Advanced glycation end products and their circulating receptors and level of kidney function in older community-dwelling women.
BACKGROUND
Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) are implicated in the pathogenesis of kidney disease; however, their relation with level of kidney function has not been well characterized.


METHODS
Cross-sectional and prospective.


METHODS
548 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, MD.


METHODS
Serum carboxymethyl-lysine (CML), a dominant AGE; total soluble RAGE (sRAGE); and endogenous secretory RAGE (esRAGE).


METHODS
Glomerular filtration rate (GFR), prevalent and incident decreased GFR (GFR < 60 mL/min/1.73 m(2)). Serum CML, sRAGE, and esRAGE.


RESULTS
Of 548 women, 283 (51.6%) had decreased GFR at baseline. Serum CML level was associated with decreased GFR (OR [all expressed per 1 SD], 1.98; 95% CI, 1.41 to 2.76; P < 0.001) in a multivariate logistic regression model adjusting for age, race, hemoglobin A(1c) level, and chronic diseases. Serum sRAGE and esRAGE levels (both in nanograms per milliliter) were associated with decreased GFR (OR, 1.42; 95% CI, 1.12 to 1.79; P = 0.003; OR, 1.42; 95% CI, 1.14 to 1.77; P = 0.001, respectively) in separate multivariate logistic regression models adjusting for potential confounders. Of 230 women without decreased GFR at baseline, 32 (13.9%) developed decreased GFR by the follow-up visit 12 months later. Serum CML (in micrograms per milliliter), sRAGE, and esRAGE levels at baseline were associated with the prevalence of decreased GFR 12 months later (OR, 1.80; 95% CI, 1.19 to 2.71; P = 0.005; OR, 1.32; 95% CI, 1.01 to 1.74; P = 0.05; and OR, 1.33; 95% CI, 1.01 to 1.77; P = 0.05, respectively) in separate multivariate logistic regression models adjusting for potential confounders.


CONCLUSIONS
Small number of incident cases, limited follow-up, creatinine values not standardized.


CONCLUSIONS
AGE and circulating RAGE levels are independently associated with decreased GFR and seem to predict decreased GFR. AGEs are amenable to interventions because serum AGE levels can be decreased by change in dietary pattern and pharmacological treatment.
Semba
Richard D
RD
Johns Hopkins Medical Institutions, 550 N Broadway, Baltimore, MD 21205, USA. rdsemba@jhmi.edu
Ferrucci
Luigi
L
Fink
Jeffrey C
JC
Sun
Kai
K
Beck
Justine
J
Dalal
Mansi
M
Guralnik
Jack M
JM
Fried
Linda P
LP
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007668:Kidney / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives / Q000097:blood; D015233:Models, Statistical; D015999:Multivariate Analysis; D011446:Prospective Studies; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000097:blood*; D012111:Residence Characteristics; D015398:Signal Transduction / Q000502:physiology
D015415:Biomarkers; D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C048496:N(6)-carboxymethyllysine; D008239:Lysine
Circulation. 2007 Jul 3;116(1):85-97
17606856
Curr Med Chem. 2006;13(17):1971-8
16842191
J Am Soc Nephrol. 2003 Mar;14(3):728-31
12595509
Kidney Int. 2002 Mar;61(3):939-50
11849448
Circulation. 2001 Sep 25;104(13):1464-70
11571237
Am J Nephrol. 2007;27(6):605-14
17823506
Kidney Int. 1998 Feb;53(2):416-22
9461101
Am J Kidney Dis. 2006 Mar;47(3):406-11
16490618
JAMA. 2007 Nov 7;298(17):2038-47
17986697
JAMA. 2007 Sep 12;298(10):1163-70
17848650
Atherosclerosis. 2008 Jan;196(1):9-21
17826783
Am J Nephrol. 2004 Jan-Feb;24(1):32-40
14685005
Diabetologia. 1996 Feb;39(2):149-60
8635666
J Psychiatr Res. 1975 Nov;12(3):189-98
1202204
Am J Clin Nutr. 2007 May;85(5):1236-43
17490958
J Clin Invest. 1997 Feb 1;99(3):457-68
9022079
Clin Chem. 2007 Apr;53(4):766-72
17332152
Diabetologia. 2006 Nov;49(11):2756-62
16969649
Clin Chem Lab Med. 2005;43(5):503-11
15899672
Diabetes Res Clin Pract. 2006 Aug;73(2):158-65
16488505
J Am Soc Nephrol. 1996 Aug;7(8):1198-206
8866413
Am J Hypertens. 2004 Apr;17(4):328-33
15062886
Biochem J. 2003 Mar 15;370(Pt 3):1097-109
12495433
Proc Natl Acad Sci U S A. 1994 Nov 22;91(24):11704-8
7972128
J Biol Chem. 1992 Jul 25;267(21):14987-97
1321822
FASEB J. 2003 Sep;17(12):1762-4
12958202
Ann Intern Med. 1999 Mar 16;130(6):461-70
10075613
Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9436-40
7937785
Diabetologia. 2004 Aug;47(8):1376-9
15258735
Am J Kidney Dis. 2003 Sep;42(3):532-8
12955681
Curr Diab Rep. 2007 Jun;7(3):235-41
17547841
N Engl J Med. 1991 Sep 19;325(12):836-42
1875967
Cardiovasc Res. 2004 Sep 1;63(4):582-92
15306213
J Am Soc Nephrol. 2003 Jun;14(6):1614-22
12761263
J Am Diet Assoc. 2004 Aug;104(8):1287-91
15281050
Am J Kidney Dis. 2006 Oct;48(4):571-9
16997053
J Biol Chem. 1992 Jul 25;267(21):14998-5004
1378843
J Clin Invest. 1996 Jan 1;97(1):238-43
8550841
J Am Soc Nephrol. 2005 Aug;16(8):2363-72
15930093
Biochemistry. 1995 Aug 29;34(34):10872-8
7662668
J Am Soc Nephrol. 2000 Jan;11(1):149-151
10616851
Clin J Am Soc Nephrol. 2008 May;3(3):691-8
18256374
Clin Chem. 2005 Sep;51(9):1749-50
16120960
Obes Res. 2001 Nov;9 Suppl 4:228S-233S
11707546
Mol Cell Biochem. 2007 Aug;302(1-2):35-42
17318407
J Am Soc Nephrol. 2004 Jul;15(7):1889-96
15213278
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6474-9
9177242
Am J Physiol Renal Physiol. 2005 Oct;289(4):F645-59
16159899
J Card Fail. 2005 Apr;11(3):191-5
15812746
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15596-601
12429856
Arterioscler Thromb Vasc Biol. 2005 May;25(5):879-82
15863717
Nephron. 2001 Apr;87(4):295-303
11287772