Protection against loss of innate defenses in adulthood by low advanced glycation end products (AGE) intake: role of the antiinflammatory AGE receptor-1.

CONTEXT: Increased oxidant stress and inflammation (OS/infl) are linked to both aging-related diseases and advanced glycation end products (AGEs). Whereas AGE receptor-1 (AGER1) reduces OS/infl in animals, this has not been assessed in normal humans. OBJECTIVE: The objectives of the study were to determine whether AGER1 correlates with AGEs and OS/infl and a reduction of dietary AGEs (dAGEs) lowers OS/infl in healthy adults and chronic kidney disease (CKD-3) patients. DESIGN: This study was cross-sectional with 2-yr follow-up studies of healthy adults and CKD-3 patients, a subset of which received a reduced AGE or regular diet. SETTING: The study was conducted at general community and renal clinics. PARTICIPANTS: Participants included 325 healthy adults (18-45 and >60 yr old) and 66 CKD-3 patients. INTERVENTION: An isocaloric low-AGE (30-50% reduction) or regular diet was given to 40 healthy subjects for 4 months and to nine CKD-3 patients for 4 wk. MAIN OUTCOME: Relationships between age, dAGEs, serum AGEs, peripheral mononuclear cell AGE-receptors, and OS/Infl before and after reduction of dAGE intake were measured. RESULTS: AGEs, oxidant stress, receptor for AGE, and TNFalpha were reduced in normal and CKD-3 patients after the low-AGE diet, independently of age. AGER1 levels in CKD-3 patients on the low-AGE diet resembled 18- to 45-yr-old normal subjects. Dietary, serum, and urine AGEs correlated positively with peripheral mononuclear cell AGER1 levels in healthy participants. AGER1 was suppressed in CKD-3 subjects, whereas receptor for AGE and TNFalpha were increased. CONCLUSIONS: Reduction of AGEs in normal diets may lower oxidant stress/inflammation and restore levels of AGER1, an antioxidant, in healthy and aging subjects and CKD-3 patients. AGE intake has implications for health outcomes and costs and warrants further testing.

Diet, inflammation, and chronic kidney disease: getting to the heart of the matter.

Cardiovascular disease (CVD) remains a leading cause of death in patients with chronic kidney disease (CKD). CVD is now thought to result from the interplay of several factors including inflammation, oxidative stress and endothelial dysfunction. Advanced glycation end products (AGE) are known to be elevated in patients with CKD and these compounds possess these pro-oxidant, pro-inflammatory and anti-endothelial properties. There has been a great deal of literature linking diet and inflammation, and recent work has shown the diet to be a significant contributor to the body's AGE pool. We herein hypothesize that a diet high in AGE plays an important role in the initiation of chronic subclinical inflammation that seems to underlie the high prevalence of CVD in CKD patients. Herein we will briefly examine the evidence linking different components of diet with inflammation in CKD patients. We will then focus on the role of dietary AGEs in inflammation and potentially CVD in CKD, and in conclusion, we will propose dietary modifications as part of a multifactorial approach to ameliorate unhealthy lifestyles among CKD patients. The most important message is that simple changes in culinary technique rather than in the food nutrient composition may be the most important part of preventing CVD in this population.