Journals of Gerontology: MEDICAL SCIENCES
Cite journal as: J Gerontol A Biol Sci Med Sci. 2012 December;67(12):1410–1416
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Advance Access publication October 29, 2012
Special Issue on the Aging Kidney
Managing Chronic Inflammation in the Aging
Diabetic Patient With CKD by Diet or Sevelamer
Carbonate: A Modern Paradigm Shift
H. Vlassara,1 W. Cai,1 X. Chen,1 E. J. Serrano,1 M. S. Shobha,1 J. Uribarri,1,2 M. Woodward,3
and G. E. Striker1,2
1Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Care and
2Division of Nephrology, Department of Medicine, Mount Sinai School of Medicine, New York.
3George Institute for Global Health, NSW 2050, Australia.
Address correspondence to Helen Vlassara, MD, Division of Experimental Diabetes and Aging, Department of Geriatrics and Palliative Care,
Mount Sinai School of Medicine, 1 Gustave Levy Place, NY 10029. Email: email@example.com
The maintenance of normal metabolism and body defenses depends on the balance between cellular antioxidant and anti-
inflammatory factors. This balance can be disrupted by agents/mechanisms in the extracellular milieu that induce excess
reactive oxygen species (ROS) and inflammation. Cytopathic advanced glycation endproducts, present in ever increasing
amounts in the modern diet, are one of the major environmental factors that cause excess ROS and/or inflammation at all
ages and induce complications in aging, such as chronic kidney disease (CKD) and type 2 diabetes. Increased ROS and/
or inflammation are present in both aging and CKD, and are associated with reduced cellular defenses against ROS and/
or inflammation. Affected individuals have reduced defenses against further stress and are predisposed to organ failure,
now a well-known phenomenon in aging. Thus, new methods are urgently needed to safely reduce ROS and/or inflam-
mation in the aging type 2 diabetes patient with CKD. Studies of both normal aging and diabetic patients with kidney
disease underline the fact that increased ROS and/or inflammation can be managed in these conditions by economical,
safe, and effective interventions that reduce the uptake of advanced glycation endproducts by either modifying prepara-
tion of food or an oral drug. This communication reviews these data and adds new information on the efficacy of a drug,
sevelamer carbonate, required to reduce ROS and/or inflammation in the aging type 2 diabetes patient complicated by
CKD. If larger and longer studies confirm the hypothesis that one or both of these interventions reduce progression of
CKD, it could represent a new paradigm in the management of complications in the type 2 diabetes patient with CKD.
Key Words: Diabetes—Hemodialysis—AGEs—Diet—Inflammation—Aging.
Received July 12, 2012; Accepted August 30, 2012
Decision Editor: Luigi Ferrucci, MD, PhD
diabetes, obesity, and cardiovascular disease. The causes of
these epidemics are not known (1,2), but they have been
linked to changes in diet that promote reactive oxygen spe-
cies (ROS) and/or inflammation (3). The current high inci-
dence of decreased renal function in the aging population
also fits into the definition of an epidemic, and is also asso-
ciated with high levels of circulating and cellular markers of
inflammation and oxidative stress (OS) (4,5). The potential
relation between diabetes and aging was shown in a study
in which diabetes was induced in aged mice (6). This com-
bination of two causes of increased ROS and/or inflamma-
tion (ie, diabetes and aging) was sufficient to precipitate
EVERAL chronic inflammatory diseases have reached
“epidemic” proportions over the last 50 years, including
severe chronic kidney disease (CKD) in a mouse strain
that is otherwise resistant to the development of CKD.
Importantly, reducing inflammation and ROS completely
blocked the development of renal failure. If these data apply
to humans, the control of increased ROS and/or inflamma-
tion in aging becomes important issue. In fact, the body bur-
den of advanced glycation endproducts (AGEs) increases
with age in humans and animals and because AGEs induce
increased inflammation/OS and increase with age, they
could contribute to the development of the type 2 diabetes
(T2D) as well as the CKD of aging. In addition, increased
levels of AGEs have been shown to be associated with both
the development of type 1 diabetes (T1D) (7) and the pres-
ence of complications in long-term survivors of T1D (8).
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