaped associations were present in all subgroups, except patients with eGFR,[30] ml/min per 1.73 m2, in whom higher BMI levels were not associated with significant increases in mortality (Supplemental Figure 1)
BMI levels above 35 kg/m2 were associated with higher mortality, except in patients with advanced CKD, in whom the association was attenuated and nonsignificant
Summary
Obesity defined by elevated body mass index (BMI) has been regarded as a cardiovascular risk factor in the general population.[1,2,3,4] Obesity is associated with increased risk of incident CKD5–9 and ESRD.[10,11,12,13] Negative effects of obesity include those effects mediated by conditions caused or worsened by it, such as diabetes mellitus (DM) or hypertension, and direct adverse metabolic effects, such as inflammation, increased synthesis of apolipoprotein B and very LDLs, increased production of insulin, and insulin resistance.[14] Obesity induces glomerular hyperfiltration,[15] and weight loss in morbidly obese patients attenuates proteinuria.[16]. We examined the association of BMI with all-cause mortality and progressive CKD in a large national cohort of United States veterans with eGFR,[60] ml/min per 1.73 m2
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