Advanced glycation end‐products and the kidney

Busch, Martin; Franke, Sybille; Rüster, Christiane; Wolf, Günter

doi:10.1111/j.1365-2362.2010.02317.x

Cited by 191 publications

(152 citation statements)

References 167 publications

(205 reference statements)

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“…Third, AGEs bind to cell membrane receptors (particularly the cell receptor for AGEs) and may induce several intracellular cascades, resulting in the release of cytokines (9), inflammation (36), tumor growth (37), neurodegenerative processes (38), and amyloidosis (39). The cell receptor for AGEs has also been implicated in CKD and CVD pathogenesis, and it is associated with arterial stiffness (10)(11)(12). Although the details of many such pathophysiological mechanisms have not yet been fully elucidated, these examples suggest that AGEs may influence both cardiovascular and non-CVD processes and mortality.…”

Section: Discussionmentioning

confidence: 99%

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Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Fraser

Roderick

McIntyre

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Novel markers may help to improve risk prediction in CKD. One potential candidate is tissue advanced glycation end product accumulation, a marker of cumulative metabolic stress, which can be assessed by a simple noninvasive measurement of skin autofluorescence. Skin autofluorescence correlates with higher risk of cardiovascular events and mortality in people with diabetes or people requiring RRT, but its role in earlier CKD has not been studied.Design, setting, participants, & measurements A prospective cohort of 1741 people with CKD stage 3 was recruited from primary care between August 2008 and March 2010. Participants underwent medical history, clinical assessment, blood and urine sampling for biochemistry, and measurement of skin autofluorescence. Kaplan-Meier plots and multivariate Cox proportional hazards models were used to investigate associations between skin autofluorescence (categorical in quartiles) and all-cause mortality.Results In total, 1707 participants had skin autofluorescence measured; 170 (10%) participants died after a median of 3.6 years of follow-up. The most common cause of death was cardiovascular disease (41%). Higher skin autofluorescence was associated significantly with poorer survival (all-cause mortality, P,0.001) on KaplanMeier analysis. Univariate and age/sex-adjusted Cox proportional hazards models showed that the highest quartile of skin autofluorescence was associated with all-cause mortality (hazard ratio, 2.64; 95% confidence interval, 1.71 to 4.08; P,0.001 and hazard ratio, 1.84; 95% confidence interval, 1.18 to 2.86; P=0.003, respectively, compared with the lowest quartile). This association was not maintained after additional adjustment to include cardiovascular disease, diabetes, smoking, body mass index, eGFR, albuminuria, and hemoglobin.Conclusions Skin autofluorescence was not independently associated with all-cause mortality in this study. Additional research is needed to clarify whether it has a role in risk prediction in CKD.

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Section: Discussionmentioning

confidence: 99%

“…Serum AGEs are subject to fluctuation and have been shown to be a poor indicator of AGE accumulation in tissue compared with skin biopsy (12). Assessment of AGE accumulation in practice has been simplified by devices that measure skin autofluorescence (AF).…”

Section: Introductionmentioning

confidence: 99%

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Fraser

Roderick

McIntyre

et al. 2014

Clinical Journal of the American Society of Nephrology

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“…[4][5][6][7][8] So, we further examined whether DPP-4 deficiency could affect ICAM-1 gene expression in the kidneys and expansion of glomerular area of STZ rats. As shown in Figure 3a and b, renal ICAM-1 gene expression and glomerular area expansion were increased in STZ rats at 9 weeks old compared with agematched Control rats, both of which were significantly blocked in DPP-4-deficient STZ rats at the same age.…”

Section: Effects Of Dpp-4 Deficiency On Oxidative Stress Levels In Thmentioning

confidence: 99%

“…[1][2][3] There is a growing body of evidence that AGEs and their receptor (RAGE) interaction evoke oxidative stress generation and inflammatory and fibrotic reactions, thereby causing progressive alteration in renal architecture and loss of renal function in diabetes. [4][5][6][7][8] Furthermore, RAGEoverexpressing diabetic mice have been shown to exhibit progressive glomerulosclerosis with renal dysfunction, compared with diabetic littermates lacking the RAGE transgene. 9 Diabetic homozygous RAGE null mice displayed diminished albuminuria and glomerulosclerosis and failed to develop significantly increased mesangial matrix expansion or thickening of the glomerular basement membrane.…”

mentioning

confidence: 99%

Dipeptidyl peptidase-4 deficiency protects against experimental diabetic nephropathy partly by blocking the advanced glycation end products-receptor axis

Matsui

Nakashima

Nishino

et al. 2015

Laboratory Investigation

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Advanced glycation end products (AGEs) and their receptor (RAGE) have a role in diabetic nephropathy. We have recently found that linagliptin, an inhibitor of dipeptidyl peptidase-4 (DPP-4), could inhibit renal damage in type 1 diabetic rats by suppressing the AGE-RAGE axis. However, it remains unclear whether DPP-4 deficiency could also have beneficial effects on experimental diabetic nephropathy. To address the issue, we rendered wild-type F344/NSlc and DPP-4-deficient F344/DuCrl/Crlj rats diabetic by injection of streptozotocin, and then investigated whether DPP-4 deficiency could block the activation of AGE-RAGE axis in the diabetic kidneys and resultantly ameliorate renal injury in streptozotocin-induced diabetic rats. Compared with control rats at 9 and 11 weeks old, body weight and heart rates were significantly lower, while fasting blood glucose was higher in wild-type and DPP-4-deficient diabetic rats at the same age. There was no significant difference of body weight, fasting blood glucose and lipid parameters between the two diabetic rat strains. AGEs, 8-hydroxy-2′-deoxyguanosine (8-OHdG) and nitrotyrosine levels in the kidney, renal gene expression of RAGE and intercellular adhesion molecule-1, glomerular area, urinary excretion of 8-OHdG and albumin, and the ratio of renal to body weight were increased in wild-type diabetic rats at 9 and/or 11 weeks old compared with age-matched control rats, all of which except for urinary 8-OHdG levels at 11 weeks old were significantly suppressed in DPP-4-deficient diabetic rats. Our present study suggests that DPP-4 deficiency could exert beneficial actions on type 1 diabetic nephropathy partly by blocking the AGE-RAGE axis. DPP-4 might be a novel therapeutic target for preventing diabetic nephropathy. Sugars, including glucose and fructose, can react nonenzymatically with the amino groups of proteins, lipids and nucleic acids to form reversible Schiff bases, and then Amadori products. 1-3 These early glycation products undergo further complex reactions such as rearrangement, dehydration and condensation to become irreversibly cross-linked, heterogeneous fluorescent derivatives called 'advanced glycation end products (AGEs)'. 1-3 The process of non-enzymatic glycation is also known as Maillard reaction, and formation and accumulation of AGEs in various tissues have progressed at a physiological aging and at an extremely accelerated rate under diabetes. [1][2][3] There is a growing body of evidence that AGEs and their receptor (RAGE) interaction evoke oxidative stress generation and inflammatory and fibrotic reactions, thereby causing progressive alteration in renal architecture and loss of renal function in diabetes. [4][5][6][7][8] Furthermore, RAGEoverexpressing diabetic mice have been shown to exhibit progressive glomerulosclerosis with renal dysfunction, compared with diabetic littermates lacking the RAGE transgene. 9 Diabetic homozygous RAGE null mice displayed diminished albuminuria and glomerulosclerosis and failed to develop significantly increased mesan...

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“…RAGE is a transmembrane receptor and mediates activation of intracellular signal transduction pathways after binding diverse ligands such as AGEs, high mobility group box 1 protein (HMGB1), and S100/calgranulins (12,13). Activation of RAGE triggers intracellular signaling that promotes the proinflammatory tran-scriptional factor NF-B (13,14) and the mitogen-activated protein kinase (MAPK) pathway (15,16). Given the recent studies reporting that AGEs and RAGE are involved in diabetic nephropathy, several methods have been developed to cure chronic kidney disease by interfering with the pathophysiological effect of AGE (12).…”

Section: Autosomal Dominant Polycystic Kidney Disease (Adpkd)mentioning

confidence: 99%

Targeting of Receptor for Advanced Glycation End Products Suppresses Cyst Growth in Polycystic Kidney Disease

Park

Kim

Lee

et al. 2014

Journal of Biological Chemistry

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Background: Receptor of advanced glycation end product (RAGE) mediates not only proinflammatory signaling, but also stimulates cell proliferation and survival-related signaling. Results: Inhibiting RAGE resulted in slowed cyst growth in an autosomal dominant polycystic kidney disease (ADPKD) mouse model and improved renal function. Conclusion: RAGE inhibition is highly effective against cyst enlargement in vivo. Significance: RAGE signaling may play a role in cystogenesis and could be a new therapeutic target for PKD.

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Advanced glycation end‐products and the kidney

Cited by 191 publications

References 167 publications

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Skin Autofluorescence and All-Cause Mortality in Stage 3 CKD

Dipeptidyl peptidase-4 deficiency protects against experimental diabetic nephropathy partly by blocking the advanced glycation end products-receptor axis

Targeting of Receptor for Advanced Glycation End Products Suppresses Cyst Growth in Polycystic Kidney Disease

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