Smoking, Oxidative Stress and Inflammation: Impact on Resting Energy Expenditure in Diabetic Nephropathy

Rajiv Agarwal


BMC Nephrology. 2005;6 

In This Article

Abstract and Background

Background: Inflammation is associated with increased resting energy expenditure (REE) in patients with chronic kidney disease. Oxidative stress, on the other hand, appears not to increase REE. Smoking is a common mechanism for generating oxidative stress and inflammation. Whether smokers have increased REE and if so, whether it is accounted for by the pro-oxidant and inflammatory state is not known.
Methods: A case control study of 11 smokers and 24 non-smokers with overt diabetic nephropathy was performed to evaluate the chronic effect of smoking on REE. REE (indirect calorimetry), glomerular filtration rate (iothalamate clearance), markers of oxidative stress (urinary and plasma malondialdehyde (MDA), and protein carbonyls) and inflammation (C-reactive protein, tumor necrosis factor-alpha, interleukin-6) were measured on two occasions four months apart.
Results: Biomarkers of inflammation (C-reactive protein) and oxidative stress (urinary and plasma MDA) were increased in smokers. REE was increased in smokers, 24.3 kcal/kg/day compared to 21 kcal/kg/day (p = 0.009) in non-smokers. After adjusting for age, GFR, MDA, C-reactive protein, and hemoglobin A1C the difference in REE between the two groups persisted (adjusted difference 3.51 kcal/kg/d, 95% confidence interval 0.59 - 6.45, p = 0.020).
Conclusion: Patients with overt diabetic nephropathy who smoke have a higher REE, oxidative and inflammatory state. Elevated REE is not attributable to heightened oxidative stress and inflammatory state. Smoking is an independent risk factor for elevated REE in patients with diabetic nephropathy and provides an additional mechanism by which it may lead to poor outcomes.

Diabetic nephropathy is the commonest cause of end-stage renal disease (ESRD). Malnutrition in patients with ESRD is associated with increased morbidity and mortality. Nutritional decline begins long before patients with progressive CKD become dialysis dependent[1,2] which in part is related to the spontaneous reduction in dietary protein and caloric intake with reduction in glomerular filtration rate (GFR).[3,4,5,6,7,8]

Recent studies point out that chronic subclinical inflammation in patients with CKD is associated with an increase in REE.[9] Other studies, done in patients without CKD, show that oxidative stress is not associated with increase in REE.[10] Smoking is associated with both an increase in oxidative stress and subclinical inflammation, thus serves as a model to study the effect of oxidative-inflammatory state on REE.[11] Smoking may therefore compound the oxidative stress and the inflammatory state in patients with CKD.[2,12,13,14] Whether smoking-induced oxidative-inflammatory state is sufficient to account for elevated REE is not known.

Although smoking-induced increase REE is thought to be acute and transient - in part due to nicotine-induced sympathoadrenal activation - more recent studies point to a chronic elevation in REE.[15] In epidemiological studies, increased REE is seen in young women who smoke compared to women who do not, even after controlling for differences in body size and overnight abstinence from smoking.[16] Smoking cessation often leads to weight gain.[17] Thus, smoking may accelerate malnutrition via accelerating attrition in renal function in addition to elevating REE.

In this study we asked the question whether smokers with diabetic nephropathy have an increased REE compared to non-smokers with equally severe diabetic nephropathy. If so, is the increased REE mediated by the pro-oxidant and inflammatory state.


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