Kidney Function Declines with age and AGEs and Is A Major Source of Mortality

According to a recent paper, 1 twenty million adults in the U.S. 20 years or older have an increased serum creatinine level (creatinine is cleared by the kidneys) and the incidence increases with age. The paper further notes that more than 20% of those age 65 years or older have decreased kidney function, even when corrected for obvious causes of kidney dysfunction such as hypertension and diabetes. Moreover, there is a strong association between age-associated chronic kidney disease and cardiovascular disease, since inflammatory mechanisms are involved in both. 1 Surprisingly, “results from a longitudinal study of normal [not diabetic] aging adults in Italy showed that the most significant correlation with mortality was the level of renal [kidney] function.” 1,1b(emphasis added)

Hence, if you have reached 65 years of age, having successfully avoided being done in prematurely by cardiovascular disease and cancer, declining kidney function is a major factor to consider in all-cause mortality and you should have your kidney functions tested regularly as part of your health assessment. Declining kidney function in aging is associated with increased levels of the cytokine IL-6, C-Reactive Protein, and other markers of inflammation and oxidative stress. Importantly, increasing quantities of serum AGEs accumulate in the kidneys and impair their function. In a recent paper, 1the authors refer to studies showing that reducing AGEs in the diet of both animals and humans (by, for example, cooking foods at a lower temperature) is one effective way of reducing serum AGEs and protecting kidney function. Other ways (not discussed in this paper) include dietary supplements of nutrients that decrease the formation of AGEs or interfere with the pathways of damage initiated by AGEs.

Serum Advanced Glycation End Products (AGEs) Associated with Kidney Function Decline

The kidneys are the major way the body has for excreting AGEs to maintain the body load of AGEs at nontoxic levels. 1 It has been shown that during aging and in diabetes, the glomerular basement membrane of the kidneys are thickened, leading to less efficient kidney filtration. 2 (Interestingly, thickening of the basement membrane of other organs, such as the testes, also occurs with aging.) This thickening has been linked to glycosylation (an early part of the process that produces AGEs) of the collagen type IV that makes up more than 80% of the glomerular basement membrane material. 2 AGE inhibitors have been reported to provide significant protection against cardiovascular disease as well as age-associated decline in kidney function.

Reducing Accumulation of AGEs in Kidneys with L-Arginine

The amino acid L-arginine has been shown to be a reducer of cross-linking in aging collage type IV and is strongly associated with a reduction of collagen accumulation of N-epsilon-(carboxymethyl)lysine (an AGE) in aging mice and in diabetic mice. 2

Another paper attests to the kidney protective effects of L-arginine. 3 12-13 month old rats treated for 8 months with L-arginine had their glomerular filtration rate increased by 50% as compared with untreated controls. Another study4 reported that 12 week old hyperlipidemic, hyperglycemic Golden Syrian hamsters had enhanced accumulation of fluorescent AGE-proteins in the vascular mesenteric bed and in the lens, which was decreased significantly by L-arginine treatment.

Reducing the Accumulation of AGEs with Rutin, Alpha-lipoic acid, Carnosine, Benfotiamine, Histidine, and Pyridoxine hydrochloride (Vitamin B6)

As we have written earlier (see “Reducing Glycation Reactions for Better Health and Longer Life” in the February 2008 issue of Life Enhancement), certain nutrients, such as those listed above, have been found to be remarkably effective in preventing the formation of damaging AGEs. We incorporated the listed nutrients in our antiAGE formulation that includes rutin, alpha-lipoic acid, carnosine, benfotiamine, histidine, and pyridoxine hydrochloride (vitamin B6) and we each take 6 capsules a day. As an AGE-reduced diet in mice has been found to induce some of the same genetic changes as CR (calorie restricted) fed mice, 1 we hope that taking AGE-reducing nutrients (as well as reducing cooking temperature as often as possible to decrease AGE formation in food) may provide us with similar benefits. In addition, to the antiAGE formulation, we also take two servings a day of our L-Arginine (6 grams per serving) plus cofactors formulation.

1 Vlassara et al. Identifying advanced glycation end products as a major source of oxidants in aging: implications for the management and/or prevention of reduced renal function in elderly persons. Semin Nephrol 29(6):594-603 (2009). 
1b Pizzarelli et al. Predictivity of survival according to different equations for estimating renal function in community-dwelling elderly subjects. Nephro. Dial Transplant 24:1197- 1205 (2009). 
2 Radner et al. L-arginine reduces kidney collagen accumulation and N-epsilon-(carboxymethyl)lysine in the aging NMRI-mouse. J Gerontology: Med Sci 49(2):M44- M46 (1994). 
3 Reckelhoff et al. Long-term dietary supplementation with L-arginine prevents age-related reduction in renal function. Am J Physiol 272(6 pt 2):R1768-74 (1997). 
4 Georgescu and Popov. Age-dependent accumulation of advanced glycation endproducts is accelerated in combined hyuperlipidemia and hyperglycemia, a process attenuated by L-arginine. J AmerAging Assoc 23:33-40 (2000).